MaxiMize Today PrePare for ToMorrow

MaxiMize Today

PrePare for ToMorrow

Bradley Glick, d.o., faocddavid Grice, d.o., faocd

ProGraM chairs

2012Amer ican Osteopath ic

Co l lege o f Dermato logyAnnua l Meet ing

San D iego , Ca l i fo rn iaOctober 6 -10 , 2012

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FACULTYBradley Glick, D.O., FAOCDAOCD President

Dr. Brad P. Glick, is a Board Certified Dermatologist practicing in Margate and Wellington, Florida. He performs a blend of dermatologic and cosmetic/aesthetic services.

He graduated from Emory University with a B.A. in chemistry and received his M.P.H. at Emory University School of Public Health. He earned his medical D.O. degree with honors at Nova Southeastern University. His internship in internal medicine was performed at Humana South Broward Hospital and his residency in dermatology was performed at Wellington

Regional Medical Center Palm Beach County Public Health Unit and Greater Miami Skin and Laser Center at Mount Sinai Medical Center which included Cutaneous and Laser Surgery.

Dr. Glick is a Diplomate of the American Osteopathic Board of Dermatology, American Osteopathic Board of Family Practice and National Board of Osteopathic Medical Examiners. He held staff positions at University of Florida College of Medicine, Nova Southeastern University College of Osteopathic Medicine, Northwest Medical Center, University Hospital and Medical Center, Coral Springs Medical Center and Mount Sinai Medical Center. Dr. Glick has been the author of numerous publications including journal articles and textbook chapters. He is a guest lecturer for the Novartis and Merz Pharmaceutical Speakers Bureaus and has received numerous honors during his career and was recently elected Program Chairman of the Broward County Dermatologic Society.

David Grice, D.O., FAOCDAOCD President-Elect

Dr. Grice is a Board Certified dermatologist and a fellow of the American Osteopathic College of Dermatology. He has been in dermatology practice since 1996 serving Grand Prairie now for over 14 years. He is a 1989 graduate of the Texas College of Osteopathic Medicine. Dr. Grice completed a one-year internship and a year of internal medicine at Dallas/Fort Worth Medical Center in Grand Prairie, where he also completed a three-year dermatology residency.

Education Undergraduate: Pearland High School Pearland, Texas 1976 -1980 Graduate: St. Mary’s University San Antonio, Texas BA 1980 -1984

Medical School TCOM Fort Worth, Texas D.O. 1985 -1989 Residency: Dallas/Fort Worth Medical Center Grand Prairie, Texas 1993 -1996

Board Certifications/Associations AOBD - 1996 AOCD, AOA, TOMA, AAD Dallas/Fort Worth Dermatologic Society Texas Dermatological Association Texas Medical Association Dallas County Medical Association

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Gregory Papadeas, D.O., FAOCD

Dr. Papadeas is a Denver native. He is board certified in dermatology and an active member of the American Academy of Dermatology. He attended Cherry Creek High School. After completing his undergraduate degree at San Diego State University, he furthered his studies in Europe while playing competitive basketball. Dr. Papadeas earned his medical degree at the Philadelphia College of Osteopathic Medicine and his dermatology training was completed at Ohio University, Grandview Hospital and Medical Center. He is past-president of the Colorado Dermatological Society and The American Osteopathic College of Dermatology.

Daniel Siegel, MD, AAD President

Dr. Siegel attended Rensselaer Polytechnic Institute where he received his magna cum laude undergraduate education as part of a combined six year biomedical program with Albany Medical College from which he received his Doctor of Medicine Degree in 1981.

Daniel Mark Siegel, M.D. has been practicing Mohs surgery since completing his Fellowship in Mohs Micrographic Surgery and Dermatologic Surgery at the Baylor College of Medicine in Houston, Texas in 1986.

Currently, he is Clinical Professor of Dermatology at the State University of New York at Downstate School of Medicine where he teaches residents, medical students and Fellows; directs the American College of Graduate Medical Education approved Procedural Dermatology Fellowship and the American College of Mohs Surgery training program and spends part of his week at both the Brooklyn Veterans Administration Hospital and SUNY Downstate.

Victoria Werth, M.D.

Victoria Werth was initially on the full-time staff at NYU until 1989, at which time she joined the dermatology faculty at the University of Pennsylvania. She has been at Penn since 1989, and has clinical and research interests in medical dermatology. This includes caring for patients with autoimmune blistering and connective tissue diseases, as well as research into the cause of photo-exacerbated skin diseases such as lupus erythematosus and dermatomyositis. She also is conducting a multicenter trial looking at the role of dapsone as a steroid-sparing agent in pemphigus vulgaris. She co-founded the Medical Dermatology Society and spearheaded an effort to have a 5-year combined residency program in internal medicine and dermatology.

Disclosure Attestation:Consultant for Pfizer, Medimmune, Lups Foundation of America, Stiefel, Sanofi, Rigel, CelgeneLicensing: Lupus Foundation, Amgen, Celgene, NovartisGrants: Celgene, Amgen

Brian Kim, M.D.

EducationB.S.: Haverford College 2001M.D.:University of Washington 2007Internship: University of Washington 2008

Disclosure Attestation: None listed

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Emily Chu, M.D., Ph.D

EducationB.S., M.S., Yale University 1999Ph.D., University of Pennsylvania 2005M.D., University of Pennsylvania 2006


Michael Ming, M.D., M.S.C.E.

EducationMedical School: Harvard Medical SchoolInternship: Massachusetts General HospitalResidency: Harvard UniversityFellowship: University of California/San Francisco


Fred Ghali, MD

Dr. Ghali has completed advanced training to become a pediatric dermatologist. He is board-certified in Pediatric Dermatology, General Pediatrics, and General Dermatology. He is an active fellow in both the American Academy of Dermatology and the American Academy of Pediatrics.

Upon completion of his dermatology residency, he served a brief interim as a Clinical Instructor in the Department of Dermatology at the University of Texas Medical School at

Houston. His next position was the Chief of Pediatric Dermatology (1999-2001), Cook Children’s Medical Center, Ft. Worth.

In 2001, Dr. Ghali founded Pediatric Dermatology of North Texas, PA, a private practice clinic providing dermatologic care exclusively for pediatric and adolescent patients. Located in Grapevine, his office offers a central location for families in the Metroplex. In addition to his private practice, Dr. Ghali serves as Clinical Assistant Professor of Dermatology at UT Southwestern Medical School in Dallas. He invests much of his time educating dermatology residents in Pediatric Dermatology.

EducationB.S. (Biology), Dallas Baptist University; Dallas, TX, 1989.M.D., UT Southwestern Medical School; Dallas, TX, 1993.Pediatrics Residency, UT Southwestern/Children’s Medical Center; Dallas, TX, 1996.Dermatology Residency, University of North Carolina at Chapel Hill; Chapel, Hill, NC, 1999.

Disclosure Attestation:Speaker, consultant, Advisory Board: Galderma Labs; Promius; Top MD, Inc.Research: Astellas; Top MD, Inc.Investor: Top MD, Inc.

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Melinda Greenfield, D.O., FAOCD

Melinda F. Greenfield is a board certified dermatologist specializing in the diagnosis and treatment of the skin, hair and nails. Her additional areas of expertise include cutaneous surgery, Botox, Fillers, leg vein treatment (sclerotherapy) and other cosmetic procedures.

She is an Associate Clinical Professor at the Georgia Campus of the Philadelphia College of Osteopathic Medicine and the Georgia Health Sciences University (Medical College of

Georgia). She is on the board of the Dougherty County Medical Society, as well as the Georgia Osteopathic Medical Association and will be president of the Georgia Osteopathic Medical Association for the 2011-2012 term. She is also an Associate Editor of The Journal of the American Osteopathic College of Dermatology.

Dr. Greenfield received her Bachelor of Science degree from the University of Maryland, and received her medical degree with honors from Nova Southeastern University in Ft. Lauderdale, Florida. She completed a year of internal medicine at Sinai Hospital of Baltimore prior to her three year dermatology residency at St. Barnabas Hospital in Bronx, New York.


Stephen Purcell, D.O., FAOCD

Dr. Purcell is a graduate of Muhlenberg College and Chicago College of Osteopathic Medicine. He completed his dermatology residency program at Lackland Air Force Base in San Antonio, Texas. He served eight years on active duty as a physician in the Air Force. He received his license in New York in 1981 and in Pennsylvania in 1988. Dr. Purcell returned to the east coast in 1988 to begin practicing dermatology in Allentown and Pottsville. He is certified by the American Board of Dermatology and the American Osteopathic Board of Dermatology. In addition, he received a certificate of special competency in dermatopathology from the American Osteopathic Association. Dr. Purcell’s medical articles have been

published in several dermatologic journals. He has lectured at national, regional, and local medical meetings. Dr. Purcell is Chief of the Division of Dermatology at Lehigh Valley Health Network and Program Director of Lehigh Valley Health Network and Philadelphia College of Osteopathic Medicine Dermatology Residency Program. He is also Chairman of the Division of Dermatology at Philadelphia College of Osteopathic Medicine. Dr. Purcell is Chairman of the American Osteopathic Board of Dermatology


Michael Morgan, M.D.

EducationB.A., Rollins College 1985M.D., University of South Florida College of Medicine 1989Internship, University of South Florida 1990Residency (Anatomic/Clinical Pathology), University of South Florida 1994Fellowship (Dermatopathology), University of Oklahoma 1995

Residency (Dermatology), University of Oklahoma 1996


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Anthony Dixon, M.D.

Dr. Dixon graduated Medical School from The University of Melbourne in 1982.

His interest in skin cancer dates from his junior resident days in 1983-1985. An ophthalmologist with a special interest in skin cancer on the eyelids taught Dr. Dixon the beginnings of management of skin cancer and the complexity of its treatment. His first experiences and training revolved around eyelid and nose skin cancers.

His interest, training and skills have developed since that time. He has a particular interest in large and/or difficult tumors in awkward areas of the face. A host of repair and reconstruction techniques are employed to close defects remaining after skin cancers are excised.

From a rural surgical background, now Dr. Dixon is exclusively focused on this important sub specialty area. It had been described as the area where dermatology and plastic surgery merge.

Dr. Dixon is involved in advanced post graduate skin cancer management training. He runs comprehensive training programs to assist doctors in their skills managing skin cancer. He is also involved in cutting edge research in skin cancer management. In particular, Dr. Dixon is involved in progressing new techniques in reconstruction following tumor excision.

His Ph.D. studies pertained to research on the complications of skin cancer surgery and their risk factors.

These original studies have been published in the major international journals, including the British Journal of Surgery, Dermatologic Surgery, British Journal of Dermatology, British Medical Journal, Journal of American Academy of Dermatology and the Journal of Plastic Reconstructive and Aesthetic Surgery.

Disclosure Attestation:Stock/Bond Holdings: Allmedic Pty. Ltd.

Steven Grekin, D.O., FAOCD

Dr. Steven Grekin has made it his personal and professional mission to help his patients put their best face forward. Years of research at the International Skin Rejuvenation Institute in Paris, France, and Quebec, Canada, have led Dr. Grekin to understand the secrets to younger, smoother, more radiant skin. He now brings these secrets to his patients in America.

Respected here and abroad as an expert in cosmetic dermatology, Dr. Grekin comes from a long line of physicians-six are dermatologists. He has participated in international teaching and training courses, and is an internationally recognized lecturer in his field.

Guided by cutting-edge principles of modern dermatology, natural medicine, and the highest quality medical care, Dr. Grekin offers his patients an elegant, intelligent program distinguished by its unique flexibility to restore every skin type to its youthful, natural best!

His family has been providing health care in the United States for almost 100 years. Dr. Grekin is committed to helping patients from all over the world. He now offers his programs on-line, so that he may reach out and help as many people as he can put their best face forward.


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Peter Saitta, D.O

EducationB.A., New York University 2003D.O., University of Medicine and Dentistry of New Jersey School of Osteopathic Medicine 2008Internship, Richmond Heights Medical Center 2009Residency, Oakwood Southshore Healthcare System 2012


Francisca Kartono, D.O., FAOCD

EducationB.S., UCLA 2003D.O, Western University of Health Sciences 2007Residency, Botsford General Hospital 2011Fellowship, Ohio State University Wexner Medical Center 2012

Disclosure Attestation: Subinvestigator/Clinical Trials: Abbott, Johnson & Johnson, Celgene

Robert Greenberg, M.D.Trained at UCSF Medical Center, Dr. Greenberg has become a leader in his field using the most up to date therapies for the treatment of medical dermatology. Dr. Greenberg has participated in many studies involving Psoriasis, Eczema, Acne and Rosacea.

Dr. Greenberg frequently lectures on the topics of Psoriasis, Inflammatory Skin disorders, Acne and Rosacea. Using an interactive technique with his attendees, he has become a popular spokesperson for the companies that he represents through lectures, roundtables and CME

programs.

Dr. Greenberg uses his expertise and clinical experience to educate his colleagues on disease states and therapeutic options. His expert opinion is highly valued, particularly with the use of Combination Therapies, Phototherapy, Biologic Therapy, Traditional Systemic Therapies and Topical Medications. Dr. Greenberg has become a major referral source for difficult to treat patients in the Bay Area.

Disclosure Attestation:Speaker/Advisor: Abbott, Amgen, Centocor, Galderma, Medicis, Leo, Onset, Ranbaxy, Promius, Allergan, Bayer

Joseph Jorizzo, M.D.

EducationAB Boston University 1972 MD Boston University School of Medicine 1975 Internship Internal Medicine North Carolina Mem Hosp 1976Residency Dermatology North Carolina Mem Hosp 1979

Clinical Specialties

Rheumatologic/Immunodermatology, Allergic Skin Disease, Nail Disease, Skin Care, Skin and Systemic Disease, Dermatology (general), Pediatric Dermatology, Phototherapy, Skin Cancer

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Angela McKinney, D.O. Botsford Hospital/McLaren-Oakland, Pontiac, MI

Alma AcMoody, D.O. Summa Western Reserve Hospital, Cuyahoga Falls, OH

Keith Robinson, D.O. Summa Western Reserve Hospital, Cuyahoga Falls, OH

Stephen Weis, D.O. UNTHSC/TCOM, Fort Worth, TX

Paul Aanderud, D.O. Oakwood Southshore Medical Center, Warren, MI

Peter Knabel, D.O. Northeast Regional Medical Center, Kirksville, MO

Grace Kim, D.O. Valley Hospital Medical Center, Las Vegas, NV

Mari Batta, D.O. Alta Dermatology, Mesa, AZ

Jeremy Bingham, D.O. Advanced Desert Dermatology, Peoria, AZ

Helia Eragi, D.O. Pacific Hospital, Torrance, CA

Tatyana Groysman, D.O. PCOM/Lehigh Valley Health Network, Allentown, PA

Mounir Wassef, D.O. Columbia Hospital, West Palm Beach, FL

Alison Himes, D.O. O’Blenness Hospital, Dublin, OH

Sanjosh Singh, D.O. St. John’s Episcopal Hospital, Lindenhurst, NY

Charlotte Noorollah, D.O. St. John’s Episcopal Hospital, Lindenhurst, NY

James B. Young, D.O. St. Joseph Mercy Health System, Clinton Twp., MI

Heather Orkwis, D.O. St. Joseph Mercy Health System, Clinton Twp., MI

Libby Rhee, D.O. St. Barnabas Hospital, Bronx, NY

Blakely Richardson, D.O. University Hospitals, Cleveland, OH

Ashley Kittridge, D.O. University Hospitals, Cleveland, OH

Ellecia Cook, D.O. Largo Medical Center, Port Richey, FL

RESIDENT FACULTY

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ACCREDITATION The American Osteopathic College of Dermatology is accredited by the American Osteopathic Association to award con-tinuing medical education to physicians. This activity has been planned and implemented in accordance with the Policies of the Council on Continuing Medical Education of the AOA.

MEETING OBJECTIVES: The 2012 Annual Meeting will provide a diversified CME program focusing on the art and science of Dermatology. Infor-mation will be presented through lectures and scientific paper presentations. Attendees will be updated on a broad range of new developments in dermatology and acquire a better understanding of advances in medical and surgical therapies. They will also gain greater insight into current trends in practice management as well as financial and medical/legal chal-lenges facing today’s clinician.

It is expected that attendees of this meeting will increase diagnostic skills in a wide range of dermatology as well as derma-topathology. In addition to increased diagnostic competence, enhanced concepts of therapy and treatment in dermatologic care will be taken back for implementation in everyday practice. The overall result being improved physician/provider per-formance and increased positive patient outcomes.

NEEDS ASSESMENTS The program was developed based upon the needs of physicians within the association identified through:

• A program evaluation/survey provided to meeting participants at both our annual and midyear meeting, • Recommendations received through the mail, email, or by phone, • Recommendations from previous program chair, • New advances in dermatologic treatment identified in major publications or research studies. • The Board of Trustees also meets to discuss previous conferences and to provide additional topics and potential

speaker contacts.

FACULTY DISCLOSURE As a sponsor accredited by the AOA, it is the policy of the AOCD to require the disclosure of anyone who is in a position to control the content of an educational activity. All relevant financial relationships with any commercial interests and/or manufacturers must be disclosed.

DISCLOSURE of COMMERCIAL SUPPORT of CME As you undoubtedly know from the national media, there has been much discussion concerning the relationships between CME sponsors, faculty and commercial companies providing support of CME.

Both the American Osteopathic Association and the Committee on Continuing Medical Education have adopted regula-tions for ethical actions in this area which the American Osteopathic College of Dermatology endorse and have adopted for all our educational activities.

Please be assured that having an affiliation with a company does not imply in any way that something is wrong or improp-er; however, we want to inform attendees that such a relationship exists.

Should you have any questions regarding the facilities, handouts, program content, or concerns about CME compliance with the AOA “Uniform Guidelines,” feel free to contact the AOCD representative:

Marsha A. Wise, B.S. Executive Director P.O. Box 7525 Kirksville, MO 63501 660-665-2184 800-449-2623

Unresolved issues regarding compliance with the AOA “Uniform Guidelines” can be brought to the attention of the AOA Division of CME by calling:

800-621-1773, extension 8262 or by writing:

AOA CME Office 142 East Ontario Street

Chicago, IL 60611

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All Events to take place in the San Diego Convention Center unless otherwise noted.

7:00 am - 8:00 am AOCD Registration

8:00 am - 8:30 am CLIA – Proficiency Tests Gregory Papadeas, D.O., FAOCD

8:30 am - 9:00 am Daniel Siegel, MD, AAD President

9:00 am - 12:00 am 2nd Annual University of Pennsylvania Symposium

9:00 am - 9:45 am Update in Autoimmune Skin Disease Victoria Werth, M.D. University of Pennsylvania Health System

9:45 am - 10:30 am Atopic Dermatitis Brian Kim, M.D. University of Pennsylvania Health System

10:30 am - 11:15 am Newer Drug Reactions Emily Chu, M.D., Ph.D. University of Pennsylvania Health System

11:15 am - 12:00 pm Issues in Melanoma Michael Ming, M.D., M.S.C.E. University of Pennsylvania Health System

12:00 pm - 1:00 pm Lunch on your own

1:00 pm - 2:00 pm Novel Topical Dermatologic Treatments for the Pediatric Patient Fred Ghali, M.D. Pediatric Dermatology of North Texas, PA, Grapevine, TX

2:00 pm - 3:00 pm Cosmeceuticals Steven Grekin, D.O., FAOCD

3:00 pm - 3:15 pm Break

3:15 pm - 5:00 pm AOCD General Business Meeting

6:00 pm - 9:00 pm Presidential Celebration (Ticketed Event) San Diego Marriott

MONDAY, OCTOBER 8, 2012

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Pathophysiology of atopic dermatitis update

Brian S. Kim, MD Department of Dermatology

Perelman School of Medicine at the University of Pennsylvania

October 8th, 2012

Immune dysregulation hypothesis

IL-4, IL-5, IL-13

Th2 cells

Naïve T cell

Antigen-presenting

cell

IgE production

Allergens

Skin

Primary immunodeficiency Wiskott-Aldrich syndrome IgE deficiency IPEX syndrome SCID/Omenn syndrome Job syndrome DOCK8 deficiency

Barrier dysfunction hypothesis

IL-4, IL-5, IL-13

Th2 cells IgE production

Allergens

Skin Filaggrin mutations Netherton syndrome

Naïve T cell

Antigen-presenting

cell

Barrier dysfunction hypothesis

IL-4, IL-5, IL-13


Allergens

Skin Filaggrin mutations Netherton syndrome

Naïve T cell

Antigen-presenting

cell

Filaggrin is a key skin barrier protein

• Mutations in filaggrin underlie ichthyosis vulgaris

• Filaggrin products include urocanic acid (regulates pH) and hygroscopic amino acids (retains moisture)

• Cetaphil Restoraderm®

Osawa et al. Allergol Int 2011 Weidinger et al. J Allergy Clin Immunol 2006

Filaggrin mutations are associated with atopic dermatitis

Osawa et al. Allergol Int 2011 Weidinger et al. J Allergy Clin Immunol 2006

SNP Variable P value OR (95% CI)

2282del4

Mutant allele

0.0013 2.5 (1.4-4.3)

R501X Mutant allele

<0.0001 4.1 (2.2-7.9)

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The history of filaggrin

Brown and McLean J Invest Dermatol 2012

Filaggrin mutations may initiate allergic inflammation in the skin and

the ‘atopic march’

Osawa et al. Allergol Int 2011

How is allergic inflammation in the skin initiated?

IL-4, IL-5, IL-13


Allergens

Skin Filaggrin mutations

? Targeted by: Cyclosporine Calcineurin inhibitors

Naïve T cell

Antigen-presenting

cell

How is allergic inflammation in the skin initiated?

IL-4, IL-5, IL-13


Allergens


IL-25, IL-33 and TSLP

Brandt et al. J Clin Cell Immunol 2011

Targeted by: Cyclosporine Calcineurin inhibitors

Naïve T cell

Antigen-presenting

cell

Epidermal-derived cytokines IL-25, IL-33 and TSLP in human atopic dermatitis

Control Atopic Dermatitis

IL-25

IL-33

TSLP Soumelis et al. Nat Immunol 2002

Hvid et al. J Invest Dermatol 2010

Pushparaj et al. PNAS 2009

Filaggrin expression is related to IL-25, IL-33 and TSLP

Lee et al. Exp Dermatol 2011 Hvid et al. J Invest Dermatol 2010 Savinko et al. J Invest Dermatol 2010

Human Keratinocytes Human Keratinocytes Filaggrin-deficient Mouse Skin

IL-25 TSLP IL-33

Fila

ggrin

in %

of u

nstim

ulat

ed

IL-25 (ng/ml) TSLP

(sta

ined

are

a/ep

ider

mis)

Rela

tive

Uni

ts

Flaky tail mice

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Epithelial cell-derived cytokines directly elicit innate cell populations at

other barrier surfaces Allergens

Gut

Th2 cells

Lymph Node

ILCs MPP

IL-33 IL-25

Siracusa et al. Nature 2011 Neill et al. Nature 2010 Saenz et al. Nature 2010

Basophil

TSLP

Helminths

Antigen- presenting cell Naïve T cell

Summary • Mutations in filaggrin are associated with atopic

dermatitis

• Filaggrin defects are associated with dysregulation of epidermal-derived cytokines (IL-25, IL-33 and TSLP) that promote allergic inflammation

• Novel or previously unrecognized innate cell populations are elicited by epidermal derived cytokines

Pattern Recognition Receptors: A primary modality of innate immunity

Kaufmann Nat Rev Micro 2007

What is the role of bacterial colonization on AD?

Brandt et al. J Clin Cell Immunol 2011

S. aureus colonization Allergens Skin Barrier Defects: Filaggrin/Claudin-1

S. aureus induces TSLP in human keratinocytes

Primary Human Keratinocytes

Vu et al. J Allergy Clin Immunol 2010

Concentration (U/ml)

S. Aureus membrane

TSLP

(pg/

ml)

S. aureus colonization is associated with flares of AD and decreased commensal microbial diversity

Kong et al. Genome Res 2012

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Depletion of commensal bacteria enhances allergic inflammation

March 2012

Summary

• S. aureus may enhance allergic inflammation via epidermal cell-derived cytokines such as TSLP

• S. aureus is associated with flares of atopic dermatitis

• Commensal bacterial diversity is associated with improved atopic dermatitis

Pathogen vs. Commensal

Commensals

Pathogens

What is the role of skin bacteria?

• Does short-term antimicrobial therapy work because of S. aureus-targeted therapy?

• Is there a role for “probiotic” therapy?

Topical bleach baths and intranasal mupirocin improves eczema severity

%BS

A

EASI

Sco

re

Huang et al. Pediatrics 2009

Months Months

What is the role of (commensal) fungi?

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Darabi et al. J Am Acad Dermatol 2009

Subtype of atopic dermatitis • (1) head and neck lesions • (2) exacerbations during adolescence or young

adulthood • (3) severe lesions recalcitrant to conventional

therapy • (4) other atopic diseases.

• 1- to 2-month course of daily itraconazole or

ketoconazole followed by long-term weekly treatment.

Candida overgrowth is associated with Th2 cytokine responses in the lung

Noverr et al. Infect Immun 2005

Antibiotic

Untreated

Eosin

ophi

ls (1

06 )

Seru

m I

gE (n

g/m

l)

IL-5

(pg/

ml)

IL-1

3 (p

g/m

l)

The current paradigm of atopic dermatitis

IL-4, IL-5, IL-13

Th2 cells

Naïve

APC IgE production

Allergens


Bacteria or Fungi

Epidermal cell-derived cytokines IL-25, IL-33 and/or TSLP

Newly identified innate cell populations (eg, basophils and ILCs)

Acknowledgements

• David Artis

• Artis Laboratory – Mark Siracusa – Steven Saenz – Laurel Monticelli

• Department of Dermatology at the Perelman School of Medicine at Upenn – George Cotsarelis – John R. Stanley – William D. James

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19

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Novel Topical Therapies Pediatric Dermatology

Fred Ghali, MD Pediatric Dermatology

of North Texas, PA

Disclosures

• Many of the novel topicals therapies discussed in tonight’s program are considered ‘off-label’, and some are not FDA-approved for the particular condition and/or age

• Industry Relations: – Advisory Board,

Consultant & Speaker: • Galderma, Promius,

Triax, Top MD, Valeant

– Research: • Astellas (Apples Study) • TopMD (CLn™ Pilot)

– Shareholder: • TopMD, Inc.

Topics

• War On Staph: Strategies For ‘Containment’

• Refractory Warts

• Vitiligo

• New Breakthroughs

Staphylococcal ‘Containment’

‘Containment’ May Be A More Practical Goal Than ‘Decolonization’

Prevention & Maintenance Primary vs Secondary

Skin & Soft Tissue Infections (SSTI)

Primary SSTI’s Impetigo Cellulitis

Folliculitis Boils/Furunculosis

Secondary SSTI’s Infected Eczema (AD) Infected Dermatitis

Burns Wounds

Skin Barrier Intact Skin Barrier Impaired

Clinical Practice Guidelines by the Infectious Diseases Society of America for the Treatment of

MRSA Infections in Adults and Children: Executive Summary

• Decolonization strategies should be offered in conjunction with ongoing reinforcement of hygiene measures and may include the following: – i. Nasal decolonization with mupirocin twice daily for 5–10 days

(C-III). – ii. Nasal decolonization with mupirocin twice daily for 5–10

days and topical body decolonization regimens with a skin antiseptic solution (eg, chlorhexidine) for 5–14 days or dilute bleach baths. • For dilute bleach baths, 1 teaspoon per gallon of water [or ¼ cup

per ¼ tub or 13 gallons of water given for 15 min twice weekly for 3 months can be considered.)

CID 2011:52 ( February).

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‘Biocide’ Resistance (Cross Resistance Becoming An Issue)

• Because biocides tend to act concurrently on multiple sites within the microorganism, resistance is often mediated by non-specific means.

• Most Mentioned: – Triclosan – Benzalkonium chloride

• Report of linked to oxacillin resistance in Staphylococcus aureus. (Akimitsu et al)

• Mechanisms: – Decreased cell wall

permeability • Decreases biocide reaching

the cell

– Efflux pumps – Change in biofilm – Induction of genes

(Plasmid-generated) – Enzymatic transformation

Scientific Committee on Emerging and Newly Identified Health Risks SCENIHR. Assessment of the Antibiotic Resistance Effects of Biocides, 2009 report

Resistance To Topicals

• Resistance rates to topical therapies such as mupirocin and fusidic acid are increasing and have been reported

• Mupirocin resistance rates among S. aureus isolates in SSTI documented – US: 5.2% (SENTRY

Antimicrobial Surveillance Program 2000)

– Multiple reports worldwide

Oranje AP et al.. Dermatology 2007;215:331–340. Simor AE et al. Antimicrob Agents Chemother 2007;51: 3880–3886. Deshpande et al. l Infect Dis 2002;42:283–290. SENTRY Antimicrobial Surveillance Program Upton A, et al. . J Antimicrob Chemother 2003;51:613–617.

History of Bleach Dakin’s Solution

• Developed by English chemist, Henry Drysdale Dakin, and French surgeon, Alexis Carrel, after a long search for an ideal wound antiseptic

• Prepared by passing chlorine into a solution of sodium hydroxide

• Used in WW I as a wound

antiseptic

• Dakin’s solution is highly diluted antiseptic

– Sodium hypochlorite 0.5% • Sometimes this higher % can be cytotoxic

– Boric acid 4% – This higher % of sodium hypochlorite can

be cytotoxic to tissues

• References in the literature show that a sodium hypochlorite (Dakin’s) solution diluted to 0.005% is bactericidal while being non-cytotoxic to fibroblasts. – More dilute variations of Dakin’s

solution marketed by Century Pharmaceuticals

Mechanisms of Bleach (HOCL)

• Reacts with DNA, RNA, fatty acids, cholesterol, lipids, proteins

• Additionally, the increased pH is harmful to cells

• Specifics: – 1) Reaction with protein

sulfhydryl groups1

– 2) reaction with protein amino groups (chloramination-AA decompose)1

– 3) oxidative unfolding and aggregation of proteins (heat shock protein 33)2

1) Estrela et al, Braz Dent J, 2002:13: 113-117; 2) Winter et al., Cell, 2008; 135:691-701

Bleach Dilutions (6%)

Sodium Cups Bathtub (40-60 gallon) Hypochlorite (%) 0.009% (90 ppm) ¼ cup ¼ tub 0.019% (190 ppm) ½ cup ¼ tub 0.005% (50 ppm) ¼ cup ½ tub 0.009% (90 ppm) ½ cup ½ tub 0.005% (50 ppm) ½ cup Full tub

References: Bathtub: 40-60 gallons; 1 gallon = 128 oz, 40 gallons = 5120 oz; 1 cup = 8 oz Swimming pool reference: 3 parts per million (available chlorine)

8-10 minutes, 2-3 times/wk Infant tub: 1-2 tsp/gallon Rinse after

Product Indication Availability NaOCL Diluted Dakins Mechanically cleanse OTC (510K) 0.0125% (Di-Dak-Sol®) and debride open wounds Aurstat® Gel Abrasions Rx (510K) KIT 0.002% lacerations, irritations Atrapro™ HydroGel Pain, burning, itching Rx (510K) * with various dermatoses *(also HOCL)

Atrapro™ Spray Management of Rx (510K) 0.004% wounds (also 0.003% HOCL)

CLn® BodyWash Clean and relieve Cosmetic 0.0061% dryness/flaking of skin

Commercially Available Products (Sodium hypochlorite)

* = Present only to ‘preserve’ hydrogel

24

S. Aureus & AD

S. aureus & AD • AD skin found to deficient

in antimicrobial peptides – Decreased levels of

cathelicidins are thought to be due to IL-4, which is increased in atopics

• S. aureus • Eczema herpeticum

• Superantigens of S. aureus

cause T-cell dysfunction – Also increased IgE Ab

• S. aureus Colonization: – ~ 10% carrier state in non-

atopic patients – Much higher in atopic

patients • Lesional (~40-93%) • Non-lesional (~40-76%) • Nares (~40-79%)

Leyden et al (Br J Dermatol 1974) Balma-Mena et al. Int J Dermatol. 2011:682-8.

MRSA in Atopics Colonization vs Infection

• Colonization: (cross-sectional studies)

– 16% MRSA (7/43 patients), 80% were colonized with S. aureus (43 ⁄ 54)1 (Philly)

– 1 case/200 MRSA; 62% colonization of S. aureus (Canada)

– 13.5% MRSA 57% (57/100) colonized with S. aureus (Sri Lanka)

– 31% (24 /168) were MRSA 78/168, overall 46% healthy children with AD colonized with S. aureus, and (Taiwan)

• Infection : – Same prior study showed 60%

MRSA (12/20) (Taiwan) – 11/78 isolates of SSTI’s (14.1%)

from atopics were MRSA, significantly lower than 44% in general peds population (658 /1482)

• Colonization and infection are on a continuum – My experience:

• Mild-mod: 20% • Mod-severe: 44% • Severe plus: 50%

1Suh et el., Pediatric Dermatol Vol. 25 No. 5 528–534, 2008 2Balma-Mena et al. Int J Dermatol. 2011:682-8. 3 Tang et al., Pediatr Int. 2011 Jun;53(3):363-7. 4 Matiz et al., Pediatr Dermatol. 2011 Jan-Feb;28(1):6-11

MRSA & Atopic Dermatitis

• Key Presentation: Folliculitis, pustules, boils, and abscesses Refractory Dermatitis +/- oozing

• consider cultures or empiric treatment with a different oral antibiotic


MRSA positive & patient responded to oral clindamycin, incision & drainage, & topical steroids for active eczema areas

This child had both refractory dermatitis, classic oozing, and boils


This child had refractory dermatitis, but no boils

*Grew out MRSA

Did not respond to oral cephalexin x 2 wks

~35% of our atopic patients who are infected grow out MRSA

25

Sodium Hypochlorite (Bleach) Baths: A Potential Measure to Reduce the Incidence of Recurrent, Cutaneous Staphylococcus aureus Superinfection among Susceptible Populations

John Browning, MD1, Moise Levy, MD1,2, Alexandra Rousseau, MD1, Raphael Rousseau, MD1,

Sheldon Kaplan, MD2, and Denise Metry, MD1,2

Departments of Dermatology1 and Pediatrics2, Baylor College of Medicine and Texas Children’s Hospital, Houston, TX

INTRODUCTION

PATIENTS AND METHODS

RESULTS

DISCUSSION AND CONCLUSION

Table 2. Decrease in MRSA and MSSA superinfections in patients with atopic dermatitis after starting sodium hypochlorite baths and intranasal mupirocin.

REFERENCES

Patients with atopic dermatitis (AD) are more susceptible to cutaneous superinfection due to an impaired skin barrier that is both inherent and secondary to pruritus-induced excoriations. In turn, secondary infection further exacerbates the inflammatory process of AD (Figures 1 and 2).

Greater than 90% of AD patients harbor large numbers of Staphylococcus aureus bacteria, which can be cultured not only from eczematous plaques, but also from clinically normal skin, the anterior nares, and subungual spaces. While in the past these S. aureus strains have been primarily susceptible to methicillin (MSSA), increasing numbers of resistant staphylococcal strains (MRSA) are being identified in healthy patients without any risk factors: so-called “community-acquired” MRSA (CA-MRSA). A dramatic rise in such infections has been increasingly reported from our and other institutions, and has been reflected in our pediatric dermatology population, particularly patients with AD (Table 1).

Recurrent cutaneous superinfection with S. aureus is problematic, and to our knowledge, no standard treatment recommendations exist. Along with other authors, we have observed the resolution of cutaneous infection, both when an oral antibiotic was given to which the organism was later found to be non-susceptible, and even in the absence of any treatment. Given these observations, along with known concerns regarding antibiotic overuse and increasing bacterial resistance patterns, we have tended to reserve systemic antibiotics for patients with evidence of more widespread cutaneous infection and/or those with systemic symptoms. Accordingly, we have also sought alternative measures to reduce patient susceptibility to recurrent cutaneous staphylococcal superinfection.

Beginning in May of 2002, we implemented “anti-Staphylococcal measures” among patients and their household members with a history of cutaneous superinfection. These measures combine the use of intranasal mupirocin (pea-sized amount of mupirocin ointment applied to the anterior nares twice daily for 7 days a month for 6 months) with sodium hypochlorite baths (2 teaspoons of 6% sodium hypochlorite household bleach per gallon of bath water or ¼ cup per full tub of water, twice weekly for 6 months) (Figure 3).

Sodium hypochlorite has been used to prevent bacterial skin infections among burn patients, as well as those with epidermolysis bullosa. In one study, concentrations of 0.25%, 0.025%, and 0.0125% sodium hypochlorite were investigated. Concentrations as low as 0.0125% were found to be bactericidal to gram positive organisms without causing tissue toxicity (Heggers, et al). A second study found sodium hypochlorite concentrations as low as 0.01% to be bactericidal against S. aureus (Rutala, et al). Our recommended dilution yields a similar concentration of sodium hypochlorite (2 tsp per gallon compared to 1.6 tsp/gallon necessary to achieve a .0125% dilution, compared to .06 tsp per gallon in a normally chlorinated swimming pool).

Sodium hypochlorite is bactericidal due to a direct effect on the bacteria cells and thus carries no risk for increased resistance. Thus, the effect of sodium hypochlorite on S. aureus is similar to that of benzoyl peroxide on Propionibacterium acnes.

Potential risks of sodium hypochlorite, particularly among the AD population, include irritation and xerosis, although we have found this modality to be well-tolerated by our patients. We recommend rinsing with clean water followed by immediate emollient application, and reassuring families who can be anxious about the use of “bleach” that the recommended dilution is low. While other antiseptic products are certainly available, sodium hypochlorite is a readily accessible, inexpensive and well-tolerated option. Although prospective, controlled studies are greatly needed, we believe that the additional use of sodium hypochlorite baths, in combination with intranasal mupirocin, may be an effective measure towards reducing the incidence of recurrent staphylococcal cutaneous superinfection, including MRSA, among susceptible populations.

In an IRB-approved retrospective chart review performed on

243 children clinically diagnosed with AD who were seen in our outpatient dermatology clinics between January 1999 and October 2002, we observed a dramatic decrease in culture confirmed

staphylococcal skin infections concomitant with implementation of these measures (Figure). In continuing these preventative measures, we observed a decrease from 60 cases of staphylococcal infections a year (August 2001 – July 2002) to 6 cases a year (August 2003 – July 2004).

1. Purcell K, Fergie J. Epidemic of community-acquired methicillin-resistant Staphylococcus aureus infections: a 14-year study at Driscoll Children’s Hospital. Arch Pediatr Adolesc Med. 2005;159(10):980-5.

2. Kaplan SL, Hulten KG, Gonzalez BE, et al. Three-year surveillance of community-acquired Staphylococcus aureus infections in children. Clin Infect Dis 2005; 40:1785-1791.

3. Heggers JP, et al. Bactericidal and wound-heali ng properties of sodium hypochlorite solutions: the 1991 Lindberg Award. J Burn Care Rehabil 1991; 12(5):420-

4. McGuire, Joseph. Personal communication.

5. Rutala WA, Cole EC, Thomann CA, Weber DJ. Stability and bactericidal activity of chlorine solutions. Infect Cont Hosp Epi 1998; 19(5):323-7.

Figure 1. Eczematous patches along the anterior neck, superinfected with CA-MRSA.

Figure 2. Child with atopic dermatitis who developed a cutaneous abscess from CA-MRSA superinfection.

Table 1. Identification of community-acquired MRSA infections at Texas Children’s Hospital between August 2001 and December 2003

Figure 3. “Anti-Staphylococcal measures” implemented in May 2002.

0

20

40

60

80

100

120

140

160

180

200

8 10 12 2 4 6 8 10 12 2 4 6 8 10 12

MSSA MRSA

Application of mupirocin (Bactroban ®) to the anterior nares twice a day for 7 days every month for 6 months.

Bathing in water with sodium hypochlorite (2 tsp per gallon of water or ¼ cup per full tub of water) twice a week for 6 months.

0

2

4

6

8

10

12

04/99

-06/99

07/99

-09/99

10/99

-12/99

01/00

-03/00

04/00

-06/00

07/00

-09/00

10/00

-12/00

01/01

-03/01

04/01

-06/01

07/01

-09/01

10/01

-12/01

01/02

-03/02

04/02

-06/02

07/02

-09/02

10/02

-12/02

Nu

mb

er

of

ca

se

s

MSSAMRSAOther

Startpoint of mupirocin prophylaxisand sodium hypochlorite baths

Treatment of Staph Colonization Huang et al. Pediatrics 2009; May 808-814

• Double-blind, placebo-controlled, ~25 patients for follow-up

• Chronic use of dilute bleach baths with intermittent intranasal application of mupirocin ointment decreased the clinical severity of atopic dermatitis in patients with clinical signs of secondary bacterial infections.

• Patients with atopic dermatitis do not seem to have increased susceptibility to infection or colonization with resistant strains of S aureus. –I DISAGREE (35% TX)

• The mean EASI scores for the head and neck did not decrease for patients in the treatment group, whereas scores for other body sites (submerged in the dilute bleach baths) decreased at 1 and 3 months, in comparison with placebo-treated patients.

Reserve for Clinically Infected • F.J. Bath-Hextall; Interventions to Reduce Staphylococcus

aureus in the Management of Atopic Eczema: An Updated Cochrane Review. Br J Derm 2010.

• Conclusions:

– We failed to find any evidence that commonly used anti-staphylococcal interventions are clinically helpful in people with eczema that is not clinically infected.

– Their continued use should be questioned in such situations, until better and longer-term studies show clear evidence of clinical benefit.

What about infection-prone patients?? Colonization vs Infection –Sometimes A Slippery Slope

CLn® Body Wash

• Indication: – Clean and relieve

dryness/flaking of skin

• Available as cosmetic product – In-office dispensing – Web site (www.clnwash.com)

• Passed All Basic Testing:

– Epiocular™; Repeat insult patch test; US/Euro Antimicrobial Effectiveness Test

• Kill Rates S. aureus: • 98% kill rate at 2 min • 99.9 at 3 and 5 min

• Studies: – Completed Pilot Study

• 18 moderate-severe atopics (submitted for publication)

– Planned: • 50 patient multi-center study

in moderate-severe atopics • 20 patient single-center

comparative study for hand eczema (investigator-initiated)

• 30 patient acne pilot study

Efficacy of CLn® BodyWash in AD Study Design:

• A single-center, 12-week pilot retrospective & prospective study of 18 moderate to severe atopic patients, ages 2 to 15 years, who were instructed to bathe 3 days per week with the body wash formulated with sodium hypochlorite (CLn™ BodyWash). – Primary Parameters: IGA, BSA – Secondary: Bacterial counts & Patient Tolerability

• Patients continued their standard treatment regimen, including

topical and/or systemic therapies.

• Exclusion criteria - clinically significant active infection at baseline, current or recent topical/oral antibiotic use in the prior 2 weeks.

C Ryan, R Shaw, C Cockerell, S Hand, , F Ghali. Submitted for review.

Mean Reduction in BSA


26

Mean Change In IGA


Case (7) Baseline

6 weeks

2 weeks

10 weeks

Case (11)

Baseline 8 weeks

Results: CLn® BodyWash

• Changes in BSA and IGA showed statistically significant results.

• Adverse Events: – 3 reported burning/stinging

• Tolerability:

– CLn Body Wash™ was well-tolerated and overall patient preference was statistically significant over the traditional bleach baths.

• Bacteriology: – Decreasing trend in

quantitative S. aureus counts; statistically significant at 1 month • MRSA colonization rate

44%, higher than in other studies

• Conclusions:

– Similar to traditional bleach baths, this study supports the adjunctive use of CLn® BodyWash in AD.


‘Containment’ Maintenance Strategies

Primary Staph (SSTI’s)

Secondary Staph SSTI’s

Chlorhexidine Antimicrobial Soaps

Sodium Hypochlorite

(Bleach) Topical

Antibiotics

Topical Antibiotics

Sodium Hypochlorite

(Bleach)

Refractory Warts

Topical Contact Immunotherapy

27

Be Cautious!!

‘Ring Warts’

Cantharadin Outpatient & In-Office Cryo

Cantharadin

• Extract of blister beetle

• Not FDA approved – But is included under the

Bulk Substance Act for compounding to physicians or ordered from Canada

• I use only for warts on the

palms/soles

• Advantage: – Painless procedure

• Two Major Forms: (Both mixed in collodion)

– Cantharadin 0.7% – Cantharadin Plus is

my preference for small (<5 mm) warts (plantar/plantar) • Cantharadin 1% • Podophyllin 5% • Salicylic acid 30%

Ring Warts & Cantharadin

• Very common occurrence, especially on dorsal surfaces of the skin

• I tend to use only for warts located on the palms/soles – Will not use on the fingers,

cuticles, face, or other areas – This will translate to very

little development of ring warts

Ring wart

In-Office

Ring Warts OTC, Histofreeze/Verruca-Freeze • There is a very high risk of ring

warts with ‘over-freezing” Hook-m Horns

Ring wart

Topical Contact Sensitization • General Principle

– In-office application to a skin site (usually the arm) to induce contact allergy (sensitization)

– At home patients use a lower concentration painted on warts to induce immune response • Advancing 3x/wk…4x/wk…daily

• Squaric acid is more popular w/ pedi derms

– DNCB not used much in peds b/c of mutagenic potential

• Side effects: – Contact dermatitis

• At sensitization site, wart site, possible id reaction

Squaric Acid My Experience

Step 1: Sensitize w/ 2% in the office

– On upper arm Step 2: Apply weaker % at home

– After ~ 2 wks, pt applies 0.4% at home to the warts

Step 3: Recheck in the office

– If no response in 2 mos, double strength

At Home

Expected erythema around warts

28

Squaric Acid My Experience

• “Recall” Phenomena – Appears at original

sensitization site – When the patient

begins applying the weaker % of sq acid onto the treated warts

– It does mean they are truly sensitized

• Its presence does correlate well with a good response – But its absence does not

translate into a failure as the majority of responders do not demonstrate this reaction

At Home Squaric Acid My Experience

• I avoid use on the face/neck/groin

• ~ 70% effective – Seems to work best

against plantar warts – Duration: 2-4 months

2 months later 0.4%

Squaric Acid Case Examples

• Advantages – Non-painful – May combine w/ other

treatments – Ease of sensitization in

most patients – Lack of mutagenicity – Scarcity in common

human environments 3 mos later (0.4%)

Side Effects-Contact Dermatitis

• May occur at the sensitization site or any applied site – Less likely can develop

“Auto-eczema”/ “id”

• Treatment: – Decrease applications – Potent topical steroid or

oral steroid if severe

At Home

Case Example

Baseline S/P Squaric acid 0.6% x 2 mos

When It Fails… And Your Back Is Against The Wall

• May do 1-1.5% outpt protocol – Must be extra-

careful!!

• Or apply 2% in-office & return in 2 wks

Before

This patient failed 0.4%…0.8%..but responded to 1.5%

After

29

When It Fails…

Baseline S/p squaric acid 1.25% x 2 mos

Vitiligo Tacrolimus

Topical oxsoralen Topical Steroids

Tacrolimus 0.1% Use in Vitiligo

• Several case series in the literature

• Major Points: – Improvement is slow – Better results when combined with “cautious”

natural UV exposure • Best for face and neck

Literature Review Tacrolimus 0.1% & Vitiligo

• Skin Types: – Topical tacrolimus is

effective irrespective of skin tone, with greatest benefit in type 3-4 skin

– Repigmentation of lesions on the head and neck is superior to repigmentation of the body and extremities in all racial subgroups.1

• Children vs Adults: – Study showed that children

had approximately nine times higher odds (95% CI = 1.09, 81.88) of having better response to the treatment than adults. The disease duration of 5 years or less also showed a better response.2

1Silverberg, J Drugs Dermatol. 2011 May;10(5):507-10 2Udompataikul M, J Dermatol. 2011 Jun;38(6):536-40

Tacrolimus 0.1% for Vitiligo

Baseline 3 months

Tacrolimus 0.1% for Vitiligo (off-label usage)

Baseline

5 months

30

Tacrolimus 0.1% for Vitiligo Baseline 4 months

Tacrolimus & UV Therapy

• Tacrolimus 0.1% in combination with narrowband UVB 2-3X/week (off-label) – Signed consent discussing possible skin cancer

risk, black box, etc. – Combination therapy is vastly more effective than

tacrolimus or NBUVB alone

• Facial skin tends to be the most responsive – Not great for thicker-skinned body sites

Combination NB-UVB and Tacrolimus Is Better

Comparative Studies • Randomized, double-blind comparative study shows that

the combination of NB-UVB and tacrolimus ointment (0.1%) is more effective than UV treatment alone in patients with vitiligo. The effect is tacrolimus total dose-dependent.2

• Another comparative study showed addition of topical tacrolimus increases overall repigmentation and also reduces the cumulative NB-UVB dose needed to achieve a therapeutic benefit in affected patients3

2Nordal et al., J Eur Acad Dermatol Venereol. 2011 Dec;25(12):1440-3 3 Majid. Photodermatol Photoimmunol Photomed. 2010 Oct;26(5):230-4

Combo therapy began 2 months

Tacrolimus & NBUVB

Steroids not helpful Not better w/ NBUVB x 2 mos

Combo Therapy Started

3 wks after combo tx

2 months later

Above stomach

Non-facial sites with thinner skin may also respond well

Does improvement last??

Using Topical Oxsoralen • Oxsoralen is diluted to

1:1000 concentration ointment

• Applied QOD

• Exposed to natural sunlight and gradually increase as tolerated – 5..10..20..30 minutes

• Choose right patient – Heard of lawsuits

• Choose right body site

– Better for trunk/extr – I feel that we should

avoid using this product on the face, as reaction is too unpredictable; blisters

Be Cautious With This Therapy

31

Pre-tx 1 mo 2 mos

4 mos 9 mos Topical oxsoralen

Segmental type

Topical Steroids

• Class 1 or 2

• Applied cyclic fashion – 2-3 wks ‘on’, 1 wk ‘off’

• Helps reduce atrophy potential

• Variable response

– Knees and shins work the best! 3 months

Baseline

BreakThroughs

Hemangiomas Angiofibromas

Timolol Ophthalmic for HOI

• A quick direct inhibitory effect on the growth of the HOI, followed by slower regression (showed in many studies in Derm/Ophtho)

• Best for superficial types

– Smaller, but not always

• Formulations: – GFS: 0.5% ; 0.25% – Solution: 0.5%, 0.25%

• Applied bid-tid during proliferative phase

• Cohort Study: Multi-center – 72/73 improved, with a mean

improvement of 45

29.5%.(visual analog)

– Predictors of better response were superficial type (p=0.01), 0.5% timolol concentration (p=0.01), and duration of use longer than 3 months (p = 0.04).

• Sleeping disturbance was noted in one patient. T

– This study further demonstrates the efficacy and tolerability of topical timolol maleate and gradual improvement with longer treatment in patients with superficial IH.

Chakkittakandiyil A et al, Pediatr Dermatol 2012; Jan

Timolol GFS 0.05%

Baseline PHACES ruled out

1 month

6 months

Angiofibromas (Adenoma sebaceum)

• Hallmark skin finding of Tuberous Sclerosis

• May present during the pre-pubertal period

• Appear as erythematous, acneiform papules on the perinasal and malar cheek regions

32

Tumors in TS • Background:

– Hamartin and tuberin respectively, form a tumor suppressor complex that controls a key regulatory kinase, mammalian Target of Rapamycin (mTOR). (1)

– When mutations occur in either gene, the hamartin-tuberin complex does not function properly and the mTOR pathway is constitutively activated which leads to dysregulated protein translation, cell growth and proliferation (2)

• As cells that lack normal tuberin or hamartin cannot down-regulate the mTOR signaling pathway, there is significant interest in investigating the utility of mTOR inhibitors – Such as rapamycin and its

analogs, to treat TSC-related tumors.

– Rapamycin ( Sirolimus, Rapamune) is an mTOR kinase inhibitor that is FDA approved for immunosuppression following kidney transplantation.

– The beneficial effects of mTOR inhibitors have been shown in preclinical studies of TSC rodent models, where reductions were seen in kidney, subcutaneous and pituitary tumors

1-Gao X et al.. Nat Cell Biol. 2002;4:699–704. doi: 10.1038/ncb847. 2-Findlay et al. Curr Opin Genet Dev. 2005;15:69–76. doi: 10.1016/j.gde.2004.11.002. 3- Inoki K et al. . Nat Genet. 2005;37:19–24. doi: 10.1038/ng1494.

Initial Reports Topical Sirolimus

• Nude Mouse Model – RESULTS: Treatment with topical rapamycin

improved survival and reduced tumor growth. Topical rapamycin treatment resulted in systemic drug levels within the known therapeutic range and was not as effective as injected rapamycin.

– CONCLUSION: Topical rapamycin inhibits TSC-

related tumor growth. These findings could lead to a novel treatment approach for facial angiofibromas and other TSC skin lesions.

• Human Case Report – We report a patient with TSC

with recurrent life-threatening haemorrhage from both kidneys due to extensive angiomyolipoma formation leading to bilateral nephrectomy and renal transplantation.

– Immunosuppressive treatment with rapamycin, a specific mTOR inhibitor, initiated because of renal transplantation, reduced facial angiofibroma dramatically.

Rauktys et al, BMC Dermatol 2008;8:1 Hofbauer et al, Br J Dermatol. 2008 Aug;159(2):473-5

Topical Sirolimus (Rapamycin)

• Haemel et al: (2010) – 1st case report using 1%

ointment (compounded from tabs), applied bid • Labs @ 6 wks/12 wks

– Cbc, metab panel, and serum rapamycin <2.

• No systemic absorption after 3 mos

• Deklotz et al. (2011): – Recipe for compounding

in ointment to reduce potential irritancy

• Salido et al. (2011) – 10 patients treated with

0.4% sirolimus ointment 3 times a week for 9 months

• Wataya et al. (2011)

– Topical application of rapamycin-tacrolimus ointment is a safe and useful treatment for TSC-related angiofibroma

Haemel AK et al Arch Dermatol. 2010 Jul;146(7):715-8. Salido et al., J Eur Acad Derm Ven; Aug 2011 Wataya-Kaneda et al., Br J Derm; Oct 2011

Topical Sirolimus (Rapamycin) 1% Ointment

Baseline 2 months Normal labs

No side effects

Topical Sirolimus (Rapamycin) 1% Ointment

Baseline 2 months Normal labs

No side effects

A Novel Application of Topical Rapamycin Formulation, an Inhibitor of mTOR, for Patients

With Hypomelanotic Macules in TS Complex.

• Case Report (2) – Rapamycin 0.2% gel

• 2 patients reported that

had improvement of both the hypopigmented macules and “red plaque” (likely collagenoma)

• Proposed Pathogenesis: – Normal # melanocytes but

decrease in melanosome size/number

– Increase in micropthalmia transcription factor (MITF), which is show to induce melanization

• Personal:

– I’m trying it now on forehead fibrous plaques

Mari Wataya-Kaneda et al., Arch Dermatol; Jan 2012.

33

Review • War On Staph: Strategies For ‘Containment’

– Role of sodium hypochlorite

• Refractory Warts: Topical Immunotherapy

• Vitiligo: Location-dependent topical options

• New Breakthroughs – Timolol; Sirolimus

34

1

Cosmeceuticals Steven Grekin, DO, FAOCD

Program Director Oakwood Southshore Medical Center

2

Financial Disclosures None to report pertaining to this topic

3

Objectives Evaluate the definition “cosmeceutical” Examine the evidence regarding the efficacy of

common ingredients Discuss the relevance to everyday clinical

practice

4

Why is this an important topic for our profession?

We live in a society that believes in holding onto youthfulness, despite an aging population with increased life expectancy.

Skin is the organ that most vividly

gives away our age!

5

Unfortunately, as we age we accumulate damage to the skin over time and lose the youthful quality to our skin. This is seen in the development of rhytides, lentigines, telangiectasias, and dyschromia.

Many are willing to trade wealth for youth, which has resulted in a demand for the development and manufacturing of high-end, anti-aging products.

This search for youthfulness has resulted in the establishment and growth of the cosmeceutical industry.

Brandt FS, Cazzaniga A, Hann M. Cosmeceuticals: current trends and market analysis. Semin Cutan Med Surg. 2011;30(3):141-3. Giacomoni PU. Advancement in skin aging: the future cosmeceuticals. Clin Dermatol. 26(4):364-6. Martin KI, Glaser DA. Cosmeceuticals: the new medicine of beauty. Mo Med. 108(1):60-3.

6

Aging defined… Chronological aging vs. photoaging and the overlap… It is important to understand that chronological aging is

defined primarily by the passage of time, while photoaging is defined by the accumulation of damage to the skin from UV irradiation.

Of course, an overlap exists and even sun protected skin ages with time, but is usually thinner, more evenly pigmented, laxer, and more finely lined than chronologically aged skin with superimposed photodamage.

Fisher, GJ, Kang S, et. al. Mechanisms of photoaging and chronological aging. Archives of Dermatology. 2002; 138:1462-1470

35

7

The big business of the cosmeceutical market…

Consumers, many of which are our patients, spend billions of dollars on cosmetics and cosmeceutical products each year!

Cosmeceuticals are one of the fastest growing segments of the personal care industry.

Cosmeceuticals provide patients with an alternative to surgical procedures and prescriptions, often times at a lower cost.

Sachdev M, Friedman A. Cosmeceuticals in day-to-day clinical practice. J Drugs Dermatol. 2010;9(5 Suppl ODAC Conf Pt 1):s62-6.] Newburger AE. Cosmeceuticals: myths and misconceptions. Clin Dermatol. 27(5):446-52.

8

The Smart Consumer Our patients are savvy, searching the internet and

exploring magazines for products that will make them look better, younger… and they expect results!

Patients come to us for our “expert opinion.” This makes it extremely important that we understand

the products that our patients are bringing to us to evaluate.

Often times these are products we are selling to patients in our own office!

9

Dr. Albert Kligman first popularized the term

“Cosmeceutical” in 1984 to describe a unique category of products somewhere on the continuum between drugs and cosmetics. These products are expected to have both cosmetic and therapeutic or physiologic benefits.

Brandt FS, Cazzaniga A, Hann M. Cosmeceuticals: current trends and market analysis. Semin Cutan Med Surg. 2011;30(3):141-3. Rivers JK. The role of cosmeceuticals in antiaging therapy. Skin Therapy Lett. 13(8):5-9. Kligman D. Cosmeceuticals. Dermatol Clin. 2000;18(4):609-15.

10

The Federal Food, Drug, and Cosmetic Act - 1930

The law defines cosmetics as "articles intended to be rubbed, poured, sprinkled, or sprayed on, introduced into, or otherwise applied to the human body...for cleansing, beautifying, promoting attractiveness, or altering the appearance"

[FD&C Act, sec. 201(i)]

Rivers JK. The role of cosmeceuticals in antiaging therapy. Skin Therapy Lett. 13(8):5-9. Kligman D. Cosmeceuticals. Dermatol Clin. 2000;18(4):609-15. http://www.fda.gov/regulatoryinformation/legislation/federalfooddrugandcosmeticactfdcact/default.htm Accessed 8-29-2012

11


This includes: skin moisturizers, perfumes, lipsticks, fingernail polishes, eye and facial makeup, shampoos, hair colors, and deodorants, as well as any substance intended for use as a component of a cosmetic product.

http://www.fda.gov/Cosmetics/GuidanceComplianceRegulatoryInformation/ucm074201.htm 12


The law defines drugs as "articles intended for use in the diagnosis, cure, mitigation, treatment, or prevention of disease and intended to affect the structure or any function of the body . . . "

[FD&C Act, sec. 201(g)(1)]

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Stratum Corneum: The Gatekeeper

The disconnect with these definitions is that the laws were created when the strateum corneum (SC) was thought to be an inert and complete barrier to the deeper layers of the epidermis.

It is now known that the SC is quite complex and dynamic, providing primary control over the permeation of topical compounds.

Verma P, Pathak K. Therapeutic and cosmeceutical potential of ethosomes: An overview. J Adv Pharm Technol Res. 2010;1(3):274-82. Menon GK, Cleary GW, Lane ME. The structure and function of the stratum corneum. Int J Pharm. 2012;435(1):3-9.

14

Stratum Corneum The structure of the SC has been compared to that of a

“brick and mortar” system, with protein-rich corneocytes (bricks) embedded into a hydrophobic lipid matrix (mortar), thus creating a selectively permeable environment.

http://nutritionforskinbeauty.com/?cat=1 Menon GK, Cleary GW, Lane ME. The structure and function of the stratum corneum. Int J Pharm. 2012;435(1):3-9.

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“Gray Area” The law does not recognize the category

“cosmeceutical”. A product can be a drug, a cosmetic, or a combination of both.

This creates a very blurry zone, as products are marketed as if pharmacologically active without stepping into the zone that would require them to be classified as a drug.

Newburger AE. Cosmeceuticals: myths and misconceptions. Clin Dermatol. 27(5):446-52. Kligman D. Cosmeceuticals. Dermatol Clin. 2000;18(4):609-15.

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Creative marketing of “intended use” allows for promotion of the benefits of the products without outright claims regarding the physiologic or therapeutic benefits.

17

What can they advertise to appeal to the consumer and bypass the law?

The power of creative marketing: More even skin tone Improved skin texture Increased skin radiance Decreased appearance of skin wrinkling Enhanced anti-aging benefits Draelos ZD. The cosmeceutical realm. Clin Dermatol. 26(6):627-32. 18

The “short” arm of the law: Where the law doesn‘t reach…

Cosmeceuticals are not FDA regulated, however they are regulated by the Federal Trade Commission (FTC).

The job of the FTC is to investigate advertising claims of pharmaceutical properties to assess the soundness of the advertisement.

Brandt FS, Cazzaniga A, Hann M. Cosmeceuticals: current trends and market analysis. Semin Cutan Med Surg. 2011;30(3):141-3.

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19

Are they safe? The FDA has provided guidelines for cosmetic good

manufacturing practice (GMP) to ensure against adulterated or mislabeled products, but no regulations exist.

In contrast, the law requires strict adherence to GMP requirements for drugs, and there are regulations specifying minimum current GMP requirements

However, the FDA may conduct research on cosmetic products and ingredients to address safety concerns

http://www.fda.gov/Cosmetics/GuidanceComplianceRegulatoryInformation/ucm074201.htm

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Do they really work? Efficacy is usually tested using the final formulation, making it

challenging to separate out the effect of an individual ingredient.

Most (not all) cosmeceuticals are made from ingredients that already have a proven safety record in the cosmetic market.

New, raw ingredients generally undergo extensive animal testing to determine if the ingredient is appropriate for human use.

Draelos ZD. The cosmeceutical realm. Clin Dermatol. 26(6):627-32.

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The “Catch 22”

Invasive evaluations of the effect of the product on the skin cannot be performed, because this would indicate that, in fact, the product has pharmacological effects rather than cosmetic benefits. How is the efficacy of a cosmeceutical tested?

Draelos ZD. Cosmeceuticals: undefined, unclassified, and unregulated. Clin Dermatol. 27(5):431-4..

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A brief overview… Various, non-invasive,

methods are used to test the efficacy of cosmeceuticals. Skin moisturization

measured by evaporimetry, which utilizes humidity probes to measure transepidermal water loss and assess skin barrier function.

Draelos ZD. Cosmeceuticals: undefined, unclassified, and unregulated. Clin Dermatol. 27(5):431-4. http://www.sciencephoto.com/media/296686/enlarge

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A brief overview… Skin moisturization

measured by corneometry, which uses electrical current to measure skin conductivity.

Improvement in fine lines and wrinkles measured by profilometry, which utilizes silicone on the skin surface to make a replica of the skin topography

Draelos ZD. Cosmeceuticals: undefined, unclassified, and unregulated. Clin Dermatol. 27(5):431-4. http://www.surplussalesline.com/detail.asp?ProdID=8373 24

• Improvement in skin color/tone measured by Doppler flowmetry, which measures the speed of blood flow in the skin to assess skin color.

• Improvement in skin thickness measured by A-scan ultrasound imaging, which utilizes the technique of ultrasound to assess thickness of the skin.

http://www.google.com/imgres?um=1&hl=en&biw=1024&bih=506&tbm=isch&tbnid=YFRm10IS6E2t3M:&imgrefurl=http://www.sciencedirect.com/science/article/pii/S1050173808000236&imgurl=http://ars.els-cdn.com/content/image/1-s2.0-S1050173808000236-gr1.jpg&w=546&h=297&ei=al8-UKj2GsHZqgGKwYH4BA&zoom=1&iact=hc&vpx=553&vpy=121&dur=3494&hovh=165&hovw=305&tx=164&ty=123&sig=103776399020605810590&page=1&tbnh=104&tbnw=191&start=0&ndsp=10&ved=1t:429,r:8,s:0,i:98

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25

• Improvement in skin color/tone measured by chromametry, which utilizes a special camera (originally used to match paint colors) to measure skin color.

And of course, improvement in any of the above characteristics is measured by the human eye, ideally in well-controlled, double-blind studies.

Draelos ZD. Cosmeceuticals: undefined, unclassified, and unregulated. Clin Dermatol. 27(5):431-4

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The Quality Factor Good quality, well-controlled studies compare the

efficacy of the vehicle versus the vehicle plus active ingredient, in order to determine the effect of the individual active ingredient.

While vehicles themselves are outside the scope of this lecture, we need to be mindful of the fact that vehicles can boost the efficacy of an active ingredient or inactivate it. They can themselves improve skin barrier.

Draelos ZD. Cosmeceuticals: undefined, unclassified, and unregulated. Clin Dermatol. 27(5):431-4. Rivers JK. The role of cosmeceuticals in antiaging therapy. Skin Therapy Lett. 13(8):5-9.

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The Ingredients

Due to the enormous number of active ingredients presently employed in cosmeceuticals, only a selection of the most common substances will be described.

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Categories of Cosmeceuticals

Antioxidants Growth factors Peptides Anti-inflammatories/botanicals Polysaccharides Pigment lightening agents

Choi CM, Berson DS. Cosmeceuticals. Semin Cutan Med Surg. 2006;25(3):163-8

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Hydroquinone (HQ)

An ingredient well known for its suppressive effects on melanin synthesis.

It has been used for years in topical concentrations of 2% to 4%, either alone or in combination with tretinoin, to successfully improve melasma.

Gao XH, Zhang L, Wei H, Chen HD. Efficacy and safety of innovative cosmeceuticals. Clin Dermatol. 26(4):367-74. 30

Hydroquinone: How does it work?

Covalently binds histidine or interacts with copper at the active site of tyrosinase, the rate limiting enzyme in melanin synthesis.

It inhibits RNA and DNA synthesis, altering melanosome formation, thus selectively damaging melanocytes, and exhibiting a cytotoxic effect.

Draelos ZD. The cosmeceutical realm. Clin Dermatol. 26(6):627-32. Reszko AE, Berson D, Lupo MP. Cosmeceuticals: practical applications. Obstet Gynecol Clin North Am. 2010;37(4):547-69, viii.

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31 http://www.oculist.net/downaton502/prof/ebook/duanes/pages/v4/ch038/001f.html

Hydroquinone: Mechanism of Action

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Hydroquinone: Concerns In 2006, the FDA announced that it may no longer be

safe . . . Carcinogenic properties were demonstrated in rodents

who were given high quantities of systemic HQ. Increasing reports of ochronosis (bluish-black

discoloration) from topically treated sites. Banned in Europe, Australia, and Japan in OTC

preparations. Still available in the US in OTC preparations.

Draelos ZD. The cosmeceutical realm. Clin Dermatol. 26(6):627-32. Reszko AE, Berson D, Lupo MP. Cosmeceuticals: practical applications. Obstet Gynecol Clin North Am. 2010;37(4):547-69, viii. Rivers JK. The role of cosmeceuticals in antiaging therapy. Skin Therapy Lett. 13(8):5-9. Badreshia-bansal S, Draelos ZD. Insight into skin lightening cosmeceuticals for women of color. J Drugs Dermatol. 2007;6(1):32-9.

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Hydroquinone: Limitations Clinical improvement with 2% HQ as monotherapy

for melasma has been reported

Results were seen at 4-6 weeks and plateaued at 4 months

No well-controlled studies on the efficacy of HQ at this strength

Ennes SBP, Paschoalick RC, Mota De Avelar Alchorne M. A double-blind, comparative, placebo-controlled study of the efficacy and tolerability of 4% hydroquinone as a depigmenting agent in melasma. Journal of Dermatological Treatment. 2000; 11(3): 173-179.

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Azelaic Acid Naturally occurring saturated dicarboxylic acid, originally

isolated from the yeast Pityrosporum ovale.

Effective against acne and rosacea, but can also inhibit melanin production as a weak competitive inhibitor of tyrosinase.

Has antiproliferative and cytotoxic effects on melanocytes by inhibiting thioredoxin reductase.

Draelos ZD. The cosmeceutical realm. Clin Dermatol. 26(6):627-32. Reszko AE, Berson D, Lupo MP. Cosmeceuticals: practical applications. Obstet Gynecol Clin North Am. 2010;37(4):547-69, viii. Draelos ZD. Skin lightening preparations and the hydroquinone controversy. Dermatol Ther. 20(5):308-13. Gao XH, Zhang L, Wei H, Chen HD. Efficacy and safety of innovative cosmeceuticals. Clin Dermatol. 26(4):367-74.

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Azelaic Acid A double blind study of 329 participants showed that the use of 20%

azelaic acid with a broad spectrum sunscreen over 24 weeks resulted in good or excellent results against melasma

Effects are comparable to 4% HQ, although with slightly more local irritation Despite irritation, it may be a more appropriate choice in patients with skin of

color because there is no known risk ochronosis. Added (possibly synergistic) benefit when combined with 15-20%

glycolic acid.

However, only available in concentrations up to 10% OTC.

Gao XH, Zhang L, Wei H, Chen HD. Efficacy and safety of innovative cosmeceuticals. Clin Dermatol. 26(4):367-74. Draelos ZD. The cosmeceutical realm. Clin Dermatol. 26(6):627-32. Reszko AE, Berson D, Lupo MP. Cosmeceuticals: practical applications. Obstet Gynecol Clin North Am. 2010;37(4):547-69, viii. Baliña LM, Graupe K. The treatment of melasma. 20% azelaic acid versus 4% hydroquinone cream. Int J Dermatol. 1991;30(12):893-5.

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Niacinamide (B3) A substance normally found in all human cells as part of

coenzymes NAD and NADP, which act as antioxidants and regulate numerous cellular metabolic pathways.

Known to have a role in regulation of cellular metabolism and cell renewal.

By unknown mechanism of action, Niacinamide may suppress melanosome transfer from melanocytes to surrounding keratinocytes. 5% niacinamide has been shown to inhibit 35-68% of melanosome

transfer to keratinocytes. Double blind, vehicle controlled studies over a period of three months

showed reduced signs of skin aging including hyperpigmentation, skin redness, senile lentigines, yellow discoloration, and large pore size.

Sachdev M, Friedman A. Cosmeceuticals in day-to-day clinical practice. J Drugs Dermatol. 2010;9(5 Suppl ODAC Conf Pt 1):s62-6.] Levin J, Momin SB. How much do we really know about our favorite cosmeceutical ingredients? J Clin Aesthet Dermatol. 2010;3(2):22-41. Kerscher M, Buntrock H. Update on cosmeceuticals. J Dtsch Dermatol Ges. 2011;9(4):314-26. Bissett DL, Miyamoto K, Sun P, Li J, Berge CA. Topical niacinamide reduces yellowing, wrinkling, red blotchiness, and hyperpigmented spots in aging facial skin. Int J Cosmet Sci. 2004;26(5):231-8.

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Niacinamide (B3)… Beyond Pigment Modification

Has also showed promising improvement of skin barrier, skin elasticity, as well as fine lines and wrinkles. A randomized, double-blind study on 50 white

females, who applied 5% niacinamide twice daily for 12 weeks had improvement in fine lines, wrinkles, pigmentation, and skin elasticity.

Sold in concentrations of up to 5%. Has a very good tolerability profile.

Kerscher M, Buntrock H. Update on cosmeceuticals. J Dtsch Dermatol Ges. 2011;9(4):314-26. Bissett DL, Miyamoto K, Sun P, Li J, Berge CA. Topical niacinamide reduces yellowing, wrinkling, red blotchiness, and hyperpigmented spots in aging facial skin. Int J Cosmet Sci. 2004;26(5):231-8. 38

Antioxidants: Vitamin E

Vitamin E (α-tocopherol) is considered a lipophillic antioxidant, protecting cells from free radical induced lipid peroxidation and physically blocking UVR.

Sachdev M, Friedman A. Cosmeceuticals in day-to-day clinical practice. J Drugs Dermatol. 2010;9(5 Suppl ODAC Conf Pt 1):s62-6.] Reszko AE, Berson D, Lupo MP. Cosmeceuticals: practical applications. Obstet Gynecol Clin North Am. 2010;37(4):547-69, viii.

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Vitamin E Found in countless skin care products in concentrations

of 2-20%. In the form of α-tocopherol, the most active form,

topical Vitamin E has been noted to improve the wrinkling and hyperpigmentation caused by free radicals and also have a photoprotective effect. A double-blinded, randomized, and vehicle controlled study on

10 subjects by Zhai et al. demonstrated decreased UV-induced erythema and inflammatory skin damage with the application of a topical vitamin E emulsion.

Excellent tolerability.

Kerscher M, Buntrock H. Update on cosmeceuticals. J Dtsch Dermatol Ges. 2011;9(4):314-26. Martin KI, Glaser DA. Cosmeceuticals: the new medicine of beauty. Mo Med. 108(1):60-3.

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Antioxidants: Vitamin C Vitamin C (L-ascorbic acid) functions as a free

radical scavenger, which allows it to extinguish reactive species and protect cells from oxidative stress.

Has been shown to play a role in many factors of anti-aging, including promotion of collagen synthesis, and skin lightening.

Sachdev M, Friedman A. Cosmeceuticals in day-to-day clinical practice. J Drugs Dermatol. 2010;9(5 Suppl ODAC Conf Pt 1):s62-6.] Reszko AE, Berson D, Lupo MP. Cosmeceuticals: practical applications. Obstet Gynecol Clin North Am. 2010;37(4):547-69, viii.

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Vitamin C and Pigment Studies evaluating improvement in

hyperpigmentation have shown promising results. In a split-faced clinical trial, 16 women with

melasma were treated with a nightly application of 5% ascorbic acid cream on one side, and 4% HQ on the opposite side for 16 weeks.

Both sides showed excellent results, with no statistical difference in outcome. Topical ascorbic acid was well tolerated, with much lower rates of side effects vs. HQ.

Reszko AE, Berson D, Lupo MP. Cosmeceuticals: practical applications. Obstet Gynecol Clin North Am. 2010;37(4):547-69, viii. Espinal-perez LE, Moncada B, Castanedo-cazares JP. A double-blind randomized trial of 5% ascorbic acid vs. 4% hydroquinone in melasma. Int J Dermatol. 2004;43(8):604-7.

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Vitamin C and Rhytides A double-blind, split-face, vehicle controlled

study by Fitzpatrick et. al, of 10 subjects utilizing a vitamin C complex of ascorbic acid and provitamin C demonstrated significant improvement in wrinkling when used topically for 12 weeks.

Biopsies showed increased Grenz zone collagen, as well as increased staining for mRNA for type I collagen!

Fitzpatrick RE, Rostan EF. Double-blind, half-face study comparing topical vitamin C and vehicle for rejuvenation of photodamage. Dermatol Surg. 2002;28(3):231-6.

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Vitamins C and E Vitamins C and E have been shown to act

synergistically to provide antioxidant protection from UVR when combined with ferulic acid Improved chemical stability of the vitamin C and

vitamin E Doubled photoprotection of skin from 4-fold to

approximately 8-fold as measured by MED and histological sunburn cell count on weanling white Yorkshire pig skin.

Lin FH, Lin JY, Gupta RD, et al. Ferulic acid stabilizes a solution of vitamins C and E and doubles its photoprotection of skin. J Invest Dermatol. 2005;125(4):826-32.

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Retinoids Compounds with the basic core structure of

Vitamin A and its oxidized metabolites, or synthetic compounds that share similar mechanisms of action as naturally occurring retinoids. Forms:

Retinol (Vit A alcohol) Retinal (Vit A aldehyde) Retinoic acid (Vit A acid)

Reszko AE, Berson D, Lupo MP. Cosmeceuticals: practical applications. Obstet Gynecol Clin North Am. 2010;37(4):547-69, viii. Gao XH, Zhang L, Wei H, Chen HD. Efficacy and safety of innovative cosmeceuticals. Clin Dermatol. 26(4):367-74.

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Retinoids

In the skin, retinol is reversibly oxidized into retinaldehyde (retinal), which is in turn irreversibly oxidized to retinoic acid, which is the biologically active form of Vitamin A.

Topical cosmeceuticals containing retinol and retinal theoretically work because once absorbed they are metabolized to retinoic acid, which induces pharmacological activity.

Levin J, Momin SB. How much do we really know about our favorite cosmeceutical ingredients? J Clin Aesthet Dermatol. 2010;3(2):22-41.

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Retinoids: The Limitation Unfortunately, only a

small amount of retinol and retinal can be converted by the skin, accounting for the increased efficacy seen with prescription preparations containing retinoic acid.

Draelos ZD. The cosmeceutical realm. Clin Dermatol. 26(6):627-32.

http://www.advancedskintech.com/GCScience.htm

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Retinoids: The workhorse? One of the most studied ingredients in cosmeceuticals. An effective topical treatment for photoaging, acne, and

numerous dermatological disorders. Tretinoin is considered to be one of the most potent

compounds available for treating the signs of aging and/or photodamaged skin, however side effects such as burning and scaling can limits its use and acceptance.

Retinol is available OTC and is considered the “gold standard” cosmeceutical in anti-aging. Less irritating to the skin with better tolerability than prescription

tretinoin.

Rivers JK. The role of cosmeceuticals in antiaging therapy. Skin Therapy Lett. 13(8):5-9. Levin J, Momin SB. How much do we really know about our favorite cosmeceutical ingredients? J Clin Aesthet Dermatol. 2010;3(2):22-41. Kerscher M, Buntrock H. Update on cosmeceuticals. J Dtsch Dermatol Ges. 2011;9(4):314-26. 48

Retinoids and Pigmentation Retinoids effectively reduce pigment by dispersing

melanosomes, interfering with melanocyte-keratinocyte pigment transfer, and accelerating epidermal turnover and subsequently, pigment loss.

Additionally, retinoids may inhibit melanogenesis by inhibiting tyrosinase and DOPAchrome conversion factor.

All-trans-retinoic acid (tretinoin) inhibits melanin synthesis through down regulation of tryrosinase and tyrosinase-related protein 1(TRP-1) expression in melanocytes. Reszko AE, Berson D, Lupo MP. Cosmeceuticals: practical applications. Obstet Gynecol Clin North Am. 2010;37(4):547-69, viii.

Gao XH, Zhang L, Wei H, Chen HD. Efficacy and safety of innovative cosmeceuticals. Clin Dermatol. 26(4):367-74.

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http://www.oculist.net/downaton502/prof/ebook/duanes/pages/v4/ch038/001f.html

Retinoids: Effect on pigmentation

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Retinoids and Rhytides Retinoids have been shown to also improve fine lines,

wrinkles, and overall skin tone. UV radiation induces matrix metalloprotienases

(MMPs), which degrade dermal collagen and elastin. It is suggested that that treatment with retinol

reduces MMP expression and likely increases collagen synthesis.

Nolan KA, Marmur ES. Over-the-counter topical skincare products: a review of the literature. J Drugs Dermatol. 2012;11(2):220-4. Varani J, Warner RL, Gharaee-kermani M, et al. Vitamin A antagonizes decreased cell growth and elevated collagen-degrading matrix metalloproteinases and stimulates collagen accumulation in naturally. aged human skin. J Invest Dermatol. 2000;114(3):480-6

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Pigmentation and Rhytides A recent 12 week, randomized, double-blinded, controlled

study by Ho et. al, compared non-prescription tri-retinol gradual release cream 1.1% with prescription tretinoin 0.025%. Both products showed marked improvements in fine and course

periocular wrinkles, skin firmness, tone and brightness, mottled pigmentation, and photodamage as evaluated by digital photography and self-assessment questionnaires. No significant differences in efficacy between the two products. Satisfaction of both products exceeded 93% by the end of the

study.

Ho ET, Trookman NS, Sperber BR, et al. A randomized, double-blind, controlled comparative trial of the anti-aging properties of non-prescription tri-retinol 1.1% vs. prescription tretinoin 0.025%. J Drugs Dermatol. 2012;11(1):64-9. 52

Alpha Hydroxy Acids Alpha hydroxy acids are organic carboxylic

acids commonly used in cosmeceuticals due to their hydrophilic properties and include: Citric acid Glycolic acid Lactic acid Malic acid Pyruvic acid Tartaric acid Basic Structure of Alpha Hydroxy Acids

Rivers JK. The role of cosmeceuticals in antiaging therapy. Skin Therapy Lett. 13(8):5-9.

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Alpha Hydroxy Acids (AHA)

Many forms and various sources exist,

although lactic acid and glycolic acid are the most widely studied forms of AHAs because they have a molecular size that allows effective penetration into the top layers of skin.


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AHA’s have an effect on the epidermis by disrupting corneocyte cohesion at the level of the stratum granulosum, allowing the AHA’s to penetrate to the level of the dermis. At the dermis AHA’s induce synthesis of glycosaminoglycans, prevent corticosteroid atrophy, and increase dermal thickness possibly by an induction of fibroblast proliferation. Function as anti-inflammatory agents and antioxidants, resulting in improvement of erythema associated with UV exposure.

Alpha Hydroxy Acids

Bolognia, J. L., Jorizzo, J. L., & Schaffer, J. V. (2012). Dermatology. (3rd ed., Vol. 2, p. 2488). Elsevier Saunders.

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Alpha Hydroxy Acids

OTC products must have less than a 10 percent concentration.

A 22 week, double-blind, vehicle-controlled study evaluating 8% glycolic acid and 8% L-lactic acid creams showed marked improvement in photodamaged skin.

Stiller MJ, Bartolone J, Stern R, et al. Topical 8% glycolic acid and 8% L-lactic acid creams for the treatment of photodamaged skin. A double-blind vehicle-controlled clinical trial. Arch Dermatol. 1996;132(6):631-6. 56

Alpha Hydroxy Acids

Side effects including redness, swelling, blistering, burning, itching, discoloration, and increased photosensitivity are related to the pH and concentration of AHA, vehicles used, and frequency of application.


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Soy Soy-derived products

are believed to have a range of dermatologic benefits, from depigmentation to prevention of photodamage and photoaging.

Levin J, Momin SB. How much do we really know about our favorite cosmeceutical ingredients? J Clin Aesthet Dermatol. 2010;3(2):22-41. Kerscher M, Buntrock H. Update on cosmeceuticals. J Dtsch Dermatol Ges. 2011;9(4):314-26. Leyden J, Wallo W. The mechanism of action and clinical benefits of soy for the treatment of hyperpigmentation. Int J Dermatol. 2011;50(4):470-7. 58

Soy When evaluating topical soy-containing

products, it is important to know which active ingredient(s) are within, so that the desired effect may be achieved.

Soy compounds, namely isoflavones and serine protease inhibitors (soybean trypsin inhibitor (STI) and Bowman-Birk protease inhibitor (BBI)), have been studied for their potential benefits in human skin.

Leyden J, Wallo W. The mechanism of action and clinical benefits of soy for the treatment of hyperpigmentation. Int J Dermatol. 2011;50(4):470-7.

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Soy: Serine Protease Inhibitors Improve pigmentation. Stems from the ability of STI and BBI to inhibit

keratinocyte protease-activated receptor 2 (PAR-2), thereby decreasing transfer of melanosomes to keratinocytes.

Products containing STI have demonstrated significant reductions in post-inflammatory hyperpigmentation, desquamation, and erythema following UV-exposure.

Leyden J, Wallo W. The mechanism of action and clinical benefits of soy for the treatment of hyperpigmentation. Int J Dermatol. 2011;50(4):470-7. Liu J-C, Seiberg M, Miller J, et al. Soy: potential applications in skin care. Poster presented at: 59th Annual Meeting of the American Academy of Dermatology, Washington DC, March 60

STI

http://aac.asm.org/content/53/5/1760/F1.expansion

Soy: Serine Protease Inhibitors

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Soy: Serine Protease Inhibitors A double-blind, vehicle-controlled study evaluated 65

women, with moderate facial photodamage for improvement of photoaging with the use of a soy moisturizer.

Efficacy was assessed through clinical observation, self-assessment, colorimetric evaluations, and digital photography.

The study demonstrated soy moisturizer containing non-denatured STI and BBI produced significant improvements in mottled pigmentation, along with blotchiness, dullness, fine lines, overall texture, overall skin tone, and overall appearance after 12 weeks, when compared with vehicle alone.

Wallo W, Nebus J, Leyden JJ. Efficacy of a soy moisturizer in photoaging: a double-blind, vehicle-controlled, 12-week study. J Drugs Dermatol. 2007;6(9):917-22.

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Soy: Isoflavones Improve rhytides. Increase collagen synthesis in vitro in human dermal

fibroblasts. In a placebo controlled, in vivo study using topical

application of an isoflavone-containing emulsion for two weeks, a significant increase in the number of dermal papillae per area was observed, thus giving a rejuvenated appearance to the structure of mature skin.

It has been speculated that compounds in soy other than isoflavones such as saponins, may play a larger role in the effects on collagen synthesis, and further investigation is warranted.

Südel KM, Venzke K, Mielke H, et al. Novel aspects of intrinsic and extrinsic aging of human skin: beneficial effects of soy extract. Photochem Photobiol. 81(3):581-7.

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Kinetin Plant growth factor In vitro studies have shown inhibition of the

oxidation and glycation of proteins, thereby blocking the formation of advanced glycation end products (AGE).

Kinetin has also been shown to delay aging in fibroblasts by altering cell size and shape, growth rates, cytoskeletal structure, macromolecular synthesis, and quality of lipofuscin.

Levin J, Momin SB. How much do we really know about our favorite cosmeceutical ingredients? J Clin Aesthet Dermatol. 2010;3(2):22-41. Martin KI, Glaser DA. Cosmeceuticals: the new medicine of beauty. Mo Med. 108(1):60-3.

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Kinetin

Kinetin lotion (0.01-0.1%) used twice daily for 24 weeks showed improvement in skin texture, color, blotchiness, fine wrinkles, and skin barrier function.

Improvements ranged from 17-63% over baseline.

McCullough JL, Weinstein GD. Clinical study of safety and efficacy of using topical kinetin 0.1% (Kinerase) to treat photodamaged skin. Cosmetic Dermatol. 2002; 15:29-32.

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Green Tea Polyphenols Naturally occurring antioxidants used in various

cosmetics and cosmeceutical products. Green tea polyphenols have both antioxidant and anti-

inflammatory properties. It has been suggested that green tea may have an anti-

carcinogenic effect from UV radiation. No clinical trials have ever shown long term benefits of

green tea and therefore, they will not be mentioned further.

Sachdev M, Friedman A. Cosmeceuticals in day-to-day clinical practice. J Drugs Dermatol. 2010;9(5 Suppl ODAC Conf Pt 1):s62-6.] Kerscher M, Buntrock H. Update on cosmeceuticals. J Dtsch Dermatol Ges. 2011;9(4):314-26. Nolan KA, Marmur ES. Over-the-counter topical skincare products: a review of the literature. J Drugs Dermatol. 2012;11(2):220-4.

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Topical Peptides

Short chain sequences of amino acids whose biological effects are supposed to enhance collagen production, relax dynamic skin wrinkling, and improve skin hydration and barrier function.

Revolves around the hypothesis that peptide fragments of collagen and elastin can act as positive feedback signals for their own continued synthesis.

Reszko AE, Berson D, Lupo MP. Cosmeceuticals: practical applications. Obstet Gynecol Clin North Am. 2010;37(4):547-69, viii. Martin KI, Glaser DA. Cosmeceuticals: the new medicine of beauty. Mo Med. 108(1):60-3.

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Topical Peptides Three main classes:

Signal peptides Increase fibroblast production of collagen or decrease

collagenase breakdown of existing collagen. Neuropeptides

Interfere with neurotransmitter release. Carrier/transport peptides

Stabilize and deliver trace elements (ie. copper) necessary for wound healing, enzymatic processes, and collagen regeneration into the skin.

Reszko AE, Berson D, Lupo MP. Cosmeceuticals: practical applications. Obstet Gynecol Clin North Am. 2010;37(4):547-69, viii.

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Topical Peptides

The most studied peptides include: pal-KTTKS (palmitoyl-pentapeptide 3, trade

name Matrixyl) Acetyl hexapeptide 3 (trade name Argireline) GHK-Cu (copper complex of a glycyl-L-histidyl-

L-lysine peptide)

Reszko AE, Berson D, Lupo MP. Cosmeceuticals: practical applications. Obstet Gynecol Clin North Am. 2010;37(4):547-69, viii.. Kerscher M, Buntrock H. Update on cosmeceuticals. J Dtsch Dermatol Ges. 2011;9(4):314-26.

69

Topical Peptides Various in-vivo studies have shown that pal-

KTTKS led to a stimulation new collagen synthesis and production of extracellular matrix proteins. A study by Robinson, et al., of 93 female Caucasian

patients demonstrated improvement of fines lines and wrinkles after 12 weeks of daily application.

Other studies have demonstrated increased collagen content of the dermis, detectable by sonography.

Kerscher M, Buntrock H. Update on cosmeceuticals. J Dtsch Dermatol Ges. 2011;9(4):314-26. Robinson LR, Fitzgerald NC, Doughty DG, Dawes NC, Berge CA, Bissett DL. Topical palmitoyl pentapeptide provides improvement in photoaged human facial skin. Int J Cosmet Sci. 2005;27(3):155-60.

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Topical Peptides

A study by Lintner et al. compared the clinical efficacy of a preparation containing pal-KTTKS with a preparation containing retinol. The effects on collagen metabolism did not differ significantly, although the tolerability of application of pal-KTTKS was markedly improved.

May be a better option for patients who do not tolerate retinoids well.

Kerscher M, Buntrock H. Update on cosmeceuticals. J Dtsch Dermatol Ges. 2011;9(4):314-26.

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Topical Peptides

Argireline, a hexapeptide containing six amino acids, inhibits the release of neurotransmitters in muscle cells which weakens muscle contraction, relaxes the muscle, and thus reduces dynamic wrinkles.

This synthetic peptide is patterned after an inhibitor of catecholamine release.

Reszko AE, Berson D, Lupo MP. Cosmeceuticals: practical applications. Obstet Gynecol Clin North Am. 2010;37(4):547-69, viii.. Kerscher M, Buntrock H. Update on cosmeceuticals. J Dtsch Dermatol Ges. 2011;9(4):314-26.

72 http://www.revoris.com/ARGIRELINE.asp?SEC=3

Argireline: How it Works

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Topical Peptides

In an initial uncontrolled study on 10 healthy women, Blanes-Mira et al. demonstrated that application of an oil-water emulsion containing 10% Argireline reduced wrinkle depth by 30% after 30 days when assessing by skin topography.

Blanes-mira C, Clemente J, Jodas G, et al. A synthetic hexapeptide (Argireline) with antiwrinkle activity. Int J Cosmet Sci. 2002;24(5):303-10.

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Botulinum Toxin Out of Business?

Analysis has demonstrated that Argireline inhibited neurotransmitter release with a potency similar to that of Botulinum toxin A, but with much lower efficacy.

A milder alternative for patients who fear the needle?

Blanes-mira C, Clemente J, Jodas G, et al. A synthetic hexapeptide (Argireline) with antiwrinkle activity. Int J Cosmet Sci. 2002;24(5):303-10.

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Topical Peptides The tripeptide complex GHK spontaneously

complexes with copper and facilitates its cellular uptake.

GHK-copper complexes have been demonstrated to: *increase levels of tissue inhibitors of MMPs, and thus

stimulate synthesis of collagen and elastin. *inhibit collagenase and promote activity of cytochrome

C oxidase. Clinically, GHK-copper application led to an

improvement in the appearance of fine lines/wrinkles and an increase in skin density and skin thickness.

Reszko AE, Berson D, Lupo MP. Cosmeceuticals: practical applications. Obstet Gynecol Clin North Am. 2010;37(4):547-69, viii. Lupo MP, Cole AL. Cosmeceutical peptides. Dermatol Ther. 20(5):343-9.

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Topical Peptides

The cost of all these peptides remains a challenge to cosmeceutical companies,

especially if the peptide has low potency and requires greater concentrations to

achieve efficacy.

Martin KI, Glaser DA. Cosmeceuticals: the new medicine of beauty. Mo Med. 108(1):60-3.

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What is brand new in cosmeceuticals?

A couple of new and interesting

topics of cosmeceutical conversion…

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Resveratrol – A new attack on aging!

The strength and resilience of skin is dependent on dermal extracellular matrix proteins, most notably type I and III collagen.

Protease enzymes responsible for degrading this collagen are therefore considered to be an

important target in preventing or delaying photoaging.

Lee JS, Park KY, Min HG, et al. Negative regulation of stress-induced matrix metalloproteinase-9 by Sirt1 in skin tissue. Exp Dermatol. 2010;19(12):1060-6.

47

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Resveratrol – What is it?

A polyphenolic antioxidant with diverse biological effects found in high concentrations in grapes and red wine.

Farris PK. Innovative cosmeceuticals: sirtuin activators and anti-glycation compounds. Semin Cutan Med Surg. 2011;30(3):163-6

80

Resveratrol – To preserve and prevent…

Has been shown to down regulate transcription factors involved in photoaging, and suppress expression of MMP-1 and MMP-3 in dermal fibroblasts, which may prove valuable in preserving dermal collagen

http://www.mdidea.com/products/herbextract/resveratrol/data07.html http://www.deltalabsusa.com/product_resveratrol.php

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Resveratrol: Preservation of collagen

A study by Lee et al. using a mouse skin model revealed that resveratrol pretreatment prior to UV exposure was able to reduce collagen degradation by UVR stress.

Lee JS, Park KY, Min HG, et al. Negative regulation of stress-induced matrix metalloproteinase-9 by Sirt1 in skin tissue. Exp Dermatol. 2010;19(12):1060-6. 82

Resveratrol – the future?

Objective clinical studies confirming these benefits are lacking, however the science behind resveratrol is plentiful and promising.

Studies to evaluate the efficacy of synthetic derivatives of resveratrol are currently underway.

Farris PK. Innovative cosmeceuticals: sirtuin activators and anti-glycation compounds. Semin Cutan Med Surg. 2011;30(3):163-6.

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Sebum Regulation

Independent from environmental factors, the oily appearance of skin may be due, in part, to overproduction of sebum, controlled by the enzyme 5-alpha-reductase.

Squalene, a proposed marker of human sebum, is reported to favor comedo formation.

Vogelgesang B, Abdul-malak N, Reymermier C, Altobelli C, Saget J. On the effects of a plant extract of Orthosiphon stamineus on sebum-related skin imperfections. Int J Cosmet Sci. 2011;33(1):44-52.

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Sebum and Botanicals

In a recent French study evaluating the effects of various botanical ingredients on oily skin, a potent extract from the orthosiphon stamineus leaf, or “java tea” plant, effectively decreased 5-alpha reductase activity in human skin.

Squalene synthesis was also noted to be significantly reduced.

Vogelgesang B, Abdul-malak N, Reymermier C, Altobelli C, Saget J. On the effects of a plant extract of Orthosiphon stamineus on sebum-related skin imperfections. Int J Cosmet Sci. 2011;33(1):44-52.

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Botanicals buffer the shine…

After 28 days of using a 2% extract twice daily on the whole face, 80% patients self-reported their complexion was more even, 100% said their skin was more radiant, and 92% described their skin texture improved.

A study in Thai women with similar results was produced by the same authors.

Vogelgesang B, Abdul-malak N, Reymermier C, Altobelli C, Saget J. On the effects of a plant extract of Orthosiphon stamineus on sebum-related skin imperfections. Int J Cosmet Sci. 2011;33(1):44-52. 86

Cellulite = old skin?

Although cellulite can be present in women of all ages, it may be regarded as a form of skin aging, as the characteristic “cottage cheese” appearance is partly due to a weakening of the dermis.

Non-invasive approaches to treat cellulite, which target both fat breakdown and dermal restrengthening, have been studied.

Badreshia-bansal S, Draelos ZD. Insight into skin lightening cosmeceuticals for women of color. J Drugs Dermatol. 2007;6(1):32-9.

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Cosmetic Ingredients as Anticellulites

Ingredients studied to be effective against cellulite: Retinoid

Stimulates collagen production by “aged” fibroblasts, inhibits conversion of pre-adipocytes to mature adipocytes.

Algae extract Stimulates fibroblasts to produce pro-collagen I at even

greater levels than retinoid. Conjugated linoleic acid (CLA)

Prevents triacylglycerol accumulation in adipocytes. Glaucine

Encourages lipolysis in adipocytes.

Vogelgesang B, Abdul-malak N, Reymermier C, Altobelli C, Saget J. On the effects of a plant extract of Orthosiphon stamineus on sebum-related skin imperfections. Int J Cosmet Sci. 2011;33(1):44-52. 88

The “cosmeceutical cocktail”

A topical combination of the previously described ingredients in a study by Al-Bader et al. was reported to yield a synergistic increase in glycerol release, suggesting that combinations of cosmeceuticals can act as a powerful mixture to stimulate fat breakdown.


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Anticellulites – the “cosmeceutical cocktail”

Clinically significant improvement in the appearance of cellulite on the thigh was observed, when treated with creams containing a mixture of retinoid, algae extract, CLA, and glaucine, over the course of 12 weeks.


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What’s the take home?

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How to have the conversation with your patients:

Most importantly, we, as the physician and the “expert opinion” need to stay up to date on this rapidly expanding and evolving field of cosmetic medicine and the “newest, latest, and greatest” products coming out on the market.

Education is key, for yourself, and for your patients.

Kligman D. Cosmeceuticals. Dermatol Clin. 2000;18(4):609-15.

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Dr. Kligman’s Rules: When evaluating a cosmeceutical product, be able to

logically assess… whether the product is actually able to penetrate

the stratum corneum to the level of the desired target.

whether the product can do what it claims to do at the desired target.

whether there are peer-reviewed, double-blinded, placebo-controlled, statistically significant clinical trials regarding the efficacy of the product.

Kligman D. Cosmeceuticals. Dermatol Clin. 2000;18(4):609-15.

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The Bottom Line: Limitations

Unfortunately, many of the studies that we have regarding these products are small.

More importantly, as mentioned before, the claims regarding what these products can REALLY do in-vivo is limited by these products being labeled as cosmeceuticals.

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The Bottom Line: What we know works!

More importantly, however, we must not forget to stress the importance of daily…

SUNSCREEN MOISTURIZER

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SUNSCREEN is the most biologically active antiaging ingredient in skin care products!!

80% of the formulations of OTC skin care

products primarily MOISTURIZERS (petrolatum, dimethicone, or glycerin) with added ingredients to support marketing claims

Draelos ZD. Active agents in common skin care products. Plast Reconstr Surg. 2010 Feb; 125(2):719-24.

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References: 1. Sachdev M, Friedman A. Cosmeceuticals in day-to-day clinical practice. J Drugs Dermatol. 2010;9(5 Suppl ODAC Conf Pt 1):s62-6.] 2. Newburger AE. Cosmeceuticals: myths and misconceptions. Clin Dermatol. 27(5):446-52. 3. Green JB, Metelitsa AI. Introduction. Cosmeceuticals: current trends and market analysis. Semin Cutan Med Surg. 2011;30(3):139-40. 4. Draelos ZD. The cosmeceutical realm. Clin Dermatol. 26(6):627-32. 5. Draelos ZD. Cosmeceuticals: undefined, unclassified, and unregulated. Clin Dermatol. 27(5):431-4. 6. Brandt FS, Cazzaniga A, Hann M. Cosmeceuticals: current trends and market analysis. Semin Cutan Med Surg. 2011;30(3):141-3. 7. Reszko AE, Berson D, Lupo MP. Cosmeceuticals: practical applications. Obstet Gynecol Clin North Am. 2010;37(4):547-69, viii. 8. Rivers JK. The role of cosmeceuticals in antiaging therapy. Skin Therapy Lett. 13(8):5-9. 9. Kligman D. Cosmeceuticals. Dermatol Clin. 2000;18(4):609-15. 10. Levin J, Momin SB. How much do we really know about our favorite cosmeceutical ingredients? J Clin Aesthet Dermatol. 2010;3(2):22-41. 11. Kerscher M, Buntrock H. Update on cosmeceuticals. J Dtsch Dermatol Ges. 2011;9(4):314-26. 12. Gao XH, Zhang L, Wei H, Chen HD. Efficacy and safety of innovative cosmeceuticals. Clin Dermatol. 26(4):367-74. 13. Smirnova MH. A will to youth: The woman's anti-aging elixir. Soc Sci Med. 2012; 14. Lupo M, Jacob L. Cosmeceuticals used in conjunction with laser resurfacing. Semin Cutan Med Surg. 2011;30(3):156-62. 15. Lintner K, Mas-chamberlin C, Mondon P, Peschard O, Lamy L. Cosmeceuticals and active ingredients. Clin Dermatol. 27(5):461-8. 16. Giacomoni PU. Advancement in skin aging: the future cosmeceuticals. Clin Dermatol. 26(4):364-6. 17. Amer M, Maged M. Cosmeceuticals versus pharmaceuticals. Clin Dermatol. 27(5):428-30 18. Konda S, Geria AN, Halder RM. New horizons in treating disorders of hyperpigmentation in skin of color. Semin Cutan Med Surg. 2012;31(2):133-9. 19. Vogelgesang B, Abdul-malak N, Reymermier C, Altobelli C, Saget J. On the effects of a plant extract of Orthosiphon stamineus on sebum-related skin

imperfections. Int J Cosmet Sci. 2011;33(1):44-52. 20. Hunt KJ, Hung SK, Ernst E. Botanical extracts as anti-aging preparations for the skin: a systematic review. Drugs Aging. 2010;27(12):973-85. 21. Leyden J, Wallo W. The mechanism of action and clinical benefits of soy for the treatment of hyperpigmentation. Int J Dermatol. 2011;50(4):470-7. 22. Martin KI, Glaser DA. Cosmeceuticals: the new medicine of beauty. Mo Med. 108(1):60-3. 23. Lee JS, Park KY, Min HG, et al. Negative regulation of stress-induced matrix metalloproteinase-9 by Sirt1 in skin tissue. Exp Dermatol. 2010;19(12):1060-6. 24. Farris PK. Innovative cosmeceuticals: sirtuin activators and anti-glycation compounds. Semin Cutan Med Surg. 2011;30(3):163-6. 25. Badreshia-bansal S, Draelos ZD. Insight into skin lightening cosmeceuticals for women of color. J Drugs Dermatol. 2007;6(1):32-9.

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26. Draelos ZD. Skin lightening preparations and the hydroquinone controversy. Dermatol Ther. 20(5):308-13. 27. Baliña LM, Graupe K. The treatment of melasma. 20% azelaic acid versus 4% hydroquinone cream. Int J Dermatol. 1991;30(12):893-5. 28. Bissett DL, Miyamoto K, Sun P, Li J, Berge CA. Topical niacinamide reduces yellowing, wrinkling, red blotchiness, and hyperpigmented spots in aging

facial skin. Int J Cosmet Sci. 2004;26(5):231-8. 29. Bissett DL. Common cosmeceuticals. Clin Dermatol. 27(5):435-45. 30. Gehring W. Nicotinic acid/niacinamide and the skin. J Cosmet Dermatol. 2004;3(2):88-93. 31. Bissett DL, Oblong JE, Berge CA. Niacinamide: A B vitamin that improves aging facial skin appearance. Dermatol Surg. 2005;31(7 Pt 2):860-5. 32. Espinal-perez LE, Moncada B, Castanedo-cazares JP. A double-blind randomized trial of 5% ascorbic acid vs. 4% hydroquinone in melasma. Int J

Dermatol. 2004;43(8):604-7. 33. Farris PK. Topical vitamin C: a useful agent for treating photoaging and other dermatologic conditions. Dermatol Surg. 2005;31(7 Pt 2):814-7. 34. Nolan KA, Marmur ES. Over-the-counter topical skincare products: a review of the literature. J Drugs Dermatol. 2012;11(2):220-4. 35. Varani J, Warner RL, Gharaee-kermani M, et al. Vitamin A antagonizes decreased cell growth and elevated collagen-degrading matrix metalloproteinases

and stimulates collagen accumulation in naturally aged human skin. J Invest Dermatol. 2000;114(3):480-6. 36. Kafi R, Kwak HS, Schumacher WE, et al. Improvement of naturally aged skin with vitamin A (retinol). Arch Dermatol. 2007;143(5):606-12. 37. Stiller MJ, Bartolone J, Stern R, et al. Topical 8% glycolic acid and 8% L-lactic acid creams for the treatment of photodamaged skin. A double-blind

vehicle-controlled clinical trial. Arch Dermatol. 1996;132(6):631-6. 38. Wallo W, Nebus J, Leyden JJ. Efficacy of a soy moisturizer in photoaging: a double-blind, vehicle-controlled, 12-week study. J Drugs Dermatol.

2007;6(9):917-22. 39. Liu J-C, Seiberg M, Miller J, et al. Soy: potential applications in skin care. Poster presented at: 59th Annual Meeting of the American Academy of

Dermatology, Washington DC, March 2001 40. Dreher F, Gabard B, Schwindt DA, Maibach HI. Topical melatonin in combination with vitamins E and C protects skin from ultraviolet-induced erythema:

a human study in vivo. Br J Dermatol. 1998;139(2):332-9. 41. Südel KM, Venzke K, Mielke H, et al. Novel aspects of intrinsic and extrinsic aging of human skin: beneficial effects of soy extract. Photochem Photobiol.

81(3):581-7. 42. Ho ET, Trookman NS, Sperber BR, et al. A randomized, double-blind, controlled comparative trial of the anti-aging properties of non-prescription tri-

retinol 1.1% vs. prescription tretinoin 0.025%. J Drugs Dermatol. 2012;11(1):64-9. 43. Zhai H, Behnam S, Villarama CD, Arens-corell M, Choi MJ, Maibach HI. Evaluation of the antioxidant capacity and preventive effects of a topical

emulsion and its vehicle control on the skin response to UV exposure. Skin Pharmacol Physiol. 18(6):288-93. 44. Fitzpatrick RE, Rostan EF. Double-blind, half-face study comparing topical vitamin C and vehicle for rejuvenation of photodamage. Dermatol Surg.

2002;28(3):231-6. 45. Lin FH, Lin JY, Gupta RD, et al. Ferulic acid stabilizes a solution of vitamins C and E and doubles its photoprotection of skin. J Invest Dermatol.

2005;125(4):826-32. 46. Blanes-mira C, Clemente J, Jodas G, et al. A synthetic hexapeptide (Argireline) with antiwrinkle activity. Int J Cosmet Sci. 2002;24(5):303-10. 47. Robinson LR, Fitzgerald NC, Doughty DG, Dawes NC, Berge CA, Bissett DL. Topical palmitoyl pentapeptide provides improvement in photoaged human

facial skin. Int J Cosmet Sci. 2005;27(3):155-60. 48. Lupo MP, Cole AL. Cosmeceutical peptides. Dermatol Ther. 20(5):343-9.

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49. Verma P, Pathak K. Therapeutic and cosmeceutical potential of ethosomes: An overview. J Adv Pharm Technol Res. 2010;1(3):274-82 50. Bariya SH, Gohel MC, Mehta TA, Sharma OP. Microneedles: an emerging transdermal drug delivery system. J Pharm Pharmacol. 2012;64(1):11-29. 51. Menon GK, Cleary GW, Lane ME. The structure and function of the stratum corneum. Int J Pharm. 2012;435(1):3-9. 52. Choi CM, Berson DS. Cosmeceuticals. Semin Cutan Med Surg. 2006;25(3):163-8. 53. Ennes SBP, Paschoalick RC, Mota De Avelar Alchorne M. A double-blind, comparative, placebo-controlled study of the efficacy and tolerability of 4%

hydroquinone as a depigmenting agent in melasma. Journal of Dermatological Treatment. 2000; 11(3): 173-179 54. Bolognia, J. L., Jorizzo, J. L., & Schaffer, J. V. (2012). Dermatology. (3rd ed., Vol. 2, p. 2488). Elsevier Saunders. 55. McCullough JL, Weinstein GD. Clinical study of safety and efficacy of using topical kinetin 0.1% (Kinerase) to treat photodamaged skin. Cosmetic

Dermatol. 2002; 15:29-32. 56. Fisher, GJ, Kang S, et. al. Mechanisms of photoaging and chronological aging. Archives of Dermatology. 2002; 138:1462-1470. 57. Draelos ZD. Active agents in common skin care products. Plast Reconstr Surg. 2010 Feb; 125(2):719-24.

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Images

1. http://www.oculist.net/downaton502/prof/ebook/duanes/pages/v4/ch038/001f.html 2. http://www.globalskinatlas.com/imagedetail.cfm?TopLevelid=2296&ImageID=5117&did=218 3. http://www.azelaic-acid.com/en/azelaic-acid-component/azelaic-acid/index.php 4. http://www.chemspider.com/Chemical-Structure.2179.html 5. http://www.infohealthz.org/thearticle-Antioxidant-vitamins.html 6. http://www.sciencedirect.com/science/article/pii/S0278691598000623 7. http://home.caregroup.org/clinical/altmed/interactions/Nutrients/Vitamin_E.htm 8. http://course1.winona.edu/sberg/495/Papers/DH-paper.htm 9. http://www.sciencedirect.com/science/article/pii/S1574334906160044 10. http://www.advancedskintech.com/GCScience.htm 11. http://swiftcraftymonkey.blogspot.com/2010/02/alpha-hydroxy-acids.html 12. http://aac.asm.org/content/53/5/1760/F1.expansion 13. http://www.medik8.com/en/pretox/pretox_infin8.html 14. http://www.mdidea.com/products/herbextract/resveratrol/data07.html 15. http://www.deltalabsusa.com/product_resveratrol.php 16. http://www.sciencephoto.com/media/296686/enlarge 17. http://www.surplussalesline.com/detail.asp?ProdID=8373 18. http://nutritionforskinbeauty.com/?cat=1

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6:30 am AOCD Registration

6:45 am - 8:00 am Great Cases from Osteopathic Institutions Cindy Hoffman, D.O., FAOCD Moderator

8:00 am Tats, Holes, and Landscapes: The Curious History of Body Art, Piercings, and Personal Grooming Melinda Greenfield, D.O. Albany Dermatology Center, Albany, GA

9:00 am Interesting and Unusual Dermatologic Cases Stephen Purcell, D.O., FAOCD Advanced Dermatology Associates, Allentown, PA

10:00 am Break

10:15 am - 12:00 pm Dermpath Review Michael Morgan, M.D.

12:00 pm - 1:00 pm Lunch on your own

1:00 pm PDT for Skin Cancers and Actinic Damage: Australian & Global Experience Anthony Dixon, M.D.

2:00 pm Alopecia Neoplastica Heralding a Diagnosis of Breast Cancer Mounir Wassef, D.O. Columbia Hospital, West Palm Beach, FL

2:20 pm Merkel Cell Carcinoma: A Case and Review Alison Himes, D.O. O’Blenness Hospital, Dublin, OH

2:40 pm Morphea Associated with Celiac Disease Sanjosh Singh, D.O. St. John’s Episcopal Hospital, Lindenhurst, NY

3:00 pm Linear Psoriasis in Lines of Blaschko Charlotte Noorollah, D.O. St. John’s Episcopal Hospital, Lindenhurst, NY

TUESDAY, OCTOBER 9, 2012

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3:20 pm Break

4:00 pm Parry-Romberg Syndrome Case Series James B. Young, D.O. St. Joseph Mercy Health System, Clinton Twp., MI

4:20 pm Muckle Wells Syndrome: A Cold Case Report Heather Orkwis, D.O. St. Joseph Mercy Health System, Clinton Twp., MI

4:40 pm A Curious Case of Cutaneous Angiokeratomas Libby Rhee, D.O. St. Barnabas Hospital, Bronx, NY

5:00 pm Gender as an Age-Specific Modifier for Ulcerated Malignant Melanomas Blakely Richardson, D.O. University Hospitals, Cleveland, OH

5:20 pm Diagnostic Tests for Bullous Pemphigoid Ashley Kittridge, D.O. University Hospitals, Cleveland, OH

5:40 pm Diagnosing HIV: Our Role as Dermatologists Ellecia Cook, D.O. Largo Medical Center, Port Richey, FL

6:00 pm End of Day

53

Tats, Holes and Landscapes

Melinda F. Greenfield, DO Albany Dermatology Clinic

Albany, Georgia

THE CURIOUS HISTORY OF BODY ART, PIERCING AND PERSONAL GROOMING

The Decorated Body

• The average human body measures 20 square feet

• Average dermatologist does 15-30 skin checks daily x 30 years….

• Approximately 2-4 million square feet of skin visualized during a career

Tattoos-the ancient and mysterious history

• The word Tattoo is derived from the Polynesian ‘tatau’ meaning to tap, and Tahitian ‘tatu’ meaning to mark

• It is not known when tattooing first began

• Earliest know tattoos found on Otzi the Iceman, carbon-dated 5,200 years old

• Found to have tattooed dots and small crosses on his lower spine and right knee and ankle-thought to be of therapeutic value

Otzi the Iceman

• 59 separate tattoos • Correspond to

acupuncture points • Areas of osteoarthritis

Ancient Egypt • Originally an exclusive

female practice • Found tattoos dating back

4000 years • Thought to be on women

of ‘dubious’ status • Tomb of Amunet, a high-

status priestess • Patterns of dots or dashes

on abdomen, thighs and arms

Ancient Egypt

• Although long assumed to be the mark of prostitutes, or meant to protect against STDs

• Others believe these were placed to protect the woman during childbirth as a form of a permanent amulet

• During pregnancy, these net-like dots would expand in a protective like fashion

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Egypt • This was the earliest tattoo

found that was not an abstract design

• Bes is the protector of households, mothers and children

• Regarded as the defender of everything good and the enemy of all that is bad

• Women would tattoo the image on their thighs while they were pregnant

“BES”

Japanese Tattoos The Japanese word for tattooing is ‘Irezumi‘ to insert ink

Japanese Tattoos • Tattooing has been practiced in

Japan for 10,000 years and is considered a great Japanese tradition

• Japanese Tattoos have long been associated with the criminal underworld

• From 300-1870, Japan marked their criminals with tattoos

• Criminals then started covering up their marks of shame with the more decorative tattoo designs we now see today

Japanese Tattoos • In 1870 the Japanese government

banned tattoos which drove the practice underground

• Tattooing was again legalized in 1945 at the end of the Second World War

• Never completely lost its association with the criminal underworld

• There are still bans in certain public places (health clubs, swimming pools) for people displaying tattoos

Chinese Tattoos • Chinese Tattoos have many

similarities to Japanese tattoos, from their origins in history to their use to mark criminals

• The most popular are the Chinese Character Symbols known as Hanzi

• These are far more popular in Western Culture than in China itself

• The character is actually the Japanese katakana ホ (ho) not 木 (ki, tree)

• The mistaken use of ‘ho’ is quite unfortunate considering the woman as both subject and canvas

• The hip-hop slang meaning of ‘ho’ (whore) is known in Japan and written with the same character

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Chinese Tattoos

• According to the Hanzi smatter site all of these tattoos are complete gibberish

Other Ancient Cultures

• Native Americans- Cree (A.D. 1475)- Extensive facial and body tattoos

• Polynesian- Highly elaborate geometric designs that sometimes covered the entire body

• Maori culture of New Zealand tattooed on their faces, concentrated around the nose and lips

Bridging the gap from Ancient to Today

• With the rise of Christianity in Europe, tattooing faded out

• Sailors, however, continued to circle the globe and return home with the art of the various tribes and regions that were encountered

• Some sailors got a tattoo with every voyage: • Lighthouse= guide a sailor home • Turtle= indicated crossing of the equator • Dragon= crossing of the international date line • Anchor= sailed the Atlantic

Who gets tattoos? • 2006 article in JAAD, 500 random calls were placed to

individuals 18-50 years of age • Questions were asked regarding tattoos and piercings: • 24% had tattoos, 14% piercings • Tattooing was equally common in both sexes, body piercing

was more common in women • Common associations with tattoos: lack of religious

affiliation, extended jail time, previous drinking and drug use

• Complications with piercings included: broken teeth, and increases in jewelry allergies

• Most common location of a tattoo in men: arm; women: ankle

Who gets tattoos? • A 2012 Harris survey interviewed 2016 adults and found that 21%

have at least one tattoo

• Age was a major factor: only 11% of 50-64 year olds are inked while a whopping 38% of those in their 30’s report tattoos

• Women are more likely than men to have tattoos 23% vs 19%

• 86% of those in this survey say they have never regretted their decision, 30% say it makes them feel sexy

• Among the un-tattooed, 45% say that a person with a tattoo is actually less sexy

Regulations on tattoo parlors • No federal regulations

• NM, ND, DC- unregulated

states

• Regulated states forbid tattoos or piercings on a minor

• CO, FL, ID, LA minors can be tattooed if they have signed parental permission

56

Regulations • Restricts artist from tattooing any person who is jaundice, or any part of

the skin that appears inflamed, or has a rash, boils or infection

• Patrons must be sober and in good general health

• Must be a separate area for tattooing and have a clean bathroom

• Artist must wear gloves, wash hands and arms, and use a different needle for each patron

• Equipment must be sterilized in an autoclave

• Infections must be reported to the local health department within 48 hours

Regulations • Regulated states require that tattoo parlors obtain permits before

opening

• Permits require an official inspection by the health department

• Unregulated states require no permit or inspection

• Georgia is a regulated state, prohibits tattooing within 1" of eye; tattooing of minors is prohibited; licensure required by department of health

• www.aaatattoodirectory.com to check your state

Safe Body Art Act- California

• Bill aiming to make it safer to get inked up in CA was introduced for the 3rd time after being twice vetoed by Gov. Schwartzenegger

• He stated that ‘overregulation’ is driving business out of California

History of Piercing • Nose piercing was first recorded in the Middle East ~ 4,000 years

ago

• It was mentioned in the bible in Genesis: • Abraham requested that his servant find a wife for his son, Isaac.

The servant found Rebekah and one of the gifts he gave her was a ‘golden earring’. The original Hebrew word used was Shanf, which translates as ‘nose-ring’

• This is still followed in nomadic tribes in Africa

• The size of the ring denotes the wealth of the family, and is ‘security’ for the wife in case of divorce

Nose Piercing • Brought to India in the 16th

century

• In India a stud is worn in the left nostril, sometimes joined by a chain to the ear

• Left side is most common

• In Ayurvedic medicine the nose is associated with the female reproductive organs, piercing is supposed to make childbirth easier and lessen menstrual pain

Nose Piercings

• In the west, nose piercing first appeared among hippies who traveled to India in the late 60’s

• It was later adopted by the punk movement of the 70’s as a sign of rebellion

57

Ear Lobe Piercing • Oldest mummified body dates back to over 5,000

years, was found to have pierced ears with hole that were enlarged to 7-11mm

• Ears were pierced for magical purposes • Primitive tribes believed that demons entered the

body through the ear and because demons and spirits are repelled by metal, ear piercing prevents them from entering the body

• Sailors would pierce their ears so that if their body washed up somewhere it would pay for a Christian burial

Lip Piercing • Piercing of the lips is widely practiced throughout the

world

• Among the Dogon Tribe of Mali, lip piercing was done for religious purposes

• They believe that the world was created by their ancestor spirit "Noomi" weaving thread through her teeth, but instead of thread out came speech

• Lips are either pierced with a ring or a labret, which consists of a pin of wood, ivory, metal, or even crystals

Genital Piercing • The Prince Albert

• Named after Queen Victoria’s husband (19th century)

• Albert had his penis pierced with a ring called a ‘dressing ring’ so he could manipulate his privates to prevent an unseemly bulge when he wore tight trousers

Landscapes

Pubic Hair: Who is Shaving?? • Poll taken by Leipzig psychologist published in 2009 stated that 50%

of women between the ages of 18-25 admit to shaving their pubic hair, and 25% of men either shave or trim

• Article goes on to state that “it used to be only women or gay men in the ‘depilation studio’ but nowadays no man needs to feel ashamed when ordering the standard selection of ‘back, crack and sack’”

• In a study commissioned by Wilkinson, 61.9% of women want men to shave their pubic hair, and the men in the study supposedly stated that “unshaved women have fewer sex prospects”

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Matching the carpet to the drapes

58

Art history of Pubic Hair • In ancient Egyptian art, female pubic

hair is indicated in the form of painted triangles

• In medieval and classical European art, it was very rarely depicted, and male pubic hair was often omitted

• The same was true in much Indian art, and in other Eastern portrayals of the nude

• In 16th century southern Europe Michelangelo showed the male David with stylized pubic hair, but female bodies remained hairless below the head

• Michelangelo’s male nudes on the Sistine chapel ceiling display no pubic hair

1540 “Eve”

Art History

• Francisco Goya’s The Nude Maja ca. 1800, has been considered as the first European painting to show woman's pubic hair, though others had hinted at it

• The painting was considered quite pornographic at the time

Art History • Before the twentieth century, fine-art paintings and

sculpture in the Western tradition usually depicted women without pubic hair

• John Ruskin, the famous author, artist, and art critic, was apparently accustomed to these depictions and unaware of the actual appearance of nude women

• On his wedding night, he was allegedly so shocked by his discovery of his wife Effie's pubic hair that he rejected her, and the marriage was legally annulled

Pubic Hair in Society • Among the upper class in 19th

century Victorian Britain, pubic hair from one's lover was frequently collected as a souvenir

• The curls were worn like cockades in men's hats as potency talismans, or exchanged among lovers as tokens of affection

• The museum of St. Andrews University in Scotland has in its collection a snuff box full of pubic hair of one of King George IV's mistresses

Removal of Pubic Hair • Trimming or removing pubic hair is a custom in many cultures

• In Islamic societies removing the pubic hair is a religiously endorsed

practice, and is as important as cleaning the teeth, nostrils and removing armpit hair

• It is generally recommended: Both men and women should remove armpit and pubic hair at least every 40 days

• For men a beard is desirable

• Women can remove 'unnatural' facial hair but should not reshape eyebrows for reasons of vanity

History of Hair Removal • Europeans have been

generally accepting of body hair, except for a short period in the Middle Ages when returning Crusaders made the Arabic idea of total body depilation for women fashionable

• The Hanafi branch of Islam, which includes the Sunni Turks, demands that every part of the body be free from hair

59

History of hair removal • In Japan there is a long

tradition of fastidiousness in matters of personal hygiene.

• There have been several Japanese studies of laser depilation and the technique seems widespread.

• The main difference between Japanese and Western practice is that waxing is less commonly used and 'sandpaper' friction strips are particularly popular

Sikh • The Sikh religion forbids

cutting or shaving any bodily hair

• Orthodox Sikhs always carry a dagger with them, lest someone try to force them to do something against their religion

• The dagger is considered one of the five "outer badges"

• The others are wearing hair and beard unshorn; wearing a turban; wearing knee-length pants; and wearing a steel bracelet on the right wrist

The Bikini • The bikini was created in 1946 by Louis Reard • It wasn’t until the ‘sexual revolution’ in the 1960’s that

America could accept the bikini • It was, in fact, banned from the Mrs. World pageant • In the 1970s the string bikini became popular in Brazil • Bloomingdale’s first shipment of 150 string bikinis in

1974 sold out in less than 2 weeks • With the increase in popularity so became the increase

in pressure to remove pubic hair in order to wear the latest fashion

Shaving trends • With the ease of access

modern day pornography and in the increase in popularity of ‘shaved styles’, more adults and teens are jumping on the bandwagon

• Along with this trend comes issues such as folliculitis, infected cysts, contact dermatitis, and other issues we couldn’t even begin to imagine

• As physicians we need to be prepared to address the issues and be open to these new trends

60

Interesting and Unusual Dermatologic Cases

Stephen M. Purcell, D.O.

San Diego

2012

Objectives

■ Present several clinical and clinical-histopathological cases

■ Emphasize interesting or unusual aspect of the case

■ Offer a pearl of wisdom for your edification

Case #1

Case • HPI: 10 year old previously healthy Hispanic female. Developed fever (104o) on

6/22 accompanied by myalgias, abdominal pain, headache, minor epistaxis, oral ulcers. 2 days later, became confused/unconscious. Developed tonic-clonic seizures.

• PMHx: Recurrent oral ulcers, headaches, seasonal allergies, constipation, tonsillectomy

• Social Hx: Had been swimming in a lake 1 week prior to becoming ill. No sick

contacts. No hx of animal bites. • ROS: (-) N/V, (-) diarrhea, (-) conjunctival injection, (-) lymphadenopathy, • (-) muscle weakness, (-) arthralgias • Gen: Sedated, intubated

• Skin: No abnormal skin findings

Studies • CBC:

– WBC: 8.8 – Hgb: 8.3 – Platelets: 226

• BMP: WNL • Blood Cx: (-) • Urine Cx: >100,000 non-lactose fermenting G(-) rods • O & P stool: (-) • Tox Screen: (+) BZD • Lyme, HSV1, HSV2, EBV, Enterovirus, CMV, VZV, Arbovirus, West Nile

Virus: Negative • CSF: Glucose, protein WNL • C-ANCA, P-ANCA: WNL

Plan

• Imp: 10 year old female with encephalopathy, refractory seizures of unknown etiology.

• Dermatology consult:

61

Plan

• Imp: 10 year old female with encephalopathy, refractory seizures of unknown etiology.

• Dermatology consult:

R/O RABIES

Rabies

• Zoonotic virus that causes acute encephalomyelitis

• Travels to brain via peripheral nerves

• Median Incubation period ~ 9 weeks (10 days – 3 years)

• Most cases occur in wild animals like raccoons, skunks, bats, coyotes, and foxes

Rabies • 55,000 human deaths/year. 1-2 in US

• Early sxs: fever, headache, weakness

• Later sxs: insomnia, confusion, partial paralysis,

agitation, hypersalivation, violent movements, and hydrophobia coma

• Post exposure tx: 1 dose of human rabies immunoglobulin + 4 doses of rabies vaccine over 14 days (CDC)

Rabies Positive Indicators for Rabies: • Nonspecific prodrome prior to onset of neurologic signs • Neurologic signs consistent with encephalitis or myelitis

– dysphagia – hydrophobia – paresis

• Progression of neurologic signs • Negative test results for other etiologies of encephalitis Negative Indicators for Rabies: • Improvement or no change in neurologic status • Illness with ≥ 2 to 3 week duration

Rabies Ante Mortem Testing

• Contact state health department prior to submitting samples to Rabies Lab at CDC

• All 4 samples listed are required by CDC: – Saliva – Serum – CSF – NUCHAL BIOPSY

Rabies Ante Mortem Testing

• Contact state health department prior to submitting samples to Rabies Lab at CDC

• All 4 samples listed are required by CDC: – Saliva – Serum – CSF – NUCHAL BIOPSY

62

Nuchal Biopsy • 5-6 mm punch from posterior neck at

hairline • Biopsy to include a minimum of 10 hair

follicles • Sufficient depth to include cutaneous

nerves at base of follicle • Place specimen on piece of sterile

gauze moistened with sterile water • Labs: RT/PCR and immunofluorescent

staining for viral antigen in frozen sections

Nuchal Biopsy

• Viral nucleocapsids are located in nerve endings surrounding the base of hair follicles

• Skin biopsy specimens tested by RT-hnPCR targeting L polymerase gene (>98% sensitive)

• Saliva samples provide 2nd best result for sensitivity: 63-70% – Approaches 100% if collected serially for 3 days

PEARL

Nuchal biopsy may be helpful in

the diagnosis of rabies

References

• Dacheux L, Reynes JM, Buchy P, et al. A Reliable Diagnosis of Human Rabies Based on Analysis of Skin Biopsy Specimens. Clinical Infectious Diseases 2008;1410-7

• CDC website: www.cdc.gov/rabies. Accessed

7/12/12

Acknowledgements

■ Luis Soro, D.O.

Case #2

63

Case • A 47 year male was diagnosed with basal cell nevus

syndrome at age 18 based on the findings of odontogenic keratocysts, calcification of the falx cerebri and palmar pits.

• At age 33 he began to develop multiple basal cell carcinomas requiring numerous surgeries including Mohs and curettage and electrodesiccation.

Case • In May of 2010, the patient enrolled in a trial of GDC-

0449, an oral drug that inhibits Hedgehog pathway signaling.

• The 18 month trial ended in November of 2011.

• The patient experieinced significant side effects including recalcitrant nausea and loss of taste resulting in weight loss of 25 pounds. Additionally, he experieinced abdominal pain, diarrhea, fatigue and generalized alopecia.

Case • His symptoms resolved after discontinuation of the

trial, suggesting he was not in the placebo arm.

• His existing basal cell carcinoma tumors resolved and he has not developed any new tumors since.

• Interestingly, his palmar pits disappeared.

GDC-0449

• Vismodegib (ErivedgeTM) • First drug approved by the U.S.

Food and Drug Administration • Indication

– Metastatic BCC – Locally advanced BCC that has

recurred following surgery – Those who are not candidates for

surgery or radiation

http://www.globalpharmasectornews.com/wp-content/uploads/2012/02/Erivedge.jpg

64

Sonic Hedgehog Signaling (SHH) Pathway Inhibitors

• Majority of sporadic BCCs have mutations in genes encoding patched 1 (PTCH1) or smoothened (SMO)

SHH pathway Loss-of-PTCH1 mutation Inhibition of smoothened (SMO) signaling by GDC-0449

N Engl J Med. 2009 Sep 17;361(12):1164-72. PMID: 19726763

Vismodegib Efficacy • Evaluated in a single multicenter clinical study • 96 patients with locally advanced or metastatic

BCC • 21% carried a diagnosis of BCNS • Metastatic disease

– 30% partial response • Locally advanced disease

– 21% complete response – 22% partial response

Vismodegib Activity in Patients with Locally Advanced BCC

60-year-old man with BCNS with lesions of the posterior scalp at baseline and after 5 months 41-year-old woman with facial lesions at baseline and after 2 months

N Engl J Med. 2009 Sep 17;361(12):1164-72. PMID: 19726763

Vismodegib in BCNS ■ Phase II clinical trial ■ Incidence of new BCCs after 8 months

– Vismodegib arm - 0.07 cancers per month – Control arm - 1.74 cancers per month

■ 25-fold reduction in the rate of new BCCs ■ Existing tumors decreased in size within

the first month ■ Clearance of palmar and plantar pits and

odontogenic keratocysts ■ No tumor resistance observed

Vismodegib Side Effect Profile

■ Taste loss (83%) ■ Muscle spasms (70%) ■ Alopecia (50%) ■ Weight loss ■ Fatigue ■ Arthralgias

■ Diarrhea ■ Decreased appetite ■ Constipation ■ Nausea ■ Vomiting

Vismodegib Therapy

■ All side effects reversed 1 month after discontinuation

■ After stopping therapy, tumors did not return to baseline size or increase in number during the next 6 months

■ Intermittent regimen with the aim of minimizing side effects – 3 months on therapy, 2 months off

65

PEARL

Vismodogib (Erivedge) may be

beneficial in patients with BCNS or those with unresectable BCC

References • De Smaele E, Ferretti E, Gulino A. Vismodegib, a small-molecule inhibitor of the hedgehog pathway

for the treatment of advanced cancers. Curr Opin Investig Drugs 2010;11:707-718 • Dlugosz AA, Talpaz M. Following the hedgehog to new cancer therapies. N Engl J Med

2009;17;361(12):1202-5 • ErivedgeTM [package insert]. South San Francisco, CA: Genentech USA, Inc; 2012 • Göppner D, Leverkus M. Basal cell carcinoma: from the molecular understanding of the

pathogenesis to targeted therapy of progressive disease. J Skin Cancer 2011;2011:650258 • Gupta S, Takebe N, LoRusso P. Targeting the Hedgehog pathway in cancer. Ther Adv Med Oncol

2010;2:237-250 • Jancin B. AAD: Oral Vismodegib Promising for Basal Cell Nevus Syndrome. Skin & Allergy News

Digital Network February 7, 2011 <www.skinandallergynews.com/news/medical-dermatology/single-article/aad-oral-vismodegib-promising-for-basal-cell-nevus-syndrome/545d88a3f3.html>

• Scare H, Kalthoff F, Meingassner JG, et al. Topical treatment of Basal cell carcinomas in nevoid Basal cell carcinoma syndrome with a smoothened inhibitor. J Invest Dermatol 2011;131(8):1735-4

• Von Hoff DD, LoRusso PM, Rudin CM, Reddy JC, Yauch RL, Tibes R, Weiss GJ, Borad MJ, Hann CL, Brahmer JR, Mackey HM, Lum BL, Darbonne WC, Marsters JC Jr, de Sauvage FJ, Low JA. Inhibition of the hedgehog pathway in advanced basal-cell carcinoma. N Engl J Med 2009 Sep 17;361(12):1164-72. PMID: 19726763

Acknowledgements

■ Tatyana Groysman, D.O. ■ Steven A. Oberlender, M.D.

Case #3

Case • HPI: 35 y.o. female with intermittent pruritic urticarial eruption on the chest and

back. Associated symptoms include headaches, fevers, debilitating fatigue, joint pain and swelling, eye redness and blurred vision. Triggers include cold weather, exercise, fatigue, and stress. Patient noted significant association between symptoms and cutaneous surgery.

• Medical Hx: Basal cell nevus syndrome (BCNS) • Family Hx: Mother has BCNS, daughter does not have BCNS but has same

symptoms as described above. • Labs: CBC, CMP, TSH, ESR and thyroid auto-antibodies all WNL.

• Histopathology: dermal edema and sparse perivascular lymphocytic infiltrate

consistent with the clinical diagnosis of urticaria

4x Back

66

40x Back

7A

7B

Diagnosis:

Muckle-Wells Syndrome in a patient with

Basal Cell Nevus Syndrome

Muckle-Wells Syndrome • Muckle-Wells syndrome (MWS) is a cryopyrin associated periodic

syndrome (CAPS), which is a rare group of cytokine disorders.

• Common to all CAPS are recurrent episodes of multisystem inflammation with recurrent urticaria that begins in infancy or childhood.

• The three phenotypes of CAPS are: – Neonatal-onset multisystem inflammatory disease (NOMID) – MWS – Familial cold auto-inflammatory syndrome

Muckle-Wells Syndrome • MWS is rare and symptoms may overlap with other

conditions leading to a delay in diagnosis.

• Symptoms may arise spontaneously without provocation or be triggered by cold, stress or exercise.

• In our patient, her symptoms were triggered by cutaneous surgery.

• A review of the literature failed to reveal an association between MWS and BCNS.

67

Muckle-Wells Syndrome • MWS results from a gain-of-function gene mutation

of the NLRP3 gene coding for cryopyrin.

• Results in the formation of an intracellular complex known as an inflammasome.

• Defects in the inflammasome lead to overproduction of interleukin-1 (IL-1) which lead to the inflammatory symptoms.

Muckle-Wells Syndrome • Therapy of MWS is directed toward inhibition of IL-1

production.

• Anakinra – a recombinant human IL-1 receptor antagonist

• Canakinumab – an IL-1B antibody

• Rilonacept – a dimeric fusion protein that fuses the Fc portion of IgG1

PEARL

IL-1 inhibitors such as anakinra

may be helpful in the treatment of MWS

References

• Kanazawa N, Furukawa F. Autoinflammatory syndromes with a dermatological perspective. The Journal of Dermatology 2007;34:601-618.

• Newell L, August S, Foria V, Godfrey K. Lifelong urticarial and multiple unexplained systemic symptoms. Clin and Exper Derm 2011;36:431-433.

• Yu JR, Leslie KS. Cryopyrin-Associated Periodic Syndrome: An update on diagnosis and treatment response Curr Allergy Asthma Rep 2011;11:12-20.

Acknowledgements

■ Marie Lewars, D.O. ■ Joseph Laskas, D.O.

Case #4

68

Case • HPI: 82 y.o. female presented in October 2010 with an asymptomatic

pink-purple patch on the right medial breast. This had developed in an area of radiation therapy for breast cancer. Biopsy was obtained and no malignancy was noted. The area remained asymptomatic and stable in size for a year. In December 2011, the lesion became tender and grew rapidly over two weeks to 4X the original size.

• Medical Hx: Breast cancer, melanoma, dementia, osteoporosis, anemia • Surgical Hx: Bilateral lumpectomy (right breast stage T2 N0 with radiation

treatment, total radiation dose 62.40 Gy, last radiation dose 2005, left breast T0).

• Physical Examination: October 2010: 2.0 x 3.0cm pink to purple patch on

the right breast. December 2011: 10.0 x 14.0cm pink to purple indurated plaque on the right breast.

10x Right Breast (10/2010)

20x Right Breast (10/2010) 10x Right Breast (12/2011)

69

20x Right Breast (12/2011)

Diagnosis:

Angiosarcoma vs.

Atypical Vascular Lesion

Angiosarcoma

• Relative risk of developing angiosarcoma following radiation treatment is 10-fold

• Incidence falls within an estimated range of 0.09% to 0.16%

• Result of breast-conserving surgery, chemotherapy, or post lumpectomy radiation treatment

• Time to presentation of angiosarcoma 6 years

Atypical Vascular Lesions

• Originally described by Fineberg and Rosen in 1994

• Occur in areas of previous radiation treatment

• Tend to follow a benign course

• Increase in incidence with breast conserving surgery


• Angiosarcoma and Atypical Vascular Lesions (AVLs) have overlapping features

• Important to distinguish atypical vascular lesions from angiosarcoma


• Present in women in their 50’s

• Average cumulative radiation dose of 40-60gy

• Time to presentation of AVLs 3 years

• AVLs and angiosarcoma are part of a continuous spectrum

70


Overlapping clinical findings can be seen in both atypical vascular lesions and angiosarcoma

Both lesions may have characteristics that appear benign

Currently histopathological criteria do not reliably distinguish AVLs from angiosarcoma


• MYC is proto-oncogene that encodes a transcription factor believed to regulate expression of up to 15% of all human genes

• Exerts transcriptional activation function through heterodimerization with MAX

• MYC/MAX complex binds to specific DNA elements and acts as a transcriptional activator


• FISH for MYC amplification

J Cutan Pathol 2012: 39: 234–242


■ FISH for MYC amplification • MYC is NOT expressed in AVLs

• MYC gene amplification is found in secondary

angiosarcoma lesions arising from either chronic lymphedema or radiation

• MYC amplification is NOT seen in primary angiosarcoma

Atypical Vascular Lesion

■ Results • MYC gene amplification was NOT seen in the

biopsy specimen of our patient


Treatment • Conservative surgical excision • Careful observation

Our Patient • Careful observation • Serial breast exams • Biopsy of new or changing areas

71

PEARLS

• Differentiation of AVLs and angiosarcoma can be difficult

• Many different overlapping features suggest a lesional spectrum

• FISH for MYC amplification may be used as an adjunct to distinguish lesions

References • Brenn T, Fletcher C. Radiation-associated cutaneous atypical vascular lesions and angiosarcoma: clinicopathologic analysis of 42 cases. Am. J. Surg. Pathol. 2005; 29:983-966. • Brenn T, Fletcher C. Postradiation vascular proliferations: an increasing problem. Histopathology. 2006;48:106-114. • Patton K, Deyrup A, Weiss S. Atypical vascular lesions after surgery and radiation of the breast: a clinicopathologic study of 32 cases analyzing histologic heterogeneity and association with angiosarcoma. Am. J. Pathol. 2008;32:943-950. • Fernandez A, Sun Y, Tubbs R, Goldblum J, Billings S. FISH for myc amplification and anti myc immunohistochemistry: useful diagnostic tools in the assessment of secondary angiosarcoma and atypical vascular lesion proliferations. J Cutan Pathol. 2012;29:234-

242 • Bolognia J, Jorizzo J, Rapini R. Dermatology 2nd edition. Elsevier/Mosby 2007.

Acknowledgements

■ Christian Oram, D.O.

72

Photodynamic therapy in skin cancer

The experience in Australia and elsewhere

Anthony Dixon PhD MB BS FACRRM

Conflicts of interest • Allmedic ® – ALA PDT supplier

– Shareholding granted on trial start • We donated this to charity • Externally managed

– Manager decided to donate all income • To child obesity research

• Dixon family cannot – Make decisions on shareholding – Benefit from shareholding

PDT for invasive SCC

• Unacceptable • All studies terrible outcomes

• Nice summary of collated data: • Braathen J A A D Jan 2007 • (All authors paid by Galderma)

PDT for Bowens Disease

• 4 studies reviewed • 225, 40, 19 and 16 patients • Around 90% clearance rate

• Comparable with cryotherapy • ? Better cosmesis • Braathen J A A D Jan 2007

PDT for superficial BCC

• 12 studies reviewed • Patient numbers: 147 118, 80, 80, 55, 47, 39,

38, 37, 32, 23, 6

• Clearance rates around 90%

• Recurrence rates 18 – 38% !! • Braathen J A A D Jan 2007

ALA PDT Vs Surgery – nodular BCC

• RCT 85 PDT Vs 88 Excision • 3 year follow up

• Failure rates: – 2.3% Surgery (3 mm margin) – 30% PDT p<0.001

• PDT not good enough for nodular BCC • Mosterd BJD Sep 2008

73

ALA PDT for nodular BCC

• “High and sustained efficacy . . . “ ??? • 60 BCCs on 44 patients

– Curette prior to PDT – 10 year follow up

• 75% response – failures all within 3 years • Cosmesis “good” or “excellent” in 91%

• Christensen BJD June 2012 • Is this actually a good result ? ? ?

Recurrence after treating BCCs • 90 patients with 157 BCCs • Recurrence rates observed:

– 7% at 3 months – 19% at 6 months – 27% at 12 months – 31% at 24 months

• Worse if patients > 60 years 35% Vs 19% • Worse if BCC nodular 28% Vs 13% Spfcl • Lindberg-Larsen 2012 Act Derm-Ven

Our photodynamic therapy trial

• Our trial of PDT for actinic keratoses

• I was approached – By Allmedic Pty. Ltd. ® – Lead an industry initiated & sponsored RCT – Their newly marketed PDT – For face actinic field damage

– March 2008

Field damage RCT

• Inclusion criteria: – Previous invasive skin cancer on face

• Randomized controlled trial • 6 centres across Australia • Face treated with field Allmedic ALA ®

– Versus observation

Protocol details

• Intervention patients: • 2 treatments with Allmedic ALA ®

– (aminolevulonic acid)

• 2 weeks apart • All patients followed up for 2 years + • Any suspicious lesions biopsied • Any cancers excised

Trial end point • Does treatment with field PDT

–Reduce future risk of skin cancer?

• Concept was: –If future cancer risk clearly reduced –Then face PDT should follow

• Excision of cancer from face

74

Severe adverse events

• 5 of the 34 intervention patients • & the control who had PDT

• Total 6 out 35 = 17%

% of trial patients developing one or more new skin cancers on face – 3 year follow up

0

5

10

15

20

25

30

35

40

Intervention Control

InterventionControl

%

All new cancers were BCCs or SCCs

Except for two patients who had PDT

Kaplan Meier Curve

Complex face surgery pain versus PDT

0

5

10

15

20

25

30

35

40

45

No pain Minimal Paracetamol Strong tabs Severe Worst ever

Large face Surgery PDT

Highly significant P < 0.0001 Mann Whitney U

% Kruskal Wallace Test 0

1

2

3

4

5

6

7

PDT N=34 Major face N=68 All face N=170 All sites N=563

OpenHighLowClose

Pain score ordinal 1 to 6

75

FDA much tougher

• I think some Australian doctors

• Would be in serious legal trouble • If they were doing same in USA

• Australia needs to toughen up • TGA needs to have power to act • Australians need to be protected

PDT and langerhans cells? • When PDT used to treat BCCS • Epidermal langerhans cells sharply reduced • Effect sustained 24 hours

• Is this effecting anti tumour responses?

• Could this explain high recurrence rates

– When PDT used to treat cancers? • Evangelou BJD May 2012

Sentinel node

Activated Dendritic cell

T lymphocyte

Barnetson 2004 Clin & Exp Derm Kalb 2012 ## J Immunology

Mechanism of action - imiquimod

## Have their own cytotoxic properties

Langerhan’s cell dysfunction

• Does this in part explain • Why PDT has shown:

• Very high recurrence rates –When treating cancer

• Lack of cancer prevention –When treating actinic damage

That’s all folks

Anthony Dixon PhD MB BS

FACRRM

Special thanks to: • Jason Mazzurco DO • Lloyd Cleaver DO • Howard Steinman MD • Stuart Anderson MD • Ken Harvey MD • John Dixon MD

- For their totally unpaid contributions and advice towards our clinical trial on Allmedic ® PDT

76

Mounir Wassef, D.O. PGY 6 Robin Shecter, D.O. FAOCD

Palm Beach Center of Graduate Medical Education (PBCGME)

ALOPECIA NEOPLASTICA HERALDING A DIAGNOSIS OF BREAST CANCER

A 64 year old woman presented to our dermatology clinic complaining of a tender scalp

lesion of 3 weeks duration. There was a 2 cm x 1.5 cm erythematous plaque devoid of hair with central

ulceration on the right occipital scalp.

Biopsy revealed an atypical glandular neoplasm in the dermis which had prominent glandular

differentiation, was strongly positive for CK-7 and negative for CK-20.

A breast primary was suspected. An ultrasound guided needle core biopsy of the left breast revealed an invasive ductal carcinoma. A Brain MRI revealed

small right temporal lobe metastasis.

DISCUSSION:

Cutaneous metastases are of diagnostic importance because they may be the first manifestation of an undiscovered internal malignancy (as was the case

with our patient) or the first indication of metastasis of a supposedly adequately treated malignancy.

The site of the primary tumor, if unknown, may be suspected by the histopathology and

immunoperoxidase studies.

DISCUSSION:

Cutaneous metastases of breast carcinoma that occur predominantly by lymphatic dissemination include inflammatory carcinoma, carcinoma en

cuirasse, telangiectatic and nodular carcinoma, and carcinoma of the inframammary crease.

Alopecia neoplastica and mammary carcinoma of the eyelid are probably caused by hematogenous

spread.

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Clinical features: 1. Alopecia neoplastica occurs as oval plaques or patches of the scalp and may be confused clinically

with alopecia areata or a scarring alopecia. 2. Alopecia neoplastica is defined as hair loss

secondary to a visceral malignancy that has metastasized to the scalp.

3. Although cancers that primarily present in the skin-such as basal cell carcinoma, squamous cell

carcinoma, and angiosarcoma can morphologically appear as alopecia, this presentation does not

fulfill the definition of alopecia neoplastica.

Pathology: The tumor cells have elongated nuclei similar to fibroblasts, but the nuclei are larger, more angular,

and more deeply basophilic. The tumor cells often lie singly; however, in some areas, they may form small groups or single rows between fibrotic and thickened collagen bundles. This latter feature of “Indian filing”

is of particular diagnostic importance and may be seen in any histologic variety of metastatic breast

cancer.

Immunoperoxidase Studies: Cutaneous metastases are positive with most

cytokeratins, except for CK20, and often are positive with epithelial membrane antigen (EMA) and

carcinoembryonic antigen (CEA). Expression of CK7 was found in the majority of cases of carcinoma, with

the exception of those arising from the colon, prostate, kidney, thymus, carcinoid tumors of the

lung and gastrointestinal tract, and Merkel cell tumors of the skin

Differential diagnosis : Ironically, the lack of distinctive clinical features may be a

clue to the diagnosis of cutaneous metastases. Anatomic location, the primary morphology, and lesional color can

sometimes be helpful. When distinct clinical features are not present, the primary morphology of most metastases is a papule or especially a nodule. Most sources cite the usual

morphologic differential diagnosis of a dermal/subcutaneous nodule, i.e. a cyst, lipoma,

appendageal tumor or fibroma. Since the pathogenesis of metastasis intimately involves angiogenesis, the primary color is often some shade of red. As a result, metastatic

carcinoma can simulate a number of benign and malignant vascular lesions.

Treatment : Therapy can be tailored to treat any combination of

primary cancer and cutaneous metastasis. Treatment of the latter includes chemotherapy, immunotherapy, radiotherapy,

excision, heat and observation. Occasionally intralesional and topical (e.g. imiquimod) agents are employed. Tumor

burden, maintaining daily function, cosmesis, and the possibility of pain, bleeding and infection are factored into

the treatment algorithm. Although the disease course depends on the underlying malignancy and its therapeutic response, cutaneous metastasis is a marker of advanced disease and, historically, life expectancy has been short.

REFERENCES:

1. Schwartz RA. Cutaneous metastatic disease. J Am Acad Dermatol 1995; 33: 161 2. Wesche WA, Khare VK, Chesney TM, et al. Non-hematopoietic cutaneous metastases in children and adolescents: thirty years experience at St. Jude Children’s Research Hospital. J Cutan Pathol 2000;27: 485–492 3. Reingold IM: Cutaneous metastases from internal carcinoma Cancer 1966; 19:162-168. 4. Brownstein MH, Helwig EB: Spread of tumors to the skin. Arch Dermatol 1973; 107:80-86. 5. Murray S, Simmons I, James C. Cutaneous angiosarcoma of the face and scalp presenting as alopecia. Australas J Dermatol 2003; 44:273-276.

78

Merkel Cell Carcinoma: An Interesting Case and Review

Alison Dawson Himes, DO O’Bleness Memorial Hospital Athens, Ohio

•No relevant disclosures

Outline • Case presentation • Clinical features • Diagnosis/Staging • Prognosis • Treatment

• 56 year old female with progressively enlarging growth on the left arm

• Present for 9 months • Initially treated as a “spider bite” • Burning sensation • Past Medical History: hypertension • Past Family History: melanoma, lung cancer

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Examination revealed a 10cm x 7cm brightly erythematous, firm, multi-lobular tumor with evidence of peripheral extension with an underlying violaceous hue of the left forearm

Biopsy Results Monomorphic infiltrate of malignant cells with nuclei exhibiting a powdery, finely dispersed chromatin. These cells were distributed in cords and nests within the dermis

Additional staining patterns • Positive for CK 20 in a perinuclear dot pattern • Positive for neuron specific enolase and chromogranin • Negative for thyroid transcription factor

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• Consistent with primary Merkel Cell Carcinoma • Chest and Pelvic CT scans showed no evidence of metastatic disease • Underwent radical resection and sentinel lymph node biopsy. • Evidence of lymphovascular invasion and positive left axillary

sentinel lymph node • Axillary dissection showed 2/39 positive nodes • Had external beam radiotherapy • Stage IIIa: T3, N1a, M0 • 1 year later no evidence of recurrence

Why is MCC important? • More lethal than melanoma

- 30-33% mortality (about 15% for melanoma) • Incidence is increasing

- Quadrupled since 1986 • Approximately 1500 cases a year

Merkel Cells • Discovered in 1875 by Frederick Merkel • High density on fingertips and lips • Mechanoreceptor- essential for touch • 1972 Toker described 5 cases of “trabecular carcinoma of the

skin” • 1978 Tang and Toker discovered dense core granules on EM

that were typical of Merkel cells • 1980 the name Merkel Cell Carcinoma was applied to this

tumor

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Clinical Presentation • Asymptomatic • Expanding rapidly • Immune Compromised • Older than 50 • UV- exposed fair skin

89% of MCC > 3 features

Additional features • 94% of patients are older than 50 yrs of age • Median age of 76

Location: • Head and neck (41-50%) • Extremities (32-38%) • Trunk (12-14%)

Clinician Impression at time of biopsy • Benign 56%

- cyst, acneiform lesion - lipoma - dermatofibroma • Malignant 36%

- non-melanoma skin CA - lymphoma - metastatic carcinoma - merkel cell carcinoma (1%)

• Indeterminate - nodule Heath. JAAD 2008

Incidence increase Increase in Risk Factors: • Prolonged sun exposure • Immune suppression • Age > 50

Increased detection • Cytokeratin-20 stain introduced in 1990’s

Immune Suppression in Merkel cell carcinoma • HIV patients

- 13 fold increase • Solid organ transplant patients

- 10 fold increase • Chronic lymphocytic leukemia

- 30-50 fold increase

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Staining pattern • CK20 in perinuclear dot pattern • Thyroid Transcription Factor-1 is

negative in MCC and positive in small cell lung cancer

• CK7 is negative in MCC and positive in small cell lung cancer

• Neuron Specific enolase is positive in MCC • Leukocyte common antigen is negative in MCC (positive in

lymphomas) • S100 negative in MCC (differentiate from melanoma)

Staging • 2010 AJCC Staging System • Tumor size • Lymph node staging (incorporates how they are staged:

clinical or pathologic) • Metastasis

• Merkel cell can have occult nodal disease in clinically negative disease (30% of people have nodal disease, 5% nodal disease in melanoma)

• Significant difference in survival in clinically negative nodes versus pathologically negative nodes - 20-30% difference in survival when you look at clinically negative nodes versus pathologically negative nodes

Lemos et al. J Am Acad Dermatol 2010

Staging AJCC 2010 system • Stage I: Local, < 2cm

- Ia Nodes negative by path exam - Ib Nodes not clinically detectable

• Stage II: Local, > 2cm - IIa Nodes negative by path exam - IIb Nodes not clinically detectable - Iic Primary tumor invading bone/muscle/cartilage

• Stage III: Regional Nodal Disease - IIIa Nodes positive by path and not clinically detectable - IIIb Nodes clinically detectable, in-transit metastasis

• Stage IV: Distant Metastatic Disease

Pathologic Evaluation in MCC • SLNB is important for prognosis and more accurate staging • Therapeutic implications

- Patients with negative SLNB may be spared radiation therapy or additional surgery

• +SLNB ranges from 11-57% in MCC

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• Most frequent sites of metastasis: - Liver (13%) - Bone (10-15%) - Lung (10-23%) - Brain (18%) - Distant skin (9-30%) - Distant lymph nodes (9%)

Prognosis • Overall 5-year survival is 40%

-Local disease: 64% 5-year survival -Regional nodal disease: 39% 5-year survival -Metastatic disease: 18% 5-year survival



Treatment of MCC • Multidisciplinary

- Dermatologist - Surgical oncologist - Radiation oncologist

Treatment of MCC • Main therapeutic modalities used include excision

and/or radiotherapy, depending on stage of disease • Adjuvant chemotherapy has not shown any survival

benefit

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Localized Disease with Clinically Negative nodes

• SLN biopsy and local excision of primary tumor ◦ If SLN positive: perform node dissection and/or radiation therapy. May also consider adjuvant chemotherapy ◦ If SLN negative: Consider observation or radiation therapy

• In head and neck cases where SLN is not performed, consider radiation therapy to primary site, nodal beds, and in-transit lymphatics

Clinically Positive Lymph Nodes

• Perform Fine Needle Aspiration with appropriate Immunopanel ◦ FNA positive: Clinically indicated imaging studies → If no evidence of distant metastatic disease: node dissection and/or radiation therapy. May consider adjuvant chemo ◦ FNA negative: Perform open biopsy of Lymph node → If open biopsy positive treat as above → If open biopsy negative, follow clinical negative nodal pathway

Metastatic disease • Multidisciplinary tumor board consultation • Consider any of the following therapies or combinations

of: ◦ Surgery ◦ Radiation therapy ◦ Chemotherapy

Excision of Merkel Cell • 1-2 cm margins to investing fascia of muscle or pericranium

with clear pathologic margins • Mohs technique • Modified Mohs (final margin for permanent section

assessment) • CCPDMA- Complete circumferential and peripheral deep

margin assessment

Chemotherapy in Merkel Cell • Local disease: not recommended

• Regional disease: not routinely recommended

◦ Cisplatin + etoposide ◦ Carboplatin + etoposide

• Disseminated disease: ◦ Cisplatin + etoposide ◦ Carboplatin + etoposide ◦ Topotecan ◦ Cyclophosphamide, doxorubicin, and vincristine

Follow up • Complete skin examination with lymph node

evaluation performed: ◦ Every 3-6 months for the first 2 years ◦ Annually thereafter

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Take Home Points • MCC is an aggressive, potentially fatal neuroendocrine

carcinoma of skin • Upon presentation, it often has a benign appearance to the

physician • Remember AEIOU: Asymptomatic, Expanding rapidly, Immune

compromised, Older than 50, UV-exposed skin • Sentinel lymph node biopsy is important in

staging/determining prognosis • Excision with narrow but clear margins (carried out at the time

of SLNB) followed by adjuvant radiation therapy is a reasonable approach to management.

References • Toker C. Trabecular carcinoma of the skin. Arch of Dermatol. 1972;105:107–110. • Hodgson NC. Merkel cell carcinoma: changing incidence trends. J Surg Oncol 2005;89(1):1-4. • Kaae J, Hansen AV, Biggar RJ, Boyd HA, Moore PS, Wohlfahrt J, et al. Merkel Cell Carcinoma: Incidence, Mortality, and Risk of Other

Cancers. J Natl Cancer Inst. 2010;102:793-801. doi:10.1093/jnci/djq120 [Pub Med] • Mott RT, Smoller BR, Morgan MB. Merkel cell carcinoma: a clinicopathologic study with prognostic implications. J Cutan Pathol.

2004;31:217–23. • Heath M, Jaimes N, Lemos B, et al. Clinical characteristics of MCC at diagnosis in 195 patients: the AIEOU features. J Am Acad Dermatol.

2008;58:375–81. • Nicolaidou, E, Mikrova A, Antoniou C, Katsambas, AD. Advances in Merkel cell carcinoma pathogenesis and management: a recently

discovered virus, a new international consensus staging system and new diagnostic codes. British Journal of Dermatol. 2011;166:16-21. • Engels EA, Frisch M, Goedert JJ et al. Merkel cell carcinoma and HIV infection. Lancet 2002; 359:497-8 • Feng H, Shuda M, Chang Y, Moore PS. Clonal integration of a polyomavirus in human Merkel cell carcinoma. Science 2008; 319;1096-

100. • Wong HH, Wang J. Merkel cell carcinoma. Arch Pathol Lab Med 2010; 134:1711-16. • Bichakjian, CK, Lowe, L, Lao CD et al. Merkel cell carcinoma: critical review with guidelines for multidisciplinary management. Cancer

2007; 110:1-12. • Kontochristopoulos GJ, Stavropoulous PG, Krasagakis K et al. Differentiation between Merkel cell carcinoma and malignant melanoma:

an immunohistochemical study. Dermatology 2000; 201:123-6. • Lemos BD, Storer BE, Iyer JG et al. Pathologic nodal evaluation improves prognostic accuracy in Merkel cell carcinoma: analysis of 5823

cases as the basis of the first consensus staging system. J Am Acad Dermatol 2010; 63:751-61. • Gupta SG, Wang LC, Penas PF, Gellenthin M, Lee SJ, Nghiem P. Sentinal lymph node biopsy for evaluation and treatment of patients with

Merkel cell carcinoma: The Dana-Farber experience and meta-analysis of the literature. Arch Dermatol 2006; 142(6):685-90. • National Comprehensive Cancer Network. Clinical Practice Guidelines in Oncology. Merkel Cell Carcinoma. V.1. Fort Washington,

PA:NCCN, 2010. • Medina-Franco H, Urist MM, Fiveash J et al. Multimodality treatment of Merkel cell carcinoma: case series and literature review of 1024

cases. Ann Surg Oncol 2001;8:204-8. • Mortier L, Mirabel X, Fournier C, Piette F, Lartigau E. Radiotherapy alone for primary Merkel cell carcinoma. Arch Dermatol.

2003;139:1587-90. • Maza S, Trefzer U, Hofmann M et al. Impact of sentinal lymph node biopsy in patients with Merkel cell carcinoma: results of a

prospective study and review of the literature. Eur J Nucl Med Mol Imaging 2006; 33:433-40. • Mojica P, Smith D, Ellenhorn JDI. Adjuvant radiation therapy is associated with improved survival in Merkel cell carcinoma of the skin. J

Clin Oncol 2007; 25:1043-7. • National Comprehensive Cancer Network. Clinical Practice Guidelines in Oncology. Merkel Cell Carcinoma. V.1.2012 Fort Washington,

PA: NCCN, 2012.

86

Morphea Associated with Celiac Disease

Sanjosh Singh, DO, MPH St.Johns Episcopal Hospital, DME Albert Strojan, DO

Department of Dermatology Program Director Marvin Watsky, DO

Assistant Program Director Sirota Rozenberg, DO

Introduction: Morphea is an idiopathic inflammatory disease of the skin characterized by localized, circumscribed sclerotic patches, or plaques with variable pigmentation, including early violaceous or late ivory and hyperpigmented changes. Morphea is classified into plaque, generalized, linear, bullous and deep subtypes according to the clinical presentation and depth of tissue involvement. Although morphea is commonly associated with various autoimmune disorders, its presentation with celiac disease is rare. There are only a few documented case reports of its association in current literature.

Case: A 56yo African American female presented to the dermatology office with complaint of a painful rash on her left shoulder for 6 weeks. She states the rash itch from time to time and experienced no relief with cocoa butter or baby oil. Her past medical history was significant for GERD and Anemia. She denied chemical exposure, trauma or diet pills. Her family history was noncontributory. On physical exam, a solitary shiny hyperpigmented plaque with atrophic area within the lesion was noted. Biopsy of the lesion revealed sclerosis with morphea or scleroderma. A diagnosis of localized morphea was then confirmed. Our patient also complained of weight loss. Her labs revealed an elevated anti-gliadin antibody level. She was referred to a gastroenterologist in which a complete work-up was consistent with celiac disease. In addition to being treated with topical calcipotriene, the patient was placed on a gluten free diet and noted significant improvement of her symptoms. The rash had subsided with notable post inflammatory hyperpigmentation. At follow-up, the patient was without reccurence.

Localized Morphea. Note the circumscribed, sclerotic, ivory-like plaques with hyperpigmentation changes.

Localized Morphea. Circumscribed, sclerotic patch with hyperpigmentation changes

Discussion Morphea, also known as localized scleroderma, is an idiopathic

inflammatory skin disease characterized by thickening and hardening of the skin and subcutaneous tissues from excessive collagen deposition

Typically limited to the skin but extracutaneous involvement is seen in 20% of patients may include seizures, headaches, arthralgias, dysphagia, visual changes, trigeminal neuralgia and laboratory abnormalities, including eosinophilia, polyclonal hypergammaglobulinemia, and positive antinuclear antibodies

Morphea is an uncommon condition that is thought to affect 1 in 1,000 people; mainly involves women with a F:M ratio of 3:1

Case reports of morphea co-existing with other systemic autoimmune diseases such as primary biliary cirrhosis, vitiligo, and systemic lupus erythematosus lend support to morphea as an autoimmune disease

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Discussion In current literature, there are only 3 other reports of co-existing

celiac disease and morphea There have been few studies of small bowel histology in

patients with scleroderma The priniciple abnormality seen is deposition of collagen among

the lobules of Brunner’s glands in the submucosa leading to malabsorption

The mechanism of malabsorption is complex and includes reduced vascular mucosal flow, lymphatic obstruction, submucosal fibrosis, failure of gut motility and small bowel bacterial overgrowth

Exhaled hydrogen breath test is an indirect method of testing small bowel bacterial overgrowth but can be falsely positive

Duodenal biopsy should be an essential investigation in scleroderma patients who suffer from malabsorption

Histopathology

Similar to Scleroderma Square-off biopsy

Epidermis normal or atrophic

Hyalinized dermis and subcutaneous fat, more

prominent in late lesions

Sparse perivascular lymphocytes, sometimes plasma cells, in dermis and/or subcutaneous fat

Dense collagen

Bound down sweat ducts

Localized Morphea (H&E) Localized Morphea. Note the swollen collagen bundles and atrophic sweat glands.

Localized Morphea. The recently deposited collagen stains weakly with the usual collagen stains and is devoid of

elastic tissue. (Verhoeff Van Gieson)

Management: Morphea is typically self resolving, however patients may seek treatment for cosmetic reasons in which topical, intra-lesional or systemic steroids may prove helpful. Antimalarials such as hydroxychloroquine or chloroquine and immunomodulators such as methotrexate, topical tacrolimus, and penicillamine have been tried although their safety and efficacy is questionable due to lack of objective studies. UVA therapy, with or without psoralens have also been tried because of its ability to penetrate deeper portions of the skin and soften the plaques by inducing enzymes that naturally degrade the collagen matrix in the skin. Case reports and observational studies suggest there is a higher frequency of family history of autoimmune diseases in patients with morphea therefore blood tests for autoantibodies are recommended such as anti-histone and anti-topoisomerase antibodies. Anti-tissue transglutaminase antibodies (tTGA), anti-endomysium antibodies (EMA) and anti-gliadin antibodies are typically elevated in celiac disease. Further work-up by a gastroenterologist is recommended

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References

1) Firoz E et al. Morphea, Diabete Mellitus Type 1, and Celiac Disease: Case Report and Review of the Literature. Pediatric Dermatology. 2010 Vol. 27 No.1 48-52

2) James WD, Berger TG, Elston DM. Andrews’ Diseases of the Skin Clinical Dermatology. 10th Ed. Philadelphia, PA: Elsevier Inc Publisher, 2006. pg.171-175

3) JL Bolognia, JL Jorizzo, RP Rapini. Dermatology. 2nd Ed. Spain: Elsevier Limited Publisher, 2003. pg. 1469-76

4) Marguerie C et al. Malabsorption caused by celiac disease in patients who have scleroderma. Br J Rheumatol. 1995 Sep;34(9):858-61

5) Rapini RP. Practical Dermatopathology. 1st Ed. Philadelphia, PA: Elsevier Inc Publisher, 2005. pg.132

6) Sheehan NJ, Stanton-King K. Co-existent celiac disease and scleroderma. Br J Rheumatol. 1996 Aug;35(8):807

89

Psoriasis in Lines of Blaschko

Charlotte Noorollah DO St Johns Episcopal Hospital, South Shore

Far Rockaway New York Program Directors: Marvin Watsky DO, Suzanne Sirota

Rozenberg DO

Case Presentation

• A 17-year-old female presented with a 3-month history of an eruption limited to her right arm, shoulder and chest

• She admitted to mild itching but denied pain, or constitutional symptoms

• Review of systems was non-contributory

Case Presentation

• PMHX: Non-Contributory • PSHX: Non-Contributory • Family Hx: She denied any personal or family

history of psoriasis • She was not on any medications prior to the onset

of the rash

Case Presentation

Case Presentation

• Differential diagnosis at the time of presentation included:

• Psoriasis • Inflammatory linear verrucous epidermal nevus

(ILVEN) • Linear lichen planus

Histopathology

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Histopathology Histopathology

Histopathology Case Presentation

• The patient was started initially on twice-daily application of mometasone furoate ointment with only mild response after two weeks

• She was later started on twice-daily application of halobetasol propionate ointment with clearing of the plaques after 3 weeks

Post-Treatment Post-Treatment

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Linear Psoriasis

• Linear psoriasis is a rare variant of psoriasis that manifests as psoriasiform plaques following the lines of Blaschko

• Typically this entity can be difficult to distinguish from inflammatory linear verrucous epidermal nevus (ILVEN) both clinically and histologically

• Age of presentation as well as response to topical treatment can help distinguish between the two entities

ILVEN

• Plaques are often verrucous and inflammatory and lesions to do not typically progress

• Lesions are usually unilateral, linear, typically found on the lower extremities and distributed along the lines of Blaschko

• Tends to develop early, within first 6 months of life

• Female predominance (4:1) • Family occurrences are usually rare or absent

ILVEN

• Often pruritic • Relatively refractory to conventional topical

treatment • Can occur in the setting of generalized psoriasis

and psoriasis can occur overlying an epidermal nevus

ILVEN

•

Linear Psoriasis

• Lesions can be more widespread characterized by erythematous scaly plaques with occasional associated pruritis

• Tends to occur later in life • A family history can be present as well as

systemic manifestations • Lesions typically respond to anti-psoriatic therapy

ILVEN Li near Ps ori asis Onset of lesions During first months of life Later in life Symptoms Very itchy Occasionally Extent Usually unilateral, linear

distribution following BlaschkoÕs lines

May be more widespread

Morphology Verrucous infiltrative inflammatory lesions

Erythematous scaly plaques

Family history of psoriasis Absent May be present Progress of lesions Slow Rapid Associations (sore throat and guttate lesions)

Absent Present

Involvement of other sites (nail/scalp/palms/soles)

Absent Present

Seasonal remissions Absent Present Response to treatment Non-responsive to treatment Responds well to

antipsoriatic treatment

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Histopathology • Epidermal hyperplasia with overlying areas of

parakeratosis, alternating with orthokeratosis, showing features of a “checkerboard”

• The parakeratosis overlies areas of absence of a granular layer

• The zones of parakeratosis are usually broader in ILVEN than in psoriasis

• Mild perivascular lymphocytic infiltrate can also be present

Histopathology

• Genetic mosaicism is used to describe individuals composed of cells of different genotypes

• The cutaneous patterns caused by genetic mosaicism manifest in lines of Blaschko forming whorls in the skin

Pathogenesis • Blaschko’s lines are thought to be caused by the migration of cells during embryogenesis where linear demarcations form between normal and mutant cells • These patterns of demarcation result from disorders of epidermal cells and were established based on the study of epidermal nevi

Genetic Mosaicism

• 1961: Mary Lyon reported similar striped patterns in mice heterozygous for certain X-linked coat-color genes

• She hypothesized that the stripes reflect two populations of cells, one expressing the maternal X chromosome and one expressing the paternal X chromosome

• 1977: Happle recognized lyonization as the cause of Blaschko’s lines in female patients heterozygous for other X-linked skin disorders

Genetic Mosaicism

• We now know that mosaicism is due to multiple factors:

• Lyonization • Somatic mutation • Half-chromatid mutation • Chromosomal non-disjunction • Chimerism

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Cutaneous Mosaicism

• Cutaneous manifestations are determined by cell migration which is dependent on the stage of development at which mosaicism occurs

• The earlier the mutation, the more widely distributed the mosaic clone and the longer the lines of migration

Cutaneous Mosaicism

• Embryonic keratinocytes: move outwards from the neural crest and proliferate forming a continuous line and cutaneous patterns form based on cell migration and surface remodeling

• Melanoblasts: move outwards by single cell migration and proliferate at or before birth locally in the skin

Pathogenesis

• It is thought that that a linear clone of psoriasis is characterized by a susceptibility mutation that gives rise to the clinically linear appearance of the lesions

Pathogenesis

• Linear psoriasis is a multifactorial inflammatory disorder with autosomal dominant or polygenic inheritance

• ILVEN is a presumed autosomal dominant lethal disorder “rescued” by mosaicism and thus never seen in a generalized form

Immunohistochemistry

• Keratin 10 and Ki-67 positive nuclei are markers for epidermal differentiation

• There tends to be a lower expression of Keratin 10 in psoriasis as compared to those levels found in ILVEN

• Reduced number of Ki-67 positive nuclei in ILVEN as compared to psoriasis

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• Assessment of elastase-positive cells can also be helpful in differentiating between ILVEN and linear psoriasis

Immunohistochemistry • De Jong et al sought to assess inflammation, proliferation

and keratinization in ILVEN and linear psoriasis by using immunohistochemical studies

• In ILVEN, they observed: • Low occurrence of elastase-positive cells (PMN) • Focal staining pattern of Ks8.2 (anti-keratin 16) • Homogeneous pattern distribution of RKSE60 (anti-

keratin 10)

• In psoriasis: • Occurrence of elastase-positive cells were more

substantial

Role of T Lymphocytes • Psoriasis is a disorder activated by T lymphocyte

production • Visser et al sought to analyze T lymphocyte

subsets to help distinguish between ILVEN and psoriasis

• They compared the number and composition of the T lymphocyte infiltrate of patients with ILVEN without any associated psoriasis and those with psoriasis

Role of T Lymphocytes

• The authors found that T-cell subsets important in the pathogenesis of psoriasis are reduced in ILVEN as compared to psoriasis; specifically CD8, CD45RO, CD2, CD94, and CD161

Human leukocyte antigen • Human leukocyte antigen (HLA) Cw6 A2 has

been found to be associated with linear psoriasis • Magalhaes et al described two cases of linear

psoriasis in Brazilian children with specific HLA class I-associated alleles

• They proposed that the HLA class I allele findings in patients with linear psoriasis differ from those in early onset psoriasis

Human leukocyte antigen

• Differences suggest that linear psoriatic lesions may represent cellular mosaicism where cells within those areas react differently due to chromosomal differences from their surrounding cells

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Treatment • Typical treatment options for linear psoriasis are

the same as those used for generalized psoriasis including:

• Topical steroid treatment • Keratolytics • Calcipotriol • Narrow-band ultraviolet B phototherapy

Treatment

• Systemic agents such as Acitretin, Methotrexate, or TNF inhibitors can be helpful for long-standing or refractory cases

Conclusion

• Psoriasis occurring in a blaschkoid distribution is a rare entity

• Distinguishing it from ILVEN both clinically and histologically can often be difficult

• Later onset of presentation and response to anti-psoriatic treatment can often help the clinician to differentiate between the two conditions

References • Purohit S, Kanodia S, Shukla SR. Linear Psoriasis. Indian J Dermatology and Leprology. 2006 Sep-

Oct;72(5):398. • Li, Wei, and Xiao Yong Man. "Linear Psoriasis." Canadian Medical Association Journal 184.7

(2012): 789. Print. • Weedon, David, Geoffrey Strutton, Adam I. Rubin, and David Weedon. Weedon's Skin Pathology.

3rd ed. [Edinburgh]: Churchill Livingstone/Elsevier, 2010. Print. • De Jong, EM, Rulo, HF and PCM Van De Kerkhof. "Inflammatory Linear Verrucous Epidermal

Nevus (ILVEN) Versus Linear Psoriasis." Arch Derm Venereol 71.4 (1991): 343-46. Print. • Saraswat, Abir, Kamaldeep Sandhu, Rajeev Shukla, and Sanjeev Handa. "Unilateral Linear Psoriasis

with Palmoplantar, Nail, and Scalp Involvement." Pediatric Dermatology 21.1 (2004): 70-73. Print. • Bolognia, Jean, Joseph L. Jorizzo, and Ronald P. Rapini. Dermatology. 2nd ed. Vol. One. [St. Louis,

Mo.]: Mosby/Elsevier, 2008. Print. • Busam, KJ. "Tumors of the Epidermis." Dermatopathology. [Philadelphia]: Saunders/Elsevier, 333-

38. 2010. Print. • Barnhill, Raymond L. Dermatopathology. 3rd ed. New York: McGraw-Hill Medical, 2010. Print. • Brinca, Ana, F. Santiago, and D. Serra. "Linear Psoriasis - A Case Report." Case Reports in

Dermatology 3 (2011): 8-12. UK Pubmed Central. Web. • Chien, Peter, Karla Rosenman, and Wang Cheung. "Linear Psoriasis." Dermatology Online Journal

4th ser. 15.8 (2009): Web. • Vissers, W. H., L. Muys, and P. E. Erp. "Immunohistochemical Differentiation between

Inflammatory Linear Verrucous Epidermal Nevus (ILVEN) and Psoriasis." European Journal of Dermatology 14.4 (2004): 216-20. Print.

• Magalhaes, RF, et al. Linear Psoriasis in Brazilian children and HLA haplotypes. Journal European Academy of Dermatology and Venerology. 2007; 21:1439. Print

• Raza N, Iqbal P, Anwer J. 填nilateral Psoriass along Blaschko Lines�. Journal Aub Med Coll Abottabad. 2005 Jan-Mar;17(1):87-8.

THANK YOU

96

Parry Romberg Syndrome: Case Series

James B Young DO, Stuart Gildenberg MD St. Joseph Mercy Hospital, Ann Arbor, MI

AOCD Annual Meeting Wednesday, November 2, 2011

Disclosures

No financial relationships exist with commercial interests

Objectives

• Present a case of recurrent unilateral linear capillaritis (ULC)

• Review the pigmented purpuric dermatoses (PPDs)

• Discuss the clinical and histopathological features

• Review treatment options

Case 1

• 42-year-old African American female • 20-year history of facial atrophy and

asymmetry – Gradual onset starting at age 10 and

progressing until age 13-14 – No history of the following:

• Pain • Neurologic abnormalities • Seizure activity • Ocular abnormalities

Case 1: Course & Therapy

• No treatments to date • Minimal change or associated symptoms

since age 14

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Case 2

• 58-year-old Caucasian female • 50-year history of progressive left hemifacial

atrophy to the ocular, dental and cutaneous areas – Age 7- Multiple episodes of head trauma

• Then gradual onset left eye visual impairment – Age 25- Dx by ophthalmology with left eye low

ocular pressure • Treatment attempted with steroid drops

– Age 30- Facial cutaneous changes began


• Cutaneous atrophy episodically progressed – Worsened during each pregnancy

• Still limited vision in the left eye • No treatment sought for cutaneous lesions

Case 3

• 52-year-old Caucasian female • 49-year history of left hemifacial atrophy

– Onset was acute and progressed over one year – Age 14- Forehead lesion was injected with silicone by a

plastic surgeon • Material subsequently migrated laterally & settled • Episodes of periodic inflammation occurred years later

– Occurred randomly, several times a year – Focal redness and irritation lasting weeks to one month

– No history of seizures, head trauma, or autoimmune disease

– Occasional piercing headaches focused over the left forehead

• Past MRI of the head/neck was negative


• Cutaneous atrophy has been relatively stable since childhood

• Episodic swelling over the silicone deposits has been bothersome

• Wears a stronger corrective lens prescription in the left eye

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Parry Romberg Syndrome

• AKA progressive hemifacial atrophy • Rare disorder • Characterized by unilateral facial atrophy affecting the

following: • Skin • Subcutaneous tissue • Muscles • Occasionally osteocartilaginous structures

• Slowly progressive over 2 to 20 yrs, then stabalizes – Usually first decade of life

• Occasionally involves the trunk & extremities • Bilateral involvement has been described

– Usually classified under Barraquer-Simons syndrome

PRS: Clinical

• Affecting dermatomes of trigeminal nerve branches – Unilateral facial shrinking & deformation – Ipsilateral enophthalmos – Lip & nose deviation

• Hyper/hypo pigmentation my present • Cicatricial alopecia reported

PRS: Histopathology

PRS: Pathogenesis

• Not well understood – many propositions

– Trauma

• Hypothesized as cause in 24-34%

– Infection • No organism has been

specifically isolated from cerebrocerebellar tissue

– Cranial vascular malformation

• Neural crest migration disorder

• Assoc. benign neural tumors, migraines & aneurysms

– Immune-mediated processes • Occasional findings of serum

autoantibodies – Fat metabolic disturbance

• Disturbance such as hyperthyroidism could cause atrophy, lipodystrophy, and diencephalic tissue melting

– Sympathetic dysfunction • Trophic malformation of the cervical

sympathetic trunk • Ablation of the superior cervical

ganglion in animals has reproduced hemifacial atrophy, enophthalmos, and bone atrophy on the side of the sympathectomy

• Ipsilateral Horner syndrome has been found in some cases

• Sympathectomy would and has, in some cases, halted progression

PRS: Systemic associations

Cardiac Endocrine Infectious Autoimmune Congenital • Hyper-

trophic cardio-myopathy

• Hyperthyroid • Hypothyroid • Lipodystrophy

• Borreliosis • Herpes • General

infectious processes

• Otitis • Dental • Diphtheria • Syphilis • Rubella • TB

• Hashimoto thyroiditis

• Grave Dz • Primary biliary

cirrhosis • Vitiligo • IBD • RA • Ankylosing

spondylitis • Multiple

sclerosis • Sjogren Dz • Autoimmune

hemolytic anemia

• Lupus

• Contralateral Poland syndrome

• Congenital lower limb hypoplasia

• Congenital ipsilateral cerebral atrophy

• Supernumerary nipple

• Microphthalmia • Congenital

torticollis • Renal

malformation

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PRS: Reported neurologic manifestations

• Seizure • Migraine • Hemiplegia • Aneurysm • Brain atrophy • Limb atrophy • Intracranial vascular malformations • Status migrainosus • Headaches • Facial pain • Cerebral microhemorrhage • Paroxysmal kinesigenic dyskinesia • Rasmussen syndrome • Trigeminal neuralgia • Cystic leukoencephalopathy • Dura matter atrophy • Subdural hygroma

• Torticollis • Syringomyelia • Sympathetic hyperactivity • Cerebellar syndrome • Agenesis of head of caudate nucleus • Trunk atrophy • Amnesic aphasia • Mental retardation • Unilateral alien hand syndrome • Mandibular cramps • Bilateral pyramidal tract involvement • Hemianesthesia • Oculomotor nerve palsy • Facial nerve palsy • Central nervous system tumor • Cortical depression • Fatal brain stem involvement • Hyperactivity of brain stem center

PRS: Reported ophthalmologic manifestations

• Enophthalmos • Uveitis • Retinal vasculitis • Third nerve paresis • Glaucoma • Eyelid atrophy • Amblyopia leading to progressive visual loss

when anisometropic • Exotropia • Hypotropia • Esotropia • Increase in pre-existing hyperopia • Diplopia • Restrictive strabismus • Cataract • Miosis • Retinal pigment changes • Chorioretinal lesions • Extraocular muscle thinning • Contralateral extraocular muscle impairment • Eyelid alterations (upper eyelid retraction) • Decreased corneal sensitivity • Band keratopathy • Loss of cilia

• Papillitis • Episcleritis • Bilateral vitreitis • Iridocyclitis • Neuroretinitis • Retinal telangiectasis • Orbital neurinomas • Phthisis bulbi • Pseudoptosis • Profound ocular hypotony • Nocturnal lagophthalmos • Blepharoptosis • Light staining of retina • Shrinkage of eyeball • Retinal detachment • Corneal exposure • Blindness • Adie pupil • Coat syndrome • Duane retraction syndrome • Fuchs syndrome • Horner syndrome

PRS: Reported ophthalmologic manifestations

• Mandibular odontogenous fibroma

• Odontogenic cys • Odontoma of mandible • Teeth involvement • Root resorption • Delayed eruption • Dilaceration • Ipsilateral reduction in

height and width of mandible

• Communication disorders • Dysphonia

Linear scleroderma

• “En coup de sabre” variant (LSCS) – Unilateral frontoparietal linear atrophy – Scarring alopecia may be present – Starts in childhood, slow and progressive over 2

to 20 years, becoming stable – Neurologic and ophthalmologic complications

reported – Unclear pathogenesis:

• Autoimmunity • Disturbed peripheral sympathetic nervous system • Disturbed trigeminal nerve • Early cerebral inflammation

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PRS vs. LSCS

• No definite criteria agreed upon to differentiate • Similarities:

– Predominently women – Slow progression with stabalization – Comparable neurologic & ophthalmologic findings – Both may respond to immunosuppressive tx

• Differentiating factors – Presence or absence of inflammation/induration – Sight affected – Severity of atrophy

• LSCS in conjunction with PRS – Reported prevalence: 36.6 - 53.6% – Both can be considered on a spectrum of scleroderma

PRS: Treatment - Progression

• First, halting the disease process • Improving symptoms

Systemic therapy Local therapy Procaine penicillin D-penicillamine Antimalarials (Hydroxychloroquine) Corticosteroids Vitamin E Retinoids Cyclosporine Tetracycline Cyclophosphamide Methotrexate (MTX) MTX + pulsed oral steroids

Emollients Vitamin D analog Vit D analog + PUVA Topical steroids Botulinum toxin Phototherapy

PRS: Treatment Cosmetic

• Once disease stabilized, aesthetic tx considered – Recommended pause of 1-2 yrs before reconstruction

Single procedure Combined procedure Facial reconstruction • Lipofilling • Polyethylene implant • Medpor implant • Cell-assisted lipotransfer Flaps & grafts • Tissue transfer with anterolateral thigh

fasciadipose flap • Pedicled superficial temporal fascia sandwich flap • Muscle flap Volume regeneration • Autologous fat transplantation • Polytetrafluoroethylene • Poly-L-lactic acid

Poly-L-lactic acid +Lipofilling + pulse light Flap + lipofilling Flap + dermis grafting Flap + Medpor implant Flap + genioplasty Flap + liposuction revision Lipoinjection + blood platelet gel Lipoinjection + galeal flaps + free dermis fat grafts + bone and cartilage grafts

Conclusion

• Although rare, PRS reported abundently • Many theories of origin exist, none universally

accepted • PRS is assoc. with multiple findings • Close relationship of PRS & LSCS exists • PRS appears to belong to a broad spectrum

of scleroderma • Treatment options in literature include both

halting progression and cosmetic appearance

101

References

1. El-Kehdy J, Abbas O, Rubiez N. A review of Parry-Romberg syndrome. J Am Acad Dermatol. 2012 Mar 7. [Epub ahead of print]

2. Gulati S, Jain V, Garg G. Parry Romberg syndrome. Indian J Pediatr. 2006;73:448–449. 3. A. Duymaz, F.E. Karabekmez, M. Keskin, Z. Tosun. Parry-Romberg syndrome: facial

atrophy and its relationship with other regions of the body. Ann Plast Surg, 63 (2009), pp. 457–461

4. Stone J. Parry-Romberg syndrome. Practical Neurology. 2006;6:185–188. 5. Lazaridou E, Giannopoulou C, et al. Parry-Romberg Syndrome. J Dermatol Case Rep.

2012 Nov: 4(2):30-32. 6. Tollefson MM, Witman PM. En coup de sabre morphea and Parry-Romberg syndrome: a

retrospective review of 54 patients. J Am Acad Dermatol. 2007;56:257–263. 7. Kreuter A, Altmeyer P, Gambichler T. Treatment of localized scleroderma depends on

the clinical subtype. Br J Dermatol. 2007;156:1363–1365. 8. Weibel L, Sampaio MC, Visentin MT, Howell KJ, Woo P, Harper JI. Evaluation of

methotrexate and corticosteroids for the treatment of localized scleroderma (morphoea) in children. Br J Dermatol. 2006;155:1013–1020.

9. Cervelli V, Gentile P. Use of cell fat mixed with platelet gel in progressive hemifacial atrophy. Aesthetic Plast Surg. 2009 Jan;33(1):22-7.

102

Muckle-Wells Syndrome: A Cold Case Diagnosis

Heather Kiraly Orkwis DO, James Ramirez MD, Anthony Baron MD, Stuart Gildenberg MD

St. Joseph Mercy Hospital

October 9, 2012

Disclosures

No financial relationships exist with commercial interests

Objectives

• Present a case of Muckle-Wells Syndrome

• Discuss the clinical and histopathological features

• Review the Cryopyrin Associated Periodic Syndromes

• Identify current treatment options

History

• 25-year-old Caucasian male – Recurrent fevers – Urticaria from infancy – Sensorineural hearing loss – Arthralgias – Myalgias – Abdominal pain

103

104

Laboratory

• CBC • CMP • Complement levels • ANA • UA • ESR • CRP

Further Evaluation

• NIH – Genetic and Rare Diseases Center

• Vision and hearing evaluations • Genetic analysis

–NLRP3 gene (CIAS1)

Diagnosis

Muckle-Wells Syndrome

Cryopyrin Associated Periodic Syndromes (CAPS)

• Muckle-Wells Syndrome

• Familial Cold Autoinflammatory Syndrome

• Neonatal Onset Multisystem Inflammatory Disease


• Autosomal Dominant – NLRP3 gene (CIAS1) •Chromosome 1q44

–Cryopyrin

105

Inflammation with fever

Cryopyrin/NLRP3 LRR

PYD

PYD PYD

CARD

CARD

CC

B box

IL-1 Processing

NF-kB modulation

Apoptosis


• Recurrent fevers, urticaria • Sensorineural hearing loss • Conjunctivitis, episcleritis, optic disc edema • Abdominal pain • Renal failure • Amyloidosis

– Secondary systemic amyloidosis – AA subtype

Cryopyrin Associated Periodic Syndromes (CAPS)




CAPS

Familial Cold Autoinflammatory Syndrome (FCAS)

Diagnosis = 4/6 criteria 1. Recurrent intermittent episodes of fever and rash that follow

generalized cold exposure 2. Autosomal dominant pattern of disease inheritance 3. Age of onset < 6 months 4. Duration of most attacks < 24 hours 5. Presence of conjunctivitis associated with attacks 6. Absence of deafness, periorbital edema, lymphadenopathy,

and serositis

Neonatal Onset Multisystem Inflammatory Disease (NOMID)

• Chronic aseptic meningitis

• Papilledema

• Joint problems

• Constant flares

• Mental and physical deficits

• Progressive hearing loss

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IL-1 Receptor Antagonists

Treatment of MWS

• Surveillance – Amyloidosis – Hearing loss

• IL-1 receptor antagonists

– Anakinra, Canakinumab, Rilonacept

Summary: CAPS




Patient Support

• NIH Rare Diseases Center http://rarediseases.info.nih.gov

• National Organization for Rare Disorders www.rarediseases.org

• Clinical trials www.clinicaltrials.gov

• NOMID Alliance www.nomidalliance.org

• Facebook www.facebook.com/pages/Cryopyrin-associated-periodic-syndrome

References

1. Kazushi Izawa, et al. Detection of Base Substitution-Type Somatic Mosaicism of the NLRP3 Gene with >99.9% Statistical Confidence by Massively Parallel Sequencing DNA Res first published online January 24, 2012 doi:10.1093/dnares/dsr047.

2. Kümmerle-Deschner, J. B., Tyrrell, P. N., Reess, F., Kötter, I., Lohse, P., Girschick, H., Huemer, C., Horneff, G., Haas, J.-P., Koitschev, A., Deuter, C. and Benseler, S. M. (2010), “Risk factors for severe Muckle-Wells syndrome.” Arthritis & Rheumatism, 62: 3783–3791.

3. Maksimovic, L., et al. "New CIAS1 Mutation and Anakinra Efficacy in Overlapping of Muckle-Wells and Familial Cold Autoinflammatory Syndromes." Rheumatology 47.3 (2008): 309-10.

4. Kuemmerle-Deschner, Jasmin, et al. Anakinra in the Treatment of Muckle-Wells Syndrome - A Series of Four Cases, 2005. COS Conference Papers Index.

5. Hoffman, Hal M., et al. "Mutation of a New Gene Encoding a Putative Pyrin-Like Protein Causes Familial Cold Autoinflammatory Syndrome and Muckle-Wells Syndrome." Nature genetics 29.3 (2001): 301-5.

6. Hoffman HM. Familial Cold Autoinflammatory Syndrome, Orphanet Encyclopedia. February 2005: http://www.orpha.net/data/patho/GB/uk-FCAS.pdf.

7. Lachmann, HJ., and Hawkins, PN Developments in the scientific and clinical understanding of autoinflammatory disorders Arthritis Research & Therapy 2009, 11:212doi:10.1186/ar2579.

8. Goldbach-Mansky R, Dailey NJ, Canna SW, et al. Neonatal-onset multisystem inflammatory disease responsive to interleukin-1β inhibition. N Engl J Med 2006;355:581-92.

9. NOMID Alliance. http://www.nomidalliance.org.

107

When Seemingly pathognomonic is actually a mystery

AOCD – Annual Meeting 2012

Libby Rhee, DO Harleen Sidhu, MD Robert Phelps, MD

Cindy Hoffman, DO

No conflicts of interests to disclose.

History of Present illness

• 24 year old female with a complaint of the sudden appearance of red-to-purple papules on the abdomen, left flank, buttocks, and right upper arm, which were progressing over the past three years.

• Lesions start as pink-to-red pinpoint macules and papules that eventually enlarge into firm violaceous papules.

• Newest lesions were on her right upper arm.

• Asymptomatic for the most part, however, they bleed easily and profusely with minor trauma.

History of Present illness

• Denied any childhood illnesses; relatively healthy.

• No family members with similar complaints/findings.

• Review of systems: Admitted to increased fatigue, intermittent arthralgias, severe

bouts of “shooting pain,” which started when she was 14 years old, paresthesias, periodic episodes of dizziness, and significant weight gain during the last three years.

Denied headaches, vision changes, changes in appetite, diarrhea, hyper- or hypohydrosis, abdominal pain, chest pain, or bone pain.

Other History

• Past medical history: Asthma, seasonal allergies

• Past surgical history: None

• Family history: Non-contributory

• Social history: Married with a healthy 3-year old daughter. Works as health care aide. Denied tobacco, etoh, drugs.

• Medications: Allegra, singular, nasonex, calcium, acidophilus, acai, folic acid

• Allergies: Shellfish

PHYSICAL EXAM

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109

• Angiokeratoma Angiokeratoma corporis diffusum (Fabry disease) Angiokeratoma of Mibelli (AKM) Angiokeratoma of Fordyce Angiokeratoma circumscriptum Solitary or multiple type of angiokeratoma

• Cherry hemangioma

• Lymphangioma circumscriptum

• Glomangioma

• Pyogenic granuloma

• Melanocytic nevi

• Melanoma

• Blue rubber bleb nevus syndrome

• Hereditary hemorrhagic telangiectasia (Osler-Weber-Rendu)

Labs

• CBC: wbc: 8.4 / Hb: 12.3 / Hct: 35.2 / platelets: 271 [all

WNL]

• BMP: WNL

• LFT: WNL

• TSH: 1.72 uIU/mL [WNL]

• ANA: negative

• RF: < 10 IU/mL [reference range: < 14 IU/mL]

HISTOLOGY

110

Further work up

• Serum alpha-galactosidase A: WNL 54.4 nmol/hr/mg p [28-80]

• Urine/Plasma GL-3: WNL

• Electron microscopy: No evidence of lysosomal storage disease (zebra-like inclusion bodies)

• Cytogenic analysis: Normal female karyotype

• Genetic mutation analysis/DNA sequencing: negative for alpha-GLA allelic mutations

• Eye exam: normal No corneal or lenticular opacities on slit lamp examination Vision, eye pressure, visual fields, pupillary examination, motility,

and fundoscopic examination all normal

ANGIOKERATOMA CORPORIS DIFFUSUM Sine Fabry?

Angiokeratomas

• Well-circumscribed vascular lesions consisting of superficial vascular ectasia and hyperkeratosis.

• Five variants: Solitary or multiple angiokeratomas Angiokeratomas of scrotum or vulva (aka, angiokeratoma of

Fordyce) Angiokeratoma of Mibelli (AKM) Angiokeratoma circumscriptum Angiokeratoma corporis diffusum (ACD)

• Result from ectatic dilation of pre-existing vessels in the papillary dermis Angiokeratoma circumscriptum capillary–lymphatic

malformation

Solitary or multiple angiokeratomas

• Small, warty, black papule on the lower extremities, but may occur anywhere on the body.

• Thought to result from injury or trauma to or chronic irritation of the venule wall in the papillary dermis.

• Solitary lesions may be confused with melanoma.

Angiokeratomas of fordyce

• Typically asymptomatic 2-to-5mm, red to black in color, may be single or multiple, and arise along superficial vessels.

• Most common in older age groups but may occur as early as the 2nd/3rd decade.

• Scrotum >> penile shaft, labia majora, inner thighs, lower abdomen.

• May be associated with thrombophlebitis, varicoceles and inguinal hernias.

• Vulvar lesions may be associated with vulvar varicosities, hemorrhoids, OCPs, or increased venous pressure during pregnancy.

Angiokeratoma of Mibelli

• Usually develop between the ages of 10 and 15 years.

• Dorsal and lateral aspects of the fingers and toes.

• Sometimes on the dorsa of the hands and feet and rarely on the elbows and knees.

• May be associated with chilblains and acrocyanosis.

• Rarely, ulceration of the fingertips may occur.

• There is a familial predisposition and the disorder may be transmitted in an autosomal dominant fashion with variable penetrance.

111

Angiokeratoma circumscriptum

• Least frequent variant of angiokeratomas.

• Capillary-lymphatic malformations.

• 3:1 female predominance.

• Commonly present at birth or develop during infancy/childhood as either a plaque of multiple discrete papules or hyperkeratotic papules and nodules that often become confluent.

• Trunk, arms or legs; unilateral in most patients.

• Rare manifestation of angiokeratoma circumscriptum naeviforme, on the neck.

Angiokeratoma corporis diffusum

• Characterized by the development of multiple, often clustered angiokeratomas, usually in a bathing trunk distribution.

• Lesions vary in number (only a few to many) and usually begin to appear during late childhood or adolescence.

• Most commonly associated with Fabry disease, which results from a deficiency of the lysosomal enzyme α-galactosidase A.

• Accumulation of the neutral glycolipid ceramide trihexidose within lysosomes of multiple cell types.

Pathology

• Marked dilatation of the papillary dermal vessels in association with an acanthotic, variably hyperkeratotic epidermis.

• Elongated rete ridges may partially or completely enclose vascular channels, and a collarette may be present.

• Fabry disease vacuoles can be detected in endothelial cells and pericytes.

• The amount of glycolipid is small and may be difficult to detect in routinely prepared sections. Deposits are PAS-positive and Sudan black-positive.

They can also be demonstrated by electron microscopy.

Fabry Disease

• Progressive and life-threatening; affects both males and females.

• X-linked recessive lysosomal storage disorder resulting from a deficiency of α-galactosidase A. GLA gene; > 370 different mutations Systemic deposition of glycosphingolipids, predominantly

globotriaosylceramide and galabiosylceramide.

• Clinical manifestations result primarily from the accumulation of glycosphingolipids in vascular endothelium.

• Affects ~1/40,000 males; all ethnicities.

• Female heterozygotes are also less frequently affected, usually with milder, late-onset forms compared to male hemizygotes.

Fabry Disease

• Skin, kidneys, heart, and nervous system primarily affected.

• Cardinal clinical features - first two-to-three decades of life: Pain and paresthesias of the extremities (with onset often

during childhood or adolescence).

Multiple angiokeratomas of the skin and mucous membranes.

Hypohidrosis.

Characteristic corneal and lenticular opacities.

• Progressive renal insufficiency develops.

• Coronary insufficiency and cerebrovascular disease.

Fabry Disease

• Angiokeratomas may be one of the earliest manifestations.

• Appear in almost all affected male patients and approximately 30% of heterozygous females.

• Lesions classically develop slowly as individual punctate, dark-red to blue–black macules or slightly elevated papules that do not blanch and may become slightly keratotic as they enlarge.

• Angiokeratomas tend to be clustered between the umbilicus and the knees in Fabry disease but can be present anywhere.

• Oral mucosa and conjunctival involvement is common.

• Anhidrosis/hypohidrosis is an early and almost constant feature.

112

Fabry Disease

• In the skin, there is evidence of lipid storage in the endothelium, pericytes and smooth muscle of capillaries, venules and arterioles, and arrector pili muscles.

• Lipid accumulation may also be observed in sweat gland epithelium and perineural cells. Ultrastructural examination of eccrine sweat glands reveals

characteristic cytoplasmic inclusions within the secretory coil, coiled duct and basal cells of the straight duct.

Inclusions are also seen in the unmyelinated axons innervating the sweat glands.

Fabry Disease

• Definitive diagnosis of Fabry disease is established by demonstration of α-galactosidase A deficiency in plasma or leukocytes.

• Polarizing microscopy of urine reveals birefringent lipid globules (‘Maltese crosses’).

Fabry Disease Testing Algorithm*

Other lysosomal Storage disorders

• Although most commonly seen in association with Fabry disease, it is important to recognize that angiokeratomas are not unique to this disorder.

• They are also observed in a number of other lysosomal storage disorders.

Fabry Disease - Treatment

• Oral phenytoin, gabapentin or carbamazepine can be very beneficial in treating the debilitating limb pain.

• End-stage renal disease has historically been treated with dialysis and renal transplantation.

• Enzyme replacement therapy is now available for Fabry disease and is administered biweekly by intravenous infusion. Agalsidase alfa (Replagal®; Transkaryotic Therapies,

Cambridge, MA, USA)

Agalsidase beta (Fabrazyme®; Genzyme Corporation, Cambridge, MA, USA)

Cutaneous variant of ACD

• 33 year old male with idiopathic type of ACD.

• 10 previously reported cases of ACD with “normal” enzyme function.

• No systemic disease or dysmorphic facies characteristic of glycoprotein metabolism enzyme deficiencies.

• The pathogenesis of these angiokeratomas in the absence of enzyme deficiency, such as in this case, is unclear.

• It may represent a partial deficiency or enzyme mosaicism.

Arch Dermatol. 2006;142:615-618

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Treatment

• No treatment is necessary if only cutaneous lesions

• Cryotherapy

• Electrocautery

• Laser therapy: • 578-nm copper vapor laser • Argon laser • Flashlamp-pumped pulse dye laser • 532-nm KTP laser

• Surgical excision

References

Jean L. Bolognia MD and Joseph L. Jorizzo MD, Dermatology e-dition, 2nd Ed: Text with Continually Updated Online Reference, 2-Volume Set, 2008. Accessed via www.expertconsult.com 10/01/11.

Tarabuso AL. Fabry Disease. Skinmed. 2011 May-Jun;9(3):173-7.

Germain DP. Fabry Disease. Orphanet J Rare Dis. 2010 Nov 22;5:30.

Sodaifi M, Aghaei S, Monabati A. Cutaneous variant of angiokeratoma corporis diffusum associated with angiokeratoma circumscriptum. Dermatology Online Journal, 2004 10 (1): 20

Kelly E, Kelly B. Angiokeratoma Corporis Diffusum in a Patient With No Recognizable Enzyme Abnormalities. Arch Dermatol. 2006 May;142(5):615-8.

Schaefer RM, Tylki-Szymańska A, Hilz MJ. Enzyme replacement therapy for Fabry disease: a systematic review of available evidence. Drugs. 2009 Nov 12;69(16):2179-205.

Fabry Disease Testing Algorithm*. Mayo Foundation for Medical Education and Research (MFMER). Accessed via www.mayomedicallaboratories.com/media/articles/algorithms/fabrydisease.pdf 10/04/11.

Poetke M, Philipp C, Berlien HP. Flashlamp-Pumped Pulsed Dye Laser for Hemangiomas in Infancy. Arch Dermatol. 2000 May;136(5):628-32.

Thank you!

114

Gender is an Age-Specific Effect Modifier for Ulcerated Malignant Melanomas

Richardson BS1, Anderson WF2, Barnholtz-Sloan JS1, Tucker MA2, Gerstenblith MR1

1Case Western Reserve University School of Medicine

2Division of Cancer Epidemiology and Genetics, National Cancer Institute, NIH

Disclosures: Char and Chuck Fowler Family Foundation

Skin Cancer Foundation Melissa K. Bambino Memorial Award This research has been presented at the SID and ASCO annual meetings

Melanoma Incidence 2012

•5th most common tumor in men

•6th most common tumor in women

•Incidence varies by age and gender, among other factors

0

10

20

30

40

50

60

70

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90

100

<20 20-29 30-39 40-49 50-59 60-69 70-79 80+

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Incidence rates 1975-2006

Age

Incidence rate per 100,000

Slide courtesy of MT Landi

0

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Age, gender, and ulceration are independent prognostic factors for cutaneous malignant melanoma

1. Age: -Younger patients have a more favorable outcome than older patients

and this difference is more pronounced in females 2. Gender: -Male gender is associated with unfavorable primary tumor

characteristics and worse outcomes 3. Ulceration:

-Ulceration is associated with decreased survival across all tumor thickness categories

--Hazard risk for ulcerated tumors is two-fold higher than non-ulcerated tumors

-Proportion of ulcerated melanomas (to total melanomas) increases with increasing tumor depth

Age, Gender, and Ulceration: Prognostic Factors

115

Age, gender, and ulceration are independent prognostic factors for cutaneous malignant melanoma

1. Age: -Younger patients have a more favorable outcome than older patients






Age, Gender, and Ulceration: Prognostic Factors Age, gender, and ulceration are independent prognostic factors for

cutaneous malignant melanoma 1. Age: -Younger patients have a more favorable outcome than older patients






Age, Gender, and Ulceration: Prognostic Factors

Balch C M et al. JCO 2001;19:3622-3634

Fig 3.

Balch C M et al. JCO 2001;19:3622-3634

Taylor R C et al. JCO 2007;25:869-875

Study Aim

• To look at the incidence of ulceration in cutaneous melanoma across tumor depth and compare across different age-gender groups

116

Hypothesis

• Age and gender modify the relationship between incidence of ulcerated melanoma and tumor depth

• The incidence of ulceration will increase with tumor depth for all groups

Methods Large-scale population-based SEER 17 Registries Database Inclusion Criteria • 2004-2008 • Age-gender groups

– ‘Younger’ 10-39 years men – ‘Younger’ 10-39 years women – ‘Older’ 40-84 years men – ‘Older’ 40-84 years women

• Tumor depths – ≤1.0mm – 1.01mm-≤2.0mm – 2.01mm-≤4.0mm – ≥4.01mm

• Melanomas – Invasive only – Ulcerated and non-ulcerated, separately – Superficial spreading, nodular, and unclassified melanoma

• Non-Hispanic whites (93.2%)

Methods

Exclusion Criteria – Lentigo maligna and acral lentiginous melanoma – Unknown depth – Unknown ulceration status

• Incidence rates calculated using SEER Stat 7.0.5

Proportion of Ulcerated to Total Melanomas in Young and Old Men and Women by Depth

0

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40

50

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70

≤1 1.01-2 2.01-4 ≥4

Depth (mm)

Ulc

erat

ed m

elan

omas

/Tot

al m

elan

omas

(%)

40-84y men40-84y women10-39y women10-39y men

Table I. Characteristics of cutaneous malignant melanoma in non-Hispanic whites from the Surveillance, Epidemiology, and End Results-17 study from 2004-2008

Sex (n) Men (n=23,068) Women (n=19,279)

Age (in years) 10-39 40-84 10-39 40-84

N 2,627 20,441 4,393 14,886

Histologic Subtype

SSM 1,099 7,198 1,927 5,602

NM 199 1,969 217 1,053

UM 1,329 11,274 2,249 8,231

Ulceration Status

Present 301 2,905 276 1,624

Absent 17,536 4,117 13,262

Table I. Characteristics of cutaneous malignant melanoma in non-Hispanic whites from the Surveillance, Epidemiology, and End Results-17 study from 2004-2008

Sex (n) Men (n=23,068) Women (n=19,279)

Age (in years) 10-39 40-84 10-39 40-84

N 2,627 20,441 4,393 14,886

Histologic Subtype

SSM 1,099 7,198 1,927 5,602

NM 199 1,969 217 1,053

UM 1,329 11,274 2,249 8,231

Ulceration Status

Present 301 2,905 276 1,624

Absent 2,326 17,536 4,117 13,262

117

Incidence Rate of Ulcerated Melanoma in Old and Young Men by Depth

0

0.4

0.8

1.2

1.6

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10-39ymen

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er 1

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ears

Incidence Rate of Ulcerated Melanoma in Old and Young Women by Depth

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1.2

1.6

≤ 1 1.01 - 2 2.01 - 4 ≥ 4

40-84ywomen

10-39ywomen

≤1 1.01 - 2 2.01 - 4 ≥4.01 Depth (mm)

Inci

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er 1

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oman

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rs


0

0.4

0.8

1.2

1.6

≤ 1 1.01 - 2 2.01 - 4 ≥ 4

40-84ymen

10-39ymen

≤1 1.01 - 2 2.01 - 4 ≥4.01 Depth (mm)

Inci

denc

e ra

te p

er 1

00,0

00 m

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0

0.4

0.8

1.2

1.6

≤ 1 1.01 - 2 2.01 - 4 ≥ 4

40-84ywomen

10-39ywomen

≤1 1.01 - 2 2.01 - 4 ≥4.01 Depth (mm)

Inci

denc

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00,0

00 w

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0

0.4

0.8

1.2

1.6

≤ 1 1.01 - 2 2.01 - 4 ≥ 4

40-84ymen

10-39ymen

≤1 1.01 - 2 2.01 - 4 ≥4.01 Depth (mm)

Inci

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0.4

0.8

1.2

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≤ 1 1.01 - 2 2.01 - 4 ≥ 4

40-84ywomen

10-39ywomen

≤1 1.01 - 2 2.01 - 4 ≥4.01 Depth (mm)

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0

0.4

0.8

1.2

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10-39ymen

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Inci

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0

0.4

0.8

1.2

1.6

≤ 1 1.01 - 2 2.01 - 4 ≥ 4

40-84ywomen

10-39ywomen

≤1 1.01 - 2 2.01 - 4 ≥4.01 Depth (mm)

Inci

denc

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00,0

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Ulcerated Melanoma and Tumor Depth

• The incidence rate of ulceration DID NOT increase with tumor depth

• The incidence rate WAS STABLE across all depths except for men age 40-84, where it increased for tumors ≥ 2.01 mm

Ulcerated Melanoma and Tumor Depth

• The pattern describing the relationship between incidence of ulcerated melanoma and tumor depth DIFFERS in four age-gender groups

118

Incidence Rate of Non-Ulcerated Melanoma in Old and Young Women by Depth

0

4

8

12

16

20

24

≤ 1 1.01 - 2 2.01 - 4 ≥ 4

40-84ywomen10-39ywomen

Inci

denc

e rat

e pe

r 100

,000

wom

an-y

ears

≤1 1.01 - 2 2.01 - 4 ≥4.01 Depth (mm)

Incidence Rate of Non-Ulcerated Melanoma in Old and Young Men by Depth

0

4

8

12

16

20

24

≤ 1 1.01 - 2 2.01 - 4 ≥ 4

40-84ymen10-39ymen

≤1 1.01 - 2 2.01 - 4 ≥4.01 Depth (mm)

Inci

denc

e ra

te p

er 1

00,0

00 m

an-y

ears

Non-ulcerated Melanoma and Tumor Depth

• The pattern describing the relationship between the incidence of non-ulcerated melanoma and tumor depth IS SIMILAR in four age-gender groups

Ulceration

• Pathogenesis unknown • Prior proposed mechanisms

– Destruction of the epidermis by neoplastic cells

– Modification of vasculature by tumor growth – Trauma – Ulcerated Melanoma is a separate distinct

entity

Ulceration

• Pathogenesis unknown • Prior proposed mechanisms

– Destruction of the epidermis by neoplastic cells

– Modification of vasculature by tumor growth – Trauma – Ulcerated Melanoma is a separate distinct

entity

Are Ulcerated Melanomas a Distinct Biologic Entity?

• Our findings support this theory • Ulcerated CM occur at a constant rate

regardless of tumor depth • Are in general more aggressive tumors

How to Explain the Differences Among the Age-Gender Groups?

• Complex tumor-host interaction • Male gender and older age may promote

ulceration or fail to inhibit it • Female gender and younger age may be

protective

119

Incidence of Ulceration in Thin Tumors

• The consistent rate of ulceration, even in

thin tumors is interesting

• We cannot exclude the possibility that our findings are not real

• Future studies needed

Study Limitations

• Inaccurate coding in SEER

• Variation in experience and interpretation of tumor ulceration vs traumatic ulceration among a variety dermatopathologists and general pathologists

Summary

• Older age at diagnosis in both men and women is associated with higher incidence rates of ulcerated and non-ulcerated melanomas

• Highest incidence rates for both occur in men at each depth Age and gender effects seen on incidence for both ulcerated and non-ulcerated melanomas

Summary

• The proportion of ulcerated to non-ulcerated tumors increased across tumor depth

• We expected that the incidence of ulceration would also increase across tumor depth

• THIS WAS NOT THE CASE

• The incidence rate of ulceration remained stable for all groups, except men 40-84, where is increased for tumors ≥ 2.01 mm

Summary

• The stable incidence rate of ulceration across depth with the

decrease in incidence rate across depth for non-ulcerated tumors explain the increase in proportion across tumor depth

Conclusions

• The incidence of ulcerated melanomas are stable across tumor depth, except for men age 40-84

• Supports the hypothesis that ulcerated melanomas are a distinct biologic entity, which occur at a constant rate, regardless of tumor depth

• Supports the hypothesis that there is a complex tumor-host interaction where male gender and older age appear to promote or fail to inhibit ulcerated CM

• Future studies are needed to verify our findings and further understand ulcerated melanoma and tumor-host interactions

120

Acknowledgements

• CWRU – Meg Gerstenblith – Jill S. Barnholtz-Sloan – Jeremy Bordeaux – Kevin Cooper

• National Cancer Institute

– William F. Anderson – Margaret A. Tucker

• Grant support

– Char and Chuck Fowler Family Foundation – Skin Cancer Foundation Melissa K. Bambino Memorial Award

References 1. Balch CM, Soong SJ, Gershenwald JE, et al. Prognostic factors analysis of

17,600 melanoma patients: validation of the American Joint Committee on Cancer melanoma staging system. J Clin Oncol. 2001;19:3622-3634.

2. Lasithiotakis, K, Leiter, U, D, Meier, F, et al. Age and gender are significant

independent predictors of survival in primary cutaneous melanoma. Cancer. 2008 Apr 15;112(8):1795-804.

3. Scoggins, CR, Ross, MI, Reintgen, DS, et al. Gender-Related Differences in

Outcome for Melanoma Patients. Ann Surg. 2006 May; 243(5): 693–700. 4. Tsai S, Balch C, Lange J. Epidemiology and treatment of melanoma in elderly

patients. Nat Rev Clin Oncol. 2010 Mar;7(3):148-52. 5. Mascaro, J, Castro J, Castel T, et al. Why Do Melanomas ulcerate? J Cutan

Pathology 1984 Aug;11(4):269-73.

6. Kashani-Sabet M, Sagebiel RW, Ferreira CM, et al. Tumor vascularity in the prognostic assessment of primary cutaneous melanoma. J Clin Oncol. 2002 Apr 1;20(7):1826-31.

7. Eggermont AM, Spatz A, Lazar V, Robert C. Curr Opin Oncol. Is ulceration in

cutaneous melanoma just a prognostic and predictive factor or is ulcerated melanoma a distinct biologic entity? 2012 Mar;24(2):137-40.

Thank You Supplementary Figures and Tables

Depth

Young men Older Men

N Rate CI N Rate CI

<1 81 0.131 0.104 0.163 610 1.023 0.942 1.108

1-2 68 0.108 0.084 0.137 619 1.046 0.964 1.133

2-4 81 0.130 0.103 0.161 853 1.434 1.338 1.535

>4 71 0.112 0.088 0.142 823 1.376 1.282 1.474

Depth

Young women Older Women

N Rate CI N Rate CI

<1 78 0.130 0.103 0.162 410 0.607 0.550 0.670

1-2 76 0.129 0.101 0.161 398 0.582 0.526 0.643

2-4 78 0.133 0.105 0.165 406 0.597 0.540 0.659

>4 44 0.075 0.054 0.100 410 0.597 0.540 0.658

Ulcerated Melanoma Non-ulcerated Melanoma

Depth

Young men Older Men

N Rate CI N Rate CI

<1 1,803 2.891 2.759 3.028 13,150 21.418 21.05 21.792

1-2 346 0.555 0.498 0.617 2,760 4.517 4.348 4.691

2-4 131 0.211 0.176 0.250 1,151 1.926 1.815 2.043

>4 46 0.074 0.054 0.098 475 0.807 0.735 0.884

Depth

Young women Older Women

N Rate CI N Rate CI

<1 3,489 5.931 5.736 6.132 10,562 15.861 15.558 16.168

1-2 454 0.770 0.701 0.845 1,828 2.731 2.606 2.86

2-4 135 0.228 0.191 0.270 601 0.884 0.815 0.959

>4 39 0.066 0.047 0.090 271 0.396 0.350 0.447

121

ULCERATED SSM + NM + UCM IN YOUNG WHITE MEN V. WOMEN, N= 571

ULCERATED SSM + NM + UCM IN OLDER WHITE MEN V. WOMEN, N=1,900

Depth ≤1.0mm ≤1.0mm

Gender N Rate IRR CI N Rate IRR CI

Women 78 0.1 referent 410 0.6 referent

Men 81 0.1 1.01 0.73-1.40 610 1 1.68 1.48-1.92

Depth 1.01mm-≤2.0mm 1.01mm-≤2.0mm



Men 68 0.1 0.84 0.59-1.18 619 1 1.80 1.58-2.04

Depth 2.01mm-≤4.0mm 2.01mm-≤4.0mm



Men 81 0.1 0.98 0.71-1.36 853 1.4 2.40 2.13-2.71

Depth ≥4.01mm ≥4.01mm



Men 71 0.1 1.50 1.02-2.25 823 1.4 2.30 2.04-2.60


0

0.4

0.8

1.2

1.6

≤ 1 1.01 - 2 2.01 - 4 ≥ 4

Depth (mm)

Incid

ence

rate

per

100

,000

man

-yea

rs

40-84y men

10-39y men


0

0.4

0.8

1.2

1.6

≤ 1 1.01 - 2 2.01 - 4 ≥ 4

Depth (mm)

Incid

ence

rate

per

100

,000

wom

an-y

ears

40-84y women

10-39y women

Incidence Rate of Non-Ulcerated Melanoma in Old and Young Men by Depth

0

4

8

12

16

20

24

≤ 1 1.01 - 2 2.01 - 4 ≥ 4

Depth (mm)

Incid

ence

rate

per

100

,000

man

-yea

rs

40-84y men

10-39y men

Incidence Rate of Non-Ulcerated Melanoma in Old and Young Women by Depth

0

4

8

12

16

20

24

≤ 1 1.01 - 2 2.01 - 4 ≥ 4

Depth (mm)

Incid

ence

rate

per

100

,000

wom

an-y

ears

40-84y women

10-39y women

122

An Evaluation of Diagnostic Tests in Bullous Pemphigoid

Ashley Kittridge, DO University Hospitals Case Medical Center, PGY4

AOCD Annual Conference 0ctober 6-11, 2012 Disclosures: None

Objectives Review background and pathophysiology of

bullous pemphigoid Discuss current diagnostic tests utilized Discuss dilemmas in diagnostic algorithm My research objective

Bullous Pemphigoid

Most common autoimmune blistering d/o Incidence: 12-13/million/year 150-190/million/year for age >80 yrs Aging population and better diagnostic tests

likely account for this increased incidence Low mortality, high morbidity Attributed to side effects of treatment

Hemidesmosome

Lamina Densa

Lamina Lucida

Wolf et al. Fitzpatrick’s Dermatology in General Medicine, 7th Ed; 2008: p455.

Pathophysiology of BP

Antibodies to hemidesmosomal proteins BP180 (BPAG2/Collagen XVII) BP230 (BPAG1) BP180- NC16A Epitopes outside NC16A domain

Cause a cascade of events Compliment activation Defective adhesion function Induction of cytokines and amplification of

inflammatory reaction Bolognia et al. Dermatology, 3rd Ed; 2012: p 476.

Current diagnostic algorithm Clinical exam: elderly patient with pruritic bullae/vesicles,

urticaria, etc

H&E: subepidermal cleft/blister or eosinophilic spongiosis with inflammatory infiltrate rich in eosinophils and neutrophils

DIF: linear BMZ deposit of IgG +/- IgA and C3 (Clinical Gold

Standard)

IIF on SSS: IgG antibodies bind to epidermal side (+/-

dermal side)

123

Typical clinical findings

©2011 Margaret Bobonich


©2011 Ashley Kittridge


Atypical clinical findings ©2011 Ashley Kittridge

©2011 Harry Dao ©2011 Ashley Kittridge

©2011 Harry Dao

©2011 Harry Dao

Clinical exam findings

Vaillant L, et al. Arch Dermatol 1998; 134: 1075-1080.

Current diagnostic algorithm: Clinical exam: elderly patient with pruritic bullae/vesicles,

urticaria, etc



Standard)


dermal side)

Light microscopy

Bolognia et al. Dermatology, 3rd Ed; 2012: p 480.


urticaria, etc


DIF: linear BMZ deposit of IgG +/- C3 (Clinical Gold Standard)


dermal side)

124

Direct Immunofluorescence

Chan et al. Experimental Dermatol 2003; 28: 651-6.


urticaria, etc



Standard)


dermal side)

Indirect Immunofluorescence

Bolognia et al. Dermatology, 3rd Ed; 2012: p 480. Kasperkiewicz M, et al. Autoimmunity 2012; 45(1):55-70.

ELISA in the diagnosis of BP

Commercial kit for BP180 NC16a and BP230 NC16a domain Less operator/interlab variability than

previous assays Quantitative study Sensitivity: (BP180 + BP230) > BP180 > BP230

Zillikens D et al. J Invest Dermatol 1997; 109(5): 679-83. Di Zezo et al. Clin Dermatol 2012; 30: 3-16.

125

Roussel A, et al. Arch Dermatol 2011; 147(3): 293-8. Charneux J, et al. Arch Dermatol 2011; 147(3): 286-291.

ELISA vs IIF

Current diagnostic algorithm Clinical exam: elderly patient with pruritic bullae/vesicles,

urticaria, etc



Standard)


dermal side)

Where does ELISA fit?

Why is ELISA underused? Performance gap? Resource gap? Knowledge gap?

Where does ELISA fit into the diagnostic algorithm of BP?

Chan L. Arch Dermatol 2011; 147(3): 291-2.

Dilemmas in current diagnostic

algorithm…in summary

ELISA BP180-NC16A +/- BP 230 • Standardized test • Sensitive and specific • Quantitative • Cheaper • NOT commonly used

IIF on SSS • Operator variability, not standardized • 10-15% no detectable circulating antibodies • False positives reported • High cost

DIF • Operator variability, not standardized • Does not distinguish between other subepidermal blistering disorders • False negatives • High cost

H & E • Not specific nor diagnostic

Clinical exam • Variable

My research objective Compare the sensitivities and specificities

of clinical exam findings, DIF, IIF on SSS and ELISA (BP180-NC16A & BP230) in the diagnosis of BP

Identify the combination of findings with highest sensitivity and specificity

Further clarify the role of ELISA in the dx of BP

Cost analysis of each combination of studies

Identify new cost-effective diagnostic algorithm

126

Hypothesis/Proposed diagnostic Algorithm:

Clinical exam (>2 criteria): age >70, no scarring, no mucosal

involvement, no H&N involvement, presence of urticaria/bullae

Perform ELISA BP180-NC16A &

BP230

Consider new diagnosis Treat

Perform ELISA BP180-NC16A

Perform ELISA BP230

Consider new diagnosis Treat

Treat

Methods

IRB approved study Prospectively enrolling patients Inclusion criteria:

• +IIF on SSS OR +ELISA BP180-NC16A/230

AND • All must have:

• Clinical findings documented

• H&E • DIF • IIF • ELISA BP180-NC16A &

BP230

Clinical findings: • No scarring • No head and neck

involvement • No oral involvement • Age > 70 years old • Urticaria/bullae

Positive H&E = Eosinophilic and/or neutrophilic infiltrate +/-spongiosis, sub- or intraepidermal blister

Positive DIF = linear IgG and/or C3 at BMZ

Positive IIF = IgG on epidermal side SSS

Positive ELISA = ≥ 9 U/mL

…. Any Questions?

76 charts reviewed

20 patients met inclusion criteria

All met clinical criteria

All met H&E criteria

16 patients +ELISA

6 patients +ELISA BP180

alone

2 patients +ELISA BP230

alone

8 patients +ELISA (BP180

& BP230)

16 patients +IIF (IgG on

epidermal side of SSS)

15 patients +DIF (linear IgG +/- C3)

44 patients did not meet inclusion criteria

9 patients with some data still

pending 3 patients with

MMP

2 patients +BP230 …. Any Questions?

127

Study/Year Test Specificity Sensitivity Comparison

Chan et al, 2003 N=23

DIF 91% IIF 96% Immunoblot (BP180 + BP230) 100%

ELISA BP180-NC16A 96%

Barnadas et al, 2008 N=28

ELISA BP180-NC16A 96% 92%

IIF 96% 74% Giovanni et al, 2008 N=49

BP230 71% BP180 NC16A 90%

BP180 non NC16A domain 96%

BP180 + BP230 100%

IIF vs ELISA (BP180 + BP230) ELISA superior

IIIF vs ELISA BP180 IIF superior

Tampoia et al, 2009 N=38

ELISA BP180 98.8% 90% ELISA BP230 98.8% 60%

Atzori et al, 2008 N=19

ELISA BP180 95%

Sitaru et al, 2007 N=118

ELISA BP180 NC16A tetramer 97.8% 89.8%

ELISA BP180 NC16A MBL 94.8% 89%

Thoma-Uszynski et al, 2004 N=127

ELISA BP180 94% 95.3% ELISA BP230 95.3% 81.5%

Feng et al, 2008 N=20

ELISA BP180 NC16a 19/20 pts + and levels correlated with dz activity

Kobayashi et al, 2002 N=64

ELISA BP180 NC16a 98.9% 84.4%

Zillikens et al, 1997 N=50

ELISA BP180NC16a 99.9% 94%

Sano et al, 2008 DIF 55.6%

128

Ellecia Cook, DO, PGY-4

Program Director: Richard Miller, DO, FAOCD

No Financial Disclosures

OBJECTIVES

• Basic overview of HIV • Present 10 cases of cutaneous

manifestations of HIV • Review 6 atypical presentations of

dermatologic conditions in HIV patients

INTRODUCTION

• 40 Million infected Worldwide • 5 Million new infections per year worldwide • Leading cause of death in Africa • Fourth leading cause of death worldwide

INTRODUCTION • Enveloped RNA virus • Lentivirus genus, Retroviridae family • HIV-1: West Africa

• HIV-2: United States and Europe

INTRODUCTION • > 90% develop dermatologic disorders • Cutaneous disease is often initial

manifestation of undiagnosed HIV • Dermatologists play a key role in

diagnosing HIV

129

DIFFERENTIAL DIAGNOSIS

Acne Vulgaris Seborrheic Dermatitis

SLE Rosacea

Pemphigus Foliaceus Senear Usher Syndrome

DERMATOPATHOLOGY SEBORRHEIC DERMATITIS • 85% HIV affected

• Most common cutaneous disease

• Occurs early or reflects progression

• Widespread extending to chest, trunk, groin, extremities, and at times erythroderma

• Pathogenesis Unknown


Vurruca Vulgaris SCC

SCC arising from VV Paronychia

Onychomycosis

130

DERMATOPATHOLOGY SQUAMOUS CELL CARCINOMA arising from

VERRUCA VULGARIS • HPV 16 • High risk HPV serotypes • Aggressive squamous cell carcinomas • Prompt diagnosis and aggressive

treatment required


Scabies Infestation Psoriasis

Arthropod Assault Contact Dermatitis Atopic Dermatitis

Seborrheic Dermatitis

DERMATOPATHOLOGY SCABIES INFESTATION • Most common ectoparasitic skin infestation

• Burrows are less apparent

• Ears, face, and scalp involvement

• Crusted scabies – Generalized with thousands-millions of mites

• Scrape hyponychium for protected mites

• Bacteremia and fatal septicemia reported

131

SCABIES INFESTATION • Treatment

–Permethrin • Multiple courses often required

–Ivermectin

–Salicylic Acid 6% ointment


Candidiasis Lichen Planus

Oral Hairy Leukoplakia SCC SLE

Behcet’s

DERMATOPATHOLOGY

• Epstein-Barr virus • Almost exclusively in immunosuppressed • Occurs in up to 50% untreated HIV patients • Early sign of HIV • No malignant potential • Only treated if unsightly or cause dysphagia • May regress if HAART implemented

ORAL HAIRY LEUKOPLAKIA

132


Proximal White Subungual Onychomycosis

Trauma Psoriasis

Lichen Planus

DERMATOPATHOLOGY

• Early clinical marker of HIV

• Rarest form of onychomycosis

• Trichophytun rubrum

• Invades proximal nail fold ultimately invading nail bed and spreads distally

PROXIMAL WHITE SUBUNGUAL ONYCHOMYCOSIS

• Treatment – Recalcitrant to topical modalities – Fluconazole – Itraconazole

PROXIMAL WHITE SUBUNGUAL ONYCHOMYCOSIS


Ichthyosis Vulgaris Acquired Ichthyosis Lamellar Ichthyosis X-Linked Ichthyosis Atopic Dermatitis

Xerosis

133

DERMATOPATHOLOGY • One of the most common settings • Starts on lower legs and progresses upward • Sarcoidosis, malignancy, leprosy, drug

induced • Treatment

– Often resistant to traditional therapies – Resolves once underlying condition treated – Emollients, keratolytics, topical retinoids, and

antihistamines

ACQUIRED ICHTHYOSIS


Irritant Folliculitis Pseudomonas Folliculitis Eosinophilic Folliculitis Pityrosporum Folliculitis

Miliaria Keratosis Pilaris

Ofujii’s

DERMATOPATHOLOGY EOSINOPHILIC FOLLICULITIS • Characteristic and common pruritic dermatoses

• Face and upper trunk

• Differential includes Ofujii’s

• Peripheral eosinophilia

• Associated with advanced disease

• Pathogenesis unknown

134

EOSINOPHILIC FOLLICULITIS • Treatment

– Topical corticosteroids – Systemic Antibiotics – UVB Phototherapy – Itraconazole – Isotretinoin

• Recalcitrant • Impact of HAART is controversial

DIFFERENTIAL DIAGNOSIS Idiopathic Matrical Melanotic Macule Melanoma Medication Induced B12 Deficiency Radiation Therapy Trauma Foreign Body

Pregnancy Lichen Planus SLE HIV Addisons Onychomatricoma Peutz-Jeghers Laugier-Hunziker

DERMATOPATHOLOGY

• Benign proliferation of melanocytes • Normal number of melanocytes at basal

layer • Cutaneous and oral hyperpigmentation

often accompanies • No treatment but must rule out Melanoma

HIV ASSOCIATED LONGITUDINAL MELANONYCHIA

135


Kaposi Sarcoma Bacillary Angiomatosis Pyogenic Granuloma

Angiosarcoma EBV-associated Smooth Muscle

Tumor Hemangioendothelioma

DERMATOPATHOLOGY

• HHV8

• No correlation with degree of immunosuppression

• Upper trunk, face, and oral mucosa

• Internal involvement – Gastrointestinal tract and lymphatics

• Incidence decreased since HAART

KAPOSI SARCOMA • Treatment

– Cryotherapy

– Topical Alitretinoin gel

– Superficial Radiotherapy

• CI: Oral lesions

– Intralesional vinblastine or interferon, and IV

doxorubicin, daunorubicin or paclitaxel

KAPOSI SARCOMA


Molluscum Contagiosum Verruca Vulgaris Herpes Simplex Coccidiomycosis Cryptococcosis Histoplasmosis

136

DERMATOPATHOLOGY MOLLUSCUM CONTAGIOSUM

• Classic dome-shaped umbilicated papules

• Large coalescing plaques

• Face, neck, and intertriginous regions

favored

• Treatment resistant

MOLLUSCUM CONTAGIOSUM

• Treatment

– Routine methods

– Curettage

– Imiquimod

– Topical cidofovir

HISTOPLASMOSIS

DISSEMINATED CRYPTOCOCCUS

CUTANEOUS COCCIDIOMYCOSIS

137

ATYPICAL DERMATOLOGIC PRESENTATIONS

ATYPICAL DERMATOL

OGIC PRESENTAT

IONS

138

SUMMARY • Basic overview of HIV

• Reviewed 10 cases of cutaneous manifestations of HIV

• Reviewed 6 atypical presentations of

dermatologic conditions

CONCLUSION

• HIV continues to plague our society • Dermatologist should recognize

– Cutaneous manifestations of HIV – Atypical presentations of dermatologic conditions in

HIV • Dermatologist play a significant role in

diagnosing HIV

REFERENCES • Bolognia, J., et al. Dermatology. Mosby Publishing; 2003 • Cedeno-Laurent et al. New Insights into HIV-1-primary skin disorders.”

Journal of the International AIDS Society 2011, 14:5 • Colone, E., et al. McKee’s Pathology of the Skin. Elsevier Saunders

Publishing; 2012 • Jefferson, J., and Rich, P. Melanonychia. Hindawi Publishing Corporation Dermatology Research and Practice . 2012. • Kreuter, A. and Wieland, U. Oral Hairy Leukoplakia: A clinical indicator of

immunosuppression. CMAJ; 183(8). 2011 • Moreno-Coutino, G., et al. Clinical Presentation of Onychomycosis in

HIV/AIDS: A Review of 280 Mexican Cases. Indian Journal of Dermatology. 56(1); 2011

• Shin, B., et al. A Case of Human Immunodeficiency Virus Infection Initially Presented with Disseminated Herpes Zoster. Ann of Dermatol; 22(2); 2010.

139

7:00 am AOCD Registration

7:30 am Hand Dermatitis Peter Saitta, D.O

8:30 am CTCL and Lymphoma Francisca Kartono, D.O., FAOCD

9:30 am Psoriasis and Psoriatic Arthritis Basic Review With Focus on Therapy Robert G. Greenberg, M.D., FAAD

10:30 am Break

10:45 am Complex Medical Dermatoses,Common Referral Problems in Medical Dermatology Joseph Jorizzo, M.D.

11:45 am Management of Actinic Keratosis Paradigm Medical (Ticketed event for AOCD Members-Lunch served)

1:20 pm Bones of Dermatology Angela McKinney, D.O. Botsford Hospital/McLaren-Oakland, Pontiac, MI

1:40 pm Furuncular Myiasis Endemic to Ohio: A Case Report Alma AcMoody, D.O. Summa Western Reserve Hospital, Cuyahoga Falls, OH

2:00 pm Variant of Eruptive Keratoacanthoma Keith Robinson, D.O. Summa Western Reserve Hospital, Cuyahoga Falls, OH

2:20 pm Treatment of Anal Dysplasia with IRC Stephen Weis, D.O. UNTHSC/TCOM, Fort Worth, TX

2:40 pm Generalized Fixed Drug Eruption in the Setting of Ceftriaxone Treated Gonococcemia Paul Aanderud, D.O. Oakwood Southshore Medical Center, Warren, MI

WEDNESDAY, OCTOBER 10, 2012

140

3:00 pm Break

3:20 pm Arbor Cutis: Hyperkeratotic Plaque Secondary to the Use of Imiquimod Peter Knabel, D.O. Northeast Regional Medical Center, Kirksville, MO

3:40 pm Oral Spironolactone in Post-Teenage Acne in Females Grace Kim, D.O. Valley Hospital Medical Center, Las Vegas, NV

4:00 pm Acne Scar Lysing Mari Batta, D.O. Alta Dermatology, Mesa, AZ

4:20 pm Adalimumab for the Treatment of Pityriasis Rubra Pilaris with an Overview of Disease Classification Jeremy Bingham, D.O. Advanced Desert Dermatology, Peoria, AZ

4:40 pm Primary Mucinous Carcinoma of Skin Helia Eragi, D.O. Pacific Hospital, Torrance, CA

5:00 pm Hereditary Disorders of Cornification Tatyana Groysman, D.O. PCOM/Lehigh Valley Health Network, Allentown, PA

5:20 pm End of Meeting

141

1

Peter Saitta, D.O. St. Barnabas Healthcare

3

Period prevalence Risk factors Classification systems Differential Diagnosis First-line therapy options

4

Prevalence •Number of new cases per time period

Period prevalence •Number of patients with outbreaks during a time period •Varies 2-10%1-3

5

STUDY NO AD / NO IRRITANT WATER EXPOSURE

AD / NO IRRITANT WATER EXPOSURE

AD / IRRITANT WATER EXPOSURE

Meding et al. 1990 5-9% 14-23% 34-48%

Nilsson et al. 1986 16% 38% 62-72%

Rystedt et al. 1985 5% 37-50% 60-81%

6

Atopic dermatitis •Lammintausta et al. 1991 •Coenraads et al. 1998 •Meding et al. 2000 •Meding et al. 2004 •Toledo et al. 2008

142

7

Allergic rhinitis/asthma increases risk of hand eczema •But not more than atopic dermatitis4

8

Female gender increased risk

• Coenraads et al. 1983 • Kavli et al. 1984 • Lantinga et al. 1984 • Bryld et al. 2000 • Yngveson et al. 2000 • Meding et al. 2001 • Mortz et al. 2001 • Dickel et al. 2002

9

Meding et al.5

• Wet work in 19-29 year-olds • 37.5% of women occupationally exposed • 18.2% of men

Learbek et al.6 • Private exposures

10

STUDY TYPE OF STUDY

STUDY POPULATION

INCIDENCE (PER 100)

Lantinga et al. 1984

Retrospective General Population

7.9

Uter et al. 1994 Prospective Hairdressers 152

Smit et al. 1994 Prospective Hairdressers Nurses

328 145

Brisman et al. 1998

Retrospective Bakers M: 16.7 F:34.4

Uter et al. 1998 Prospective Office workers 41

Funke et al. 2001 Prospective Industrial Factory Workers

47

11

SUPPORT RISK NEGATE RISK

Edman et al. Montnemery et al. Linneberg et al.

Lerbeack et al. Berndt et al

12

ACD7

Delay onset of treatment8

Atopic Dermatitis9

Greater area of involved skin10

> 1 year of duration8

143

13

Etiology Morphology •No clear link between morphology and etiology11

•Question the need of morphological classification system

14

Irritant contact dermatitis Allergic contact dermatitis Atopic dermatitis •80%

Idiopathic •20%

15

Irritant Contact Dermatitis11

•Most common Wet work Water Mechanic / Machinery oils Detergents Tight-fitting gloves Friction

16

Wet hands or glove wearing > 2 cumulative hours daily11,12

Greater than 20 hand washes daily12

17

Allergic Contact Dermatitis • Way more common in occupational exposures vs. private

exposures (Hobby)11

• “Hand eczema that spreads”13 Protein Contact Dermatitis

• RARE • Latex • Food proteins • Burning, stinging and itching seconds to minutes after contact14

Systemic Contact Dermatitis

• VERY RARE • Specific definition11 Positive patch test Ingest an oral version Vesicular hand/foot rash

18

Atopic dermatitis Other genetic

• Filaggrin null mutations15,16 • Twin studies show that MZ twin individuals having a

co-twin with hand eczema had an increased risk of hand eczema compared with DZ twins6 Atopic dermatitis adjusted

Idiopathic CHE 20%11

144

19

Guidelines of the Danish Contact Dermatitis Group • Chronic dry fissured hand eczema • Vesicular hand eczema • Hyperkeratotic (Tylotic) hand eczema • Interdigital hand eczema • Pulpitis • Nummular hand eczema • Mixed 50.5% demonstrate multiple morphologies17

20

21 22

23 24

145

25

Frequency based on location19

• 1. Generalized Plaque – 49.3% • 2. Localized Plaque – 16.9% • 3. Guttate – 12.8% • 4. Arthropathic – 7.7% • 5. Palmoplantar – 7.5% • 6. Pustular – 3.1% • 7. Other – 2.7%

26

Intermittent20

• Intensely pruritic • Palms/soles, nail, and sides of fingers • Attacks between 1 and 10 months

Two historical descriptions Pompholyx Dyshidrosis

27

Frequency of location20 • 1. Hands alone – 46.8% • 2. Feet alone – 24.1% • 3. Hands and feet – 15.6% • 4. Nail apparatus – 13.5%

28

Anatomic Location20 Fungi Positive Hands 1.2% Feet 47.8% Epidermophyton interdigitale 100% of feet cases

29

Lane et al.21

• 25% of any location positive fungal infection Pitche et al.22

• 10% of any location positive fungal infection Guillet et al.23

• 15.8% of any location with T. rubrum or candida infection

30

Always check the feet • Foot involvement is rare • 47.8% dermatophyte infection

146

31 32

33 34

35 36

Presence of erythema • Controversial

Progression of lesions24 • Early stage Vesicular

• Late stage Chronic dry fissured presentation Studded with pinpoint necrotic vesicles

147

37 38

Very rare Single episode of palms and

soles Vesicular and BULLOUS

eruption

39 40

Dyshidrosiform pemphigoid

Linear IgA Herpes gestationis Lymphoma

41

Localized to palms and soles25 1. Soles only 47.36% 2. Palms only 31.57% 3. Both soles and palms 21%

Mildly pruritic .

42

148

43 44

Middle-aged men NEVER VESICLES

45 46

47 48

Dominant hand Site for the start of irritant hand

dermatitis26,27

149

49 50

51 52

53 54

150

55 56

57

Very rare • Must rule out atopic dermatitis No elevated IgE or eosinophilia

Nummular Atopic Dermatitis (Bologna)

58

59

Any combination of above

60

Systems good for academic pursuit Pure clinical pictures are rare

• 50.5% demonstrate multiple morphologies17 Morphology changes frequently clinically and

histologically17 No clear link between morphology and etiology

• Johansen et al.28 • Cronin et al.29 • Diepgen et al.30

151

61

Eczematous reactive process • Acute – vesicles/bullae/erythema • Subacute – scaling/erythema • Chronic – scaling/erythema/lichenification

62

CHECK THE FEET CHECK THE FEET CHECK THE FEET

63

Palmoplantar Psoriasis Palmoplantar Pustulosis

Scabies Erythema Multiforme

Lichen Planus Id reactions

Keratolysis exfoliativa Palmoplantar keratoderma

Autoimmune blistering diseases Lymphoma

Erosio Interdigitalis Blastomycetica

64

Hand Eczema Evaluation Irritant, Atopic, Allergic What do you do for work? Do you touch liquids routinely at work? How many times a day do you wash your

hands? Do you wear gloves and touch food at

work? Do you have childhood eczema, allergies,

or asthma?

65

Standard Series • Toledo et al. • Linberg et al. • Menne et al.

Worker’s Compensation

Irritant contact dermatitis31-33

21% with positive patch test34 • 30% relevant • Nickel (100%)

ACD worse prognosis7

66

#1 Treatment is the same • #2 Blow them up • Faster clearance initially lowers risk of chronicity43

• #3 And then juice em • Systemic and topical steroids35

One episode – 38.4%

Intermittent non-cyclic – 30.8% Intermittent cyclic-28.5% Chronic – 2.3% Patients perceive systemic agents as powerful

#4 Don’t stop treatment if it gets better

152

67

#5 Shake their hands #6 What worked before, may not work

again #7 It gets better with time

• Period prevalence decreases with aging • 78% of subjects claimed improvement of

symptoms over 15 years36

68

Study Years to Follow-Up Persistence

Agrup et al. 2 years 72%

Burrows et al. 10-13 years 79%

Reichenberger et al. 15 years 46%

Fregert et al. 3 years 68%

Gooskes et al. 15 years 55%

Lammintausta et al. 5 years 34%

Driessen et al. 5 years 50%

Keczkes et al. 15 years 69%

Latinga et al. 3 years 59%

Rystedt et al. 3 years 83%

Pryce et al. 2 years 75%

Chia et al. 1 year 28%

Wall et al. 10 years 55%

Halbert et al 10 years 76%

Rosen et al 5 years 66%

Nethercott et al. 2 years 37%

Susitaival et al. 12 years 44%

69

Decrease number of washes daily (Brancaccio) Your hands are broken, if your leg was

broken would you still walk on it Alcohol based disinfectants with glycerin

are less irritating to the skin than soap and water26

Apply emollient within 2-3 minutes of wash24

Greasy as possible Fragrance free Apply as many times during day as you like

70

Use gloves when wet work or dirty work • Latex or vinyl • Tight-fitting • Cotton liner Change when damp

71

Which one should I use?17

Potent 65.5% Moderate 57.3% Superpotent 23.1% Mild 16.7%

How often and for how long?11

• Once daily dosing equal efficacy as twice daily • Two-week intervals

• Even switching in the same class can prove to be beneficial (Holland)

72

Tacrolimus 0.1% vs. mometasone furoate37 • 50% improvement in both groups

Pimecrolimus vs. mometasone furoate38

• Did not reach statistical significance

Used in combination with steroids • Clear (Cohen) • 1st week: ¾ Steroid Ointment ¼ Protopic • 2nd week: ½ Steroid ointment ½ Protopic • 3rd week: ¼ Steroid ointment ¾ Protopic • 4th week: ALL Protopic • 5th-on: AlL Protopic Fri, Sat, Sun

153

73

First Blow • Prednisone 40-60mg daily initial dose and taper

between 3-4 weeks39

• Intramuscular Kenalog 40-80mg40 Limit 4 shots per year (Wolverton)

Second Blow • Prednisolone 30mg daily for 3 days at onset of

eruptions41 • Prednisone 40-60mg x 1 dose on day 1 of the

eruption23

74

S. aureus • Systemic antibiotics superior to topicals24

75

Botulinum toxin A42

• Left versus right study • Vesicular hand dermatitis only • 100 units plus topical steroids

Botulinum toxin43 • Left versus right study • Vesicular hand dermatitis only • 162 units of botox but no steroids

76

UVA >>> NBUVB >>> UVB52

• Apoptosis of lymphocytes through reactive oxygen species and FAS ligand

• Increase in IL-10 inhibition of interferon –gamma. Efficacy PUVA53,54

• Systemic = Topical = Bath • Bath with least side effect Decreased UVA doses due to uniform absorption Phototoxicity risk disappears after 2 hours Sunblock and gloves

• High dose UVA-1 Max single dose of 130J/cm2 Cumulative dose 1720J/cm2 As effective as cream puva52

Reduction in pruritus in first week55

77

Azathioprine 100-150mg daily44

Methotrexate 15-25mg weekly45

Mycophenolate mofetil 2g/day46

Cyclosporine 2.5mg/kg/day47

Etanercept 25mg twice weekly48

78

Approved Europe • Indicated for chronic hand eczema refractory to

topical and systemic steroids • Not for vesicular hand dermatitis

Panagonist RXR, RAR Retinoid Adverse Events

• Headache, mucocutaneous dryness, elevated liver enzymes, elevated blood lipid levels, teratogenicity

No combination studies

154

79

Alitretinoin 30mg daily49 • Median time to clear hands is 12 weeks

Placebo, Alitretinoin 10mg, 20mg, 40mg daily doses for 12 weeks50 • 70% reduction in 50%

Alitretinoin 10mg, 30mg daily for 24 weeks51 • 100% reduction in 48% • More response with 30mg

80

Grenz ray • Energy less than 20kv • Deposited on skin surface

Superficial radiation therapy • Energy 50-150kv • 5mm depth of penetration

Megavoltage electron/photon beam therapy • Measured by a Gray

81

Period prevalence • 2-10%

Risk factors • Atopic dermatitis, allergic rhinitis/asthma, occupation, wet irritant

exposure Classification systems

• Etiology and morphology • Not practical day-to-day clinic

Differential Diagnosis • Check the feet

First-line therapy options • Blow em up and then juice em

82

1. Kavli et al. Hand dermatoses in Tromso. Contact Dermatitis. 1984;10:174-177. 2. Coenraads P et al. Prevalence of eczema and other dermatoses of the hands and arms in the Netherlands. Association with age and occupation. Clin Exp Dermatol. 1983;9:495-503. 3. Goh et al. Occupational dermatoses in Singapore. Contact Dermatitis. 1984;11:288-293. 4. Meding et al. Hand eczema in Swedish adults – changes in prevalence between 1983-1996. 5. Meding B etl a. Incidence of Hand Eczema – a population based retrospective study. J Invest Deramtol. 122;873-877.2004. 6. Lerbeak et al. Incidence of hand eczema in a population-based twin cohort: genetic and environmental risk factors. Br J Dermatol.2007;552-557. 7. Cahill et al. The prognosis of occupational contact dermatitis in 2004. Contact Dermatitis. 2004;51:219-226. 8. Veien N et al. Hand eczema:causes, course, and prognosis. Contact Dermatitis. 2008;58:330-4. 9. Toledo et al. Patch testing in children with hand eczema. Contact Dermatitis. 65;213-219. 10.Meding B et al. Fifteen-year follow-up of hand eczema: predictive factors. J Invest Dermatol. 2005;124:893-7. 11. Menne T et al. Hand eczema guidelines based on the Danish guidelines for the diagnosis and treatment of hand eczema. Contact Dermatitis 65;3-12. 12. Coenraads P et al. Risk for hand eczema in employees with past or present atopic dermatitis. Ach Occup Environ Health. 1998;71:7-13. 13. Molin et al. Diagnosing chronic hand eczema by an algorithm: a tool for classification in clinical practice. Clin and Exp Dermatol. 36;595-601. 14. Janssens V et al. Protein contact dermatitis: myth or reality? Br J Dermatol. 1995; 132:1-6. 15.Thyssen J et al. Filaggrin null mutations increase the risk and persistence of hand eczema in subjects with atopic dermatitis: results from a general population study. Br J Dermatol.

2010;115-120. 16.Molin S et al. Filaggrin mutations may confer susceptibility to chronic allergic and irritant hand dermatitis. Br J Deramtol. 2009;801-7. 17.Apfelbacher C et al. CARPE: a registry project of the German Dermatological Society for the characterization and care of chronic hand eczema. JDDG;2011:682-688. 18. Kumar et al. Palmoplantar lesions in psoriasis: a study of 3065 patients. Acta Derm Venerol. 82;192-195. 19. Sampogna et al. Prevalence of symptoms experienced by patients with different clinical types of psoriasis. Br J Dermatol. 2004;151:594-599. 20. Tibor B et al. Pompholyx on the hands and feet. Its etiology, pathogenesis, and specific vaccine therapy. Mycopath et Mycol applicata. 1974;53:25-44. 21. Lane et al. Dermatoses of the hands. JAMA. 128;987-993. 22. Guillet M et al. A-year causative study of pomphylox in 120 patients. Arch Dermatol. 2007;143:12:1504-8. 23. Storrs et al. Acute and recurrent vesicular hand dermatitis not pompholyx or dyshidrosis. Arch Dmeratol. 2007;143-5. 24. Brady M et al. Hands and feet that blister and peel: dyshidrosis. J Ped Health Care. 1993;7:37-8. 25. Brunasso A et al. Can we really separate plamoplantar pustulosis from psoriasis? JEADV 2010;24:611-624. 26.Kampf G et al. Prevention of irritant contact dermatitis among health care workers by using evidence-based hand hygience practices: a review. Ind health. 2007;645-652. 27.Schwanitz H et al. Interdigital dermatitis; sentinel skin damage in hairdressers. Br J Dermatol. 2000;1011-1012. 28. Johansen et al. Classification of hand eczema: clinical and etiological types. Based on the guideline of the Danish Contact Dermatitis Group. Contact Dermatitis. 65;13-21. 29. Cronin E. Clinical pattern of hand eczema in women. Contact Dermatitis. 1985;13:153-161. 30. Diepgen T etl al. European Environmental contact dermatitis research group. Hand eczema multicentre study of the etiology and morphology of hand eczema. Br J Dermatol.

2009;160:353-358. 31. Veien N et al. Hand eczema: causes, course and prognosis 1. Contact Dermatitis 2008;58:330-334. 32. Lantinga H et al. Prevalence, incidence and course of eczema on the hands and forearms in a sample of the general population. Contact Dermatitis. 1984;10:135-139. 33. Agner T. Hand eczema. Contact Dermatitis. 4th edition. Forsch PI. Berlin. Springer. 2006;pp335-344. 34. Beattie PE et al. Which dhildren should we patch test? Clin Exp Dermatol 2006;32:6-11. 35. Apfelbacher C et al. Occurrence and prognosis of hand eczema in the care industry: results from the PACO follow-up study (PACO II). Contact Dermatitis. 2008;58:322-329. 36. Meding et al. Fifteen-year follow up of hand eczema: persistence and cosequences. Br J Dermatol. 2005;152:975-980. 37. Schnopp C et al. Topical tacrolimus and mometasone furoate in treatment of dyshidrotic palmar eczema: a randomized, observer-blinded trial. J Am Acad Dermatol. 2002;46:73-7.

83

38. Belsito D et al. Multicenter Investigator group: pimecrolimus cream 1%: a potential new treatment for chronic hand dermatitis. Cutis. 2004;73(1):31-8. 39.Wollin U et al. Pharmacotherapy of pompholyx. Exper Opin Pharmaother 2004;5(7)1517-22. 40.Boettget et al. Increased vagal modulation in atopic dermatitis. J Dermatol Sci 2009;53(1):55-9. 41. Veien N. Acute and recurrent vesicular hand dermatitis. Dermatol Clin. 2009;337-353. 42. Wollina et al. Adjuvant botulinum toxin A in dyshidrotic hand eczema: controlled prospective pilot study with left-right comparison. J Eur Acad Dermatol

Venereol 2002;16:40-2. 43.Bansal C et al. Novel cutaneous uses for botulinum toxin type A. J Cosmet Dermtol. 2006;5(3):268-72. 44. Sceerri L et al. Azathioprine in dermatological practice: an overview with special emphasis on its use in non-bullous inflammatory dermatoses. Adv Exp Med

Biol 1999;455:343-8. 45.Egan et al. Low-dose oral methotrexate treatment for recalcitrant palmoplantar pompholyx. J am Acd Dmeratol. 1999;40(4)612-14. 46. Pickenacker A et al. Dyshidrotic eczema treated with mycophenolate mofetil. Arch Dermatol. 1998;134(3):378-9. 47. Reitamo S et al. Cyclosporin A in the treatment of chronic dermatitis of the hands. Br J Dermatol. 1994;130(1):75-8. 48. Ogden S. Recalcitrant hand pomphylox; variable response to etanercept. Cli and Exp Dermatol. 31; 129-156. 49. Bissonnette R et al. Successful retreatment with alitretinoin in patients with relapsed chronic hand eczema. Br J Dermatol. 2010;162:420-26. 50. Ruzicka et al. Oral alitretinoin (9-cis-retinoic acid) therapy for chronic hand eczema dermatitis in patient refractory to stand therapy: results of a randomized,

double-blind, placebo-controlled, multicenter trial. Arch Dermatol. 2004;140(12):1453-9. 51. Ruzicka et al. Efficacy and safety of oral alitretinoin (9-cis-retinoic acid_ in patients with severe chronic hand eczema refractory to topical coriticosteroids:

restuls of a randomized double blind, placebo controlled, multicentre trial. Br j Dermatol. 2008;158:808-817. 52. Krutman J. Phototherapy for atopic dermatitis. Clin Exp Deramtol. 2000;25(7):552-8. 53.Grattan C et al. Comparison of topical PUVA with UVA for chronic vesicular hand eczema. Acta Derm Venerol. 1991;71:118-22. 54.Petering H et al. Comparison of locatlized high-dose UVA2 versus topical cream psorlenUVA for treatment of chronic vesicular dyshidrotic eczema. J Am Acad

Dermatol. 2004;68-72. 55. UVA1 Irradiation is effective in ttreatment of chronic vesicular dyshidrotic hand eczema. Acta Derm Venerol 56. ansen G. Grenz rays:adequate or antiquated? J Deramtol Surg Oncol 1978;4:627-9.

155

The Ohio State University Comprehensive Cancer Center – Arthur G. James Cancer Hospital and Richard J. Solove Research Institute 1

Approaching Primary Cutaneous Lymphomas from a (General) Dermatologist’s Perspective

2012 AOCD Annual Meeting

October 10, 2012

Francisca Kartono, DO Ohio State University Medical Center

Department of Dermatology Assistant Clinical Professor

The Ohio State University Comprehensive Cancer Center – Arthur G. James Cancer Hospital and Richard J. Solove Research Institute

Disclosures

Subinvestigator for clinical trials for Abbott, Amgen, Celgene and Janssen

I have no relevant conflicts of interest pertaining to this topic


Objectives Classification of Primary Cutaneous Lymphomas

Cutaneous T-cell lymphomas Mycosis fungoides / Sezary

Cutaneous B-cell lymphomas

Treatment approach

Community dermatologist’s perspective Multidisciplinary approach ( Derm, Onc, Rads, PCP)

Patient support : a team approach


Cutaneous lymphoproliferative disease

Primary Cutaneous lymphoproliferative diseases Secondary Cutaneous involvement from a nodal or

systemic lymphoma

A constellation of morphologic, immunologic, genetic, and clinical criteria.

Behavior is distinct from nodal lymphomas Anatomic locations with distinct behavior T- cell and B cell lymphomas


CTCL

5


Immunopathogenesis (S Whittaker, Semin Oncol 2006)

Skin T cells in immunosurveillance Skin – homing malignant T cell in MF:

CD4+ T helper cells Th2 >Th1 predominance in disease progression Malignant T cell clonality

Defects in pro and anti-apoptotic signals Genomic and epigenetic changes Defects in TCR and cytokine signaling Constitutive activation STAT/NFKB/AP1 Large cell transformation Genomic instability

6

156

The Ohio State University Comprehensive Cancer Center – Arthur G. James Cancer Hospital and Richard J. Solove Research Institute 7

J Clin Invest. 2005 Apr; 115(4):798-812.


Statistics Lymphomas currently represent 4% of all cancers PCLs represent 19% of all NHL New CTCL cases ~ 3000 / yr

Total of 30,000 in the US + Canada MF accounts for about 72% of all CTCL cases SS accounts for 2.5% of CTCL cases.

Increasing incidence since 1970 till now Increase of 2.9 cases per million per decade

Median age of presentation is 57 years Male: Female ratio of 2:1 for CTCL

CTCL incidence 50% greater in African Americans


Incidence


WHO-EORTC classification of cutaneous lymphomas

MF/SS= 65% of CTCL

CD30+ = 25% of CTCL


Approach to diagnosis of CTCL in Dermatology Classic morphology

> 3-4 cm erythematous patches /plaques, “maculosquamous” , cigarette paper wrinkling, polymorphous. Skin of color : poikiloderma , reticulated

hyperpigmentation Mimicker of chronic eczema, contact dermatitis,

psoriasis Patch Plaque Tumor Erythroderma

Classic distribution Sun protected areas , rare on face


Making the diagnosis of MF

157


Pathology

13 The Ohio State University Comprehensive Cancer Center – Arthur G. James Cancer Hospital and Richard J. Solove Research Institute

Pathology Immunophenotyping IHC on paraffin or fresh tissue using antibodies that

can react with cell surface/ cytoplasmic markers IHC: CD 3, 5, 7, CD4/8 Flow cytometry

Immunogenotyping (PCR) TCR gene rearrangement : clonality


Workup

Suspect MF 2 skin biopsies, different sites

Off therapy Dermatopathologist to review If indicated:

Immunophenotyping Molecular studies ( TCR)

CLINICOPATHOLOGIC CORRELATION FOR FINAL INTERPRETATION

15


Staging


B2


CTCL patient visit

Complete history and physical exam of skin Assessment of lymph nodes

Cervical Axillary Inguinal >1.5 cm palpable nodes will need imaging workup. No need to blindly biopsy unpalpable nodes

Imaging:

CXR / nodal ultrasound staging PET/CT

Labs: periodic CBC and Sezary cell count .

CMP, LDH, TCR (tissue or blood) Flow cytometry (blood) in place of Sezary count

158


Treatment approach

General/community dermatologists Manage early stage CTCL

Tertiary care referral for advanced disease Clinical trials

Several principles in treatment:

Skin-directed-therapies first Loop-back mechanism of treatment options Combination therapy not monotherapy SUPPORTIVE CARE: improve QoL for patients


Skin directed therapies

Nitrogen Mustard Topical steroids Topical bexarotene Tazarotene / topical retinoids Imiquimod Tacrolimus **

Phototherapy PUVA/UVB:

Good combos: PUVA + po retinoid PUVA + interferon


Local or TSEB

Total Skin Electron Beam Therapy

Stanford protocol “RESET” button. Can repeat it 2-3 times over a lifetime Response is great, but may need to be bridged to a

maintenance regimen. TSEB response may be short-lived.

3,600 cGy in small fractions three times a week for approximately 10 week



Systemic Therapy Biologic response modifiers

IFN, retinoids, dinileukin diftitox

Histone Deacetylase Inhibitors Romidepsin, vorinostat,

Immunotherapy alemtuzumab

ECP Clinical trial agents Chemotherapy

Does not treat CTCL appropriately as first line tx. CHOP, Gemcitabine, Liposomal doxorubicin MTX, praletrexate


Allogeneic HSCT

Graft vs lymphoma effect Lifetime expectation of transformed MF /SS ( ~2.5

years). Allogeneic HSCT

Relapse rate 39%, time to relapse was 50 Days. Difficult to time properly as the skin may not clear

sufficiently

Duvic et al. J Clin Oncol 28(14):2365-72

159


Primary Cutaneous B cell Lymphomas

25 The Ohio State University Comprehensive Cancer Center – Arthur G. James Cancer Hospital and Richard J. Solove Research Institute

Primary cutaneous B cell lymphomas: Mostly indolent

Different from their systemic/ nodal counterparts Confined to the skin at presentation Complete staging procedures are negative ( 6

months after initial workup) Cerroni L, Signoretti S, Hofler G, et al. Primary cutaneous marginal zone B-cell lymphoma: a recently described entity of low-grade malignant cutaneous

B-cell lymphoma. Am J Surg Pathol 1997;21:1307-15.

20-25% of all cutaneous lymphomas Evolving classification

WHO-EORTC classification since 2005 , revised 2007, 2008

No standardized guidelines for care !


Epidemiology

SEER data from 16 registries representing ~26% of US population

2001-2005 total of 1105 cases pCBCL

CBCL: non Hispanic whites had highest IR ( vs Af Am in

CTCL) M>F IRR= 1.72 Metropolitan locations vs non metropolitan locations Head and neck

The Ohio State University Comprehensive Cancer Center –

Arthur G. James Cancer Hospital and Richard J. Solove Research Institute


EORTC WHO This particular study of n=556

Old Classification


Classification

WHO-EORTC Classification

Behavior B cell lymphoma type Indolent Marginal zone Indolent Follicle Center Intermediate Diffuse large B cell, other Agressive Diffuse large B cell , leg type

Blood 2005; 105: 3768-85

160


Survival


Approach to Diagnosis Clinical suspicion: paps, plaques, nodules, on head/neck,

extremities, trunk, relapses 4-6 mm punch or excision H/E for histology

Grenz zone, “bottom heavy” lymphocytic infiltrate, centroblasts, centrocytes, germinal centers, plasma cells

Relevant IHC: CD3, Cd20 or CD 79a Surface and cytoplasmic immunoglobulins Cd35 or CD 21 ( to detect reactive follicles) Ki- 67 Bcl2, Bcl6, Cd10, MUM1 , FoxP1 T(14:18) CD5, Cyclin D1 IgH gene rearrangement


Pc – Marginal Zone B cell lymphoma

http://cutaneouslymphoma.stanford.edu/docs/S048%20AAD%202011%20CL%20CBCL.pdf


PC- Marginal Zone Lymphoma

Red-violaceous plaques or tumor nodules commonly on extremities (esp. arms) or trunk; solitary or multifocal 5-yr overall survival >95% Frequent relapses on skin Rare extracutaneous dissemination

Indolent BCL of mature small B-cells “immunocytoma”

Part of MALT (GI tract, salivary gland, lung, H/N, ocular adnexa, skin, thyroid, breast)

B-cells: CD20+, CD79a+, Bcl-2+, Bcl-6-, CD10- , Cd 5- Plasma cells: CD138+, CD79a+, freq. CD20 - Molecular/Genetic

40-60% clonal IgH gene rearrangement


PC- Follicle Center Lymphoma

http:/cutaneouslymphoma.stanford.edu/docs/S048%20AAD%202011%20CL%20CBCL.pdf


PC- Follicle Center Lymphoma

Solitary, grouped, or multifocal plaques or tumor nodules, preferentially on scalp, head and neck, trunk 5-yr overall survival 95% Cutaneous relapses in 20% Extracutaneous dissemination in 5-10% patients

Tumor of neoplastic follicle center cells CD20+, CD79a+, +/- monotypic light chain expression Bcl-2-/+, Bcl-6+, CD10+/-, MUM1-

Molecular/Genetic 50-70% clonal IgH rearrangement by PCR Inactivation of p15,p16 tumor suppressor genes

in10%,30%

161


Primary Cutaneous Large B-cell Lymphoma , Leg- type


Primary Cutaneous Large B-cell Lymphoma , Leg- type

Common in elderly Rapidly growing red-violaceous tumors,

most commonly on leg, but can affect non-leg site 5-yr OS 35-50%

CD20+, CD79a+, monotypic light chain expression Bcl-2+ +, Bcl-6+/-, CD10-, MUM1+, FOXP1+,

IgM+,IgD+/-– Lack t(14;18) despite strong Bcl-2 Inactivation of p15, p16 in Frequent clonal IgH gene rearrangement by PCR


Classification


NCCN TNM classification

Staging


Staging procedures ISCL/EORTC Recommendations for Staging Evaluation in

Cutaneous Lymphomas other than MF/SS, Blood 2007;110:479-484

Complete history and review of systems

Trauma, bugbite B symptoms

Thorough physical examination

Labs: CBC, CMP, LDH, beta2 microglobulin

SPEP : monoclonal gammopathy flow cytometry of peripheral blood ( esp. if lymphocytosis

present) No need to look for Borrelia in US


Borrelia link not demonstrated in US cases

162


Imaging

Imaging studies– CT neck, chest, abdomen & pelvis w/ contrast alone or with whole body FDG-PET

Whole body integrated PET/CT as alternative

LNs > 1.0 cm in short axis and /or have significantly increased PET activity should be sampled for tissue examination (an excisional bx is preferable whenever possible)


On Bone Marrow Biopsy …

Senff NJ, et al . Br J Haematol. 2008; 28: 502-507.

11% ( 22/193) of patients with FCL present in the skin have BM involvement In 9/22, this was the ONLY sign of extrcutaneous dz

OS 44% DSS 63% in BM+ pts OS 84% DSS 95% in FCL pts without extracutaneous dz

2/ 82 MZL patients had extracutaneous involvement of BM.

Conclusion: No consensus on BMB currently. Still essential part of workup until proven otherwise


NCCN Guidelines

US Treatment Guidelines in PCBCL NCCN practice guidelines for available since 2009

www.nccn.org First available standard of care treatment guideline

in cutaneous lymphoma Help with insurance pre-auth and reimbursement


Management of PCBCL

MZL/FCl ( indolent) DLBCL leg type (Aggressive)

Solitary / Regional Generalized Solitary Multiple -Observation

-ILK -Excision -Topicals: NM, imiquimod, retinoids -XRT -Clinical trials

-Observation -Topicals -RT + sx -Biologics: Rituximab, IFN, retinoids -Chemotherapy -Clinical trials

RT ( caution) RCHOP+- IFRT Clinical trials

RCHOP +- IFRT Clinical trials


In summary

Indolent (FCL/MZL) vs. aggressive (DLBCL leg-type) Do not over treat Management driven by symptom Local tx for localized disease Rituximab only if generalized disease present and

symptomatic 40-60% relapse rate post initial therapy, regardless of tx type

Do not under treat aggressive cases Utilize NCCN practice guidelines Clinical trial for advanced cases and new targeted

therapies


Patient Support

http://www.clfoundation.org

48

163

Robert G. Greenberg, M.D., F.A.A.D. Robert G. Greenberg, M.D., Dermatologist – San Ramon, CA

As many as 7.5 million Americans have psoriasis

Common, chronic, inflammatory disease of skin and joints

Auto-immune disease caused by both genetic and environmental influences

Plaque psoriasis is the most common form

Guttate: Small, red, individual spots on skin. Usually appears on trunk and limbs.

Inverse: Found in skin folds. Lesions are very red and usually lack scale.

Pustular: White pustules surrounded by red skin.

Erythrodermic: Fiery redness on large areas of skin. Often accompanied by severe itching and pain.

Scalp Elbows/knees Lower back Navel Hands/feet

Pitting Peeling Discoloration Lifting up from the

nail bed Ridging

PsoriasisGenetic

Predisposition

TriggersTrauma, infection,

drugs, stress

Skin cell proliferationInflammation

Itch

Immune Dysregulation

Image courtesy of Kelly Cordoro, MD, UCSF

Current view of psoriasis

164

1. Psoriasis trigger is delivered to draining lymph nodes

2. Activation of T-cells

3. T-cells move from lymph nodes into the skin

4. T –cells release of inflammatory factors in the skin

5. Inflammatory factors trigger: rapid production of skin cells, widen blood vessels and, stimulate itch nerves

1.

2.

3.

4.

5.

Current view of psoriasis Psoriasis skin

But known triggers may include: Emotional stress Infection (strep) Injury to the skin (includes tattoo, piercing) Weather (cold, dry) Certain kinds of drugs (lithium, some beta blockers)

Key findings from the Psoriasis Foundation ◦ 28% have another chronic, inflammatory disease ◦ 59% suffer from physical pain from their psoriasis ◦ 63% said psoriasis negatively impacts their overall

well being ◦ 71% said they feel “helpless” and 73% said they feel

“angry” or “frustrated”

Results based on 6 years of summarized data from nearly 5,000 survey participants with psoriasis and/or psoriatic arthritis.

Treating psoriasis

Psoriasis is chronic and requires lifelong treatment

No single treatment works for everyone Switching treatments is common Many treatment options are available for

psoriasis and psoriatic arthritis Combination treatment is common

165

Localized disease <5% body surface area

Widespread disease >5% body surface

area Psoriatic arthritis Vulnerable areas

o Palms/soles o Genital area

biologics cyclosporine methotrexate retinoids

Over the counter topical treatments Salicylic acid, other keratolytics Low dose corticosteroids Tar preparations Moisturizers and other oils, salt or oatmeal bath

Prescription topical treatments: Mid-to-high strength corticosteroids Vitamin D analogs Combination corticosteroids and vitamin D Anti-inflammatory agents Retinoids (tazorac) Anthralin Intralesional corticosteroids

Calcitriol (Vectical®) Vitamin D Non-steroidal Twice-daily application Comes in ointment form

Calcipotriene and betamethasone dipropionate (Taclonex®) Vitamin D + topical corticosteroid Once-daily application Comes in ointment and a scalp solution

166

Light therapy Excimer (ultraviolet light B) laser treatment Pulse-dye laser treatment

Phototherapy Ultraviolet light B (UVB) o Broadband o Narrowband

PUVA (drug psoralen plus ultraviolet light A) Home light boxes

Traditional systemics Cyclosporine Methotrexate Acitretin (brand name Soriatane®) Sulfasalazine Hydroxyurea

Protein-based drug derived from

living cells cultured in a laboratory

Given through injection or intravenous (IV) infusion

First biologic drug approved for psoriasis was Alefacept in 2003

Biologics for psoriatic disease target a specific protein, rather than the entire immune system

Biological medications or biologics

*Alefacept (Amevive®): 20-25% Etanercept (Enbrel®): 40-50% Adalimumab (Humira®): 60-

70% Infliximab (Remicade®): 75-

80% Ustekinumab (Stelara®): 65-

75%

020406080

100FDA approved for psoriasis

*Alefacept (Amevive) was voluntarily discontinued November 16, 2011. National Psoriasis Foundation, presented at the American Academy of Dermatology in February 2007

39% of psoriasis patients with severe disease are not receiving any treatment

57% of psoriasis patients with severe disease are being treated with topical therapy alone

167

Effectiveness of the treatment Potential side effects and long-term risks Type of psoriasis Other health conditions—possible drug

interactions Disease severity—physical and psychosocial Ease of treatment application—patient

adherence Pregnancy considerations Insurance coverage/out-of-pocket costs

Psoriasis Treatment Pipeline

PSORIASIS

627 clinical trials for Psoriasis registered with ClinicalTrials.gov o 103 ongoing “interventional” trials o testing 36 different treatments

PSORIATIC ARTHRITIS

122 Clinical trials for Psoriatic arthritis registered with ClinicalTrials.gov o 21 ongoing “interventional” trials o testing 8 different treatments

Information on clinical trials, visit: www.clincaltrials.gov or www.centerwatch.com

Oral drug - Phosphodiesterase-4 inhibitor (Celegene®)

Anti-inflammatory

Phase II results: 41% PASI75 & 44% ACR20

Recruiting for Phase III

Both psoriasis and psoriatic arthritis

Two other PDE4i in the pipeline: AN2728 (Anacor®) and MK-0873 (Merck®).

Janus kinase (JAK) inhibitor (Pfizer®) Immunosuppressive Phase II results: 67% PASI 75 Recruiting for phase III in psoriasis Other JAK inhibitors in the pipeline: ASP015K

(Astellas®), INCB18424 (Incyte®)

168

Monoclonal antibody blocks IL-17 (AIN457, LY2439821) or IL-17 receptor (AMG 827)

Phase II/III Also being developed for rheumatoid

arthritis

Monoclonal antibody blocks IL-23

Phase II Pathway is also blocked by

Stelara®

Inflammatory joint disease found in up to 30% of patients with psoriasis

Stiffness, pain, swelling and tenderness of the joints and surrounding ligaments and tendons

Early recognition, diagnosis and treatment can help prevent progressive joint involvement and damage

Skin symptoms usually appear before joint symptoms, but not always

Early diagnosis and treatment is the key to preventing long-term joint damage

Sausage digit

169

Joint damage is irreversible

Symptoms to be aware of Back pain/stiffness Pain in heel or bottom of foot Morning stiffness lasting longer than 30 minutes Generalized fatigue Reduced range of motion Swollen fingers and/or toes

There is no one test that can diagnose psoriatic arthritis

Physical exam looking for signs of psoriasis and/or psoriatic arthritis ◦ Skin, joints, reflexes and muscle strength

Other tests include ◦ X-rays or other imaging tests ◦ Blood test ◦ Other tests (e.g. sample of synovial fluid)

Ruling out other diseases or conditions Rheumatoid arthritis Gout Ankylosing spondylitis Reactive arthritis Others

Nonsteroidal anti-inflammatory drugs (NSAIDs) ◦ Over-the-counter (OTC) medications such as

aspirin and ibuprofen ◦ Prescription strength products

These will help with pain and inflammation but not with the progression of the disease.

170

Disease-modifying antirheumatic drugs (DMARDs) may relieve more severe symptoms

and attempt to slow or stop joint/tissue damage and the progression of psoriatic arthritis. Methotrexate (oral and injection) Leflunomide (oral) Sulfasalizine (oral)

Biologics approved by FDA for psoriatic arthritis: Etanercept (Enbrel®) Adalimumab (Humira®) Infliximab (Remicade®) Golimumab (Simponi®)

Etanercept (Enbrel®) Administered as a self injection once or twice weekly

Adalimumab (Humira®) Administered as a self injection with a pre-filled syringe

typically once every other week

Golimumab (Simponi®) Administered as a self injection once a month

Infliximab (Remicade®) Administered through intravenous infusion every 6 to 8

weeks

Name Sponsor Mechanism Route Development phase

Apremilast Celgene Anti-inflammatory (PDE4 inihibitor)

Oral III

Cimzia (Certolizumab)

UCB TNF blocker Injectable III

Tofacitinib Pfizer Anti-inflammatory (JAK3 inhibitor)

Oral III

Stelara (Ustekinumab)

Centocor IL-12/-23 blocker

Injectable III

Secukinumab (AIN457)

Novartis IL-17 blocker Injectable II

171

Recent studies show that psoriasis, in and of itself, can cause cardiovascular risk

The greater the psoriasis severity, the greater the risk

Controlling psoriasis with certain medications shows promising results for reducing cardiovascular risk

Reference: Gelfand JM, Neimann AL; Shin DB, et al. Risk of Myocardial Infarction in Patients With Psoriasis. JAMA. 2006;296(14):1735-41.

Psoriasis is associated with increased risk of:

Ischemic heart disease - 78% Cerebrovascular disease - 70% Peripheral vascular disease - 98% * after controlling for age, sex, hypertension, diabetes mellitus, dyslipidemia, and tobacco

Atherosclerosis and Other Vascular Diseases

Reference: Prodanovich S, Kirsner RS, Kravetz JD, et al. Association of Psoriasis With Coronary Artery, Cerebrovascular, and Peripheral Vascular Diseases and Mortality. Arch Dermatol. 2009;145(6):700-3.

Uncontrolled inflammation leading to blood vessel dysfunction, altered blood lipids and vascular disease

The use of drugs such as corticosteroids, acitretin, and cyclosporine that alter blood lipid levels

The increased prevalence other risk factors: obesity, hypertension, high triglycerides, smoking

Possible causes for increased risk of heart attack in psoriasis

Begin screening for cardiovascular disease risks at age 20

Monitor and modify cholesterol levels Take measures to control depression If you smoke, quit Moderate alcohol intake Eat a healthy diet Exercise 3 times a week for 30 minutes

Kimball, et al., J. Amer. Acad. Derm. June, 2008; volume 58(6); 964-969.

Hypertension Diabetes Cancer Depression Obesity Crohn's disease

Kimball, et al., J. Amer. Acad. Derm. June, 2008; volume 58(6); 964-969.

National Psoriasis Foundation Access Action Guide – tools and tips for

navigating the health care system Web site www.psoriasis.org provides:

Step-by-step appeal process Sample letters Health plan policy database

[email protected]

172

National Psoriasis Foundation Provides support with health insurance appeals Assists with disability claims Offers assistance with discrimination cases Provides a list of corporate, government and non-profit financial resources

Questions for Dr. Greenberg

173

The Bones of Dermatology

Angela McKinney, D.O. Botsford Dermatology Residency Program

Objectives

• Provide an informative case presentation on SAPHO syndrome

• Review various dermatologic conditions with associated skeletal findings.

• Ensure prompt diagnosis and proper disease management

• To offer board relevant pearls for residents and attending physicians for their recertification exams

History of present illness • 16 year old previously healthy Caucasian male

• 2 month history of increased acne severity

• 3 week history of bilateral ankle pain, that progressed to involve his left hip and left shoulder

• Extreme worsening of his pain led to an in-patient hospital evaluation

Face

Chest Upper Back

174

Lower Back Musculoskeletal Exam • Decreased range of motion of his extremities

• Mild edema of his bilateral ankles

Labs • CBC

• WBC (18.9) • Hb (11.2); Hct (33.1) • Platelet (444)

• CHEM7 • Na (136) • K (4.2) • Cl (100) • HCO3 (27) • Glucose (83) • BUN (12) • Cr (0.5);

• CPK (44)

• CRP (9.4)

• ESR (80)

• Parvo B19 • Positive for past infection

• EBV • Positive for a past infection

• CMV (Negative)

Imaging • X-ray (Pelvis and LE) – Normal

• X-ray (Skull) – Normal

• CT (Bilateral Ankles) - Multifocal osteomyelitis along the distal growth plate of the tibia and fibula

• MRI

MRI Studies – September 2011

•

Multifocal Osteomyelitis Involving the:

Distal left clavicle

Proximal left Humerus

Right Sacrum

Bilateral Proximal Femurs

Distal Tibia and Fibula

Multiple Metatarsals

SAPHO SYNDROME

Neutrophilic Dermatosis + Spondyloarthropathy

175

Pathogenesis - Infectious trigger

• Pathogens have been isolated from different sites such as: Bone, Chest wall, Synovial Fluid & Pustules. • P. Acnes (most common), • S. aureus, • H. parainfluenza, • Actinomyces • Treponema

• Triggers the production of cross-reacting antibodies and a non-specific activation of complement and cellular mediated immunity.

Rozin AP: SAPHO syndrome: Is a range of pathogen-associated rheumatic diseases extended? Arthritis Research & Therapy 2009, 11:131

Pathogenesis – Infectious trigger

• • Periosteal bone formation

• Cortical bone resorption.

Epidemiology

• Children, Young-Middle aged adults

• Most frequently in Japan, Scandinavia, Germany and France.

EPIDEMIOLOGY

• Familial reports

• HLA-B39 and HLA-B61 correlation outside US

• Insufficient p53 response • Less effective apoptosis of inflammatory cells.

• Reduced Neutrophilic Oxidation

Reference 8,9,10

SKELETAL INVOLVEMENT

• Synovitis,

• Arthrosteitis

• Chronic recurrent multifocal aseptic osteomyelitis

SKIN INVOLVEMENT

• Neutrophilic dermatosis • Most commonly severe acne

or cystic triad

• Palmar-Plantar Pustulosis

176

IMAGING

•Bone Scintigraphy

•Plain Films

•MRI

Differential Diagnosis

• Bacterial Osteomyelitis

• Primary Bone Tumor

• Metastasis

• Langerhan Cell Histiocytosis

• Acne Fulminans

Treatment

• Osteoarticular Lesions

• Methotrexate

• Corticosteroids (IL/PO)

• Bisphosphonates

• Anti-TNF-α

• NSAIDS

• Colchicine

• Sulfasalazine

• Acne

• Long Term PO Antibiotics

• Isotretinoin

Unknowns

Case 1

• 51 year old female with recent onset of sharply demarcated, scaly erythematous plaques

• Positive nail pitting

• DIP involvement

Case 1- Pathology

177

Case 1 – Psoriasis

• Psoriatic arthritis affects 5-30% of all psoriasis patients

• Peripheral spondyloarthropathy

• Enthesitis

• Dactylitis

Psoriatic Arthritis

• Mono- and Asymmetric Oligoarthritis • Most commonly involves the DIP and PIP joints of the

hands and feet

• Sausage Digit

Psoriatic Arthritis

• Arthritis of the Distal Interphalangeal Joints • “Classic”, but uncommon

Psoriatic Arthritis

• Rheumatoid Arthritis-like Presentation • Symmetric polyarthritis that involves small and

medium joints (PIP, MCP, wrists, ankles and elbows)

• Usually seronegative

Psoriatic Arthritis

• Spondylitis and Sacroiliitis • Usually HLA-B27

positive

• Possibly association with inflammatory bowel disease and/or Uveitis

Arthritis Mutilans

178

Is it Psoriatic Arthritis or Not?

• Evidence of Psoriasis?

• Evidence of psoriatic nail changes? • Onycholysis, Pitting, Hyperkeratosis

• Negative for rheumatoid factor?

• Symmetrical?

• History of Dactylitis?

• Radiographic Evidence?

• Loss of joint cartilage

• Altered bone remodeling • Resorption, Erosions

and Pencil-Cup deformities

Case 2 A 27 year old female presents

with skin-colored to yellow

dermal papules and coalescing

plaques that are symmetrically

distributed on her trunk,

buttock, arms

Case 2 Histopathology 1) Poorly demarcated area

of increased dermal collagen

2) Haphazardly arranged collagen in the reticular dermis

3) Elastic staining demonstrates an obvious increase of thickened elastic fibers particularly in the reticular dermis.

Case 2

• A) Endoscopy looking for pyloric atresia

• B) X-ray for osteopoikilosis

• C) MRI for hippocampal calcifications

• D) Echo for mitral valve insufficiency

• E) Spinal CT for Kyphoscoliosis

What radiographic imaging is

most appropriate in diagnosing

this patient?

Case 2 Osteopoikilosis

179

Case 2 Bushke-Ollendorf

• Inheritance • AD, LEMD3

• Age of Presentation

• Birth to adulthood

• Clinical Features

• Skin – Dermatofibrosis lenticularis disseminata

• Bone – Osteopoikolosis

• Work-Up

• X-ray of hands/feet/knees,

• Skin biopsy with VVG stain

• Prognosis

• Normal life

Case 3

38 year old with multiple pearly papules

& Palmar pits

Case 3 Basal Cell Nevus Syndrome (Gorlin)

Which of the following X-Ray findings are commonly associated with this disease?

A B

C D

BCC Nevus Syndrome Answer – All of the Above

• Odontogenic Jaw Cysts

• Calcification of the Falx Cerebri

• Bifid Ribs

• Long Bone Cysts

Case 3 Basal Cell Nevus Syndrome (Gorlin)

• Inheritance

• AD; PTCH1 (PATCHED1) gene

• Age of Presentation

• Birth-Childhood

• Clinical

• Numerous BCCs; Palmoplantar pits

• Radiographic Findings

• Jaw Cysts, Frontal bossing, Bifid ribs, Kyphoscoliosis. Calcification of falx cerebri, Long bone cysts

• Work-up

• Skin biopsy, Radiographic Skeletal survey

• Treatment

• Close monitoring and treatment of BCCs

Case 4 12 year old girl comes to the

clinic for evaluation of multiple

superficial and deep purple-blue

nodules affecting her right hand.

The nodules began appearing

around the age of 7.

None of her siblings are

affected.

180

Case 4

You suspect Maffucci Syndrome

and perform radiographic

imaging of the affected sites.

What malignant tumor is most

important to rule out?

1)Endochondroma

2)Giant Cell Tumor

3)Osteochondromas

4)Chondrosarcoma

5)Hamartoma

Case 4 Maffucci Syndrome

• Inheritance • Sporadic

• PTH/PTHrP type I receptor

• Age of Presentation • Birth to early childhood

• Clinical • Superficial and deep venous

malformations of distal extremities,

• Benign enchondromas

• Chondrosarcomas (15-30%)

• Prognosis • If no malignant degeneration, normal

lifespan.

Case 5

A baby with ichthyosiform erythroderma in a blaschkoid pattern

Blaschkoid Ichthyosiform Erythroderma Differential Diagnosis

• X-Linked Dominant chondrodysplasia punctata (Conradi-Hunermann-Happle syndrome)

• X-Linked Recessive Chrondrodysplasia punctata with steroid sulfatase deficiency

• CHILD syndrome

• Incontinentia pigmenti

Case 5 – Radiographic Evaluation Case 5 – Chondrodysplasia Punctata

(Conradi-Hunermann-Happle)

• Pathogenesis

• X-linked dominant; EBP gene

• Presentation • Birth, lethal in males

• Clinical • Ichthyosiform erythroderma in

Blaschko’s lines in infancy

• Patchy alopecia, cataracts, short stature, scoliosis Frontal bossing, macrocephaly, flat nasal root

• Work Up • Bone films - Stippled epiphyses,

Asymmetric limb shortening and Scoliosis

181

Case 6 7 year old female was sent over

for dermatologic evaluation after

her ophthalmologist discovered

multiple hamartomas located on

her iris.

Upon examination, multiple

light brown macules and flesh

colored papules were noted on

her abdomen, chest and back.

Case 6

You suspect the child has Neurofibromatosis I due to the following findings: Café au lait macules, Axillary freckling, Neurofibromas and Lisch Nodules

• What radiologic finding is most diagnostic of NF-1?

• A) Ipsilateral hemiatrophy of an extremity

• B) Scoliosis

• C) Sphenoid Wing Dysplasia

• D) Polyostotic fibrous dysplasia

• E) Acro-Osteolysis

Case 6 – Neurofibromatosis-I

• Answer C – Sphenoid Wing Dysplasia Other Skeletal Findings – Macrocephaly, Scoliosis, Pseudoarthrosis of tibia, Short stature

NIH Consensus Criteria for Diagnosis of NF-1 (>2)

• > 6 CALMs

• >5 mm in pre-pubertal individuals OR >15 mm in post-pubertal

• > 2 Neurofibromas of any type OR one Plexiform neurofibroma

• Freckling in the axillary or inguinal regions

• Optic glioma

• > 2 Lisch nodules

• A distinctive osseous lesion (Ex: Sphenoid dysplasia)

• A first-degree relative with NF-1

Case 7

• A 9 year old boy with atypical gait presents for evaluation of his abnormal nails.

Case 7 Upon further examining you

notice, hyperpigmentation of

the pupillary margin of the iris

&

A flattened appearance of the

knee, which prompts you to

order radiographic imaging.

182

Case 7 – X-ray of the Knee

• What is the suspected diagnosis?

• Nail Patella Syndrome

Case 7 – Nail Patella Syndrome

What other radiographic imaging studies should be ordered to complete the diagnostic work up?

• A) X-ray of the pelvis

• B) X-ray of the skull

• C) X-ray of the thorax

• D) X-ray of the distal extremities

Case 8 Case 8

Goltz Syndrome Focal Dermal Hypoplasia

• Inheritance – X-linked dominant, POCRN gene

• Clinical Features – FOCAL

• F - Female sex • O - Osteopathia striata • C – Coloboma • A - Absent ectodermis • L - Lobster claw deformity

• Work Up – Skeletal imaging and clinical findings

• Prognosis – May be severely handicapped by skeletal and

cosmetic deformities from the skin, eyes, teeth, etc. •

Thank You!

183

References

184

Furuncular Myiasis in Ohio: A Case Report

Alma AcMoody, DO, PGY-6, 3rd-year Dermatology Resident Schield M. Wikas, DO, DF, FAOCD, Dermatology Residency Program Director

Summa Western Reserve Hospital, Cuyahoga Falls, OH

65 year-old Caucasian male

• Tender red nodule • Central chest

2

History of Present Illness

Lesion first appeared 3-4 weeks prior Review of Systems: Positive for:

painful, pruritic, non-healing lesion

Denies: Any preceding trauma to the area Any travel outside of Ohio in the past 12 months Any contact with known infected people or animals Fever, chills, or previous history of similar symptoms

PCP treated with oral antibiotics, which had no impact on the lesion

3

History & Physical Exam

History Lives in rural Ohio Past Medical and

Surgical History is unremarkable

Medications: None Allergies: NKDA

Physical Exam Firm, erythematous,

subcutaneous nodule On central upper chest No lymphadenopathy Laboratory Workup CBC wnl Skin biopsy done Pt denied further testing

4

History of Present Illness

3 days prior to evaluation The patient admits to manually extracting an

organism from the nodule Has brought the contents with him

5

Contents of Extraction

6

• Well preserved larva

• Pathology confirmed: Cuterebra species

185

Cuterebra Larva: Histopathology

7

•Thick chitinous cuticle

Cuterebra Larva: Histopathology

8

• Widely spaced spines

• Larva confirmed by pathology as Cuterebra species

Skin Biopsy

9

• Central cystic follicular invagination

Skin Biopsy

10

• Dense mixed dermal inflammatory infiltrate

• Numerous eosinophils

Final Diagnosis

Endemic Furuncular Myiasis caused by Cuterebra species

11

Myiasis

Infestation of human skin by larva of certain fly species. Cases endemic to the US are rare Most domestic cases are seen in travelers returning

from tropical and subtropical destinations. Risk Factors:

Summer season (higher risk August-October) Contact with infected hosts or animals Travel to an endemic area Sleeping outdoors Poor hygiene ** Alcoholics and homeless people have higher risk.

12

186

Myiasis

3 forms of cutaneous myiasis: 1. Furuncular: larva burrow directly into the dermis (most common) 2. Wound: Larva infestation in open wounds. 3. Migratory: Human infestation from infected animals

Furuncular myiasis Boil-like lesions with central punctum Serosanguinous discharge Painful and pruritic

Systemic manifestations can include: Fever and regional lymphadenopathy Blood workup can show leukocytosis and eosinophilia

13

Treatment Options

Occlusion Deprives the larva of oxygen May kill the larva Induces it to move upward in search of air

Manual Removal Surgical excision Manual pressure to squeeze out the larva

Antiparasitics Ivermectin

Our patient had complete resolution with oral

Ivermectin 18mg 14

Conclusion

Consider cutaneous myiasis: Non-healing pruritic nodules with a central opening Patient feels movement or sees something in the lesion When presumed bacterial infections do not respond to

antibiotic therapy. High risk patients: poor hygiene, sleeping outdoors Patients with recent travel to tropical and sub-tropical

locations

15

References

1. McGraw TA et al. Cutaneous Myiasis. JAAD 2008; 58:907-926. 2. Baird JK et al. North American Cuterebrid Myiasis. JAAD 1989; 21:763. 3. Plotinsky RN et al. Short report: Cuterebra Cutaneous Myiasis, New

Hampshire, 2004. Am J Trop Med Hyg 2007; 76:596-597. 4. Helm TN et al. Furuncular Myiasis: A Case Report. Cutis 2010; 86: 85-86.

16

Questions and Comments.

Thank you for your attention.

17

187

Case Review Multiple Keratoacanthomas and

Squamous Cell Carcinomas: A new variant of Multiple Eruptive

Keratoacanthomas

By Keith Robinson DO Jennifer Popovsky MD, Shield Wikas DO

Keratoacanthoma

Commonly occurs on elderly fair skinned individuals

Presents as a solitary lesion on the face, scalp, arms and dorsal hands

The lesion is know for a rapid exophitic growth pattern

In some cases up to 2.5cm in as little as 3 wks

Keratoacanthoma Classic clinical

presentation Large solitary

exophitic annular lesion

Keratinous center Slightly

erythematous margin

Photo courtesy of dermnetnz.org

KA Characteristics

In some cases the lesions spontaneously regress

There is no definitive timeline for complete regression to occur

Concern arises due to lesions which possess a histologic resemblance to squamous cell carcinoma (SCC)

KA and SCC H&E KA Treatment options

Solitary lesions are viewed as low grade SCC and are typically excised

Other options Methotrexate

injections PDT

188

Multi/Eruptive Keratoacanthomas

Three variants currently discussed in the literature

Each has a subtle variance in size, distribution, and inheritance pattern

I. Grzybowski II. Ferguson Smith III. Witten & Zak

Grzybowski Variant

Noted for its smaller more numerous lesions

Patients may develop thousands of pruritic small 2 to 7mm flesh colored papules

Lesions resemble milia and are commonly found on the palms, soles, and mucosal membranes

Has the tendency to regress spontaneously

Grzybowki Variant

No known etiology for this particular variant of multiple eruptive keratoacanthomas

Courtesy of dermnetnz.org

Ferguson Smith Also know as multiple self-healing

squamous epithilioma Noted for larger less numerous lesions

typically found on sun exposed skin and sites of trauma

Lesions have been known to grow upwards of 3cm in diameter

Autosomal dominant inheritance pattern, which typically develops in adolescence

Ferguson Smith

Genetic defect is located on a region of the 9q22 chromosome.

High through-put sequencing identified, 11 distinct mutations in the transforming growth factor beta receptor 1 gene (TGFβR1)

Identified in 18 predominantly Scottish kindreds [1]

Ferguson Smith

Typically the lesions spontaneously resolve in two to three weeks on average

189

Witten & Zak

Display both larger and miliary-type lesions with associated ulcerative and destructive tumors [2]

Case Review

54 year old healthy female developed multiple KAs on her lower extremities as well as a her upper extremities

Multiple lesions developed over six months

No family history Significant history of sunbathing

Past Medical History

Asthma/Allergies Depression

Medications

Prednisone intermittent Inhaled Corticosteroids Montelukast Anithistamines

Initial Presentation

October 2010

Location: Right calf Pathology results: Invasive SCC Treatment: Complete excision with clear

margins E&M: Primary dermatologist

Erupting Lesions March 2011

Lesions: 2 right shin Pathology results: SCC Treatment: Simple excision

Complications Delayed healing with the development of new

lesions around the excision site which clinically appeared to be KAs

Surgical treatment

June of 2011 Pt referred to a plastic surgeon due to

increased lesion size New lesions were diagnosed as invasive SCC Split thickness grafts harvested from the

thighs and placed on the shins. Grafts healed well, however the pt continued

to develop new lesions in close proximity

190

Mohs Evaluation July 2011

Patient referred to Mohs surgeon for further evaluation and new treatment options

Biopsies

September 2011 Three biopsies obtained from the left upper

arm and the L & R shins. Left shin and shoulder biopsies diagnosed as

keratoancanthomas Right shin biopsy diagnosed as a well differentiated SCC

Treatment options

October 2011 Photo Dynamic Therapy (PDT) with ALA &

24hr incubation Intralesional Methotrexate Excision Patient elected to undergo PDT

PDT Treatment Procedure

Ten lesions ED&C ALA applied in office to

the individual lesions 24hr incubation Lidocaine injected at

each site Blue light performed

PDT

Follow up after Blue light therapy Two days later pt experienced decreased

pruritis 2 weeks after initial treatment pruritis

returned with increased tenderness and pain No clinically significant change in the lesions

size

Invasive SCC pre-op

191

Invasive SCC excision

December 2011 Mohs resection of SCC

on R shin due to poor response to PDT

Invasive SCC post-op

12 wk follow up after excision of SCC and graft placement

Intralesional Methotrexate

February 2012 Baseline CBC, CMP, and LFTs obtained Intralesional methotrexate injections started Initial treatment 2cc of 12.5mg/cc solution

totaling 25mg Methotrexate was injected equally into 5

lesions

Methotrexate treatment

2 week Follow up No appreciable change in lesion size Patient did complain of mild nausea which

was relieved with famotidine Due to the nausea and increased fatigue,

methotrexate was not administered Labs were rechecked.

Methotrexate treatment

March 2012 Follow up Labs obtained were determined to be normal 4wks s/p injections subjective improvement

noted Injections were continued q2wks

Treatment Results

June 2012 Significant

improvement noted after 12wks

Complete resolution of some lesions and regression of others

192

Recalcitrant Lesions Conclusion Patient presented with a more aggressive variant

than currently documented Surgical mgmt not the best option due to

multiple lesions and koebnerization phenomenon

Literature recommends non surgical approach for multiple KAs due to defects leading to substantial cosmetic and functional defects [2]

PDT treatment not effective

Conclusion Methotrexate intralesional injections most

reasonable in this case Suggested dose 12.5 to 25mg/ml injected in

solitary lesions q2wks avg 1 to 4 injection [3]

Debulking recommended prior to injecting for optimal results [4]

References 1. Goudie DR, Yuille MA, Leversha MA, et al. Multiple self-healing squamous epitheliomata

(ESS1) mapped to chromosome 9q22-q31 in families with common ancestry. Nat Genet. 1993;3:165-169

2. Consigli JE, et al. Generalized eruptive keratoacanthoma (Grzybowki variant). Br J Dermatol 2000; 142: 800.

3. Annest NM, VanBeek MJ, Arpey CJ, Whitaker DC. Intralesional methotrexate treatment for keratoacanthoma tumors: a retrospective study and review of the literature. J Am Acad

Dermatol. Jun 2007;56(6):989-93. 4. Sanders S, Busam KJ, Halpern AC, Nehal KS. Intralesional corticosteroid treatment of multiple

eruptive keratoacanthomas: case report and review of a controversial therapy. Dermatol Surg. Oct 2002;28(10):954-58

193

Treatment if anal dysplasia with infrared coagulation

Stephen Weis, DO Joseph Susa, DO

S. Robert Harla, DO, FAOCD UNTHSC

Presentation Outline

Anal cancer and anal HPV epidemiology Discuss how to screen for anal cancer Demonstrate the appearance of the anal

canal during high resolution anoscopy and during infrared coagulation

Outcome of treatment program in HIV clinic

HPV- related anogenital disease Condylomata High-grade squamous dysplasia Bowen disease of perineum, perianal area,

and vulva Invasive squamous cell carcinoma-field HPV-related anogenital disease tends to be

more prevalent in HIV-infected persons, more advanced at diagnosis, and more recalcitrant to standard therapies

HIV Care

As a result of the benefits of HAART, there are now more people in the United States living with HIV infection than ever before.[18] Our expanded expertise in treating HIV infection and its complications has shifted the spectrum of diseases in HIV-infected persons

Incidence of anal cancer /100,000

1.061.26

1.61.39

1.691.84

2.042.06

0

0.5

1

1.5

2

2.5

1973-79 1980-86 1987-1993 1994-2000

MenWomen

Daling JR. Cancer 101:281-8; 2004

Incidence of anal cancer

Anal Cancer Population: 2/100,000 Anal Cancer MSM: 35/100,000 Anal cancer MSM + HIV: 70-90/100,000 Cervical Cancer before 40-50/100,000 Cervical cancer currently 8/100,000

Daling JR. NEJM 317:973-7; 1987 Goedert JJ. Lancet 351:1833-9;1998 Daling JR. Cancer 101:281-8; 2004 Bower et al. JAIDS 2004;37:1563-1565

194

HPV is double stranded DNA virus (>100 subtypes)

Oncogenic HPV types- Cause Cancer 16, 18, 31, 33, 35 39, 45, 51, 52, 56, 58, 70 Non-Oncogenic HPV Types-Cause warts 6, 11, 42, 43, 44

Veruca Vulgaris HPV types 2, 4

Anogenital Cancer HPV types 16,18 Potential Cofactors for HPV

Progression Infections: Chlamydia, HSV-2 coinfection Diet: Vitamins A, C, E, folic acid Hormonal: Parity, oral contraceptive use Immunogenetics: HLA type Smoking Host factors: Immune response (HIV) HPV related: Type, variants, viral load

Pinto AP. Natural History of Cervical Neoplasia. Clinic Obster Gyncol 2000;43:352-362

Ryan D et al. N Engl J Med 2000;342:792-800

Anatomy of the Anus Cervical cancer as model for Anal Cancer

Cervical and Anal Cancer frequently arise in transformation zone where columnar epithelium changes to squamous

Both strongly associated with oncogenic HPV strains Both associated with squamous intraepithelial

lesions after HPV infections (SIL) Cervical HSIL Cervical CA Anal HSIL are suspected Anal CA

Frisch M et al, NEJM, 1997;337:1350-8. Palefsky Joel. Multiple publications

195

Anal HPV infection in MSM Palefsky JM. JID 1998;177;361-7.

61%

93%

29%

80%

19%

38%

23%

73%

0%10%20%

30%40%50%60%70%

80%90%

100%

HPV + OncogenicHPV

Other HPV Multiple HPV

HIV NegativeHIV Positve

N=346 HIV positive, 262 HIV negative (strains1.9-3.4)

Anogenital HPV Women Palefsky JM. 1998;177;361-7.

42%

27%

68%

26%

77%

56%

83%

64%

0%10%20%30%40%50%60%70%80%90%

HIV- HIV+ CD4>500

HIV+ CD4200-500

HIV+ CD4<200

AnalCervical

89%

84%

94%

80%

70%

75%

80%

85%

90%

95%

BaselineExam

Month 12Exam

HPV-AnusHPV-Cervix

Anal HPV infection HIV infected Females

Kojic EM. Study to Understand the Natural History of HIV/AIDS (SUN) IDSA 2007.

Anal HPV infection HIV infected Females

Kojic EM. Study to Understand the Natural History of HIV/AIDS (SUN) IDSA 2007

86%

89%

50%

86%

0%10%20%30%40%50%60%70%80%90%

Baselineevaluation

12 monthevaluation

Women who haveanal sexOther women

P = NS N=682

U.S. HIV Population 50 years and Older

115,871

101,470

88,463

76,850

65,445

0 50,000 100,000 150,000

'05

'04

'03

'02

'01

CDC data from 33 reporting states. Persons over 50 now account for> 25% of all cases

As a result of high prevalence of perianal HPV disease and 3 cases of anal cancer (2 ultimately fatal) the Preventive Medicine Clinic applied for a grant from planning council in 2005.

We instituted anal dysplasia screening and treatment program March 1, 2006.

196

Protocol for Screening Anal Cytology Screening

Two first year then repeat Every 12 months

AIN 1

Follow-up Every 12 months

AIN 2 or 3

Treat

No Lesion Seen

High Resolution Anoscopy with Biopsy

Normal ASCUS HSIL LSIL Anal Lesion

Screening for anal cancer-inspection

Polyester Not Cotton Liquid Based Thin Prep Solution

Cytology results

Normal Atypical squamous cells of uncertain

significance (ASCUS) Low-grade squamous intraepithelial lesion

(LSIL) High-grade squamous intraepithelial lesion

(HSIL)

Anoscope/Colposcope for HRA

197

Anal Biopsy AIN-1

AIN-1 AIN-3

Relatively normal transformation zone High Grade dysplasia 16X

198

High Grade dysplasia 16X

Weis, SE. et al Dis Colon Rec 2012. In press

HGAIN that was treated infrared

coagulation (N=98)

74% no HGAIN (High Grade) detectable on biopsy

26% still had HGAIN None had cancer After additional IRC treatment 87% had no HGAIN detectable on biopsy

Weis, SE et al Dis Colon Rec 2012. In press

High Grade AIN (HGAIN)

Not Treated (N=42)

5 % (N=2) no HGAIN detectable on biopsy 88% (N=38) still had HGAIN 5% (N=2) had developed anal cancer

Weis, SE et al Dis Colon Rec 2012. In press

History of “Asymptomatic” after procedure

Sits on stool 5 times a day. With Loperamide goes same number of times but is stool is harder. Feels like he needs to go frequently often only passes gas. Has had for several years. Thinks multiple stools a day is “normal” for people with HIV!

Has anal pain for 2 years. Comes and goes. Believes it is “just a hemorrhoid”. Uses preparation H chronically.

Sometimes has bleeding after anal sex.

History after procedure “Plenty of itching” in anal canal. Scratches

inside anal canal with fingernails. Has “normal anal sex only.” Never used

dildos or did fisting. Does not recall any particular sexual

episode that was unusually painful. No history of herpes, syphilis, or warts. He

was certain his problem was only hemorrhoids.

199

“Asymptomatic” male

2 biopsies of large anal wart biopsies both showed AIN-2

3 biopsies borders of anal ulceration-AIN 2 Biopsy of base shows “nonspecific

ulceration”. No evidence of herpes or CMV with special stains

“Asymptomatic” male

Had bleeding and some pain for 5 days after procedure.

Went to work every day. Now is truly an “Asymptomatic male”

Anus is skin. High grade anal dysplasia is histologically squamous cell cancer in situ Anal cytology is similar in cost and takes the

same amount of time as a full body skin exam High resolution anoscopy is another way to

take a skin biopsy. Infrared coagulation of high grade dysplasia is

similar procedure to electrodessication and curettage of SCC-IS

It is low morbidity, low cost outpatient procedure.

What clinicians do • These data do not exist for most situations • There are not expert guidelines for every situations • What do clinicians do when they have an evolving

problem and there is no data? • That’s why we go to medical school, do residencies

and fellowships. Not just to become technically proficient but to be able to be flexible and work with our patients to create solutions for problems with the best with the available information.

• That is why they call it medical practice and is one of the reasons that we come together in journal clubs to share ideas and opinions to help us deal with indecision tomorrow in our exam rooms.

200

I Blame the Drugs PAUL AANDERUD, DO

Oakwood Hospital Healthcare System, Trenton, Michigan

Drug Adverse Reactions

• Common occurrence

• Variable morphology – Urticarial – Morbilliform – Hypersensitivity syndrome – Lichenoid dermatitis – Vasculitis – Fixed drug eruption (FDE) – Many more

Fixed drug Eruptions

• Underdiagnosed

– We now believe Fixed Drug Eruptions account for 20% of all cutaneous drug eruptions

• Polypharmacy makes diagnosis difficult

– The average patient is taking multiple drugs and over the counter supplements

Pathophysiology • Thought to be caused by an antibody-dependent, cell-

mediated cytotoxic response • CD8+ effector/memory T cells play an important role in

reactivation of lesions with re-exposure to the offending drug

• The offending drug is thought to function as a hapten that preferentially binds to basal keratinocytes, leading to an inflammatory response

• Cytokines such as TNF-alpha up-regulates intercellular adhesion molecule-1 (ICAM1) and this in turn helps T cells migrate to the site of injury. TNF-alpha and INF-gamma continue tissue destruction

Fixed drug Eruptions

• Multiple Types of FDE mentioned in the literature – Pigmenting fixed drug eruption – Generalized or multiple fixed drug eruption – Linear fixed drug eruption – Wandering fixed drug eruption – Nonpigmenting fixed drug eruption – Bullous fixed drug eruption – Eczematous fixed drug eruption – Urticarial fixed drug eruption – Erythema dyschromicum perstans–like fixed drug

eruption – Psoriasiform – Cellulitislike eruption

Unique Case

• Chief Complaint

A 22-year-old African American female

presented to the emergency department with complaints of chills, fever, nausea, myalgia, arthralgia, and a tender rash on the hands for 2 weeks

201

Unique Case

• History of Present Illness She also noticed a sore throat and an

occasional non-productive cough which she attributed to a recent viral infection. During her illness, a rash developed on her extremities

She has a known allergy to Penicillin with rash

formation on her abdomen

Unique Case

• Past Medical / Family History

The patient’s past medical history was

significant for asthma, GERD, osteoarthritis, avascular necrosis of the left hip, a cerebrovascular accident in 2006 with residual left-sided weakness, depression, anxiety, and systemic lupus erythematosus.

Unique Case

• Physical Examination Multiple erythematous-to-purple plaques were

present on the chest and upper extremities. Some lesions had fine wrinkling at the center

In addition the patient had tender hemorrhagic veiscles on her fingers

Unique Case

Unique Case Histopathology • Two punch biopsies revealed a vacuolar

interface dermatitis with necrotic keratinocytes.

• A superficial dermal lymphocytic infiltrate and eosinophils were present. Pigment incontinence was seen in the papillary dermis.

• A gram stain was negative.

202

Histopathology Labs

• Laboratory work showed

– ANA titer of >640 – a non-reactive HIV ELISA – low complement levels (C4 and C3)

– Blood cultures revealed gram negative

diplococci.

Course and Therapy

• The patient initially received IV methylprednisolone, hydroxychloroquine, and azathioprine to address her alleged systemic lupus exacerbation.

• Also, she was treated with ceftriaxone and azithromycin for suspected sepsis.

• After dermatologic consultation, the antibiotic coverage was switched to spectinomycin due to the suspected a cephalosporin allergy.

Comorbidities

• Gonoccocemia

• Tenosynovitis

• Lupus induced membranous glomerulonephritis

Gonoccocemia

Clinical triad of dermatitis, tenosynovitis, and migratory polyarthritis

Lesions begin as painless, nonpruritic, tiny, red papules or

petechiae that either disappear or evolve through vesicular or pustular stages, and ultimately become hemorrhagic

Upper extremity joints, especially the wrists, are most

commonly involved. Our patient had diffuse tenosynovitis and arthritis of both her ankles and wrists

Fixed Drug Eruption

Our patient had an allergy to penicillin. The patient received IV Rocephin as treatment of her

Gonoccocemia Cross reactivity between cephalosporins in penicillin-

allergic patients is well known and occurs roughly 10% of the time.

203

EM vs Fixed Drug

Only one case report of an erythema multiforme-like eruption induced by gonococcemia

Lesions look similar clinically Histopathological diagnosis can be difficult as well.

Both show vacuolar interface changes with lymphocytes. Pigment incontinence and eosinophils help for FDE.

Fixed Drug Eruption

History guides the practitioner in making the

diagnosis

Fixed Drug Eruption

Fixed drug eruptions (FDE) are known to arise from a variety of medications

The most common are analgesics,

anticonvulsants, and antibiotics. Among antibiotics, TMP-SMX, Penicillin, and

Tetracycline are most common.

Fixed Drug Eruption

Begins with a sharply demarcated oval or circinate macule

Less commonly, a FDE appear as plaques, bullae, or

erosions. Each eruption may form solitary or multiple lesions,

which typically appear within hours to days after ingestion of the drug. The lesions initially are small and solitary, but may become quite large and numerous.

Fixed Drug Eruption

Most initial eruptions are localized; recurrent eruptions localize to the same region after re-challenge with the drug

The lesions can also be generalized or random.

Lesions persist as long as the drug challenge exists and tend to resolve with scaling and hyperpigmentation.

Fixed Drug Eruption

Provocation test is the only reliable method to

confirm the causative drug

204

Clinical Scenarios

• This rash occurs

when I play tennis.

Clinical Scenarios

• The patient takes

Aleve before her tennis match

Clinical Scenarios

• I get this lesion in my mouth whenever I have a Urinary tract Infection

Clinical Scenarios

• The patient was given TMP-SMX by her PCP for UTI

Clinical Scenarios

• The patient is

currently not taking any medications or supplements

Clinical Scenarios

• Upon further

questioning the patient was found to be eating Cashews regularly.

• Provocation test was positive

205

Clinical Scenarios

• I look like this

whenever I get constipated

Clinical Scenarios

• The patient has been

taking the laxative Phenolphthalein

Clinical Scenarios

• The patient develops

this bullous rash whenever he handles bees. He is adamant he is not being stung and is an experienced bee handler

Clinical Scenarios

• The patient was found to react with Propolis. Propolis is a resinous mixture that honey bees collect from tree buds, or other botanical sources. It is used as a sealant for open spaces in the hive. It is also used in OTC supplements

Conclusion

• Fixed Drug Reactions are common

• A careful history is necessary for the diagnosis

References • 1. Roustan G, Salas C, Barbadillo E, et al. Lupus erythematosus with an erythema multiforme-like

eruption. European Journal of Dermatology, September 2000;10(6):459-62 • 2. Wheeler JK, Heffron WA, Williams RC. Migratory arthralgias and cutaneous lesions as confusing

initial manifestations of gonorrhea. American Journal of the Medical Sciences, Sept. 1970;260(3):150-159

• 3. Mahendran, SM. Disseminated gonococcal infection presenting as cutaneous lesions in pregnancy. Journal of Obstetrics and Gynaecology, August 2007;27(6):617-631

• 4. Hager JL, Mir M, Hsu S. Fluoroquinolone-induced generalized fixed drug eruption. Dermatology Online Journal 15 (12): 8

• 5. Ozkaya E. Fixed drug eruption: state of the art. J Dtsch Dermatol Ges. Nov 2008; 6: 181-188. • 6. Shiohara T, Mizukawa Y: Fixed Drug Eruption: Easily Overlooked but Needing New Respect.

Dermatology 2002;205:103-104. • 7. Bandino JP, Wohltmann WE, Bray DW, Hoover AZ. Naproxen-induced generalized bullous fixed drug

eruption. Dermatology Online Journal 15 (11): 4 • 8. Fukushima S, Kidou M, Ihn H. Fixed Food Eruption Caused by • Cashew Nut. Allergology International. 2008;57:285-287 • 9. Fixed Drug Eruption to Ingested Propolis. Dermatitis, 2012 Jul;23(4):173-5.

206

Arbor Cutis: Hyperkeratotic Plaque Secondary to

the use of Imiquimod

Peter Knabel D.O. Northeast Regional Medical Center

Kirksville, Mo 2012

Arbor Cutis: Hyperkeratotic Plaque Secondary to

the use of Imiquimod

Peter Knabel D.O. Northeast Regional Medical Center

Kirksville, Mo 2012

Case Presentation

• 81-year-old Caucasian female – Presented for routine examination – Past Medical History:

• Nonmelanoma skin caner • Actinic Kerasotes

Physical Examination

• Patient was noted to have a hyperkeratotic papule on the right forearm

• Diffuse actinic damage involving the bilateral forearms and face

Plan

• Shave biopsy of the lesion on the right forearm – Deferential diagnosis:

• Squamous cell carcinoma vs. Actinic Keratosis

• Pathology: – Invasive, well differentiated Squamous Cell

Carcinoma with margins involved

207

Plan • Patient was scheduled for wide excision and

specimen was submitted for histologic evaluation – Pathology:

• Scar with residual squamous cell carcinoma in situ involving the lateral margins

Plan • Further therapy was discussed with the patient

including – Surgical therapy – Electrodessication and curettage – Topical therapy: imiquimod

• Plan: Topical imiquimod therapy – Allow the surgical wound to heal for 4 weeks prior to

starting imiquimod – To be applied 5 days a week for 6 weeks to the well healed

surgical site (approximately 0.5-1cm to either side of the wound).

– Follow up in 8 weeks

8 Week Follow Up 2 weeks status post imiquimod

208

Plan

• Prescription for mupirocin ointment to be applied twice daily and keep the area covered

• Follow up 1 week

1 Week Follow Up (status post imiquimod 3 weeks)

3 Weeks Follow Up

Plan

• Continue Vaseline ointment daily • Follow up 1 month

209

1 Month Follow Up

Plan

• Prescription for triamcinolone 0.1% ointment to apply twice daily to the affected areas on the right forearm

• Follow up in 3 month

3 Month Follow Up

Discussion

• Imiquimod – Aldara 5% – Zyclara 2.5%, 3.75% – Belongs to the class of imidazoquinolones – FDA approved for:

• Superficial Basal Cell Carcinoma • Actinic Keratoses • Condyloma Accuminata

– Half-life 1 day – Immune response modifier

210

The Immune System

• The human immune system consists of two components that function synergistically – Innate Immune System – Acquired Immune System

• Humoral • Cellular

The Innate Immune System

• Frist line defense against pathogens • Physical and chemical barriers

– Skin – Cellular barriers – phagocytes – Molecular pattern based reactions

• Toll-like receptors – Activate phagocytes and tissue dendritic cells in response to

pathogens – Facilitates initiation of the acquired immune response – Toll-like receptor 7 specific to imiquimod

• Interferon • Complement

The Innate Immune System

• Specialized cells – produce cytokines – Leukocytes – Granular Cells

• Basophils, Mast cells, Eosinophils, and Neutrophils

– Monocytes – Macrophages

• Natural Killer Cells

The Acquired Immune System • Unique to vertebrates • Composed of the Humoral and Cellular responses • Humoral – B cell mediated

– Antibodies – Immunoglobulins

• Cellular (cell mediated response) – T cell medicated process – T cell types:

• CD4+ – helper T cells • CD8+ – cytotoxic T cells

– T cells • Cooperate with B cells to enhance production of antibodies • Release cytokines – activate and signal B cells • Monocytes/macrophage migration and activation • Cytotoxic effects

Imiquimod

• Activates (Innate) – Monocytes, macrophages, and dendritic cells

• Via binding to Toll-Like Receptor 7 – Secretion of pro-inflammatory cytokines

• Interferon alpha (IFN-α) • Tumor necrosis factor alpha (TNF- α) • Interleukin-12 (IL-12)

– Cytokines • Interleukins 1, 6, 8, and 10 • Favors a Th-1 response

Imiquimod • Activation of T-helper cells

– Th-1 • Interferon-gamma (INF-ɣ)

– Stimulates cellular immunity – Inhibits Th-2 type cytokines

• Stimulates cytotoxic T lymphocytes • Activation of Langerhans cells

– Major antigen presenting cells within the epidermis – Activation of T cells

• Antiangiogenesis – Increased levels of IL-10 and IL-12 – Mediates production of INF-ɣ

211

Imiquimod

• Enhanced cell-mediated immunity – Long term protection – Prolonged tumor clearance via the adaptive

immunity to recognize carcinogenic antigens – Field Effect

Side Effects

• Local cutaneous reactions – Erythema, inflammation, flaking, pruritus, pain,

edema, erosions, ulcerations, vesicles, desquamation, drainage, hypo/hyperpigmentation, and scabbing or crusting

• Systemic reactions – Headache, fatigue, myalgia, nausea, and influenza-like

symptoms • Rarer reactions

– Vitiligo-like depigmentation, erythema multiforme, alopecia, pemphigus foliaceus, psoriasis, and a lupus erythematosus-like reaction

Inflammation

• Severity of the reaction – Better results?

• Caution

– Topical Steroids

Clearance Rates

• No one recommended treatment – Strength (2.5%, 3.75% or 5%) – Duration (weeks) – Dosing (twice daily, daily, 5 days a week, 3 days a

weeks) – Occlusion

Clearance Rates

• Actinic Keratoses: 25%-85% • Squamous Cell Carcinoma In-situ: 73-88% • Superficial Basal Cell Carcinoma: 50-100% • Nodular Basal Cell Carcinoma: 50-100% • Lentigo maligna: 66-100%

• Surgical Excision remains gold standard

Conclusion • Surgery is still considered the Gold Standard for treatment of

cutaneous carcinomas • Imiquimod

– Surgery is not an option… • Location • Disfiguring/cosmesis • Size of lesion • Age of patient

• Close follow-up is necessary – No histologic proof of clearance – Field biopsies

• Potential skip areas • Affective • Accurate

• Ant-aging affect

212

Conclusion

Thank you

References 1. David CV, Nguyen H, Goldenbery G. Imiquimod: A Review of Off Label Clinical Applications. J of Drugs in Dermatology 2011; 10: 1300-1306 2. Garland SM. Imiquimod. Infectious Diseases 2003; 16: 85-89 3. Desai T, Chen CL, Desai A, Kirby W. Basic Pharmacology of Topical Imiquimod, 5-Fluorouracil, and Diclofenac for the Dermatologic Surgeon. Dermatol Surg 2012; 38:97-103. 4. Urosevic M, Dummer R. Role of Imiquimod in Skin Cancer Treatment. Am J Clin Dermatology 2004; 5(6): 453-458. 5. Trying S, Conant M, Marini M, et al. Imiquimod; an international update on therapeutic uses in dermatology. International Journal of Dermatology 2002; 41: 810-816 6. Amini S, Viera MH, Valins W, et al. Nonsurgical Innovations in the Treatment of Nonmelanoma Skin Cancer. J of Clinical and Aesthetic Dermatology 2010; 3(6): 20-34. 7. Ridky TW. Nonmelanoma Skin Cancer. J Am Acad Dermatology 2007; 57: 484-501. 8. Hanke CW, Beer KR, Stockfleth E, et al. Imiquimod 2.5% and 3.75% for the treatment of actinic keratosis: Results of two placebo-controlled studies of daily application to the face and

balding scalp for two 3 week cycles. J Am Acad Dermatology 2010; 62: 573-581. 9. Zeichner JA, Stern DWK, Uliasz A, et al. Placebo-controlled, double blind, randomized pilot study of imiquimod 5% cream applied once per week for 6 months for the treatment of

actinic keratosis. J Am Acad Dermatology 2009; 60: 59-62 10. Wagstaff AJ, Perry CM. Topical Imiquimod: A review of its uses in the management of anogenital warts, actinic keratosis, basal cell carcinoma and other skin lesions. Drugs 2007; 15:

2187-2210 11. Shimizu I, Cruz A, Chang KH, et al. Treatment of Squamous Cell Carcinoma in Situ: A Review. Dermatol Surg 2011; 37: 1394-1411. 12. Patel GK, Goodwin R, Chawla M, et al. Imiquimod 5% cream monotherapy for cutaneous squamous cell carcinoma in situ (Bowen’s disease): A randomized, double-blind, placebo-

controlled trial. J Am Acad Dermatol 2006 Jun; 54(6): 1025-32. 13. Eigentler RK, Kamin A, Weide BM, et al. A phase III, randomized, open label study to evaluate the safety and efficacy of imiquimod 5% cream applied thrice weekly for 8 and 12 weeks

in the treatment of low risk nodular basal cell carcinoma. J Am Acad Dermatol 2007 Oct; 57(4); 616-621. 14. Lacarrubba F, Nasca MR, Micali G. Advances in the use of topical imiquimod to treat dermatologic disorders. Therapeutics and Clinical Risk Management 2008; 4(1): 87-97 15. Raasch B. Management of superficial basal cell carcinoma: a focus on imiquimod. Clinical, Cosmetic, and Investigational Dermatology 2009; 2: 65-75. 16. Junkins-Hopkins JM. Imiquimod use in the treatment of lentigo maligna. Dialogues in Dermatology. J Am Acad Dermatology 2009 Nov; 61(5): 865-867. 17. Woodmansee CS, McCall MW. Recurrence of Lentigo Maligna and Development of Invasive Melanoma after Treatment of Lentigo Maligna with Imiquimod. Dermatol Surg 2009; 35:

1286-1289. 18. Nagore E, et al. Imiquimod para el tratamiento del lentigo maligna. Actas Dermosifiliogr 2011; 102: 559-62. 19. Sriprakash K, Godbolt A. Vitiligo-like depigmentation induced by imiquimod treatment of superficial basal cell carcinoma. Australasian Journal of Dermatology 2009; 50: 211-213. 20. Garcia-Apra M, Rodriquez-Vazquez M, et al. Erythema Multiforme Due to 5% imiquimod cream. Actas Dermosifiliogr 2010; 101(6): 551-571. 21. Conde J, David K, Ntuen E, et al. A case of imiquimod-induced alopecia. Journal of Dermatological Treatment 2010; 21: 122-124. 22. Sebaratnam DF, Martin LK, Rubin AI, et al. Reversible relapse of pemphigus foliaceus triggered by topical imiquimod suggests that Toll-like receptor 7 inhibitors may be useful

treatments for pemphigus. Clinical and Experimental Dermatology 2010; 36: 91-100. 23. Patel U, Mark NM, Machler BC, et al. Imiquimod 5% cream induced psoriasis: a case report, summary of the literature and mechanism. British Association of Dermatologists 2011;

164: 665-683. 24. Rajan N, Langtry JAA. Generalized exacerbation of psoriasis associated with imiquimod cream treatment of superficial basal cell carcinomas. Clinical and Experimental Dermatology

2005; 31: 129-156. 25. Fanti PA, Dilca E, Vaccari S, et al. Generalized psoriasis induced by topical treatment of actinic keratosis with imiquimod. International Journal of Dermatology 2006; 45: 1464-1465. 26. Chan MP, Zimarowski MJ. Lupus Erythematosus-Like Reaction in Imiquimod – Treated Skin: A Report of 2 Cases. Am J Dermatopathol 2011 July; 33(5): 523-527. 27. Caperton C, Berman B. Safety, efficacy, and patient acceptability of imiquimod for topical treatment of actinic keratosis. Clinical, cosmetic, and Investigational Dermatology 2011; 4:

35-40.

213

Grace K. Kim D.O. Valley Hospital Medical Center

PGY IV

I have no disclosures

Indications for spironolactone therapy Expected response time Guidelines for laboratory monitoring Side effects of spironolactone therapy The origin of the black box warning

◦ Poor candidates for therapy Benefits of combination (i.e. antibiotics, oral

contraceptives) therapy

Aldosterone antagonist used as a potassium sparing diuretic

Anti-androgenic effects discovered when being used to treat hypertension in women with polycystic ovarian syndrome (PCOS)

Now used for women with hormonal pattern acne vulgaris (AV) and inhibits sebaceous activity

Off label: inflammatory, tender, deep seated papules, located on the lower half of the face and anterior lateral neck region.

↓5-alpha reductase activity via ↑clearance of testosterone

↑level of steroid hormone binding globulin (SHBG) ↓circulating free testosterone more bound

Overall ↑estrogenic state gynecomastia, decreased libido

Local action competing with dihydrotestosterone (DHT) for cutaneous androgen receptors and inhibit testosterone

Physiological effects ◦ androgenic alopecia,

hirsutism, excess sebum and acne vulgaris

Fig 1 C19 steroid metabolism

Changes observed in both ends of the spectrum of acne onset Acne is starting earlier…and starting later Acne is starting earlier…and hanging around longer

Definitions of Pediatric acne (birth to 11 years)* Neonatal acne Birth through 4 weeks of age Infantile acne 1 month through 12 months of age Mid-childhood acne >1 year through 6 years of age Preadolescent acne >7 years through 11 years of

age Adolescent acne 12 years to adulthood

Definitions of Post-adolescent acne in females#

Late-onset acne >age 25 years *Mancini A, et al. Semin Cutan Med Surg 2011;30:S2-S5. #Goulden V, et al. Br J Dermatol 1997;136:66-70; Cunliffe W, et al. Br Med J 1979;26:931-35; Goulden V, et al. J Am Acad Dermatol 1999;41:577-80.

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Fig .2 Infantile acne. Multpile papulopustules and inflammatory cysts on the cheeks. Courtesy of Kalman Watsky MD.

Fig .3 Acneiform eruption secondary to high dose dexamethasone. abrupt eruption of follicular papules and pustules on the trunk

Fig. 4 Senile comedones. Small or large comedones may appear around the eyes and temples in middle-aged and older individuals. Sunlight is a predisposing factor

Perc

enta

ge (%

) With

Acn

e Vu

lgar

is

8 *Collier CN, et al. The prevalence of acne in adults 20 years and older. J Am Acad Dermatol. 2008;58:56-59. Figure reproduced with permission from Mosby, Inc.

Women and men >20 years of age completed a questionnaire about their experiences with acne vulgaris as teenagers and adults

13.3% of women and 3.6% of men reported that their acne vulgaris worsened after their teenage years

9.8% of women and 3.8% of men reported that their acne was the same during and after their teenage years

Prevalence of Acne Vulgaris Reported by Age Group

Hormonal pattern AV: ◦ Inflammatory papules lower half of cheeks, jawline,

chin and lateral neck. Relative low number or absence of comedonal

lesions Cyclic exacerbation of AV lesions with

perimenstrual flares Sometimes not always associated with clinical

features of hyperandrogenism

Fig. 7 carring secondary to acne. A Pitted scarring of the face. B Anetoderma-like papular scars of the upper trunk. B, Courtesy of Jean L Bolognia MD

Fig. 6 Adult Acne: courtesy of AAD website

• Rosacea • Perioral dermatitis • Folliculitis–culture-negative (normal

flora), staphylococcal, Gram-negative, eosinophilic, Pityrosporum, Demodex • Acne/acneiform eruptions due to topical or

systemic corticosteroids anabolic steroids or other medications (e.g. lithium, EGFR inhibitors) • Pseudofolliculitis barbae, acne keloidalis

nuchae

Table 1. Potential Indications for Spironolactone in post-teenage female patients with AV Women with acne flares that cycle with menstruation

Women on oral contraceptives (OCP) with moderate-to-severe acne vulgaris (AV) especially with a “hormonal pattern”

Women not responding to conventional therapy and not wanting oral isotretinoin or are not candidates or oral isotretinoin

Women with late-onset AV or persistent recurrent AV past teenage years even with normal hormonal levels and no other clinical signs of hyperandrogenism Women with late-onset AV (acne tarda) or sudden onset of AV

Clinical signs of hyperandrogenism (hirsutism, androgenic alopecia, and/or increased sebum production with AV)

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Most common cause of excess circulating androgen levels ◦ Polycystic ovarian

syndrome and congenital adrenal hyperplasia (CAH)

Overall prevalence of PCOS is 3-6% with 23-35 exhibiting AV clinically ◦ 83% with severe AV

Present with infertility, menstrual irregularities (anovulation), hirsutism, and diabetes

Fig. 8 hirsutism

Fig. 9 U/S of polycystic ovaries

Laboratory Test Plasma Hormone Level (ng/dl)

Suspected Diagnosis

DHEAS** >8000 Adrenal tumor 4000-8000 Congenital Adrenal

Hyperplasia (CAH) >700 Androgen secreting

tumor Normal/slightly elevated

Polycystic ovarian syndrome (PCOS) Or Cushing syndrome

Total Testosterone >200 Ovarian androgen secreting tumor

100-200 PCOS, CAH, Cushing syndrome

*Lolis MS et al. Acne and systemic disease. Med Clin North Am. 2009;93(6):1161-1181 **DHEAS: dehydroepiandrosterone sulfate

Laboratory Test Plasma Hormone Level (ng/dl)

Suspected Diagnosis

Free Testosterone Normal to elevated Hyperandrogenism LH: FSH Ratio* >2:3 PCOS

Normal CAH, Adrenal tumor, Cushing syndrome, Androgen-secreting tumor

17-Hydroxyprosterone >200 Late-onset congenital adrenal hyperplasia

Normal/increased PCOS, Adrenal tumor, Cushing syndrome, Androgen-secreting tumor

*LH:FSH ratio: leutinizing hromone: follicle-stimulating hormone ratio

Spironolactone 25-200mg/day monotherapy or used with other topical or oral acne agents ◦ For facial and truncal acne

Lower doses at 50-100mg/day still decreased sebum production and decreases side effects

12 week randomized, placebo controlled study of spironolactone 50mg daily ◦ 24 of 34 patients clear of acne

lesions compared to placebo 2 of 31 patients (p<0.001)*

*Mansurul A, Maidul Islam AZM. Effect of spironolactone on acne vulgaris-adouble blind study. Bangladesh J Dermatol Venereol Leprol.2000;171:1-4

Fig. 10 response to oral spironolactone: a) before tx b) one month after tx c) three months after tx

*Yemisci A, et al. Effects and side-effects of spironolactone therapy in women with acne. JEADV (2005)19,163–166

Before treatment (mean ± SD)

After treatment (mean ± SD)

P-value

Number of lesions

Number of lesions 32.86 ± 16.15

6.92 ± 4.99 < 0.01

Total testosterone (normal 6–86 ng/mL)

63.68 ± 32.69 62.01 ± 29.41 > 0.05

DHEAS (normal 35–490 μg/dL)

434.4 ± 279.0 317.9 ± 174.8 < 0.05

*Yemisci A, et al. Effects and side-effects of spironolactone therapy in women with acne. JEADV (2005)19,163–166

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Eight year study 28.5 months (0.5-122 months)* ◦ Diuretic (29%), menstrual irregularities

(22%), breast tenderness (17%), none cause cessation of rx

◦ No breast CA observed Breast tumors in rodents (25-

250x dose) ◦ Benign adenomas (thyroid, testes),

malignant mammary tumors, proliferative lung changes

Black box warning 1975 ◦ Based on five case reports of women

that developed breast CA and were are other concurrent meds

*Shaw JC, Whit LE, Long-term safety of spironolactone in acne: results of an 8 year follow up study. J Cut Med and Surg. 2002;12:541-545

Controversial if it produces estrogen dependent malignancies

1,475 individuals after 3-7 years similar age specific rate of breast CA *

Five case controlled studies with no overall increase in relative risk for breast CA **

Data suggest no definitive documentation with Breast CA and spironolactone after more than 30 years

Avoid in patients with personal history of breast CA or first degree relatives ◦ Encourage age appropriate breast exams and

gynecological check ups *Friedman GD, Ury HK. Initial Screening for carcinogenicity of commonly used drugs. J Natl Cancer Inst. 1980;65:723-733 **Barker DJP. The epidemiological evidence relating to spironolactone and malignant disease in man. J Drug Dev. 1978 ( Suppl 1.2):22-25

Food and Drug Administration-Approved

Clinical Data Available to Support Use

Ethinylestradiol (EE) 20/30/35ug and norethindrone (NET) 1mg (Estrostrep)

Levonorgestrel 100ug and 20ug EE (Alesse)

EE 35ug and norgestimate 0.18/0.215/0.25 (Ortho Tri-Cyclen)

EE 35ug and cyproterone actate 2mg (Diane-35)**

EE 20 ug and drospirenone (DROSP) (YAZ)

EE 30ug and DROSP 3mg (Yasmin)

**Not available in the United States *Lolis MS, Bowe WP, Shalita AR. Acne and systemic disease. Med Clin North Am 2009;93(6):1161-1181

Timepoint DHEAS* Free Testosterone Pretreatment Yes Yes 1 month of treatment Optional if abnormal Optional if abnormal Every 3 months Yes if abnormal Yes if abnormal Last month of treatment

Yes if abnormal Yes if abnormal

Blood Pressure Serum Potassium Complete Blood Cell Count

Yes Yes Optional Yes Yes Optional Optional Optional Optional Yes Yes Optional

*DHEAS: dehydroepiandrosterone sulfate

Muscle weakness, cardiac irregularities, fatigue, paresthesia, bradycardia and shock

ACE inhibitors, ARBs, TMP-SMX, elderly, renal disease

Usually seen at doses at >100mg/day ◦ Cardiac and renal disease

Left ventricular dysfunction and spironolactone (n=134) *56 ◦ Hyperkalemia (17.1%), renal function deterioration

(14.5%), gynecomastia (5.3%) Randomized Aldactone Evaluation Study (RALES)

*57 ◦ 12.5 to 25mg with ACEI, loop diuretics, digoxin were

safe with potassium monitoring *Lopes RJ, Lourenco AP, Mascarenhas J et al. Safety of spironolactone use in ambulatory heart failure patients. Clin Cardiol. 2008;31(11):509-513. **The Rales investigators. Effectiveness of spironolactone added to an angiotensin-converting enzyme inhibitor and a loop diuretic for severe congestive heart failure (the Randomized Aldactone Evaluation Stuy [RALES]). Am J Cardiol. 1996;78:902-907

Most common (22%), tiredness (16.5%), breast tenderness (17%)*

If after three months of monotherapy consider ◦ Decrease to 50-75mg daily ◦ Add OC to reduce menstrual

dysfunction ◦ “cycling” of the spironolactone

with 21 consecutive days of therapy followed by seven days off *Shaw JC, White LE. Long-term safety of spironolactone in acne: results of an 8 year follow-up study. J Cut Med

and Surg. 2002;12:541-545

217

Drugs Side effects Diuretics and Potassium sparing drugs

Hyperkalemia

ACE inhibitors Hyperkalemia Barbiturates, alcohol, and narcotics Orthostatic Hypotension Corticosteroids or adrenocorticotropin hormone (ACTH)

Electrolyte depletion, hypokalemia

Digoxin Elevated serum levels of digoxin Non-depolarizing neuromuscular blocking agents

Potentiated with spironolactone use

*Aldactazide (sprionolactone with hydrochlorothiazide) tablets [package insert]. Chicago, IL: Searle; 2003

Should be avoided in pregnancy category C

Male fetus: masculinization occurs after 6 weeks and if drug d/c early, risk is negligible

Currently, no links with congenital defects and no well controlled studies with pregnancy

Case reports of two developed healthy males after high dose tx ◦ spironolactone (200-400mg) and K

supplements maternal Bartter syndrome*

*Groves TD, Corenblum B. Spironolactone therapy during human pregnancy. Am J Ostet Gynecol. 1995;172(5):1655-1656.

skjef

Monotherapy or in combination with other agents ◦ OC (reduces side effects and risk of preg) and antibiotics ◦ Other topical acne agents

Women with hormonal pattern acne, PCOS, or hyperandrogenism state

Women with normal circulating androgen levels but with late onset acne can benefit

Recalcitrant cases, resistant to conventional treatment ◦ Many times it is a myth that it will “run its course”

Spironolactone should be considered as an armamentarium for women with adult acne ◦ Avoid in pts wanting to get pregnant ◦ Avoid in pts with breast CA risk

1.Goulden V, Clark SM, Cunliffe WJ. Post-adolescent acne: a review of clinical features. Br J of Dermatol. 1997;136:66-70. 2. Collier CN, Harper JC, Cantrell WC. The prevalence of acne in adults 20 years and older. J Am Acad Dermatol. 2008;58:56-9. 3. Cunliffe W, Gould D. Prevalence of facial acne vulgaris in late adolescence and in adults. Br Med J. 1979;26:931-5. 4. Stoll S, Shalita AR, Webster GF. The effect of menstrual cycle on acne. J Am Acad Dermatol. 2001;45:957-60. 5. Thiboutot D. Acne: hormonal concepts and therapy. Clin Dermatol. 2004;22:419-28 6. Akamatsu H, Zouboulis CC, Orfanos CE. Spironolactone directly inhibits proliferation of cultured human faciall sebocytes and acts antagonistically to testosterone and 5-alpha-dihidrotestosterone in vitro. J Invest Dermatol. 1993;100:660-62. 7. Thiboutot D, Chen W. Update and future of hormonal therapy in acne. Dermatology. 2003;206:57-67. 8. Goodfellow A, Alaghband-Zadeh J, Carter G et al. Oral spironolactone improve acne vulgaris and reduced sebum excretion. Br J Dermatol 1984;111:124-5. 9. Shaw JC, White LE. Long-term safety of spironolacone in acne: results of an 8 year followup study. J of Cut Med and Surg. 2002;12:541-45. 10. Barker DJP. The epidemiological evidence relating to spironolactone and malignant disease in man. J Drug Dev. 1978;1(Suppl1. 2):22-25. 11. Shaw JC. Hormonal therapies in acne. Exper Opin Pharmacother. 2003;3(7):865-74. 12. Lolis MS, Bowe WP, Shalita AR. Acne and systemic disease. Med Clin North Am. 2009;93(6):1161-81.

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ACNE SCAR LYSING Mari M. Batta, D.O. Alta Dermatology Group / LECOMT

Objectives

Acne scars Pathogenesis Scar subtypes Treatment modalities

Acne scar lysing using the needling method Percutaneous collagen induction Case with one year follow-up

Summary

Evolution of atrophic acne scarring

All healing scars Inflammation, granulation tissue formation with

fibroplasia neovascularization, wound contracture, tissue remodeling

Acne lesions are unusual Inflammation is initiated beneath the epidermis in the

infrainfundibular region of the pilosebaceous structure Two basic scar types Atrophic scars (80 – 90%): net loss of collagen Hypertrophic scars: net gain of collagen

Atrophic Scars Acne scar subtype Clinical features

Ice pick (60 – 70%) Narrow (<2mm), deep, sharply marginated epithelial tracts that extend vertically to the deep dermis or subcutaneous tissue.

Boxcar (20 – 30%) -Shallow (0.1 – 0.5mm) -Deep (≥ 0.5mm)

Round to oval depressions with sharply demarcated vertical edges, similar to varicella scars. They are clinically wider at the surface and icepick scars and do not taper to a point at the base. They may be shallow or deep and are most often 1.5 – 4mm in diameter.

Rolling (15 – 25%) Occur from dermal tethering of otherwise relatively normal-appearing skin and are usually wider than 4 – 5mm. Abnormal fibrous anchoring of the dermis to the subcutis leads to superficial shadowing and a rolling or undulating appearance to the overlying skin

Fabbrocini G, Annunziata MC, D’Arco V, DeVita V, Lodi G, Mauriello MC, Pastore F, Monfrecola G. Acne scars: pathogenesis, classification and treatment. Dermatol Res Pract. 2010;2010:89309

Acne scar classification system Grades of Post Acne Scarring

Level of disease

Clinical Features

1 Macular These scars can be erythematous, hyper- or hypopigmented flat marks. They do not represent a problem of contour like other scar grades but of color.

2 Mild Mild atrophy or hypertrophy scars that may not be obvious at social distances of ≥ 50cm & may be covered adequately by makeup or the normal shadow of shaved beard hair in men or normal body hair if extrafacial.

3 Moderate Moderate atrophic or hypertrophic scarring that is obvious at social distances ≥ 50cm & is not covered easily by makeup or the normal shadow of shaved beard hair in men or body hair if extrafacial, but is still able to be flattened by manual stretching of the skin (if atrophic).

4 Severe Severe atrophic or hypertrophic scarring that is evident at social distances ≥ 50cm & is not covered easily by makeup or the normal shadow of shaved beard hair in men or body hair if extrafacial & is not able to be flattened by manual stretching of the skin.


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Treatment of atrophic acne scars

Chemical peels Dermabrasion / Microdermabrasion Laser treatment Punch technique Dermal grafting Tissue augmenting agents (fat transplantation) Other tissue augmenting agents Needling Combination therapy

Fractional photothermolysis

Fig. 136.6 Histologic findings following ablative fractional photothermolysis. A microthermal zone (MTZ) of injury (arrow) is apparent after use of a CO2laser (10 600 nm) at 100 mJ/pulse. E, epidermis; D, dermis. Courtesy, Wellman Center for Photomedicine. Dermatology, 3rd edition, Bolognia (Jorizzo/Schaffer), Volume II, Ch 136, Pg 2256 http://www.solmed.com.pl/images/mosaicefekt.jpg

Subcision

Orentreich DS, Orentreich N. Subcutaneous incisionless (subcision) surgery for the correction of depressed scars and wrinkles. Dermatol Surg 1995;21:543-9.

Needle abrasion

Camirand A, Doucet J. Needle dermabrasion. Aesth Plast Surg 1997;21(1):48-51

Needling (Percutaneous Collagen Induction)

Scar formation and PCI

Transforming growth factor β TGFβ1 & TGFβ2: elicit fibrotic scarring response TGF β3: elicits a scar-free or regenerative healing response

Results 2 weeks after PCI: upregulation of TGF β (1 < 2, 3) 4 weeks after PCI: only faint expression of TFG β1 & 2 8 weeks after PCI: significant downregulation of TGF β1 & 2 8 weeks after PCI: TGF β3 remained upregulated

Aust MC, Reimers K, Repenning C, et al. Percutaneous collagen induction: minimally invasive skin rejuvenation without risk of hyperpigmentation: fact of fiction? Plast Reconstr Surg 2008;12:1553-63.

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Histologic findings 6 months after PCI

Van Gieson stain Increase in collagen

deposition Collagen laid down in normal

lattice pattern Elastica stain

Increase in elastin Hematoxylin & eosin stain (1

year later) Normal stratum corneum Thickened epidermis (40%

thickening of granular layer) Normal rete ridges

Aust MC, Fernandes D, Kolokythas P, Kaplan H, Vogt P. Percutaneous collagen Induction therapy: an alternative treatment for scars, wrinkles, and skin laxity. Plast Reconstr Surg 2008;121:1421

Regeneration and PCI Epidermal thickness: increased 112% after 8 weeks

Connective tissue fiber bundles: increased, thickened, more loosely woven

Gene expression analysis Collagen type 1 fibers: present throughout the dermis at all time points

Collagen type 3: gene expression upregulation 4 weeks after PCI

Fibroblast growth factor 7: increased expression 2 weeks after PCI

PAS staining for mucopolysaccharides (glycosaminoglycans): deeper intensity and more regularly patterned

Fibronectin staining: more intense

Vascular endothelial growth factor staining: bright fluorescence

Aust MC, Reimers K, Kaplan HM, Stahl F, Repenning C, Scheper T, Jahn S, Schwaiger N, Ipaktchi R, Redeker J, Altintas MA, Vogt PM. Pecutaneous collagen induction – regeneration in place of cicatrisation? J Plast Reconstr Aesthet Surg. 2011 Jan;64(1):97-107.

Patient satisfaction and PCI Vancouver Scar Scale Patient & Observer Scar Assessment Scale

No 72 72

Preoperative score 7.5 27

Postoperative score 4.8 19

P value ≤ 0.005 ≤ 0.005

Aust MC, Fernandes D, Kolokythas P, Kaplan H, Vogt P. Percutaneous collagen induction therapy: an alternative treatment for scars, wrinkles, and skin laxity. Plast Reconstr Surg 2008;121:1421

Dyspigmentation and PCI

Aust MC, Reimers K, Repenning C, et al. Percutaneous collagen induction: minimally invasive skin rejuvenation without risk of hyperpigmentation: fact of fiction? Plast Reconstr Surg 2008;12:1553-63.

In situ hybridization Interleukin 10 gene expression Immunofluorescence

Melanocyte staining with antibodies directed against S100

Indications for Percutaneous Collagen Induction

To restore skin tightness in the early stages of facial aging (may treat also arms, abdomen, thighs, buttocks)

To diminish fine wrinkles To avoid dermabrasion for acne scarring To avoid laser treatment

Fernandes MD. Percutaneous collagen induction: an alternative to laser resurfacing. Aesthetic Surg J 2002;22:315-7.

Percutaneous Collagen Induction

PCI does not permanently damage the skin

Thicker skin Short healing phase Less expensive than laser resurfacing Skin does not become sun-sensitive No risk of dyspigmentation Can be used after laser resurfacing

or in those with very thin skin Easy-to-master technique Can be performed with topical

anesthesia

Exposure to blood

Swelling and bruising for 4 – 7 days

Advantages Disadvantages

Fernandes MD. Percutaneous collagen induction: an alternative to laser resurfacing. Aesthetic Surg J 2002;22:315-7. Aust MC, Fernandes D, Kolokythas P, Kaplan H, Vogt P. Percutaneous collagen induction therapy: an alternative treatment for scars, wrinkles, and skin laxity. Plast Reconstr Surg 2008;121:1421

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DON’T HAVE THE NEEDLING INSTRUMENT?

Use a 30 Gauge needle!

Lysing with 30 gauge needle

Left face Left face

Right face Conclusions

No general guidelines available to optimize acne scar treatment

Percutaneous collagen induction with needling Dermal pricking Promotes regeneration rather than cicatrization Improves skin texture and thickness Complications can be minimized in all skin types Low cost, low technology…but effective!

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References Khunger N, Bhardwaj D, Khunger M. Evaluation of CROSS technique with 100% TCA in the management of ice pick acne scars in darker skin types. J Cosmet Dermatol.

2011 Mar;10(1):51-7.

Lee JW, Kim BJ, Kim MN, Lee CK. Treatment of acne scars using subdermal minimal surgery technology. Dermatol Surg. 2010 Aug;36(8):1281-7.

Manuskiatti W, Triwongwaranat D, Varothai S, Eimpunth S, Wanitphakdeedecha R. Efficacy and safety of a carbon-dioxide ablative fractional resurfacing device for treatment of atrophic acne scars in Asians. J Am Acad Dermatol. 2010 Aug;63(2):274-83.


Fabbrocini G, Fardella N, Monfrecola A, Proietti I, Innocenzi D. Acne scarring treatment using skin needling. Clin Exp Dermatol. 2009 Dec;34(8):874-9.

Cooper JS, Lee BT. Treatment of facial scarring: lasers, filler, and nonoperative techniques. Facial Plast Surg. 2009 Dec;25(5):311-5.

Rivera AE. Acne scarring: a review and current treatment modalities. J Am Acad Dermatol. 2008 Oct;59(4):659-76.

Khunger N; IADVL Task Force. Standard guidelines of care for acne surgery. Indian J Dermatol Venereol Leprol. 2008 Jan;74 Suppl:S61-7.

Alam M, Omura N, Kaminer MS. Subcision for acne scarring: technique and outcomes in 40 patients. Dermatol Surg. 2005 Mar;31(3):310-7.

Jacob CI, Dover JS, Kaminer MS. Acne scarring: a classification system and review of treatment options. J Am Acad Dermatol. 2001 Jul;45(1):109-17.

Goodman GJ. Management of post-acne scarring. What are the options for treatment? Am J Clin Dermatol. 2000 Jan-Feb;1(1):3-17.

Fernandes MD. Percutaneous collagen induction: an alternative to laser resurfacing. Aesthetic Surg J 2002;22:315-7.

Camirand A, Doucet J. Needle dermabrasion. Aesth Plast Surg 1997;21(1):48-51.

Orentreich DS, Orentreich N. Subcutaneous incisionless (subcision) surgery for the correction of depressed scars and wrinkles. Dermatol Surg 1995;21:543-9.

Aust MC, Fernandes D, Kolokythas P, Kaplan H, Vogt P. Percutaneous collagen induction therapy: an alternative treatment for scars, wrinkles, and skin laxity. Plast Reconstr Surg 2008;121:1421

Aust MC, Reimers K, Repenning C, Stahl F, Jahn S, Guggenheim M, Schwaiger N, Gohritz A, Vogt PM. Percutaneous collagen induction: minimally invasive skin rejuvenation without risk of hyperpigmentation: fact of fiction? Plast Reconstr Surg 2008;12:1553-63.

Aust MC, Reimers K, Kaplan HM, Stahl F, Repenning C, Scheper T, Jahn S, Schwaiger N, Ipaktchi R, Redeker J, Altintas MA, Vogt PM. Pecutaneous collagen induction – regeneration in place of cicatrisation? J Plast Reconstr Aesthet Surg. 2011 Jan;64(1):97-107.

223

Jeremy K. Bingham, D.O. Advanced Desert Dermatology

Clinical Case A 64 year old Caucasian male presented to the

dermatology clinic with a chief complaint of rash for 3 weeks.

Patient described a 48 hour period of intense head and upper trunk erythema followed by the development of an erythematous, pruritic, scaly rash on the scalp, face and arms.

Patient denied any constitutional symptoms preceding development of rash. Patient reported good overall health with a history of pre-diabetes only.

Patient denied taking any medications prior to development of current complaint and reported not using any medications on a regular basis.

Patient denied alcohol or drug use but was previously a tobacco smoker with a 25 year pack history who reported quitting 20 years prior.

He denied any constitutional symptoms including: malaise, fever, chills, diarrhea, or weight loss.

Prior to presentation patient was seen by his PCP and placed on a 40 mg daily prednisone burst for 5 days, Hydroxyzine, and Triamcinolone cream.

Physical Exam Erythematous, papulosquamous eruption with

prominent scale over the back, shoulders, face, and head.

The papules and plaques become confluent on the chest and back with prominent islands of sparing in some areas.

Diffuse erythema with fine scale over the face, scalp, and ears. Abdomen and lower extremities were without involvement.

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Differential Diagnosis Our differential diagnosis was broad and included:

Psoriasis Contact dermatitis Severe seborrheic dermatitis Pityriasis rubra pilaris Mycosis fungoides Drug eruption Parapsoriasis

A 4-mm punch biopsy was taken of the right shoulder revealing a broad, variably compact orthohyperkeratosis with patchy foci of parakeratosis.

Diagnosis of Pityriasis Rubra Pilaris was made.

Treatment Patient showed little clinical improvement with initial

treatment of isotretinoin 1mg/kg/day for 60 days. Additionally, patient was using clobetasol ointment

under occlusion at night and bland emollients for palmoplantar keratoderma which developed subsequent to his initial visit.

Narrow band UVB >30 treatments. Little clinical improvement.

Tumor necrosis factor-inhibitor medications were considered owing to their efficacy and safety profile in treating psoriasis patients.

Adalimumab was selected as a treatment option over Etanercept due to its more convenient 2-week interval dosing schedule.

Treatment was started with an initial subcutaneous dose of 80 mg followed by a 40 mg subcutaneous dose one week later. After just the initial two doses patient demonstrated a reduction in overall erythema and pruritis.

225

40 mg dosing continued every 2 weeks for 20 weeks of total therapy.

Patient experienced significant improvement with a total resolution of his palmar and plantar keratoderma and reports considerable improvement in his quality of life.

We estimated patient with nearly 40% total body involvement prior to treatment. Currently 1 year after treatment patient remains in remission.

Discussion Pityriasis Rubra Pilaris , also known as Devergie’s

disease, was first described by Tarral in 1828 and later classified ‘pityriasis pilaris’ by French Professor of Dermatology Alphonse Devergie in 1856.

PRP refers to a group of chronic disorders characterized by reddish orange plaques with pityriasiform scaling showing follicular keratoses and palmoplantar keratoderma.

The disease may progress to erythroderma with areas of uninvolved skin called, “islands of sparing”.

The pathogenesis is unknown. It is generally inherited in an autosomal dominant

fashion with variable expression. Autosomal recessive and X-linked inheritance have

also been reported, but sporadic remains the most prevalent mode of inheritance.

Though the etiology remains unknown there have been multiple proposed hypothesis including vitamin A deficiency and an absence of retinol-binding protein.

PRP has been associated with malignancy, trauma, infection and autoimmune diseases including myasthenia gravis and hypothyroidism.

PRP occurs in all races and affects both sexes equally. PRP occurs in a bimodal distribution, peaking in the first and fifth decades of life but may occur at any age.

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The age of onset, behavior, clinical appearance, and prognosis are considered very important for its classification.

The disease is sub classified into six types with both hereditary and acquired forms reported: classic adult type, atypical adult type, classic juvenile type, circumscribed juvenile type, and atypical juvenile type.

PRP has been reported in patients with HIV, presenting with different clinical features and a poorer prognosis earning the designation PRP type 6.

Type I Classic adult PRP Most common form

accounting for 50% of all cases.

Acute onset Erythroderma, islands of

sparing, palmoplantar keratoderma, follicular hyperkeratosis

Type I Best prognosis Reportedly about 80% of patients have remission in an

average of three years.

Type II Adult atypical PRP 5% of all cases Ichthyosiform lesions,

eczematous changes, alopecia.

Long duration- often 20+ years.

Type III Classic juvenile PRP 10% of all cases Very similar to type I Onset within the first

two years of life Remission occurs within

an average of 1 year

Type IV Circumscribed

juvenile PRP 25% of all cases Prepubertal children Sharply demarcated

areas of follicular hyperkeratosis and erythema of the knees and elbows

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Type IV Long term outcome is

unclear with improvement noted in some patients in teenage years.

Rarely progresses

Type V Atypical juvenile PRP 5% of all cases Most cases of familial

PRP belong to this group.

Early onset Chronic course

Type V Prominent follicular

hyperkeratosis Sclerodermalike changes

on the palms and soles Infrequent erythema

Type VI HIV associated Nodulocystic and pustular acneiform lesions Resistant to standard treatments May respond to antiretroviral therapies.

Treatment Multiple treatment modalities have been used with

varying degrees of success. Emollients remain a mainstay of treatment reducing

fissuring and dryness. Topical steroids may be beneficial for patient comfort

but do not have long term therapeutic effect. Systemic steroids are ineffective.

Treatment Systemic retinoids appeared to be the most effective

therapeutic agents.

In a large study it was found that 80 percent of patients had significant clearing within an average of 25 weeks of treatment with isotretinoin at a dose of 1 mg/kg/day.

Low-dose weekly methotrexate alone or in combination with retinoids has shown efficacy, although the results have proven to be inconsistent.

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An extensive side effect profile of the oral retinoids including xerotic skin, hyperlipidemia, ocular sicca, and teratogenic potential has provided an impetus in finding a safer, more convenient treatment option.

Treatment with cyclosporine, azathioprine, PUVA, and mycophenolate mofetil, have all been reported with variable degrees of success.

Newer biologic therapy has shown promise in the treatment of PRP.

Tumor necrosis factor (TNF)-alpha inhibitors, first licensed for clinical use in 1998, is one class of biologic agent.

TNF represents an important cytokine involved in normal inflammatory and immune responses.

Elevated levels of TNF have been found in psoriatic plaque and in the synovial fluid of both psoriatic and rheumatoid arthritis. Not surprisingly, given the clinical and histological overlap with psoriasis, up regulation of TNF- alpha has been detected in punch biopsies of PRP lesions

In 2009, Walling and Swick were the first to publish the use of Adalimumab in PRP treatment.

They reported a dramatic and rapid response in a 72 year male patient with a near complete resolution of PRP eruption after 8 weeks of monotherapy.

Adalimumab is a recombinant human IgG1 monoclonal antibody specific for human TNF.

Adalimumab binds specifically to TNF-alpha and blocks its interaction with p55 and p75 cell surface receptors, preventing the action of TNF on TNF receptors 1 and 2.

The release of pro-inflammatory cytokines by macrophages and keratinocytes is prevented, and the production of acute phase proteins by hepatocytes is inhibited.

Inflammation and hyperproliferation of keratinocytes are key features of PRP

Additional recent case reports have been published with encouraging findings showing prolonged efficacy with maintenance Adalimumab dosing.

Given the safety profile of Adalimumab and its convenient bi-monthly dosing it is anticipated that additional reportings will be published on its successful use in PRP patients.

Thank you.

229

References REFERENCES 1. Klein A, Landthaler M, Karrer S. Pityriasis Rubra Pilaris: A Review of Diagnosis and Treatment. Am J Clin Dermatol 2010; 0 (0): 0-0 1175-

0561. 2. Sehgal VN, Srivastava G, Dogra S. Adult onset pityriasis rubra pilaris. Indian J Dermatol Venereol Leprol 2008; 74: 311-21. 3. Griffiths WAD. Pityriasis rubra pilaris. Clin Exp Dermatol 1980; 5: 105-12. 4. Miralles ES, Nunez M, Se Las Heras ME, et al. Pityriasis rubra pilaris and human immunodeficiency virus infection. Br J Dermatol 1995;

133: 990-3. 5. Vasher M, Smithberger E, Lien MH, Fenske NA. Familial pityriasis rubra pilaris: report of a family and therapeutic response to etanercept.

J Drugs Dermatol. 2010; 9: 844-50. 6. Chan H, Liu FT, Naguwa S. A review of pityriasis rubra pilaris and rheumatologic associations. Clin Dev Immunol 2004; 11: 57-60. 7. Seghal VN, Jain MK, Mathur RP. Pityriasis rubra pilaris in Indians. Br J Dermatol 1989; 121: 821-22. 8. Weller R, Hunter J, Savin J et al. Clinical Dermatology, 75-77. Fourth Edition. Blackwell publishing, 2008. 9. Bolognia J, Jorizzo J, Rapini R. Dermatology. Second Edition: Elsevier, 2008. 10. Lu R, George SJ, Hsu S. Pityriasis rubra pilaris: failure of combination treatment with acitretin and infliximab. Dermatol Online J 2006;

12:18. 11. Martinez Calixto LE, Suresh L, Matsumura E, et al. Oral pityriasis rubra pilaris. Oral Sur Oral Med Oral Pathol Oral Radiol Endod 2006;

101: 604-7. 12. Champion A. Pityiriasis rubra pilaris in Disorders of Keratinization: Follicular Keratosis. Textbook of Dermatology. Fifth Edition.

Blackwell Scientific, 1992. 13. Van de Kerkhof PCM, Steijlen PM. Topical treatment of pityriasis rubra pilaris with calcipotriol. Br J Dermatol 1994; 130: 675-8.

References 14. Dickens CH. Treatment of classic pityriasis rubra pilaris. J Am Acad Dermatol. 1994; 31:997-9. 15. Clayton BD, Jorizzo JL, Hitchcock MG, et al. Adult pityriasis rubra pilaris: a 10 year case series. J Am Acad Dermatol.

1997;36:959-64. 16. Albert MR, Mackool BT. Pityriasis rubra pilaris. Int J Dermatol. 1999;38:1-11. 17. Zhang Y, Zhou Y, Ball N, Su M, Xu J, Zheng Z. Type I pityriasis rubra pilaris: upregulation of tumor necrosis factoe a

and response to adalimumab therapy. J Cutan Med Surg. 2010;14(4):185-188 18. Müller H, Gattringer C, Zelger B, et al. Infliximab monotherapy as first-line treatment for adult onset pityriasis

rubra pilaris: case report and review of the literature on biologic therapy. J Am Acad Dermatol 2008; 59(suppl 5):S65–S70.

19. Seckin D, Tula E, Ergun T. Successful use of etanercept in type I pityriasis rubra pilaris. Br J Dermatol 2008; 158:642-

4. 20. Walling Hobart W, Swick Brian L. Pityriasis rubra pilaris responding rapidly to adalimumab. Arch. Dermatol.

2009;145(1):99-101. 21. Schreml S, Zeller V, Babilas P, Karrer S, Landthaler M, Szeimies RM. Pityriasis rubra pilaris successfully treated with

adalimumab. Clin Exp. Dermatol. 2010;35(7):792-793. 22. O’Kane D, Devereux CE, Walsh MY, Hoey SHE. Rapid and sustained remission of pityriasis rubra pillaris with

adalimumab treatment. Clin exp. Dermatol. 2010;35(4):e 155-e156. 23. Palacios A, Gonzalez R, Agesta N, Acebo E, Diaz-Ramon L, Gardeazabal J. Successful use of adalimumab (Humira ®)

in pityriasis rubra pilaris. J. Eur. Acad. Dermatol. Venereol. 2010;24(Suppl 4):75-76.

Type I pic 1 http://accessemergencymedicine.com/content.aspx?aid=5203019 Type I Pic 2 http://www3.dermis.net/dermisroot/en/32821/image.htm Type IV http://dermatlas.med.jhmi.edu/derm/indexDisplay.cfm?ImageID=-1125586974 http://skinworld.blogspot.com/2008/05/drug-hypersensitivity-syndrome.html Type V http://casereports.bmj.com/content/2010/bcr.11.2009.2453.full?sid=804984da-340a-4a3b-

a394-1d5c000a243f

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Primary Mucinous Carcinoma of the skin

Helia Eragi, DO, PGY-4 10/10/12

Pacific Hospital Long Beach, California Program director: Dr. David Horowitz

Case Presentation

49 yo Asian male presented to the dermatology clinic with a clear mass on his chin.

Patient states the lesion has been there for the past two years, enlarging over the past few months.

Denies any pain or other physical complaints.

Case presentation

Review of system: negative for weight loss, fever, night sweats or other constitutional symptoms

Past medical history: none Medication: none

Case presentation

Physical exam revealed a 3.0 x 2.0 cm clear flesh colored cystic structure on the chin.

No tenderness on palpation. Lesion was initially thought to be a cyst

and was removed using an elliptical excision , during which a profuse amount of mucin was drained.

Histopathology

The histopathology revealed expansive lakes of mucin diffusely replacing the dermis and focally extending into the skeletal muscle and biopsy margins.

Extended within the lakes of mucin were islands of epithelial cells arranged in cohesive nests and forming ductal structures and focal cribriform features.

Histopathology

There were possible apocrine differentiation as well as focal peripheral palisation.

There was no definitive attachment to the overlying epidermis.

It stained positive for PAS stain and diastase resistant.

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The specimen stained positive for S-100, CEA, EMA, Pancytokeratin, Cytokeratin 7, D2-40.

Negative for cytokeratin 20 and p63.

Based on the morphology of the tumor cells combined with immunohistochemical findings, and lack of direct epidermal attachment, the diagnosis of mucinous carcinoma of the skin was made.

Patient was referred to oncologic surgery to exclude visceral malignancy and further treatment of his cancer.

Primary Mucinous Carcinoma of the skin

Primary mucinous carcinoma of the skin (PMCS) is a rare malignant neoplasm, deriving from sweat glands or their germinal structures.

First described by lennox et al. in 1952 and then revisited by Mendoza et al. in 1971.

PMCS

Only 228 cases reported since Must rule out metastasis from

primary internal malignancy such as breast, gastrointestinal tract, lung, kidney, ovaries, pancreas and prostate

Clinical presentation

Can present as a solitary, slow growing, soft, papule, nodule or cyst

painless Ranging in size from 3-4 mm to 20

cm The nodule can be indurated,

reddish, gray-blue, pink or purple

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Clinical presentation

Male> Female Predilection for white (62%) and

black (34%) Elderly, average age 62.6 y.o Head and neck, most commonly

periorbital

Pathophysiology

Variant of sweat gland carcinoma The origin thought to favor eccrine

more than apocrine differentiation

Pathophysiology

Some literature suggests that PMCS develops as a progression of abnormal apocrine or eccrine ducts similar to mucinous carcinoma of the breast, ranging from ductal hyperplasia, atypical ductal hyperplasia or ductal carinoma in situ or combination of all three

Pathophysiology

Presence of copious amount of mucin serves as a physical barrier, compressing the tumor stroma, and decreasing the rate of angiogenesis by inhibiting DNA synthesis

Thus contributes to the benign nature of this tumor and it’s low metastatic potential

Histopathology Well circumscribed dermal tumor

consisting of islands of epithelial cells surrounded by large pool of basophilic mucin

Sialomucin, stains positive with PAS, with or without diastase, hyaluronidase resistant

This mucin also stains positive with mucicarmine, alcian blue at pH 2.5 and colloidal iron

Histopathology

Epithelial cells show moderate nuclear pleomorphism

Forms glandular patterns Tumor cells are small, cuboidal and

bland May have vacuolated eosinophilic

cytoplasm Mitoses and cellular pleomorphism

rare

233


Tumor is positive for low molecular weight cytokeratin, CEA, EMA, S100

Some cases, estrogen and progesterone receptor and GCDFP-15 positive

Negative for CK 20- excluding metastatic colorectal carcinoma


Metastatic adenocarcinoma Cystic Basal cell carcinoma Hidrocystoma Epidermoid cyst Sebaceous cyst Sebaceous Carcinoma


Pilomatricoma Hemangioma Melanoma Squamous cell carcinoma Lipoma

Work up Since primary mucinous carcinoma of

the skin is a very rare neoplasm, a full work up to rule out metastasis from other primary internal malignancies such as breast, gastrointestinal, lung, kidney, prostate, pancreas and ovaries must be done.

The location of tumor can provide some clue to differentiate PMCS from metastasis.

Breast metastasis tends to show preference for the chest, breast and axilla and very unlikely to metastasize to the face.

Breast and gastrointestinal malignancies in particular can have very similar histopathology and immunohistochemistry.

Organ specific immunohistochemistry markers should be done

PMCS stains negative for CK20 which is a marker colonic mucinous carcinoma

PMCS stain positive for estrogen receptor, progesterone receptor and GCDFP-15.

234

Qureshi, et al. suggested that finding an in-situ component of tumor cell staining positive for p63 and CK 5/6 favors PMCS and excludes metastasis from breast.

Prognosis

PMCS has a favorable prognosis with low mortality rate and low metastatic rate of 9.6%

However, it has a high recurrence rate of 29.4%

It can be locally invasive and metastasize to regional lymph nodes, lungs, and parotid glands

Treatment

Wide local excision with at least 1 cm margin and dissection of lymph nodes.

If high grade tumor, prophylactic lymph node dissection is recommended

Treatment

Several reports suggesting success with Mohs micrographic surgery using low-molecular weight immunostaining.

PMCS not responsive to chemotherapy or radiation.

Follow up

Due to it’s high recurrence rate, patients should be followed up annually and examined for development of lymphadenapathy.

References

1. Breiting L, Christensen L, Dahlstrøm K, Breiting V, Winther JF. Primary mucinous carcinoma of the skin: a population-based study. Int J Dermatol. Mar;47(3):242-5, 2008.

2. Miyasaka M, Tanaka R, Hirabayashi K, Yamazaki A, Shinohara H, Taira H, Akamatsu T. Primary mucinous carcinoma of the skin: a case of metastasis after 10 years of disease-free interval. European Journal of Plastic Surgery. 32: 189-193, 2008.

3. Scholz IM, Hartschuh W. Primary mucinous eccrine carcinoma of the skin--a rare clinical tumor with many differential diagnoses. Journal of German Society of Dermatology. 8(6):446-8, 2010.

4. Levy G, Finkelstein A, McNiff JM. Immunohistochemical techniques to compare primary vs. metastatic mucinous carcinoma of the skin. J Cutan Pathol. 37(4):411-5, 2010.

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5. Cecchi R, Rapicano V. Primary cutaneous mucinous carcinoma: report of two cases treated with Mohs' micrographic surgery. Australas J Dermatol. 47(3):192-4, 2006.

6. S. R. Martinez & S. E. Young : Primary Mucinous Carcinoma of the Skin: A Review . The Internet Journal of Oncology. Volume 2 Number 2, 2005.

7. Brietling LB, Christensen L, Dahlstrom K, Winther JF, Breiting VB, Kalialis LV. Primary mucinous carcinoma of the skin--a literature review. Ugeskr Laeger. 170(43):3399-402,2008.

8. Ivan D, Nash JW, Prieto VG,et al. Use of p63 expression in distinguishing primary and metastatic cutaneous adnexal neoplasms from metastatic adenocarcinoma to skin. J Cutan Pathol 34: 474–480, 2007.

9. Vodovnik A. Primary mucinous carcinoma of the skin. J Cutan Pathol 33: 61, 2006.

10. Breitling L, Dahlstrom K, Christensen L,Winther J, Breitling V. Primary mucinous carcinoma of the skin. Am J Dermatopathol 29: 595, 2007.

11. Qureshi H, Salama M, Chitale D, et al. Primary cutaneous mucinous carcinoma: presence of myoepithelial cells as a clue to the cutaneous origin. Am J Dermatopathol 26: 353, 2004.

12. Yugue ros, Patricia M.D.; Kane, William J. M.D.; Goellner, John R. M.D. Sweat Gland Carcinoma: A Clinicopathologic Analysis of an Expanded Series in a Single Institution. Plastic & Reconstructive Surgery. Issue: Volume 102(3) pp 705-710, 1998.

13. Snow SN, Reizner GT. Mucinous eccrine carcinoma of the eyelid. Cancer 1992;15:2099-104

14. UrsoC, Bondi R, Paglierani M, Salvadori A, Anichini C, Giannini A. Caricinomas of sweat glands: report of 60 cases. Arch Pathol Lab Med 2001; 125:498-505

15. Carson, HJ, Gattuso P, Raslan WF, Reddy V. Mucinous carcinoma of the eyelid. An immunohistochemical study. AM J Dermatopathol 1995; 17:494-8.

16. Balin AK, Fine RM, Golitz LE. Mucinous carcinoma. J Dermatol Surg Concol 1988;14:521-4.

17. Fukamizu H, Tomita K, Inoue K, Takigawa M. Primary

mucinous carcinoma of the skin. J Dermatol Surg Oncol 1993; 19:625-628.

18. Gupta A, Flowers FP, Lessner AM. Asymptomatic eyelid papule in a 57 year old healthy man. Arch Dermatol 2000; 136:1409-14

19. Jih MH, Friedman PM, Kimyai-Asaeli A, Golderberg LH. A rare case of fatal primary cutaneous mucinous carcinoma of scalp with multiple in transit and pulmonary metastasis. J AM Acad Dermatol. 52: 576-80, 2005.

20. Indian J Opthalmol. 2009 Mar-Apr; 57(2):150-152

236

Unusual Case of Symmetrical Hyperkeratotic Plaques

Tatyana Groysman, DO

October 10, 2012

AOCD Annual Meeting

Case Presentation • CC: 54 year-old African American female presented to

dermatology with multiple “birthmarks” on trunk and extremities.

• HPI: Patient reported the lesions to be present for “as long as she could remember.” They are mostly asymptomatic, occasionally pruritic and are not migratory. Treated with daily application of Vaseline. She denied any blisters or skin peeling at birth or throughout her life. No known history of eryhtroderma or collodion at birth.

Case Presentation • ROS: Positive for myalgias and arthralgias. Negative

for neurological deficits including hearing.

• PMH: Rheumatoid arthritis, hypertension, osteopenia, dyslipidemia, chronic kidney disease, anemia of chronic disease

• Meds: Atenolol, ferrous sulfate, alendronate, celecoxib, calcium with D, prednisone 5mg daily, famotidine, lovastatin, nifedipine

• Family History: Mother and sister have similar cutaneous findings.

Physical Exam Thick, hyperpigmented, hyperkeratotic, well demarcated plaques on elbows and left dorsal hand.

Thinner, less demarcated, hyperpigmented plaques with exaggerated skin marking present in all flexural areas of trunk and extremities.

Palmar/plantar keratoderma with honeycomb appearance more prominant on the palms.

Ulnar deviation and multiple joint deformities are present on the hands and feet.

Differential Diagnosis • Lichen simplex chronicus

• Acanthosis nigricans

• Epidermal nevus

• Atopic dermatitis

• Ichthyosis Curth-Macklin

• Superficial epidermolyic ichthyosis (ichthyosis bullosa of Siemens)

• Epidermolytic ichthyosis (epidermolytic hyperkeratosis)

• Keratosis linearis-ichthyosis congenita-keratoderma

• Loricrin Keratoderma

• Erythrokeratodermia variabilis

237

Histology (neck)

10X 20X

Histology (neck)

40X 40X

Working Diagnosis • Loricrin Keratoderma vs

Erythrokeratodermia Variabilis

• Gene testing for GJB3 and GJB4 is pending

Keratins in the Skin

• Intermediate filament

• Regulation of apoptosis

• Cell architecture stress response

• Protein synthesis

• Organelle and vesicle distribution

Shimomura Y, Wajid M, Kurban M, Sato N, Christiano AM. Mutations in the keratin 85 (KRT85/hHb5) gene underlie pure hair and nail ectodermal dysplasia. J Invest Dermatol. 2010 Mar;130(3):892-5.

Epidermal Integrity Components

• Structural proteins – Keratins

• Cornified envelope – Loricrin

– Transglutaminase

• Cohesion – Plakophilin

– Desmoplakin

– Desmoglein 1

• Cell-to-cell communication – Connexins

Keratin in Hereditary Diseases • Diseases causes by keratin gene mutations are

characterized by – Keratinocyte fragility (cytolysis)

– Keratin filament aggregation

– Intra-epidermal blistering

– Hyperkeratosis

• Phenotype depends on

– Type of mutated keratin

– Level of expression

– Location of the mutations

– Epigenetic and/or environmental factors

238

• Epidermolytic hykeratosis Epidermolytic ichthiosis (EI)

• Ichthyosis bullosa of Siemens Superficial epidermolyic ichthyosis (SEI)

• Ichthyosis hysterix of the Curth–Macklin type Ichthyosis Curth-Macklin (ICM)

Classification of Hereditary Disorders of Cornification

• Non-syndromic + Autosomal Dominant

– Ichthyosis bullosa of Siemens Superficial epidermolyic ichthyosis (SEI)

– Epidermolytic hykeratosis Epidermolytic ichthiosis (EI)

– Annular epidermolytic ichthyosis (AEI)

– Ichthyosis hysterix of the Curth–Macklin type Ichthyosis Curth-Macklin (ICM)

– Loricrin keratoderma (LK)

– Erythrokeratodermia variabilis (EKV)

EI SEI ICM LK EKV

Gene(s) KRT1/KRT10 KRT2 KRT1 LOR GJB3/GJB4

Onset At birth At birth Early childhood At birth At birth

Initial clinical presentation

Erythroderma, large erosions

Erythroderma, widespread blistering

Striate or diffuse PPK

Erythroderma or collodion baby

Transient, migratory erythematous patches

Disease course

Resolution of erosions replaced by hyperkeratosis in first months

Within weeks development of hyperkeratosis particularly over extensor sides of joints

Progressive worsening of PPK and development of hyperkeratotic plaques over joints and/or on trunk

Improvement and development of PPK

Relapsing-remitting, erythema are fleeting, hyperkeratosis more stable

EI SEI ICM LK EKV

Skin Distribution

Generalized, or predilection for friction areas, over joints

Friction areas Palms and soles and large joints

Generalize mild scaling with accentuated hyperkeratosis over joints, flexural areas

Generalized or focally accented hyperkeratosis, predominately on extremities, buttocks

Palmoplantar involvement

KRT1: epidermolytic PPK KRT10: palms and soles are spared (exceptions possible)

Usually no Massive PPK leading to deep, bleeding, and painful fissures; flexural contractures; constriction bands

Noninflammatory diffuse PPK with honeycomb pattern, mild digital constriction, brown hyperkeratosis, knuckle pads over back aspects

Diffuse PPK present in about 50% of patients

EI SEI ICM LK EKV

Skin Distribution

Generalized, or predilection for friction areas, over joints

Friction areas Palms and soles and large joints

Generalize mild scaling with accentuated hyperkeratosis over joints, flexural areas

Generalized or focally accented hyperkeratosis, predominately on extremities, buttocks

Palmoplantar involvement

KRT1: epidermolytic PPK KRT10: palms and soles are spared (exceptions possible)

Usually no Massive PPK leading to deep, bleeding, and painful fissures; flexural contractures; constriction bands

Noninflammatory diffuse PPK with honeycomb pattern, mild digital constriction, brown hyperkeratosis, knuckle pads over back aspects

Diffuse PPK present in about 50% of patients

Epidermolytic Ichthyosis

Oji V et al. Revised nomenclature and classification ofinherited ichthyoses: results of the First Ichthyosis Consensus Conference inSorèze 2009. J Am Acad Dermatol. 2010 Oct;63(4):607-41.

239

Superficial Epidermolytic Ichthyosis


Ichthyosis Curth-Macklin

Niemi KM, Virtanen I, Kanerva L, Muttilainen M. Altered keratin expression in ichthyosis hystrix Curth-Macklin. A light and electron microscopic study. ArchDermatol Res. 1990;282(4):227-33.

Loricrin Keratoderma

Oji V et al. Revised nomenclature and

classification ofinherited

ichthyoses: results of the First Ichthyosis

Consensus Conference inSorèze

2009. J Am Acad Dermatol. 2010

Oct;63(4):607-41.

Erythrokeratodermia Variabilis


Summary ■ We presented a case of Loricrin Keratoderma

■ Reviewed the differential diagnosis for Non-Syndromic, Autosomal Dominant keratodermas

References ■ Shimomura Y, Wajid M, Kurban M, Sato N, Christiano AM.

Mutations in the keratin 85 (KRT85/hHb5) gene underlie pure hair and nail ectodermal dysplasia. J Invest Dermatol. 2010 Mar;130(3):892-5.

■ Eckert RL, Sturniolo MT, Broome AM, Ruse M, Rorke EA. Transglutaminasefunction in epidermis. J Invest Dermatol. 2005 Mar;124(3):481-92.

■ Oji V et al. Revised nomenclature and classification ofinherited ichthyoses: results of the First Ichthyosis Consensus Conference inSorèze 2009. J Am Acad Dermatol. 2010 Oct;63(4):607-41.

■ Niemi KM, Virtanen I, Kanerva L, Muttilainen M. Altered keratin expression in ichthyosis hystrix Curth-Macklin. A light and electron microscopic study. ArchDermatol Res. 1990;282(4):227-33.

240

Acknowledgements • Tanya Ermolovich, D.O.

• Stephen M. Purcell, D.O.

• Thomas D. Griffin, M.D.

• Fellow Residents

241

RESIDENT POSTER PRESENTATIONSPorokeratotic Eccrine Ostial and Dermal Duct Nevus: A Case Report and Literature Review Nicholas Benner, D.O. O’Bleness Hospital, Dublin, OH

CREST Syndrome Mariel Bird, D.O. Oakwood Southshore Medical Center, Warren, MI

An Uncommon Cause of Purpura Fulminans: Pasteurella multocida Sepsis Lise Brown, D.O. Alta Dermatology, Mesa, AZ

Treatment of Verruca Vulgaris with Nd:YAG 1064nm Laser Winifred Chu, D.O. St. John’s Episcopal Hospital, Lindenhurst, NY

Painful Palmar Petechiae: An Atypical Presentation of Dermatitis Herpetiformis Nathan Cleaver, D.O. St. Joseph Mercy Health System, Clinton Township, MI

A Review and Update on Melanocyte Stimulating Hormone Therapy: Afamelanotide Jordan Fabrikant, D.O. NSUCOM/Larkin Community Hospital, Miami, FL

Muir-Torre syndrome: A Case Associated with an Infrequent Genetic Mutation Christina Feser, D.O. Oakwood Southshore Medical Center, Warren, MI

Linear Morphea Treated with Methotrexate and Excimer Laser Anne Hanson, D.O. St. Joseph Mercy Health System, Clinton Township, MI

Epidermolytic Hyperkeratosis Trey Haunson, D.O. LewisGale Hospital, Blacksburg, VA

An Atypical Presentation of a Common Disease in a Middle-Aged HIV Positive Male Jared Heaton, D.O. Largo Medical Center, Port Richey, FL

Cutaneous Polyarteritis Nodosa Teresa Ishak, D.O. Western University/Pacific Hospital, Long Beach, CA

Primary Dermal Melanoma: Differing Characteristics from Conventional Melanoma? Jesse Jensen, D.O. McLaren Oakland Hospital, Commerce Township, MI

Iatrogenic Kaposi’s Sarcoma Arising After Renal Transplant Immunosuppression Katherine Johnson, D.O. McLaren Oakland Hospital, Commerce Township, MI

Exaggerated insect bite-like reaction in a patient with chronic lymphocytic leukemia Holly Kanavy, D.O. St. Barnabas Hospital, Bronx, NY

Sweet’s Syndrome in Concordance with Acute Coronary Syndrome Michael Kassardjian, D.O. Western University/Pacific Hospital, Long Beach, CA

Lichen Planus Pemphigoides: Review of Treatment Options Raymond Knisley, D.O. Advanced Desert Dermatology, Peoria, AZ

Persistent Rash in a 75 Year Old Male Cathy Koger, D.O. NRMC, Kirksville, MO

Invasive Ductal Breast Carcinoma Presenting as Lipoma in a Male: A Case Report and a Review of the Literature James Landero, D.O. Wellington Regional Medical Center, Margate, FL

Metachronous Classical Kaposi Sarcoma in a Hispanic Male Tang Le, D.O. South Texas Dermatology, Houston, TX

Carcinoid Tumors and Carcinoid Syndrome: A Review From A Two-Point Perspective Katy Matthews, D.O. Columbia Hospital, West Palm Beach, FL

Sweet’s Syndrome Masquerading as Disseminated Herpes Zoster in an HIV Positive Patient Charisse McCall, D.O. St. John’s Episcopal Hospital, Lindenhurst, NY

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Carcinoma Erysipeloides Morgan McCarty, D.O. St. Joseph Mercy Health System, Clinton Township, MI

Successful Treatment of Advanced Inoperable Basal Cell Carcinoma with Vismodegib Suzanne Horwitz, D.O. Wellington Regional Medical Center, Margate, FL

Case of a Peculiar Fungating Nose Lesion Panagiotis Mitropoulos D.O. NSUCOM/BGMC, Hollywood, FL

Multiple Sebaceous Trichofolliculomas on the Face Megan Morrison, D.O. St. Joseph Mercy Health System, Clinton Township, MI

High-Risk Cutaneous Squamous Cell Carcinoma: A Case Report and Review of Literature Julian Ngo, D.O. Largo Medical Center, Port Richey, FL

Atypical Vascular Lesion Arising in an Area of Previous Radiation Treatment on the Breast Christian Oram, D.O. PCOM, Allentown, PA

A Case of Persistent Acantholytic Dermatosis Sital Patel, D.O. University Hospitals, Cleveland, OH

Treatment of Inflammatory Linear Verrucous Epidermal Nevi with Monotherapy Topical Retinoid Ryan Pham, D.O. UNTHSC/TCOM, Fort Worth, Texas

Mohs Surgery in Patients with Immunobullous Diseases: Should Prednisone be Increased Prior to Surgery? Justin Rubin, D.O. NSUCOM/BGMC, Hollywood, FL

Potential Complications of Psoriasis Therapy: A Case Report and Review of Catastrophic Antiphospholipid Syndrome (CAPS) Nicholas Rudloff, D.O. Summa Western Reserve Hospital, Cuyahoga Falls, OH

A report of cutaneous spread of Multiple Myeloma Clayton Schiltz, D.O. Genesys Regional Medical Center, Grand Blanc, MI

McCune-Albright Syndrome Pezham Shoureshi, D.O. University Hospitals, Cleveland, OH

A Case of Classic Kaposi’s Sarcoma Treated with Electron Beam Radiation Therapy Luis Soro, D.O. PCOM, Allentown, PA

Cutaneous Metastatic Crohn’s Disease of the Leg: A Rare Case Report and Review of the Literature Brooke Walls, D.O. Largo Medical Center, Port Richey, FL

A Prominent Eruption in a Female with Myelodysplastic Syndrome Dustin Wilkes, D.O. St. Joseph Mercy Health System, Clinton Township, MI

Telangiectasia Macularis Eruptiva Perstans: A Case Report Samuel Wilson, D.O. LewisGale Hospital, Blacksburg, VA

Recalcitrant Headaches Secondary to Facial Filler Injecions Matthew Zarraga, D.O. Wellington Regional Medical Center, Margate, FL

243

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Duc

t Nev

us. B

r. J.

Derm

atol

. 19

80;1

03:4

35-4

1.

3. S

toof

TJ,

Star

ink

TM, N

iebo

er C

. Por

oker

atot

ic E

ccrin

e O

stia

l and

Der

mal

Duc

t Nev

us: R

epor

t of

a c

ase

of a

dult

onse

t. J.

Am. A

cad.

Der

mat

ol. 1

989;

20:9

24-2

7.

4. B

irol A

, Erk

ek E

, Boz

doan

O, e

t al.

A ca

se o

f Por

oker

atot

ic E

ccrin

e O

stia

l and

Der

mal

Duc

t N

evus

of l

ate

onse

t. J.

Euro

pean

Aca

d. D

erm

. Ven

ereo

l. 20

04;1

8:61

9-21

. 5.

Leu

ng C

S, Ta

ng W

YM, F

ung

WKK

, LO

Kk.

Por

oker

atot

ic E

ccrin

e O

stia

l and

Der

mal

Duc

t N

evus

with

der

mat

omal

invo

lvem

ent:

liter

atur

e re

view

and

repo

rt o

n ef

ficac

y of

lase

r tr

eatm

ent.

Br. J

. Der

mat

ol. 1

998;

138:

684-

88.

6. C

ambi

aghi

S, G

iano

tti R

, Cap

uto

R. W

ides

prea

d po

roke

rato

tic e

ccrin

e os

tial a

nd d

erm

al d

uct

nevu

s alo

ng B

lasc

hko

lines

. Ped

. Der

mat

ol. 2

007;

24(2

)162

-67.

7.

Ber

gman

R, L

icht

ig C

, Coh

en A

, et a

l. Po

roke

rato

tic E

ccrin

e O

stia

l and

Der

mal

Duc

t Nev

us:

An a

bnor

mal

ly k

erat

inizi

ng e

pide

rmal

inva

gina

tion

or a

dila

ted,

por

oker

atot

ical

ly p

lugg

ed

acro

syrin

gium

and

der

mal

duc

t? A

m. J

. Der

mat

opat

hol.

1992

;14:

319-

22.

8. M

azue

cos J

, Ort

ega

M, R

ios J

J, et

al.

Long

-term

invo

lutio

n of

uni

late

ral p

orok

erat

otic

ecc

rine

ostia

l and

der

mal

duc

t nev

us. A

cta.

Der

m. V

ener

eol.

2003

;83:

147-

49.

9. D

el P

ozo

J, M

artin

ez W

, Ver

ea M

M, e

t al.

Poro

kera

totic

Ecc

rine

Ost

ial a

nd D

erm

al D

uct

Nev

us: T

reat

men

t with

carb

on d

ioxi

de la

ser.

Br. J

. Der

mat

ol. 1

999;

141:

1144

-45.

Abst

ract

/ In

trod

uctio

n

A 5-

year

-old

Cau

casia

n fe

mal

e pr

esen

ted

for e

valu

atio

n of

a

birt

hmar

k to

the

4th a

nd 5

th d

igits

of t

he ri

ght h

and.

Phy

sical

ex

am re

veal

ed m

ultip

le v

erru

cous

, hyp

erke

rato

tic, f

lesh

-to

ned

papu

les w

ith so

me

plaq

ues p

ositi

oned

line

arly.

The

re

was

no

eryt

hem

a pr

esen

t and

no

othe

r sig

nific

ant s

kin

findi

ngs w

ere

foun

d on

exa

m. T

he p

laqu

es a

nd p

apul

es

wer

e fir

st o

bser

ved

by h

er p

aren

ts w

hen

she

was

3-4

m

onth

s of a

ge, b

ut m

ay h

ave

been

pre

sent

sinc

e bi

rth.

The

y w

ere

loca

ted

on th

e ul

nar a

nd p

alm

ar a

spec

ts o

f the

4th

dig

it of

the

right

han

d, a

nd th

e pa

lmar

asp

ect o

f the

5th

dig

it of

th

e rig

ht h

and

(Fig

ures

1,2

). T

he p

atie

nt co

mpl

aine

d of

mild

pr

uritu

s, b

ut w

as o

ther

wise

asy

mpt

omat

ic.

She

had

rece

ived

no

prev

ious

trea

tmen

t with

topi

cal o

r des

truc

tive

met

hods

. A p

unch

bio

psy

spec

imen

was

obt

aine

d fr

om o

ne

of th

e pa

pule

s of t

he 5

th d

igit.

(Fi

gure

s 3,4

). O

ur p

atie

nt

was

refe

rred

for c

arbo

n di

oxid

e la

ser t

hera

py, b

ut w

as,

unfo

rtun

atel

y, lo

st to

follo

w u

p.

Case

Rep

ort

Clin

ical

and

Hist

opat

holo

gic

Imag

es

Fig.

1

Figu

re 1

& 2

. Non

-infla

med

, ver

ruco

us, h

yper

kera

totic

, fle

sh-c

olor

ed p

apul

es in

a li

near

orie

ntat

ion

on th

e rig

ht

hand

.

Fig.

2

Figu

re 3

. Epi

derm

is de

mon

stra

tes s

light

pso

riasif

orm

hy

perp

lasia

and

col

umns

of p

arak

erat

osis

over

lyin

g ec

crin

e du

cts a

nd fo

llicu

lar o

rific

es

(hem

atox

ylin

and

eos

in, m

agni

ficat

ion

X 40

). Fi

gure

4.

Num

erou

s ecc

rine

glan

ds a

nd d

ucts

are

ap

pare

nt in

ass

ocia

tion

with

the

folli

cula

r str

uctu

re

(hem

atox

ylin

and

eos

in, m

agni

ficat

ion

X 10

0).

Poro

kera

totic

Ecc

rine

Ost

ial a

nd D

erm

al D

uct N

evus

(P

EODD

N) w

as fi

rst d

escr

ibed

in 1

979

by M

arsd

en, e

t al,

calli

ng it

“com

edo

nevu

s of t

he p

alm

.”1 It w

as fu

rthe

r de

scrib

ed in

198

0 by

Abe

ll an

d Re

ed w

ho g

ave

the

lesio

ns

thei

r cur

rent

nam

e. T

he h

istol

ogic

al fi

ndin

gs o

f bot

h ca

ses

wer

e ne

arly

the

sam

e. A

bell

and

Reed

des

crib

ed li

near

ep

ider

mal

nev

i on

the

side

of a

foot

. Th

e m

icro

scop

ic

exam

inat

ion

of th

eir p

atie

nt’s

biop

sy sp

ecim

en re

veal

ed

corn

oid

lam

ella

e as

soci

ated

with

ecc

rine

swea

t gla

nds a

nd

ostia

. The

y co

nsid

ered

the

lesio

n a

ham

arto

ma

of th

e ec

crin

e gl

ands

.2

Clas

sical

ly, p

atie

nts a

re b

orn

with

the

diso

rder

, how

ever

cas

es

of la

te o

nset

PEO

DDN

hav

e be

en re

port

ed.3,

4 Th

ere

appe

ars

to b

e no

gen

etic

com

pone

nt to

its e

tiolo

gy a

s the

re h

ave

been

no

repo

rts o

f a p

ositi

ve fa

mily

hist

ory.

Mos

t cas

es re

port

ed,

to d

ate,

hav

e pr

esen

ted

with

a u

nila

tera

l, di

stal

ext

rem

ity

affe

cted

. Th

e le

sions

are

gen

eral

ly lo

caliz

ed to

the

palm

ar o

r pl

anta

r sur

face

. Th

ere

are

two

clin

ical

type

s of l

esio

ns se

en in

PEO

DDN

ac

cord

ing

to L

eung

, et a

l.5 Th

e fir

st is

pal

mop

lant

ar p

apul

es

rese

mbl

ing

com

edon

es w

ith k

erat

in p

lugs

filli

ng c

entr

al p

its.

The

seco

nd is

ker

atot

ic p

apul

es a

nd p

laqu

es, r

esem

blin

g lin

ear v

erru

cous

epi

derm

al n

evi o

n ot

her a

reas

. A fe

w

hist

olog

ical

hal

lmar

ks h

ave

been

des

crib

ed. T

hese

incl

ude

corn

oid

lam

ella

e ex

clus

ivel

y as

soci

ated

with

ecc

rine

acro

syrin

gia5 ,

and

para

kera

totic

col

umns

ove

rlyin

g ec

crin

e du

cts4 ,

the

latt

er o

f whi

ch is

som

etim

es c

onsid

ered

pa

thog

nom

onic

for t

he c

ondi

tion.

Cas

es o

f rar

er le

sion

loca

tions

hav

e be

en re

port

ed su

ch a

s tho

se a

long

de

rmat

omes

and

Bla

schk

o lin

es.5,

6 Th

e et

iolo

gy o

f the

co

nditi

on re

mai

ns u

ncle

ar, a

lthou

gh se

vera

l pro

posa

ls ha

ve

been

mad

e. O

ne is

that

epi

derm

al in

vagi

natio

ns a

re w

idel

y di

late

d, k

erat

in-p

lugg

ed, a

cros

yrin

geal

duc

ts w

ith d

erm

al

duct

s con

tinui

ng fr

om th

e ba

se.3 A

noth

er p

ropo

sal i

s tha

t the

ep

ider

mal

inva

gina

tions

are

abn

orm

al c

lone

s of e

pide

rmal

ce

lls th

at p

rodu

ce a

cor

noid

lam

ella

-like

col

umn.

7 Th

ere

is no

evi

denc

e to

supp

ort t

hat a

n as

ympt

omat

ic p

atie

nt

with

PEO

DDN

mus

t be

trea

ted.

Alth

ough

it is

per

siste

nt,

case

s of i

nvol

utio

n of

the

lesio

ns w

ith ti

me

have

bee

n re

port

ed.8

Vario

us tr

eatm

ents

hav

e be

en a

ttem

pted

, inc

ludi

ng to

pica

l an

d sy

stem

ic re

tinoi

ds.

In c

ases

of l

ocal

dise

ase,

surg

ical

re

mov

al is

a re

ason

able

opt

ion.

If l

esio

ns a

re m

ore

wid

espr

ead,

few

trea

tmen

ts h

ave

prov

en e

ffect

ive.

The

use

of

car

bon

diox

ide

lase

r has

repo

rted

ly e

ffect

ivel

y tr

eate

d la

te o

nset

dise

ase

in o

ne c

ase.

9 U

ltra-

pulse

d ca

rbon

dio

xide

la

ser h

as a

lso b

een

show

n to

impr

ove

cosm

etic

out

com

es

with

succ

essf

ul tr

eatm

ent.5

Disc

ussio

n

Poro

kera

totic

Ecc

rine

Ost

ial a

nd D

erm

al D

uct N

evus

: A C

ase

Repo

rt a

nd L

itera

ture

Rev

iew

.

Benn

er N

A, C

ampb

ell S

, Hol

singe

r JM

, Sro

a N

. Ohi

o U

nive

rsity

Her

itage

Col

lege

of

Ost

eopa

thic

Med

icin

e/O

’Ble

ness

Mem

oria

l Hos

pita

l, De

pt. o

f Der

mat

olog

y, At

hens

, Ohi

o.

Fig.

3

Fi

g. 4

Poro

kera

totic

Ecc

rine

Ost

ial a

nd D

erm

al D

uct N

evus

(P

EODD

N) i

s a ra

re, b

enig

n, li

near

, ver

ruco

us co

nditi

on

mos

t com

mon

ly o

ccur

ing

on th

e pa

lms a

nd/o

r sol

es o

f in

fant

s at b

irth

or sh

ortly

ther

eafte

r. It

is re

lativ

ely

asym

ptom

atic

, with

onl

y oc

casio

nal r

epor

ts o

f pru

ritus

. Al

thou

gh se

vera

l etio

logi

c th

eorie

s exi

st, i

nclu

ding

ke

ratin

-plu

ggin

g an

d ab

norm

al e

pide

rmal

cel

l clo

nes,

the

hist

opat

holo

gic

findi

ngs a

re fa

irly

cons

isten

t. Th

ere

is a

corn

oid

lam

ella

e in

ass

ocia

tion

with

ecc

rine

acro

syrin

gia

and

para

kera

totic

col

umns

ove

rlyin

g ec

crin

e du

cts.

Pr

ogno

sis is

unc

lear

, but

sev

eral

trea

tmen

t mod

aliti

es

have

bee

n ut

ilize

d w

ith v

aryi

ng su

cces

s. T

hese

incl

ude

surg

ical

exc

ision

, sys

tem

ic a

nd to

pica

l ret

inoi

ds, a

nd

vario

us la

sers

. Whe

ther

lesio

ns w

ill re

turn

afte

r tr

eatm

ent i

s not

yet

kno

wn.

Disc

ussio

n

244

CR

ES

T S

yn

dro

me

M

arie

l Bird

, DO

, PGY

-III;

Stev

en G

reki

n, D

O, P

rogr

am D

irect

or

Mic

higa

n St

ate

Uni

vers

ity D

epar

tmen

t of D

erm

atol

ogy

Oak

woo

d Ho

spita

l Hea

lthca

re S

yste

m, T

rent

on, M

ichi

gan

Case

Pre

sent

atio

n Ch

ief C

ompl

aint

A 4

8-ye

ar-o

ld C

auca

sian

fem

ale

pres

ente

d w

ith f

irm

nodu

les o

n th

e le

ft 3

rd d

istal

fing

er.

Hist

ory

of P

rese

nt Il

lnes

s

The

pa

tient

re

port

ed

the

lesio

ns

deve

lope

d on

e m

onth

prio

r, bu

t w

ere

rapi

dly

enla

rgin

g an

d be

com

ing

pain

ful.

She

had

sim

ilar l

esio

ns in

the

past

that

she

was

ab

le t

o ex

trud

e to

the

sur

face

and

con

tain

ed a

cha

lky

whi

te m

ater

ial.

She

also

com

plai

ned

of fr

iabl

e, b

leed

ing

cutic

les.

Revi

ew

of

syst

ems

was

po

sitiv

e fo

r he

mat

oche

zia a

nd c

old

into

lera

nce.

Pas

t med

ical

hist

ory

was

unr

emar

kabl

e an

d th

e pa

tient

did

not

tak

e an

y m

edic

atio

ns.

She

deni

ed a

ny s

imila

r sy

mpt

oms

in o

ther

fa

mily

mem

bers

. Ph

ysic

al E

xam

inat

ion

Phy

sical

exa

min

atio

n re

veal

ed a

wel

l-app

earin

g pa

tient

with

thre

e 1-

2 m

m h

ard,

whi

te, m

obile

nod

ules

on

the

left

3rd

dist

al d

igit

(Fig

ure

1).

The

skin

of t

he le

ft

2nd

digi

t was

taut

and

shin

y w

ith a

reas

of e

xfol

iatio

n.

Alte

rnat

ing

dila

ted

capi

llary

loop

s wer

e pr

esen

t in

the

prox

imal

nai

l fol

ds a

nd m

ultip

le sc

atte

red,

mat

ted

tela

ngie

ctas

ia w

ere

pres

ent o

n th

e pa

lmar

surfa

ce o

f bo

th h

ands

(Fig

ures

2 a

nd 3

). La

bora

tory

Dat

a

The

AN

A tit

er w

as re

activ

e at

1:2

560

with

a

cent

rom

ere

patt

ern

(ant

icen

trom

ere)

. An

ti-sjo

gren

was

ne

gativ

e an

d ur

ic a

cid

leve

ls w

ere

with

in n

orm

al li

mits

. Co

urse

and

The

rapy

The

pat

ient

was

refe

rred

to su

rger

y fo

r rem

oval

of t

he

nodu

les a

nd p

rovi

ded

with

topi

cal l

idoc

aine

for

tem

pora

ry u

se.

Addi

tiona

lly, s

he w

as re

ferr

ed to

rh

eum

atol

ogy

to e

valu

ate

for t

he p

rese

nce

of in

tern

al

orga

n in

volv

emen

t.

Disc

ussi

on

Sy

stem

ic s

cler

osis

(SSc

) is

a fib

rosin

g au

toim

mun

e co

nnec

tive

tissu

e di

seas

e of

an

unkn

own

etio

logy

that

affe

cts

the

skin

, bl

ood

vess

els,

and

inte

rnal

org

ans.

Tw

o m

ajor

clin

ical

sub

type

s ex

ist in

reg

ards

to

cuta

neou

s di

strib

utio

n:

limite

d an

d di

ffuse

. Li

mite

d SS

c is

char

acte

rized

by

fibro

sis r

estr

icte

d to

the

fing

ers,

han

ds, a

nd fa

ce a

nd in

clud

es t

he

CRES

T sy

ndro

me.

Th

e ca

rdin

al f

eatu

res

of C

REST

syn

drom

e in

clud

e: C

alci

nosis

, Ray

naud

’s ph

enom

enon

, Eso

phag

eal

dysm

otili

ty, S

cler

odac

tyly

and

Tel

angi

ecta

sia.1

Cu

tane

ous

calc

ifica

tion

occu

rs in

25-

40%

of

patie

nts

with

lim

ited

SSc,

typ

ical

ly 1

0 ye

ars

or m

ore

afte

r di

seas

e on

set.2

Clin

ical

ly, c

alci

nosis

is u

sual

ly r

estr

icte

d to

are

as o

f re

curr

ent

mic

rotr

aum

a, s

uch

as t

he f

orea

rms,

elb

ows,

or

finge

rs,

but

may

also

be

seen

ove

r bo

ny p

rom

inen

ces

and

tend

ons.

Ext

rusio

n of

a c

halk

y m

ater

ial

and

loca

lized

ul

cera

tion

can

occu

r, pa

rtic

ular

ly o

n th

e vo

lar a

spec

ts o

f the

fing

ertip

s.1,

2

Ra

ynau

d’s

phen

omen

on, e

piso

dic

vaso

spas

m o

f the

dig

ital a

rter

ies,

usu

ally

pre

cede

s ot

her m

anife

stat

ions

of t

he

synd

rom

e.1,

3 N

ail f

old

capi

llary

exa

m c

an a

ide

in t

he d

iagn

osis

as a

dist

inct

pat

tern

of

capi

llary

loss

alte

rnat

ing

with

di

late

d lo

ops i

s cha

ract

erist

ic o

f SSc

, and

pro

xim

al n

ail f

old

abno

rmal

ities

are

pre

sent

in m

ore

than

90%

of p

atie

nts.

1

Esop

hage

al d

ysm

otili

ty m

ay p

rese

nt w

ith s

ympt

oms

of e

soph

agea

l ref

lux

incl

udin

g dy

spha

gia

and

post

pran

dial

bl

oatin

g. G

astr

oint

estin

al in

volv

emen

t is

not l

imite

d to

the

esop

hagu

s an

d m

ay in

volv

e ei

ther

the

uppe

r or l

ower

trac

t.

Sym

ptom

s m

ay in

clud

e he

mat

oche

zia, c

onst

ipat

ion

or d

iarr

hea,

and

abd

omin

al d

isten

tion

or d

ecre

ased

bow

el s

ound

s m

ay b

e pr

esen

t on

phys

ical

exa

m.1

Sc

lero

dact

yly

has

an e

arly,

rap

id e

dem

atou

s ph

ase

char

acte

rized

by

pitt

ing

edem

a.

A su

bseq

uent

indu

rate

d ph

ase

occu

rs in

whi

ch t

he s

kin

deve

lops

a t

aut,

shin

y ap

pear

ance

. Di

gita

l pitt

ing

scar

s or

loss

of

subs

tanc

e fr

om t

he

finge

r pad

may

also

be

seen

. An

atr

ophi

c ph

ase

follo

ws w

ith g

radu

al so

fteni

ng o

f the

skin

.1

Te

lang

iect

asia

occ

ur m

ore

com

mon

ly in

pat

ient

s w

ith li

mite

d di

seas

e th

an d

iffus

e di

seas

e.

Mos

t of

ten

they

pr

esen

t on

the

lips o

r pal

ms w

ith a

“squ

ared

-off

” or

mat

ted

appe

aran

ce.

Al

thou

gh C

REST

synd

rom

e is

a de

signa

tion

give

n to

a

subs

et o

f pat

ient

s w

ith li

mite

d SS

c, b

y de

finiti

on th

e di

seas

e is

syst

emic

and

a m

ajor

ity o

f pa

tient

s ha

ve in

tern

al o

rgan

in

volv

emen

t. T

he m

ost

com

mon

ly a

ffect

ed o

rgan

s ar

e th

e ga

stro

inte

stin

al t

ract

, lu

ngs,

hea

rt a

nd k

idne

ys,

and

the

lead

ing

caus

e of

dea

th is

due

to p

ulm

onar

y di

seas

e.1

W

hile

dia

gnos

is of

CRE

ST sy

ndro

me

cont

inue

s to

rely

m

ainl

y on

clin

ical

find

ings

, aut

oant

ibod

y te

stin

g is

usef

ul t

o co

nfirm

the

dia

gnos

is.

82-9

6% o

f pa

tient

s ha

ve e

leva

ted

titer

s of

ant

inuc

lear

ant

ibod

ies

with

an

anti-

cent

rom

ere

patt

ern.

1,4

CR

EST

synd

rom

e ha

s no

cur

e.

Asid

e fr

om s

urgi

cal

rese

ctio

n , n

o re

liabl

e th

erap

y fo

r cal

cino

sis h

as b

een

foun

d.

Rayn

aud’

s ph

enom

enon

is t

reat

ed w

ith b

ehav

iora

l the

rapy

or

va

sodi

lato

rs.

Esop

hage

al

dysm

otili

ty

is m

anag

ed

by

hist

amin

e bl

ocke

rs.

The

scl

erod

erm

atou

s co

mpo

nent

of

CRES

T sy

ndro

me

pose

s a

maj

or c

halle

nge,

as

it is

diffi

cult

to

asse

ss o

utco

me

mea

sure

s in

ski

n in

dura

tion

that

pro

gres

ses

slow

ly o

ver

long

per

iods

of

time.

1 Tr

eatm

ents

trie

d ha

ve

incl

uded

pen

icill

amin

e, m

inoc

yclin

e, a

nd m

etho

trex

ate,

but

no

ne h

ave

been

pro

ven

effe

ctiv

e.1,

5-7

The

pulse

d-dy

e la

ser i

s ef

fect

ive

cosm

etic

tr

eatm

ent

for

tela

ngie

ctas

ia.1

Mos

t im

port

antly

, pat

ient

s m

ust

be m

onito

red

for

inte

rnal

org

an

invo

lvem

ent,

whi

ch is

the

caus

e of

sig

nific

ant m

orbi

dity

and

m

orta

lity

in th

is di

seas

e.

Refe

renc

es

1. B

olog

nia

J, Jo

rizzo

J, R

apin

i R. D

erm

atol

ogy,

2nd e

dn. M

osby

Else

vier

, 20

08:5

85-5

96.

2. R

eite

r N

, El

-Sha

braw

i L,

Lei

nweb

er B

, et

al.

Calc

inos

is Cu

tis.

Part

I

Diag

nost

ic P

athw

ay. J

Am

Aca

d De

rmat

ol. 2

011;

65:1

-12.

3.

May

es M

D, L

acey

JV J

r, Be

ebe-

Dim

mer

J,et

al.

Prev

alen

ce, i

ncid

ence

, su

rviv

al, a

nd d

iseas

e ch

arac

teris

tics

of s

yste

mic

scl

eros

is in

a la

rge

US

popu

latio

n. A

rthr

itis R

heum

200

3;48

:224

6-55

. 4.

Aes

chlim

ann

A, M

eyer

O,

Bour

geoi

s P,

et

al.

Anti-

Scl-7

0 an

tibod

ies

dete

cted

by

imm

unob

lott

ing

in p

rogr

essiv

e sy

stem

ic s

cler

osis:

spe

cific

ity

and

clin

ical

cor

rela

tions

. Ann

Rhe

um D

is 19

89;4

8:99

2-7.

5.

Cle

men

ts P

J, Fu

rst D

E, W

ong

WK,

et a

l. Hi

gh-d

ose

vers

us lo

w-d

ose

D-pe

nici

llam

ine

in e

arly

diff

use

syst

emic

scl

eros

is: a

naly

sis o

f a

two-

year

, do

uble

-blin

d, r

ando

mize

d, c

ontr

olle

d cl

inic

al

tria

l. Ar

thrit

is Rh

eum

. 19

99;4

2:11

94-2

03.

6.

May

es M

D, O

’Don

nell

D, R

othf

ield

NF,

et a

l. M

inoc

yclin

e is

not

effe

ctiv

e in

sys

tem

ic s

cler

osis:

resu

lts o

f an

open

-labe

l mul

ticen

ter

tria

l. Ar

thrit

is Rh

eum

200

4;50

:553

-7.

7. P

ope

JE, B

ella

my

N, S

eibo

ld JR

, et a

l. A

rand

omize

d co

ntro

lled

tria

l of

met

hotr

exat

e ve

rsus

pla

cebo

in

early

diff

use

scle

rode

rma.

Art

hriti

s Rh

eum

. 200

1;44

:135

1-8.

Figu

re 2

: Alte

rnat

ing

dila

ted

capi

llary

loop

s Fi

gure

1: 1

-2 m

m fi

rm w

hite

no

dule

s Fi

gure

3: S

quar

ed o

ff an

d m

atte

d te

lang

iect

asia

245

TEM

PLAT

E D

ESIG

N ©

200

8

ww

w.P

oste

rPre

sent

atio

ns.c

om

An U

ncom

mon C

ause

of P

urpu

ra F

ulmina

ns: P

aste

urell

a mult

ocida

Sep

sis

Lise D

. Bro

wn D

.O.1 ,

Ther

esa C

ao D

.O.1 ,

David

Dro

ller M

.D.2 A

ngela

Com

bs, D

.O. 3 T

racy

Fav

reau

, D.O

.3

ABST

RACT

DI

SCUS

SION

(con

t’d)

DISC

USSI

ON (c

ont’d

)

CONC

LUSI

ON

1.W

yson

g A, V

enka

tesan

P. A

n app

roac

h to t

he pa

tient

with

retifo

rm pu

rpur

a. De

rmato

lol

Ther

apy.

2011

Mar

ch-A

pr; 2

4(2)

:151-

172.

2.Ch

almer

s E, C

oope

r P, F

orma

n K, G

rimley

C, K

hair K

, Minf

ord A

, Mor

gan M

, Mum

ford

AD. P

urpu

ra fu

lmina

ns: r

ecog

nition

, diag

nosis

and m

anag

emen

t. Arch

Dis

Child

2010

3.

Fran

cis R

B. A

cquir

ed pu

rpur

a fulm

inans

. Sem

in Th

romb

Hae

mosta

t 199

0 16:3

10-2

5. 4.

Nolan

J, S

inclai

r R. R

eview

of m

anag

emen

t of p

urpu

ra fu

lmina

ns an

d two

case

repo

rts.

Br J

Anae

sth. 2

001 8

6:581

-6.

5.Ga

llowa

y RE.

Mam

malia

n bite

s. J E

merg

Med

1988

;6:32

5-31

. 6.

Web

er D

J, Ha

nsen

AR.

Infec

tions

resu

lting f

rom

anim

al bit

es. In

fect D

is Cl

in No

rth A

m.

1991

;5:66

3-80

. 7.

Zurlo

JJ. P

asteu

rella

spec

ies. M

ande

ll, Do

uglas

, and

Ben

nett’s

Prin

ciples

and P

racti

ce

of Inf

ectio

us D

iseas

es. 7

th ed.

2009

Chu

rchill

Living

stone

. 8.

Web

er D

J, W

olfso

n JS,

Swa

tz MN

, Hoo

per D

C. P

asteu

rella

mult

ocida

infec

tions

. Rep

ort

of 34

case

s and

revie

w of

the lit

eratu

re. M

edici

ne. 1

984 M

ay, 6

3(3)

:133-

54.

9.Go

ldstei

n EJ.

Bite

woun

ds an

d infe

ction

. Clin

Infec

t Dis

1992

14:63

3-63

8.

10.

Fern

ande

z-Vale

ncia

JA, G

arcia

S, P

rat S

. Pas

teure

lla m

ultoc

ida se

ptic s

hock

after

a ca

t sc

ratch

in an

elde

rly ot

herw

ise he

althy

wom

an: a

case

repo

rt. A

m J E

merg

Med

. 200

8.

11.

Golds

tein E

JC, R

einha

rdt J

F, Mu

rray P

M. O

utpati

ent th

erap

y of b

ite w

ound

s: de

mogr

aphic

data,

bacte

riolog

y, an

d a pr

ospe

ctive

, ran

domi

zed t

rial o

f am

oxoc

illin/c

lavula

nic ac

id ve

rsus p

enici

llin +/

- dicl

oxac

illin.

Int J

Derm

atol 1

987;2

6:124

-7.

12

.Am

erica

n Aca

demy

of P

ediat

rics.

Pastu

rella

infec

tions

. In R

ed B

ook:

2009

Rep

ort o

f the

Comm

ittee o

n Infe

ctiou

s Dise

ases

, 28th e

d. Pi

cker

ing, L

K (E

d), A

m Ac

ad P

ed, E

lk Gr

ove

Villa

ge, Il

2009

, p. 4

93.

(for p

atien

ts 18

year

s of a

ge an

d olde

r), d

oxyc

yclin

e (for

child

ren 8

ye

ars o

f age

and o

lder),

and t

he ex

tende

d spe

ctrum

ceph

alosp

orins

su

ch as

cefix

ine or

cefpo

doxim

e, as

well

as tr

imeth

oprim

-su

lfame

thoxa

zole,

altho

ugh m

etron

idazo

le sh

ould

be ad

ded t

o the

se

antib

iotics

for a

naer

obic

cove

rage

.11 C

linica

l failu

res h

ave b

een n

oted

in pa

tients

trea

ted w

ith or

al ma

crolid

es, s

emi-s

ynthe

tic pe

nicilli

ns su

ch

as di

cloxa

cillin

, first

-gen

erati

on ce

phalo

spor

ins an

d clin

damy

cin an

d thu

s sho

uld be

avoid

ed.12

CASE

REP

ORT

A 74

year

old C

auca

sian w

oman

with

a pa

st me

dical

histor

y sign

ifican

t for

hype

rtens

ion an

d car

otid a

rtery

disea

se w

as fo

und u

nres

pons

ive in

he

r car

on a

hot s

umme

r day

. In th

e ER,

she w

as no

ted to

be

hypo

tensiv

e and

hype

rther

mic w

ith a

tempe

ratur

e of 1

07 de

gree

s Fa

hren

heit.

Her la

bs su

gges

ted sh

e was

in ea

rly di

ssem

inated

int

rava

scula

r coa

gulop

athy.

Over

her b

ack a

nd an

terior

thigh

s wer

e re

tiform

purp

ura a

nd la

rge,

hemo

rrhag

ic bu

llae (

Figur

e 1.),

as w

ell as

pe

techia

e of th

e fac

e (Fig

ure 2

.). S

he w

as pl

aced

on po

sitive

inotr

opic

supp

ort, c

ooled

to a

tempe

ratur

e of 1

02 de

gree

s, mu

ltiple

blood

cu

lture

s wer

e dra

wn, a

nd sh

e was

star

ted on

broa

d spe

ctrum

empir

ic an

tibiot

ics. T

he pa

tient

was

place

d in r

espir

atory

isolat

ion w

ith a

pres

umpti

ve di

agno

sis of

men

ingoc

occe

mia b

ased

on pr

elimi

nary

blood

cultu

res p

ositiv

e for

Gra

m ne

gativ

e coc

coba

cilli.

She a

lso

rece

ived s

ubcu

taneo

us lo

w-mo

lecula

r weig

ht he

parin

. Fur

ther h

istor

y fro

m the

patie

nt’s f

amily

reve

aled t

wo da

ys pr

ior sh

e had

been

bitte

n on

the l

eg by

her in

door

pet c

at an

d dev

elope

d cell

ulitis

(Figu

re 3.

). On

ly on

e of s

ix blo

od cu

lture

s tak

en ov

er a

perio

d of tw

o day

s sho

wed

grow

th of

pan-

sens

itive P

aste

urell

a m

ultoc

ida. A

cere

bros

pinal

fluid

analy

sis w

as no

t per

forme

d due

to se

vere

thro

mboc

ytope

nia. A

deep

tis

sue c

ultur

e fro

m the

pupu

ric fu

lmina

ns er

uptio

n on t

he th

igh w

as

nega

tive f

or gr

owth.

Immu

noglo

bulin

leve

ls an

d a se

rum

prote

in ele

ctrop

hore

sis w

ith im

muno

fixati

on w

ere o

rder

ed to

rule

out a

n un

derly

ing im

muno

defic

iency

. Whil

e the

stud

ies di

d not

demo

nstra

te a

mono

clona

l gam

mopa

thy, s

he di

d hav

e acq

uired

IgG

defic

iency

se

cond

ary t

o sep

sis an

d sub

sequ

ently

rece

ived I

VIG.

Ove

r the

fol

lowing

two w

eeks

, the p

atien

t was

wea

ned f

rom

vaso

pres

sor

supp

ort. H

er la

b valu

es no

rmali

zed,

howe

ver, s

he re

maine

d mini

mally

re

spon

sive a

nd w

as su

bseq

uentl

y tra

nsfer

red t

o a ch

ronic

venti

lator

an

d reh

abilit

ation

unit f

or se

vere

ence

phalo

pathy

attrib

uted t

o the

hy

perth

ermi

a she

had s

ustai

ned.

Unfor

tunate

ly, th

e pati

ent p

asse

d aw

ay a

month

and a

half l

ater.

CLIN

ICAL

IMAG

ES

DISC

USSI

ON 1 D

erma

tolog

y Res

ident,

Nov

a Sou

theas

tern U

niver

sity C

olleg

e of O

steop

athic

Medic

ine/B

rowa

rd G

ener

al Me

dical

Cente

r, For

t Lau

derd

ale, F

lorida

; 2 Divi

sion o

f Infec

tious

Dise

ases

, Bro

ward

Gen

eral

Medic

al Ce

nter, F

ort L

aude

rdale

, FL;

3 Co-

Prog

ram

Dire

ctor, N

ova S

outhe

aster

n Univ

ersit

y Coll

ege o

f Oste

opath

ic Me

dicine

/Bro

ward

Gen

eral

Medic

al Ce

nter D

erma

tolog

y Res

idenc

y, Fo

rt La

uder

dale,

Flor

ida

Figu

re 1.

Pur

pura

fulm

inans

of th

e bila

teral

thigh

s.

Fres

h fro

zen p

lasma

also

conta

ins pr

otein

C, bu

t in le

sser

co

ncen

tratio

ns. H

epar

in, w

hile t

heor

etica

lly in

dicate

d in p

atien

ts wi

th thr

ombo

sis (i.

e., pa

tients

in D

IC),

is lim

ited b

y the

degr

ee of

thr

ombo

cytop

enia;

a no

t unc

ommo

n find

ing in

critic

ally i

ll pati

ents.

Th

ere a

re ar

gume

nts fo

r givi

ng he

parin

befor

e clot

ting f

actor

s are

re

place

d, in

orde

r to a

void

furthe

r thr

ombo

sis.4 A

t time

s, su

rgica

l de

bride

ment

of ne

crotic

skin,

esch

aroto

mies

, and

fasc

iotom

ies m

ay

be in

dicate

d, as

well

as su

bseq

uent

skin

graft

ing. D

eep n

ecro

sis of

lim

bs or

digit

s may

be ex

tensiv

e eno

ugh t

o war

rant

ampu

tation

. Sp

ecies

of th

e gen

us P

aste

urell

a ar

e non

motile

, facu

ltativ

e ana

erob

ic,

gram

-neg

ative

cocc

obac

illi th

at inh

abit t

he or

al ca

vity a

nd

gastr

ointes

tinal

tract

of ma

ny an

imals

, with

dogs

and c

ats ha

ving

partic

ularly

high

colon

izatio

n rate

s. Th

e mos

t com

mon h

uman

isola

tes

belon

g to t

he P.

mult

ocida

grou

p. Ap

prox

imate

ly 15

% to

20%

of do

g bit

e wou

nds a

nd up

to 50

% of

cat b

ite w

ound

s bec

ome i

nfecte

d.5 M

ost

infec

tions

that

deve

lop fr

om do

g and

cat b

ites a

re p

olymi

crobia

l. In a

stu

dy of

107 s

ubjec

ts wi

th do

g and

cat b

ite in

fectio

ns, m

ixed a

erob

ic an

d ana

erob

ic inf

ectio

ns w

ere p

rese

nt in

56%

of al

l wou

nds (

dogs

: 48

%; c

ats: 6

3%).

Paste

urell

a spe

cies w

as th

e mos

t com

mon

patho

gen i

solat

ed fr

om bo

th do

g (50

%) a

nd ca

t (75

%) b

ites f

ollow

ed

by S

trept

ococ

ci (4

6% of

both

types

of bi

te inf

ectio

ns).6

Paste

urell

a spe

cies a

re fa

stidio

us an

d can

be di

fficult

to is

olate

espe

cially

from

nons

terile

spec

imen

s suc

h as s

putum

.7 In G

ram

staine

d spe

cimen

s, the

y gen

erall

y app

ear a

s a si

ngle

bacil

lus, o

ften

with

bipola

r stai

ning,

but m

ay al

so be

seen

in pa

irs or

shor

t cha

ins an

d ca

n be c

onfus

ed w

ith N

eisse

ria m

ening

itidis.

Th

e mos

t com

mon t

ypes

of in

fectio

ns ca

used

by P.

mult

ocida

are l

ocal

woun

d infe

ction

s foll

owing

anim

al bit

es or

scra

tches

. Abs

cess

es an

d ten

osyn

ovitis

are t

he m

ost fr

eque

nt co

mplic

ation

s of P

aste

urell

a soft

tis

sue i

nfecti

on, w

ith se

ptic a

rthriti

s and

oste

omye

litis b

eing l

ess

comm

on.8 O

ther s

ites o

f infec

tion,

besid

es sk

in an

d soft

tissu

e, ar

e un

comm

on an

d hav

e bee

n des

cribe

d in c

ase r

epor

ts an

d sma

ll cas

e se

ries.

Exam

ples i

nclud

e men

ingitis

, foca

l bra

in les

ions,

uppe

r and

lowe

r re

spira

tory t

ract

infec

tions

, and

intra

-abd

omina

l infec

tions

and t

ypica

lly

occu

r in pr

edisp

osed

patie

nts w

ith un

derly

ing lu

ng or

liver

dise

ase.

9 A

high p

ropo

rtion o

f pati

ents

with

comp

licati

on of

septi

c sho

ck ex

hibite

d se

rious

unde

rlying

med

ical c

ondit

ions.

A lite

ratur

e rev

iew fo

r Pa

steur

ella s

eptic

shoc

k in a

n othe

rwise

healt

hy pa

tient

yields

only

a few

case

repo

rts, w

hich d

escri

be pr

eviou

sly he

althy

indiv

iduals

who

de

velop

ed se

ptic s

hock

and D

IC.10

Spe

cific

skin

findin

gs in

cludin

g pu

rpur

a fulm

inans

wer

e not

desc

ribed

. Em

piric

antim

icrob

ial th

erap

y for

infec

ted do

g and

cat b

ite w

ound

s sh

ould

includ

e cov

erag

e aga

inst P

aste

urell

a, str

eptoc

occi,

sta

phylo

cocc

i, and

anae

robic

spec

ies. T

he co

mbina

tion o

f a pe

nicilli

n wi

th a b

eta-la

ctama

se in

hibito

r is w

idely

reco

mmen

ded f

or pa

tients

wi

th no

histo

ry of

penic

illin a

llerg

y. Ot

her o

ption

s inc

lude

levofl

oxac

in

We d

escri

be a

case

of P

aste

urell

a sep

sis co

mplic

ated b

y dis

semi

nated

intra

vasc

ular c

oagu

lopath

y with

skin

findin

gs of

purp

ura

fulmi

nans

. The

mos

t com

mon i

nfecti

ons c

ause

d by P

. mult

ocida

are

local

woun

d infe

ction

s foll

owing

anim

al bit

es or

scra

tches

. Mor

e se

vere

infec

tions

inclu

ding s

epsis

, men

ingitis

, or p

ulmon

ary d

iseas

e typ

ically

occu

r in pa

tients

with

unde

rlying

med

ical p

roble

ms. A

lite

ratur

e sea

rch re

veals

only

a han

dful o

f cas

e rep

orts

of P.

mult

ocida

se

psis

occu

rring

in pr

esum

ably

healt

hy in

dividu

als. M

anag

emen

t of

purp

ura f

ulmina

ns is

also

revie

wed.

Figu

re 3.

Pun

cture

wou

nd of

the

lower

leg f

rom

a cat

bite.

The t

erm

'retifo

rm pu

rpur

a' de

scrib

es le

sions

that

demo

nstra

te an

an

gulat

ed or

bran

ched

confi

gura

tion a

nd oc

curs

in a v

ariet

y of

disor

ders

as a

cons

eque

nce o

f disr

upted

vasc

ular f

low in

the s

kin or

su

bcuti

s due

to ve

ssel

occlu

sion.

1 Ves

sel o

cclus

ion ca

n res

ult fr

om

throm

bosis

or ve

ssel

wall d

estru

ction

. If is

chem

ia is

prolo

nged

, skin

ne

crosis

due t

o infa

rction

may

be pr

esen

t.

The t

erm

'purp

ura f

ulmina

ns' re

fers t

o wide

spre

ad re

tiform

purp

ura a

nd

occu

rs in

seve

ral c

linica

l sett

ings,

most

notab

ly in

patie

nts w

ho ar

e cri

ticall

y ill w

ith D

IC. P

urpu

ra fu

lmina

ns in

the l

atter

case

is th

ough

t to

be a

resu

lt of a

cquir

ed pr

otein

C de

ficien

cy 2 ,

and i

s mos

t com

monly

att

ribute

d to m

ening

ococ

cemi

a.

Purp

ura f

ulmina

ns in

a se

ptic p

atien

t is an

omino

us si

gn to

the

serio

usne

ss of

the u

nder

lying

cond

ition.

Repla

ceme

nt of

defic

ient

blood

comp

onen

ts wi

th fre

sh fr

ozen

plas

ma an

d clot

ting f

actor

s and

tre

ating

the u

nder

lying

caus

e are

the m

ainsta

y of th

erap

y. St

udies

with

ac

tivate

d pro

tein C

conc

entra

te ha

ve sh

own p

romi

sing r

esult

s in

reve

rsing

purp

ura f

ulmina

ns on

ce th

e pro

cess

has b

egun

.3

REFE

RENC

ES

This

case

demo

nstra

tes an

unus

ual c

ause

of p

urpu

ra fu

lmina

ns in

a pa

tient

with

Paste

urell

a sep

sis. I

t stre

sses

the i

mpor

tance

of

reco

gnizi

ng ca

t bite

s as a

poten

tial c

ause

for m

ore s

eriou

s infe

ction

s, ev

en in

seem

ingly

healt

hy in

dividu

als. P

roph

ylacti

c anti

biotic

s sho

uld

be im

pleme

nted w

ithin

24 ho

urs f

or pu

nctur

e wou

nds,

espe

cially

if the

pa

tient

has u

nder

lying

cirrh

osis.

Anti

biotic

choic

e sho

uld be

base

d on

the m

ultipl

e stud

ies de

mons

tratin

g tha

t cat

and d

og bi

te wo

unds

are

polym

icrob

ial. O

ur ca

se al

so de

mons

trates

that

in se

ptic p

atien

ts,

multip

le blo

od cu

lture

s may

be ne

cess

ary t

o ide

ntify

the cu

lprit,

given

tha

t cer

tain o

rgan

isms s

uch a

s Pas

teur

ella

mult

ocida

are f

astid

ious.

Al

thoug

h a tis

sue c

ultur

e fro

m the

bite

woun

d was

not p

erfor

med,

in re

trosp

ect, i

t may

have

been

helpf

ul sh

ould

the bl

ood c

ultur

es ha

ve

rema

ined n

egati

ve. F

urthe

rmor

e, ea

rly re

cogn

ition o

f pur

pura

fulm

inans

inf

ectio

ns m

ay tr

ansla

te int

o ear

ly im

pleme

ntatio

n of fr

esh f

roze

n pla

sma o

r pro

tein C

conc

entra

te to

halt e

volut

ion of

skin

lesion

s.

Purp

ura i

s a br

oad t

erm

used

to de

scrib

e non

blanc

hable

, he

morrh

agic

skin

lesion

s tha

t res

ult fr

om lo

cal e

xtrav

asati

on of

red

blood

cells

in th

e skin

. Plat

elet d

isord

ers o

r exc

essiv

e pre

ssur

e ap

plied

to th

e skin

may

caus

e dam

age t

o sup

erfic

ial ca

pillar

ies or

sm

all ca

liber

vess

els an

d pre

sent

as sm

all, p

urpu

ric le

sions

1 - 2

mm

in dia

meter

refer

red t

o as p

etech

iae.

DISC

USSI

ON (c

ont’d

)

Figu

re 2.

Pete

chiae

.

246

Tem

plat

e pr

ovid

ed b

y: “p

oste

rs4r

esea

rch.

com

”

Trea

tmen

t of

Ver

ruca

Vul

gari

s w

ith

Nd:

YAG

106

4nm

Las

er

Win

ifred

S. C

hu, D

.O.,

M.P

.H.

St. J

ohn’

s Ep

isco

pal H

ospi

tal-

Dep

artm

ent o

f Der

mat

olog

y- D

r. M

arvi

n W

atsk

y, D

.O.

Prog

ram

Dire

ctor

Abst

ract

C

ase P

rese

ntat

ion

V

erru

ca vu

lgaris

(com

mon w

arts)

are c

ause

d by H

PV in

fectio

n of th

e epit

helia

l tis

sues

of th

e skin

and m

ucou

s mem

bran

es. T

hey m

ay be

foun

d any

wher

e on t

he sk

in,

partic

ularly

on th

e dor

sum

of the

hand

, betw

een t

he fin

gers,

and a

roun

d the

nails

(p

eriun

gual)

. Tre

atmen

t opti

ons o

f ver

ruca

inclu

de: c

ryothe

rapy

with

liquid

nitro

gen,

salic

ylic

acid,

duct

tape,

canth

aridi

n, ble

omyc

in, su

rgica

l abla

tion,

cure

ttage

and d

esicc

ation

, 5-

Fluor

oura

cil, tr

etino

in, ci

metid

ine, im

iquim

od, in

trales

ional

immu

nothe

rapy

, and

lase

r tre

atmen

t usin

g puls

ed dy

e las

er, an

d CO2

lase

r. La

sers

such

as N

d:YAG

and K

TP 53

2nm

we

re re

porte

d to b

e effe

ctive

but th

ere i

s les

s evid

ence

for t

heir u

se. W

e pre

sent

a cas

e of a

39

year

-old

female

with

a wa

rt on

her f

inger

that

was r

esist

ant to

diffe

rent

thera

pies.

Ho

weve

r, afte

r the

use o

f four

Nd:Y

AG 1

064n

m las

er tr

eatm

ents,

the w

art w

as co

mplet

ely

destr

oyed

. This

case

illus

trates

and s

uppo

rts th

e effe

ctive

ness

of us

ing N

d:YAG

1064

nm

laser

ther

apy f

or tr

eatm

ent o

f ver

ruca

vulga

ris th

at do

not r

espo

nd to

stan

dard

ther

apy.

Ear

ly ins

titutio

n of th

is tre

atmen

t opti

on ca

n help

to pr

even

t war

t gro

wth a

nd sp

read

ing, a

nd al

low

for ea

rly di

seas

e rem

ission

.

A

39-ye

ar-o

ld Ca

ucas

ian fe

male

pres

ents

to a p

rivate

derm

atolog

y pra

ctice

with

a 2m

m, no

n-pr

uritic

, per

iungu

al, ve

rruco

us pa

pule

on he

r righ

t third

finge

r. Th

e les

ion w

as fir

st no

ticed

to be

a fle

sh-co

lored

bump

whic

h gre

w in

size o

ver t

he pa

st few

mon

ths.

A dia

gnos

is of

verru

ca vu

lgaris

was

mad

e, an

d pati

ent r

eceiv

ed m

ultipl

e tre

atmen

t ses

sions

using

liquid

nit

roge

n for

war

t des

tructi

on. H

owev

er, sh

e rep

orted

no im

prov

emen

t at h

er fo

llow-

up vi

sits

and t

he w

art r

emain

ed to

be of

the s

ame s

ize. S

ubse

quen

tly, p

atien

t was

pres

cribe

d top

ical

treatm

ents

includ

ing A

ldara

5% cr

eam,

Ver

egen

15%

ointm

ent, a

nd Z

yclar

a but

they d

id no

t sig

nifica

ntly h

elp to

decre

ase t

he si

ze of

the w

art.

At he

r ten

th vis

it to o

ur of

fice,

patie

nt be

gan t

o rec

eive N

d:YAG

1064

nmm

laser

ther

apy f

or w

art tr

eatm

ent a

t two w

eeks

inter

val.

After

the c

omple

tion o

f the f

ourth

lase

r tre

atmen

t, the

war

t was

comp

letely

destr

oyed

. HP

I: 39 y

ear-o

ld Ca

ucas

ian fe

male

pres

ents

to the

derm

atolog

y offic

e c/o

a non

-itchy

, un

painf

ul bu

mp on

her f

inger

that

has b

een i

ncre

asing

in si

ze fo

r the

past

few m

onths

. PM

H: de

nies

PS

H: de

nies

Me

ds: d

enies

Al

lergie

s: NK

DA

Socia

l Hx:

denie

s tob

acco

, alco

hol o

r illic

it dru

g use

FH

: non

-contr

ibutor

y RO

S: de

nies a

ny sy

stemi

c sym

ptoms

PE

: 2mm

flesh

-color

ed, fi

rm, h

yper

kera

totic,

verru

cous

papu

le wi

th dis

rupti

on of

norm

al fin

gerp

rint li

nes a

nd di

splay

of sm

all bl

ack d

ots (t

hrom

bose

d cap

illarie

s) on

right

midd

le thi

rd

finge

r clos

e to t

he na

il Dx

: Ver

ruca

Vulg

aris

(bas

ed up

on cl

inica

l app

eara

nce)

Ma

nage

ment:

cryo

thera

py w

ith liq

uid ni

troge

n, po

doph

yllin,

Alda

ra 5%

crea

m Qd

x8 w

ks,

Vere

gen 1

5% oi

ntmen

t Tid

x 4 w

ks, Z

yclar

a 3.75

% cr

eam

Qd x

4wks

, 4 tr

eatm

ents

with

Nd:Y

AG 10

64 nm

lase

r (2m

m sp

ot, po

wer 8

/9, 2

pass

es).

Disc

ussio

n

Figu

re 2.

Bef

ore (

left)

and A

fter (

right

) Las

er Tr

eatm

ent

Ve

rruca

vulga

ris ar

e cau

sed b

y HPV

infec

tion (

subty

pes 1

,2,4,2

7,57,

and 6

3), a

nd oc

cur

mostl

y in c

hildr

en an

d you

ng ad

ults.

The

y are

usua

lly as

ympto

matic

, and

are t

rans

mitte

d via

skin-

to-sk

in co

ntact.

Tra

uma a

nd m

acer

ation

may

facil

itate

initia

l epid

erma

l inoc

ulatio

n, an

d spr

eadin

g ma

y sub

sequ

ently

occu

r by a

utoino

culat

ion.

Comm

on w

arts

are o

ften p

rese

nt as

well

-de

marca

ted, r

ough

, har

d nod

ules o

r plaq

ues w

ith irr

egula

r sur

faces

. Diag

nosis

of v

erru

ca is

ba

sed u

pon c

linica

l app

eara

nce.

Spo

ntane

ous r

emiss

ion of

war

ts oc

curs

in up

to tw

o-thi

rds o

f pa

tients

with

in tw

o yea

rs; he

nce,

obse

rvatio

n is a

n opti

on fo

r all p

atien

ts. H

owev

er, re

curre

nce o

f ve

rruca

is co

mmon

, so i

t is be

tter a

nd ea

sier t

o tre

at a w

art w

hen i

t is sm

aller

in si

ze th

an w

ait

until

it enla

rges

or m

ultipl

e to i

nitiat

e tre

atmen

t.

Trea

tmen

t of v

erru

ca in

volve

s two

appr

oach

es: d

estru

ction

of w

art a

nd in

ducti

on of

loca

l im

mune

reac

tion w

ith im

muno

thera

py.

Destr

uctiv

e meth

ods a

re m

ost c

ommo

nly us

ed as

initia

l the

rapy

and t

hey i

nclud

e cryo

surg

ery,

electr

ocau

tery,

cure

ttage

, exc

ision

, lase

r the

rapy

. Im

muno

thera

py is

aime

d at e

licitin

g an

immu

ne re

spon

se to

HPV

whic

h may

be ac

hieve

d by

apply

ing to

pical

irrita

nt su

ch as

salic

ylic a

cid, c

antha

ridin,

trich

loroa

cetic

acid

, pod

ophy

llum

resin

, 5-

Fluor

oura

cil, o

r tre

tinoin

over

the w

art.

Thes

e com

poun

ds ca

n also

be us

ed in

comb

inatio

n or

with

a des

tructi

ve m

ethod

. Anti

viral

effec

t can

be ac

hieve

d with

bleo

mycin

and i

nterfe

ron ɑ

2b bu

t the

y are

rese

rved f

or re

calci

trant

warts

. Imi

quim

od 5%

crea

m ma

y be u

sed t

o ind

uce s

kin lo

cally

to

prod

uce a

ntivir

al cy

tokine

s. In

trales

ional

immu

nothe

rapy

with

skin

test a

ntige

ns (ie

: mum

ps,

Cand

ida, o

r Tric

hoph

yton a

ntige

ns) a

nd H

PV va

ccine

have

demo

nstra

ted su

cces

s in t

reati

ng

warts

. Les

ions t

hat h

ave f

ailed

to re

spon

d to r

outin

e offic

e mod

alitie

s are

often

succ

essfu

lly

treate

d with

lase

r the

rapy

such

as ca

rbon

diox

ide or

pulse

d dye

lase

r. Nd

:YAG

1064

nm la

ser

have

also

been

repo

rted t

o be s

ucce

ssful

in tr

eatin

g ver

ruca

, and

has r

eceiv

ed F

DA cl

eara

nce f

or

this i

ndica

tion.

The N

d:YAG

106

4nm

laser

trea

tmen

t invo

lves t

he de

liver

y of la

ser li

ght ir

radia

tion a

t wa

velen

gth 10

64nm

, whic

h allo

ws p

enetr

ation

into

deep

er an

d thic

ker t

issue

comp

aring

to sh

orter

wa

velen

gth la

sers,

and t

he la

ser u

sed i

n this

stud

y doe

s not

conta

ct the

verru

ca. T

his la

ser is

also

us

ed fo

r tre

ating

vasc

ular &

pigm

ented

lesio

ns, h

air an

d PFB

remo

val, s

kin re

juven

ation

, on

ycho

myco

sis an

d man

y othe

r aes

thetic

and m

edica

l trea

tmen

ts. A

minim

um o

f one

to tw

o tre

atmen

t ses

sions

are n

eede

d, wi

th se

ssion

s spa

ced b

etwee

n two

to th

ree w

eeks

apar

t. Tr

eatm

ent s

essio

ns us

ually

begin

using

a foc

used

lens

with

a 2m

m sp

ot un

der t

he se

ttings

of

1.5ms

pulse

dura

tion a

nd en

ergy

mod

e of 8

or 9

(fluen

ce of

255 J

/cm² t

o 287

J/cm

²). A

s in t

he

case

of ou

r pati

ent, a

total

of tw

o pas

ses o

ver t

he w

art w

ere a

pplie

d with

each

trea

tmen

t ses

sion

and p

atien

t toler

ated t

he tr

eatm

ent v

ery w

ell. U

pon t

he en

d of th

e fou

rth tr

eatm

ent s

essio

n, the

pa

tient’

s war

t was

comp

letely

destr

oyed

. Bas

ed on

the c

ase t

hat w

e hav

e jus

t pre

sente

d, we

have

de

mons

trated

the s

ucce

ss of

utiliz

ing N

d:YAG

1064

nm la

ser in

trea

ting v

erru

ca th

at ha

d fail

ed in

re

spon

ding t

o stan

dard

trea

tmen

t. Der

matol

ogist

s sho

uld co

nside

r usin

g this

lase

r the

rapy

early

in

the co

urse

of tr

eatin

g res

istan

t war

ts sin

ce it

is we

ll tole

rated

by pa

tients

, and

it pr

ovide

s tim

ely,

signif

icant

resu

lts w

hich h

elp to

bring

dise

ase r

emiss

ion.

Tabl

e I.

Refe

renc

es

Figu

re 1.

Nd:

YAG

1064

nm L

aser

Pen

etra

tion

of d

epth

– T

echn

olog

y E

volu

tion

Bour

ke J

F, Be

rth-

Jone

s J,

Hutc

hins

on P

E. C

ryot

hera

py o

f com

mon

vira

l war

ts a

t int

erva

ls of

1, 2

and

3 w

eeks

. Br

J De

rmat

ol 1

995;

132

:433

. Bu

nney

MH,

Nol

an M

W, W

illia

ms D

A. A

n as

sess

men

t of m

etho

ds o

f tre

atin

g vi

ral w

arts

by

com

para

tive

trea

tmen

t tria

ls ba

sed

on a

stan

dard

des

ign.

Br J

Der

mat

ol 1

976;

94:

667.

Fo

cht D

R, S

pice

r C, F

airc

hok

MP.

The

effi

cacy

of d

uct t

ape

vs p

lace

bo in

the

trea

tmen

t of v

erru

ca v

ulga

ris (t

he c

omm

on

war

t).

Arch

Ped

iatr

Ado

lesc

Med

200

2; 1

56:9

71.

Jam

es W

D, B

erge

r TG,

Elst

on D

M. A

ndre

w’s

Dise

ases

of t

he S

kin:

Clin

ical

Der

mat

olog

y, 10

th E

d. P

hila

delp

hia:

WB

Saun

ders

, 20

00: 4

03-4

07.

John

son

SM, R

ober

son

PK, H

orn

TD.

Intr

ales

iona

l inj

ectio

n of

mum

ps o

r Can

dida

skin

test

ant

igen

s: a

nov

el

imm

unot

hera

py fo

r war

ts.

Arch

Der

mat

ol 2

003;

20:

268.

Ro

ss B

S, L

evin

e VJ

, Neh

al K

, et a

l. Pu

lsed

dye

lase

r tre

atm

ent o

f war

ts: a

n up

date

. Der

mat

ol S

urg

1999

; 25:

377.

Sl

oan

K, H

aber

man

H, L

ynde

CW

. Ca

rbon

dio

xide

lase

r-tr

eatm

ent o

f res

istan

t ver

ruca

e vu

lgar

is: re

tros

pect

ive

anal

ysis.

J

Cuta

n M

ed S

urg.

199

8; 2

(3):1

42-5

. ht

tp:/

/ww

w.m

erck

man

uals.

com

/pro

fess

iona

l/sec

10/c

h122

/ch1

22c.

htm

l.

247

Pai

nfu

l Pal

mar

Pet

ech

iae:

An

Aty

pica

l P

rese

nta

tion

of

Der

mat

itis

Her

peti

form

isN

ath

an C

leav

er D

O, A

nn

LaF

ond

MD

, Je

nn

y C

otto

n M

D P

hD

, Jam

es R

amir

ez M

D

St. J

osep

h M

ercy

Hos

pita

l •

Ann

Arb

or, M

ichi

gan

REM

AR

KA

BLE

MED

ICIN

E. R

EMA

RK

AB

LE C

AR

E.

Cas

e R

epor

t:H

PI:

57-

year

-old

Cau

casi

an m

ale

pres

ente

d w

ith

a on

e-m

onth

his

tory

of p

ainf

ul le

sion

s on

his l

eft h

and.

T

he p

atie

nt d

enie

d an

y tr

aum

a to

the

area

or h

isto

ry o

f sim

ilar a

ppea

ring

lesi

ons.

Pri

or to

pre

sent

atio

n,

the

prim

ary

care

phy

sici

an h

ad o

rder

ed a

n ec

hoca

rdio

gram

to ru

le o

ut e

ndoc

ardi

tis a

nd tr

eate

d hi

m w

ith

oral

cor

tico

ster

oids

wit

hout

relie

f.

PM

Hx:

Dia

bete

s m

elli

tus

type

I, p

revi

ous

myo

card

ial

infa

rcti

on, c

oron

ary

arte

ry d

isea

se,

hype

rten

sion

, and

hyp

erch

oles

tero

lem

ia.

PE

: A

ngul

ated

pet

echi

ae w

ere

obse

rved

on

the

dors

al le

ft h

and

and

mul

tipl

e di

gits

(Fi

gure

1 a

nd 2

). A

t th

e tw

o-w

eek

follo

w-u

p, h

e w

as c

onti

nuin

g to

dev

elop

new

pur

puri

c, h

yper

kera

toti

c pa

tche

s on

the

left

th

enar

em

inen

ce (

Figu

re 3

). O

n f

ollo

w-u

p si

x w

eeks

lat

er, t

he

pati

ent

retu

rned

wit

h k

erat

otic

, er

ythe

mat

ous p

apul

es a

nd sc

alin

g of

the

late

ral e

lbow

s and

the

left

late

ral t

high

(Fi

gure

4 a

nd 5

).

Ref

eren

ces:

1.

Bol

otin

D, P

etro

nic-

Ros

ic V

. Der

mat

itis

Her

peti

form

is. J

Am

Aca

d D

erm

atol

. Jun

e 20

11; 6

4 (6

):

1017

-103

3.2.

Hei

nlin

et a

l. D

erm

atit

is H

erpe

tifo

rmis

Pre

sent

ing

as D

igit

al P

etec

hiae

. Ped

iatr

ic D

erm

atol

ogy.

20

12; 2

9 (2

): 2

09-2

12.

3. K

arpa

ti S

, Tor

ok E

, Kos

nai I

. Dis

cret

e pa

lmar

and

pla

ntar

sym

ptom

s in

child

ren

wit

h de

rmat

itis

he

rpet

iform

is D

uhri

ng. C

utis

198

6; 3

7: 1

84–1

87.

4. N

aylo

r et a

l. Le

ukoc

ytoc

last

ic V

ascu

litis

as t

he P

rese

ntin

g Fe

atur

e of

Der

mat

itis

Her

peti

form

is.

Arc

h D

erm

atol

. 201

1; 1

47 (

11):

131

3-13

16.

Figu

res

1, 2

See

n at

pre

sent

atio

n w

hen

the

orig

inal

bio

psy

was

per

form

ed w

ith H

&E s

tain

ing.

Fi

gure

3 A

t the

2-w

eek

follo

w-u

p, a

dditi

onal

lesi

ons

deve

lope

d. A

sec

ond

biop

sy w

as p

erfo

rmed

for D

IF.

Figu

res

4, 5

‘Cla

ssic

’ DH

lesi

ons

of th

igh

& el

bow

that

app

eare

d 1

mon

th fo

llow

ing

confi

rmat

ory

DIF

bio

psy.

Con

clu

sion

: T

he d

iffe

rent

ial d

iagn

osis

of p

alm

ar p

etec

hiae

has

cla

ssic

ally

bee

n as

soci

ated

wit

h

vari

ous

cond

itio

ns in

clud

ing:

vas

culo

path

ies,

end

ocar

diti

s, t

raum

a, a

nd m

edic

atio

ns.

T

his c

ase

of D

H e

xpan

ds o

n th

e di

ffere

ntia

l dia

gnos

is o

f pal

mar

pet

echi

ae a

nd sh

ould

al

ert c

linic

ians

of p

oten

tial

und

erly

ing

asso

ciat

ions

and

the

need

for a

mul

tidi

scip

linar

y ap

proa

ch to

man

agem

ent.

Intr

odu

ctio

n:

Der

mat

itis

Her

peti

form

is (

DH

) is

a c

hron

ic b

ullo

us d

isea

se th

at ty

pica

lly p

rese

nts w

ith

sym

met

rica

l pru

riti

c ve

sicl

es o

f the

kne

es, e

lbow

s, bu

ttoc

ks, o

r sca

lp.

Pu

rpur

ic a

nd p

etec

hial

lesi

ons o

n th

e ha

nds a

nd fe

et h

ave

been

repo

rted

in c

hild

ren,

but

are

exc

eedi

ngly

rare

in a

dult

s.

Lab

orat

ory:

An

exte

nsiv

e co

agu-

lopa

thy

and

vasc

ulop

athy

wor

k-up

re

veal

ed n

o ab

norm

alit

ies.

How

-ev

er, t

issu

e tr

ansg

luta

min

ase

IgA

, en

dom

ysia

l IgA

ant

ibod

ies,

and

IgA

gl

iadi

n an

tibo

dies

wer

e al

l sig

nifi-

can

tly

elev

ated

. Tw

o pu

nch

bi

opsi

es f

or H

&E

an

d di

rect

im

mun

ofluo

resc

ence

(D

IF)

wer

e pe

rfor

med

(Fi

gure

6 a

nd 7

).

Der

mat

itis

Her

peti

form

is:

• A

utoi

mm

une

blis

teri

ng d

isea

se th

at re

pres

ents

the

cuta

neou

s man

ifest

atio

n of

cel

iac

di

seas

e.

• M

C in

mal

es o

f Nor

ther

n Eu

rope

an d

esce

nt

• H

uman

Leu

kocy

te a

ssoc

iati

ons:

DR

3, D

Q2,

DQ

8

Clin

ical

pre

sent

atio

n•

The

cla

ssic

clin

ical

pre

sent

atio

n is

sym

met

ric,

pru

riti

c pa

pule

s and

ves

icle

s loc

ated

on

the

exte

nsor

surf

aces

, sca

lp a

nd b

utto

cks.

• P

urpu

ra a

nd p

etec

hiae

hav

e be

en re

port

ed in

up

to 6

4% o

f ped

iatr

ic p

atie

nts w

ith

D

H, b

ut th

ere

are

only

few

cas

e re

port

s of t

his fi

ndin

g in

adu

lts.

•

The

re h

ave

been

no

repo

rted

cas

es a

ffect

ing

only

the

dors

al h

ands

.

His

tolo

gy•

Neu

trop

hilic

mic

roab

sces

ses w

ithi

n th

e de

rmal

pap

illae

• P

etec

hial

lesi

ons h

ave

a m

ixed

per

ivas

cula

r infl

amm

ator

y in

filtr

ate

• D

IF: g

ranu

lar d

epos

itio

n of

IgA

wit

hin

the

derm

al p

apill

ae

Pat

hoph

ysio

logy

• C

utan

eous

lesi

ons f

orm

as a

resu

lt o

f im

mun

e co

mpl

exes

of I

gA a

nd e

pide

rmal

tran

sglu

-ta

min

ase

that

acc

umul

ate

in th

e ci

rcul

atio

n as

wel

l as w

ithi

n th

e pa

pilla

ry d

erm

is.

Figu

re 6

His

topa

thol

ogy

reve

aled

find

ings

co

nsis

tent

with

leuk

ocyt

ocla

stic

vas

culit

is

with

dis

cret

e pa

pilla

ry m

icro

absc

esse

s an

d

a m

ixed

infla

mm

ator

y in

filtra

te.

Figu

re 7

DIF

dem

onst

rate

d gr

anul

ar

depo

sits

of I

gA w

ithin

the

derm

al p

apilla

e.

Figu

re 1

Figu

re 2

Figu

re 3

Figu

re 4

Figu

re 5

Figu

re 6

Figu

re 7

Clin

ical

Cou

rse:

The

pat

ient

was

star

ted

on d

apso

ne 2

5 m

g pe

r da

y.

Foll

owin

g fo

ur w

eeks

of

trea

tmen

t, a

ll

lesi

ons h

ad c

lear

ed w

ith

sym

ptom

atic

relie

f. A

col

onos

copy

re

veal

ed c

hron

ic in

flam

mat

ion

wit

h ex

tens

ive

inte

stin

al

met

apla

sia

cons

iste

nt w

ith

an in

flam

mat

ory

ente

ropa

thy.

T

he p

atie

nt w

as re

ferr

ed to

a d

ieti

cian

who

impl

emen

ted

a

glut

en fr

ee d

iet.

DE

RM

AT

OL

OG

Y-

Phy

sica

l exa

min

atio

n, r

outi

ne

hi

stop

atho

logy

and

DIF

- T

issu

e an

d ep

ider

mal

tra

nsgl

utam

inas

e

to c

onfir

m t

he d

iagn

osis

and

mon

itor

dise

ase

acti

vity

. -

Dap

sone

the

rapy

req

uire

s

cl

inic

al f

ollo

w-u

p an

d re

gula

r

la

bora

tory

mon

itor

ing.

GA

STR

OE

NT

ER

OL

OG

Y

- In

crea

sed

risk

for

ente

ropa

thy

asso

ciat

ed T

-cel

l lym

phom

a.

NU

TR

ITIO

N

- G

lute

n fr

ee d

iet

is t

he o

nly

trea

tmen

t th

at w

ill lo

wer

the

risk

of

ente

ropa

thy

asso

ciat

ed

m

alig

nanc

y.

EN

DO

CR

INO

LO

GY

-

Incr

ease

d ri

sk f

or a

utoi

mm

une

diso

rder

s, h

ypot

hyro

idis

m t

he

m

ost

prev

alen

t.

Mul

tidi

scip

linar

y M

anag

emen

tof

DH

248

QU

ICK

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hea

ders

to

sepa

rate

top

ics

or c

once

pts

wit

hin

your

pre

sent

atio

n.

Text

pla

ceho

lder

M

ove

this

pre

form

atte

d te

xt p

lace

hold

er t

o th

e po

ster

to

add

a ne

w b

ody

of t

ext.

Pi

ctur

e pl

aceh

olde

r M

ove

this

gra

phic

pla

ceho

lder

ont

o yo

ur p

oste

r, s

ize

it

firs

t, a

nd t

hen

clic

k it

to

add

a pi

ctur

e to

the

pos

ter.

RES

EAR

CH

PO

STER

PR

ESEN

TATI

ON

DES

IGN

© 2

011

ww

w.P

oste

rPre

sent

atio

ns.c

om

QU

ICK

TIPS

(-

-TH

IS S

ECTI

ON

DO

ES N

OT

PRIN

T--)

Th

is P

ower

Poin

t te

mpl

ate

requ

ires

bas

ic P

ower

Poin

t (v

ersi

on 2

007

or n

ewer

) sk

ills.

Bel

ow is

a li

st o

f co

mm

only

as

ked

ques

tion

s sp

ecif

ic t

o th

is t

empl

ate.

If

you

are

usi

ng a

n ol

der

vers

ion

of P

ower

Poin

t so

me

tem

plat

e fe

atur

es m

ay n

ot w

ork

prop

erly

.

Usi

ng t

he t

empl

ate

Veri

fyin

g th

e qu

alit

y of

you

r gr

aphi

cs

Go

to t

he V

IEW

men

u an

d cl

ick

on Z

OO

M t

o se

t yo

ur

pref

erre

d m

agni

fica

tion

. Th

is t

empl

ate

is a

t 50

% th

e si

ze

of t

he f

inal

pos

ter.

All

text

and

gra

phic

s w

ill b

e pr

inte

d at

20

0% t

heir

siz

e. T

o se

e w

hat

your

pos

ter

will

look

like

w

hen

prin

ted,

set

the

zoo

m t

o 20

0% a

nd e

valu

ate

the

qual

ity

of a

ll yo

ur g

raph

ics

befo

re y

ou s

ubm

it y

our

post

er

for

prin

ting

. U

sing

the

pla

ceho

lder

s To

add

tex

t to

thi

s te

mpl

ate

clic

k in

side

a p

lace

hold

er a

nd

type

in o

r pa

ste

your

tex

t. T

o m

ove

a pl

aceh

olde

r, c

lick

on

it o

nce

(to

sele

ct it

), p

lace

you

r cu

rsor

on

its

fram

e an

d yo

ur c

urso

r w

ill c

hang

e to

thi

s sy

mbo

l:

Then

, cl

ick

once

and

dra

g it

to

its

new

loca

tion

whe

re y

ou c

an r

esiz

e it

as

need

ed.

Addi

tion

al p

lace

hold

ers

can

be f

ound

on

the

left

sid

e of

thi

s te

mpl

ate.

M

odif

ying

the

layo

ut

This

tem

plat

e ha

s fo

ur

diff

eren

t co

lum

n la

yout

s.

Righ

t-cl

ick

your

mou

se

on t

he b

ackg

roun

d an

d

clic

k on

“La

yout

” to

see

th

e la

yout

opt

ions

. Th

e co

lum

ns in

the

pro

vide

d la

yout

s ar

e fi

xed

and

cann

ot

be m

oved

but

adv

ance

d us

ers

can

mod

ify

any

layo

ut b

y go

ing

to V

IEW

and

the

n SL

IDE

MAS

TER.

Im

port

ing

text

and

gra

phic

s fr

om e

xter

nal s

ourc

es

TEXT

: Pa

ste

or t

ype

your

tex

t in

to a

pre

-exi

stin

g pl

aceh

olde

r or

dra

g in

a n

ew p

lace

hold

er f

rom

the

lef

t si

de o

f th

e te

mpl

ate.

Mov

e it

any

whe

re a

s ne

eded

. PH

OTO

S: D

rag

in a

pic

ture

pla

ceho

lder

, si

ze it

fir

st,

clic

k in

it a

nd in

sert

a p

hoto

fro

m t

he m

enu.

TA

BLES

: Yo

u ca

n co

py a

nd p

aste

a t

able

fro

m a

n ex

tern

al

docu

men

t on

to t

his

post

er t

empl

ate.

To

mak

e th

e te

xt f

it

bett

er in

the

cel

ls o

f an

impo

rted

tab

le,

righ

t-cl

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tabl

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lick

FORM

AT S

HAP

E t

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clic

k on

TEX

T BO

X an

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ange

the

INTE

RNAL

MAR

GIN

val

ues

to 0

.25

Mod

ifyi

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olor

sch

eme

To c

hang

e th

e co

lor

sche

me

of t

his

tem

plat

e go

to

the

“Des

ign”

men

u an

d cl

ick

on “

Colo

rs”.

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th

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bina

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you

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© 2

011

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erPr

esen

tatio

ns.c

om

2

117

Four

th S

tree

t , U

nit C

Ber

kele

y C

A 9

4710

pos

terp

rese

nter

@gm

ail.c

om

Stud

ent

disc

ount

s ar

e av

aila

ble

on o

ur F

aceb

ook

page

.

Go

to P

oste

rPre

sent

atio

ns.c

om a

nd c

lick

on t

he F

B ic

on.

A Re

view

and

Upd

ate

on M

elan

ocyt

e St

imul

atin

g H

orm

one

Ther

apy:

Afa

mel

anot

ide

Afam

elan

otid

e (

[Nle

4-D

-Phe

7]-a

lpha

-MSH

) is

an

anal

og o

f al

pha-

mel

anoc

yte

stim

ulat

ing

horm

one

(alp

ha-M

SH)

give

n as

a s

ubcu

tane

ous

inje

ctio

n. A

fam

elan

otid

e is

cur

rent

ly u

nder

goin

g ph

ase

II an

d III

tri

als

in E

urop

e an

d th

e U

S fo

r sk

in d

isea

ses

incl

udin

g vi

tilig

o an

d er

ythr

opoi

etic

pro

topo

rphy

ria.

Af

amel

anot

ide

is c

urre

ntly

on

the

mar

ket

in It

aly

and

Swit

zerl

and

for

pati

ents

wit

h er

ythr

opoi

etic

pro

topo

rphy

ria.

U

nreg

ulat

ed a

nalo

gs a

re b

eing

sol

d on

line

ahea

d of

for

mal

app

rova

l. T

hese

“M

elan

otan

s,”

a co

unte

rfei

t fo

rmul

atio

n, c

an b

e pu

rcha

sed

onlin

e by

the

pub

lic a

nd a

re s

elf-

inje

cted

for

tan

ning

pur

pose

s.

A so

luti

on t

o th

e di

stri

buti

on o

f co

unte

rfei

t m

edic

atio

n m

ay b

e to

app

rove

the

dru

g fo

r ta

nnin

g if

pro

ven

safe

in r

igor

ous

clin

ical

tr

ials

.

Abst

ract

Jord

an F

abrik

ant,

DO*

Kha

sha

Toul

oei,

OM

S –I

V,**

Sta

nley

E S

kopi

t DO,

MSE

, FAO

CD**

*

* 2

nd y

ear D

erm

atol

ogy

Resid

ent,

Lark

in C

omm

unity

Hos

pita

l – N

ova

Sout

heas

tern

Uni

vers

ity C

olle

ge o

f Ost

eopa

thic

Med

icine

, Dep

artm

ent o

f Der

mat

olog

y, M

iam

i, FL

**

Inte

rn, L

argo

Med

ical C

ente

r, La

rgo,

FL

**

*Der

mat

olog

y Re

siden

cy P

rogr

am D

irect

or, N

SUCO

M/L

arki

n Co

mm

unity

Hos

pita

l , S

outh

Mia

mi,

FL

Intr

oduc

tion

Afte

r su

nlig

ht e

xpos

ure,

the

ph

otos

ensi

tivi

ty o

f EP

P ca

uses

pai

n,

follo

wed

by

eryt

hem

a, e

dem

a, a

nd

crus

ting

.

Med

icat

ion

prof

ile

Poly

mor

phic

lig

ht e

rupt

ion

(PM

LE)

is a

n ac

quir

ed d

isor

der

that

is

char

acte

rize

d by

pru

riti

c pa

pule

s, s

mal

l ve

sicl

es,

and

plaq

ues

trig

gere

d by

UVR

. Th

is d

isea

se a

ffec

ts m

ainl

y pe

ople

of

nort

hern

Eur

opea

n de

scen

t w

ho h

ave

skin

rea

ctio

n fo

llow

ing

sunl

ight

exp

osur

e.

Prel

imin

ary

resu

lts

have

bee

n re

port

ed b

y fr

om a

dou

ble

blin

d,

plac

ebo

cont

rolle

d tr

ial,

whi

ch d

emon

stra

ted

that

at

day

15,

pati

ents

ha

d a

redu

ctio

n in

Phy

sici

an G

loba

l Se

veri

ty In

dex

(P=0

.077

) bu

t no

t by

da

y 12

0 (P

=0.4

48).

Afa

mel

anot

ide

is c

urre

ntly

in P

hase

III t

rial

s in

Au

stra

lia a

nd E

urop

e fo

r PM

LE (

20).

Poly

mor

phic

ligh

t eru

ptio

n

Conc

lusi

on

Thus

far

, st

udie

s in

vit

ro a

nd i

n vi

vo in

dica

te t

hat

afam

elan

otid

e is

nei

ther

tox

ic n

or c

arci

noge

nic

and,

in h

uman

s,

afam

elan

otid

e ha

s be

en s

how

n to

indu

ce p

igm

enta

ry r

espo

nse.

Add

itio

nally

, af

amel

anot

ide

redu

ces

the

toxi

c re

spon

se o

f su

nbur

ned

cells

, w

hile

it a

lso

has

the

abili

ty t

o in

duce

pig

men

tary

cha

nge

in p

atie

nts

who

hav

e po

lym

orph

ism

s of

MC1

R ge

ne.

It h

as n

ot b

een

prov

en if

alp

ha-M

SH a

nalo

gues

will

dec

reas

e th

e ri

sk o

f sk

in c

ance

r in

pe

ople

who

are

sus

cept

ible

, bu

t th

ere

is s

uffi

cien

t ev

iden

ce t

hat

alph

a-M

SH d

oes

not

caus

e m

alig

nant

tr

ansf

orm

atio

n or

unc

ontr

olle

d ce

llula

r pr

olif

erat

ion

of m

elan

ocyt

es.

Cur

rent

ly,

it h

as o

nly

been

app

rove

d in

Ita

ly

and

Swit

zerl

and

for

peop

le w

ho a

re a

fflic

ted

wit

h er

ythr

opoi

etic

pro

topo

rphy

ria

(EPP

). F

inal

ly,

the

prol

onge

d ac

ting

de

pot

form

ulat

ion

has

show

n m

inim

al a

dver

se e

ffec

ts t

hus

far.

A r

evie

w o

f th

e lit

erat

ure

reve

als

that

afa

mel

anot

ide

has

grea

t po

tent

ial

to b

e an

eff

ecti

ve a

nd s

afe

ther

apeu

tic

tool

in a

num

ber

of s

kin

dise

ases

in t

he f

utur

e, h

owev

er

furt

her

tria

ls a

re n

eede

d.

Refe

renc

es

Wit

h ul

trav

iole

t ra

diat

ion

caus

ing

skin

agi

ng a

nd s

kin

canc

er,

the

use

of m

elan

otro

pic

pept

ides

are

slo

wly

bec

omin

g m

ore

popu

lar

as c

onsu

mer

s ar

e lo

okin

g fo

r al

tern

ativ

e w

ays

to o

btai

n a

facu

ltat

ive

tan.

How

ever

, th

e pr

oduc

ts a

re

unre

gula

ted

and

can

be o

btai

ned

thro

ugh

the

inte

rnet

, gy

ms,

and

tan

ning

sal

ons.

Th

ey a

re m

arke

ted

as

‘Mel

anot

ans’

whi

ch c

an in

duce

ski

n ta

nnin

g.

Ther

e is

onl

y on

e re

gula

ted

alph

a-M

SH a

nalo

g kn

own

as a

fam

elan

otid

e ([

Nle

4-D

-Phe

7]-a

lpha

-MSH

). It

was

app

rove

d in

Ital

y in

201

0 an

d Sw

itze

rlan

d in

201

2 fo

r pa

tien

ts d

iagn

osed

wit

h er

ythr

opoi

etic

pro

topo

rphy

ria

(EPP

). T

he

trea

tmen

t pr

opos

ed is

cur

rent

ly in

tri

als

in t

he U

S fo

r EP

P an

d vi

tilig

o.

Clin

ical

tri

als

in E

urop

e an

d Au

stra

lia i

nclu

de

EPP,

pol

ymor

phic

lig

ht e

rupt

ion

(PLE

), v

itili

go,

acti

nic

kera

tose

s (A

K),

and

squa

mou

s ce

ll ca

rcin

oma

(SCC

) in

org

an

tran

spla

nt r

ecip

ient

s. T

he c

ompo

und

serv

es a

s a

phot

o pr

otec

tive

dru

g fo

r pa

tien

ts w

ho a

re m

ost

at r

isk

from

UV

and

sun

expo

sure

, an

d as

a t

hera

peut

ic o

ptio

n in

non

-seg

men

tal v

itili

go (

NSV

).

Skin

pig

men

tati

on i

s a

stro

ng c

ompo

nent

of

phot

o pr

otec

tion

. T

he e

pide

rmal

chr

omop

hore

mel

anin

act

s as

a f

ilter

to

att

enua

te u

ltra

viol

et (

UV)

ligh

t. In

crea

sed

mel

aniz

atio

n de

crea

ses

the

effe

cts

expe

rien

ced

from

ult

ravi

olet

ra

diat

ion

(UVR

) in

clud

ing

decr

ease

d su

nbur

n an

d di

rect

DN

A da

mag

e fr

om u

ltra

viol

et-B

(U

VB).

Mel

anin

abs

orbs

UVB

, U

VA a

nd v

isib

le l

ight

, pl

ayin

g a

grea

t ro

le in

pho

topr

otec

tion

. W

ith

afam

elan

otid

e’s

abili

ty t

o pr

olon

g sk

in m

elan

in

prod

ucti

on,

it c

an b

e us

ed f

or t

he p

reve

ntio

n of

ski

n di

seas

es t

hat

are

caus

ed b

y su

nlig

ht.

Alph

a m

elan

ocyt

e st

imul

atin

g ho

rmon

e (A

lpha

-MSH

) is

13

amin

o ac

ids

in le

ngth

and

is s

ynth

esiz

ed f

rom

2 s

ourc

es:

the

pitu

itar

y gl

and

and

skin

. Al

pha-

MSH

is s

ynth

esiz

ed b

y en

dopr

oteo

lyti

c de

com

posi

tion

of

prop

iom

elan

ocor

tin(

POM

C).

UVR

dam

ages

DN

A in

the

ker

atin

ocyt

e w

hich

lea

ds t

o an

incr

ease

in a

lpha

-MSH

sy

nthe

sis

and

rele

ase(

9).

D

urin

g th

e re

pair

pro

cess

, PO

MC

gene

tra

nscr

ipti

on o

ccur

s an

d th

e ge

ne p

rodu

ct a

lpha

-MSH

is s

ynth

esiz

ed.

Alph

a-M

SH b

inds

to

the

mel

anoc

orti

n-1

rece

ptor

(M

C1R)

whi

ch is

pre

sent

in d

erm

al c

ells

incl

udin

g m

elan

ocyt

es,

kera

tino

cyte

s, e

ndot

helia

l cel

ls,

skin

fib

robl

asts

and

mas

t ce

lls.

MC1

R is

not

exp

ress

ed in

mel

anoc

yte

stem

cel

ls,

or

mel

anob

last

s. W

hen

MC1

R is

sti

mul

ated

, m

elan

ogen

esis

occ

urs

by in

crea

sing

tyr

osin

ase

acti

vity

and

incr

easi

ng

mel

anoc

yte

prol

ifer

atio

n. P

hysi

olog

ic a

lpha

-MSH

, re

leas

ed f

rom

ker

atin

ocyt

es,

acts

loc

ally

on

adja

cent

mel

anoc

ytes

vi

a a

para

crin

e m

echa

nism

and

on

them

selv

es v

ia a

n au

tocr

ine

mec

hani

sm (

1-8)

.

Curr

ent

tria

ls r

evea

l tha

t th

e re

gula

ted

med

icat

ion,

afa

mel

anot

ide,

is

wel

l tol

erat

ed b

y pa

tien

ts,

wit

h na

usea

and

he

adac

hes

as p

rim

ary

side

eff

ects

. H

owev

er,

ther

e ar

e ri

sks

asso

ciat

ed w

ith

buyi

ng u

nreg

ulat

ed p

rodu

cts,

incl

udin

g th

e po

tent

ial

impu

rity

of

chem

ical

s, a

nd in

fect

ive

com

plic

atio

ns s

econ

dary

to

need

le s

hari

ng.

Ther

e ha

ve b

een

seve

ral c

ases

of

atyp

ical

rap

idly

pig

men

ting

eru

ptiv

e ne

vi f

orm

ing

from

unr

egul

ated

ver

sion

s. T

he m

ain

issu

e is

the

in

abili

ty t

o re

trie

ve in

form

atio

n on

fre

quen

cy o

f us

e an

d or

igin

of

chem

ical

s pu

rcha

sed.

The

adm

inis

trat

ion

of t

he

unre

gula

ted

med

icat

ion

can

chan

ge t

he c

linic

al p

rese

ntat

ion

of p

atie

nts

wit

h pi

gmen

ted

lesi

ons

caus

ing

atyp

ical

cl

inic

al a

nd h

isto

logi

cal

feat

ures

. It

has

bee

n as

soci

ated

wit

h ch

ange

s in

the

clin

ical

pre

sent

atio

n of

pre

-exi

stin

g ne

vi a

nd t

he d

evel

opm

ent

of n

ew n

evi.

One

cas

e of

mal

igna

nt m

elan

oma

has

been

pub

lishe

d in

a m

elan

otan

I us

er.

Mul

tipl

e st

udie

s in

dica

te t

hat

the

utili

zati

on o

f th

ese

anal

ogue

s al

ters

the

pig

men

t in

mel

anoc

ytic

les

ions

the

reby

re

duci

ng t

he a

bilit

y to

ass

ess

pati

ents

' cur

rent

lesi

ons

for

mal

igna

nt p

oten

tial

(17

-19)

.

The

MT-

1 th

at t

he p

ublic

buy

s fr

om g

yms,

tan

ning

sal

ons,

and

the

inte

rnet

is a

dif

fere

nt p

rodu

ct f

rom

the

reg

ulat

ed

afam

elan

otid

e be

ing

pres

crib

ed f

or s

tudi

es.

The

form

er is

unr

egul

ated

and

off

ered

onl

ine

for

self

-adm

inis

trat

ion,

w

here

by s

ynth

esis

, or

igin

and

for

mul

atio

n ar

e al

l unk

now

n. U

sage

of

thes

e pr

oduc

ts a

re s

tron

gly

disc

oura

ged

by

seve

ral a

genc

ies

incl

udin

g th

e U

K an

d D

anis

h go

vern

men

tal h

ealt

hcar

e ag

enci

es,

and

the

Med

icin

es a

nd H

ealt

hcar

e Re

gula

tory

Age

ncy

(MH

RA).

The

FD

A ha

s is

sued

sta

tem

ents

for

the

pub

lic t

o st

op p

urch

asin

g M

T I &

II.

Alth

ough

a

war

ning

ove

r th

eir

sale

and

use

has

bee

n is

sued

by

auth

orit

ies,

the

y ha

ve n

ot b

anne

d an

y pr

oduc

ts (

9-16

).

Sinc

e M

T1 h

as b

een

asso

ciat

ed w

ith

unre

gula

ted

prod

ucts

sol

d ov

er t

he in

tern

et a

nd a

t gy

ms,

it w

ill n

ot b

e fu

rthe

r re

ferr

ed t

o in

thi

s po

ster

. Af

amel

anot

ide

is m

ore

resi

stan

t to

enz

ymat

ic b

reak

dow

n, w

hich

incr

ease

s it

s po

tenc

y an

d al

so p

rolo

ngs

the

dura

tion

of

acti

on a

t th

e M

C1R

. In

the

ear

ly 1

990s

, in

vest

igat

ors

foun

d th

at s

ubcu

tane

ous

afam

elan

otid

e in

ject

ions

inc

reas

e sk

in p

igm

enta

tion

. Af

amel

anot

ide

indu

ces

incr

ease

s in

eum

elan

in/p

heom

elan

in

rati

o of

nor

mal

sub

ject

s w

ith

skin

typ

es I

to V

I des

pite

the

abs

ence

of

sunl

ight

exp

osur

e.

In a

dou

ble

blin

d ph

ase

I tri

al,

30 s

ubje

cts

wer

e gi

ven

0.16

mg/

kg/d

ay f

or 1

0 da

ys a

fam

elan

otid

e or

pla

cebo

. Th

e m

ain

find

ing

in t

his

stud

y w

as t

hat

mel

anin

den

sity

incr

ease

d in

pat

ient

s w

ho w

ere

trea

ted

wit

h af

amel

anot

ide.

An

ad

diti

onal

res

ult

was

tha

t U

V in

duce

d su

nbur

n ce

lls w

ere

decr

ease

d in

pat

ient

s w

ho h

ad a

ris

k fo

r U

V in

duce

d sk

in

dam

age.

Stu

dies

hav

e sh

own

that

the

odd

s ra

tio

for

skin

can

cers

dec

reas

es b

y a

fact

or o

f 2

for

ever

y pe

rcen

t in

crea

se in

mel

anin

den

sity

. Th

e fi

ndin

gs f

rom

thi

s st

udy

indi

cate

tha

t af

amel

anot

ide

can

be m

ost

bene

fici

al in

pr

otec

ting

aga

inst

UV

skin

dam

age

in f

air

skin

ned

peop

le.

Si

nce

afam

elan

otid

e do

es n

ot p

enet

rate

the

epi

derm

is,

a to

pica

l do

sage

was

not

sho

wn

to b

e ef

fica

ciou

s. H

ence

a

subc

utan

eous

rou

te w

as c

hose

n, s

ince

it’s

mor

e ef

fect

ive

for

prot

ein

and

pept

ide

base

d dr

ugs.

Init

ially

it

was

ap

plie

d su

bcut

aneo

usly

in s

alin

e so

luti

on.

Due

to

its

shor

t ha

lf-l

ife,

sal

ine

inje

ctio

ns w

ere

requ

ired

dai

ly.

Thu

s, a

su

stai

ned

cont

rolle

d re

leas

e fo

rmul

atio

n w

as c

reat

ed w

hich

has

red

uced

adv

erse

eff

ects

and

impr

oved

eff

icac

y.

Th

ese

impl

ants

, ro

ughl

y th

e si

ze o

f a

grai

n of

ric

e, w

ere

deve

lope

d to

allo

w o

ne s

ingl

e ad

min

istr

atio

n to

pro

vide

m

axim

al t

anni

ng f

or t

wo

to t

hree

mon

ths.

The

y ar

e ad

min

iste

red

by p

hysi

cian

s in

the

fat

ty t

issu

e ab

ove

the

hip

for

roug

hly

ten

days

, an

d th

e ef

fect

of

the

drug

is s

een

for

abou

t 60

day

s. In

rec

ent

tria

ls,

the

med

icat

ion

is g

iven

onc

e ev

ery

60 d

ays.

Onc

e th

e dr

ug is

pre

sent

in t

he b

ody,

it t

akes

tw

o da

ys f

or s

kin

to b

ecom

e da

rker

. C

urre

ntly

, 16

mg

of a

fam

elan

otid

e gi

ven

subc

utan

eous

ly r

esul

ts in

max

imal

tan

ning

eff

icac

y w

ith

a ha

lf-l

ife

of l

ess

than

50

min

utes

.

1. M

ahne

C.

Impl

ant

Off

ers

Tann

ing

Revo

luti

on.

2002

. Av

aila

ble

at:

http

://n

ews.

bbc.

co.u

k/1/

hi/h

ealt

h/22

3199

1.st

m (

last

acce

ssed

7 J

une

2010

).

2.

Lan

gan

EA,

Nie

Z,

Rhod

es L

E. M

elan

otro

pic

pept

ides

: m

ore

than

jus

t ‘B

arbi

e dr

ugs’

and

‘su

n-ta

n ja

bs’?

Br

J D

erm

atol

201

0; 1

63:

451–

5.

3.

Gar

be C

, Bu

ttne

r P,

Wei

sz J

et

al.

Risk

fac

tors

for

dev

elop

ing

cuta

neou

s m

elan

oma

and

crit

eria

for

iden

tify

ing

pers

ons

at r

isk:

m

ulti

cent

er c

ase–

cont

rol s

tudy

of

the

cent

ral m

alig

nant

mel

anom

a re

gist

ry o

f th

e G

erm

an D

erm

atol

ogic

al S

ocie

ty.

J In

vest

D

erm

atol

199

4; 1

02:6

95–9

.

4. B

arne

tson

RS,

Ooi

TKT

, Zh

uang

L e

t al

. [N

le4-

d-Ph

e7]-

alph

a-m

elan

ocyt

e-st

imul

atin

g ho

rmon

e si

gnif

ican

tly

incr

ease

d pi

gmen

tati

on a

nd d

ecre

ased

UV

dam

age

in f

air-

skin

ned

Cauc

asia

n vo

lunt

eers

. J

Inve

st D

erm

atol

200

6; 1

26:1

869–

78.

5.

Dor

r RT

, Er

tl G

, N

et

al.

Effe

cts

of a

sup

er p

oten

t m

elan

otro

pic

pept

ide

in c

ombi

nati

on w

ith

sola

r U

V ra

diat

ion

on t

anni

ng o

f th

e sk

in in

hum

an v

olun

teer

s. A

rch

Der

mat

ol 2

004;

140

:827

–35.

6. B

renn

er M

, H

eari

ng V

. Th

e pr

otec

tive

rol

e of

mel

anin

aga

inst

UV

dam

age

in h

uman

ski

n. P

hoto

chem

Pho

tobi

ol 2

008;

84:

539–

49.

7.

Kai

dbey

K,

Agin

P,

Sayr

e R

et a

l. P

hoto

prot

ecti

on b

y m

elan

in –

a c

ompa

riso

n of

bla

ck a

nd C

auca

sian

ski

n. J

Am

Aca

d D

erm

atol

19

79;1

:249

–60.

8. K

ollia

s N

, Sa

yre

R, Z

eise

L e

t al

. Ph

otop

rote

ctio

n by

mel

anin

. J

Phot

oche

m P

hoto

biol

B 1

991;

9:1

35–6

0.

9.

Afa

mel

anot

ide:

Mel

anoc

orti

n M

C1 r

ecep

tor

agon

ist

phot

opro

tect

ive

agen

t.E.

I. D

rugs

of

the

Futu

re 2

010

35:5

(36

5-37

2

10.

Cui,

R.,

Wui

dlun

d, H

.R.,

Feig

e, E

. et

al.

Cen

tral

rol

e of

p53

in t

he s

unta

n re

spon

se a

nd p

atho

logi

c hy

perp

igm

enta

tion

. Ce

ll 20

07,

128(

5):

853-

64

11.

ME,

Dor

r RT

. M

elan

ocor

tin

pept

ide

ther

apeu

tics

: hi

stor

ic m

ilest

ones

, cl

inic

al s

tudi

es a

nd c

omm

erci

aliz

atio

n. P

epti

des

2006

; 27

:921

–30

12.

Valv

erde

P,

Hea

ly E

, Ja

ckso

n I,

Ree

s JL

, Th

ody

AJ.

Vari

ants

of

the

mel

anoc

yte-

stim

ulat

ing

horm

one

rece

ptor

gen

e ar

e as

soci

ated

wit

h re

d ha

ir a

nd f

air

skin

in h

uman

s. N

at G

enet

199

5;11

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13.

Spen

cer

JD,

Scha

llreu

ter

KU.

Regu

lati

on o

f pi

gmen

tati

on in

hum

an e

pide

rmal

mel

anoc

ytes

by

func

tion

al h

igh-

affi

nity

bet

a-m

elan

ocyt

e-st

imul

atin

g ho

rmon

e/m

elan

ocor

tin-

4 re

cept

or s

igna

ling.

End

ocri

nolo

gy 2

009;

150:

1250

-8

14.

Schi

oth

HB,

Chh

ajla

ni V

, M

ucen

iece

R,

et a

l. M

ajor

pha

rmac

olog

ical

dis

tinc

tion

of

the

ACTH

rec

epto

r fr

om o

ther

mel

anoc

orti

n re

cept

ors.

Lif

e Sc

i 199

6;59

:797

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15.

Levi

ne N

, Sh

efte

l SN

, Ey

tan

T et

al.

Indu

ctio

n of

tan

ning

by

subc

utan

eous

adm

inis

trat

ion

of a

pot

ent

synt

heti

c m

elan

otro

pin.

JA

MA

1991

; 22

6:27

30–6

16

. H

unt

G,

Kyne

S,

Wak

amat

su K

et

al.

[Nle

4-D

-Phe

7]-a

-MSH

incr

ease

s th

e eu

mel

anin

: ph

eom

elan

in r

atio

in c

ultu

red

hum

an

mel

anoc

ytes

. J

Inve

st D

erm

atol

199

5; 1

04:8

3–5

17.

Pain

e-M

urri

eta

GD

, Ta

ylor

CW

, Cu

rtis

RA,

Lop

ez M

HA,

Dor

r RT

, Jo

hnso

n CS

, et

al.

Hum

an t

umor

mod

els

in t

he s

ever

e co

mbi

ned

imm

une

defi

cien

t (s

cid)

mou

se.

Canc

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hem

othe

r Ph

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199

7;40

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18.

Crom

bie,

I.K.

Var

iati

on o

f m

elan

oma

inci

denc

e w

ith

lati

tude

in N

orth

Am

eric

a an

d Eu

rope

. Br

J C

ance

r 19

79,

40(5

):77

4-81

.

19.

Dw

yer

T, B

lizza

rd L

, As

hbol

t R,

Plu

mb

J, B

erw

ick

M,

Stan

kovi

ch J

M.

Cuta

neou

s m

elan

in d

ensi

ty o

f Ca

ucas

ians

mea

sure

d by

sp

ectr

opho

tom

etry

and

ris

k of

mal

igna

nt m

elan

oma,

bas

al c

ell c

arci

nom

a, a

nd s

quam

ous

cell

carc

inom

a of

the

ski

n. A

m J

Ep

idem

iol 2

002;

155:

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20.

Nor

weg

ian

Med

icin

es A

genc

y. L

egem

iidee

lver

ket.

adv

arer

mot

bru

kav

Mel

atoa

n 20

08.w

ww

.lef

emid

dvek

er.n

o/tr

ampl

es/i

nter

page

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10.a

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21.

G.

Biol

cati

, J.

C. D

eyba

ch,S

. H

anne

ken,

P.

Wils

on,

S. W

ahlin

,§ G

. Va

rigo

s,–

L. R

hode

s, C

. Au

rizi

, C.

Min

der,

B.

Coff

in,

N.

Neu

man

n, F

. D

e Ro

oij,

G.

Ross

, F.

Ste

war

t an

d E.

Min

der

A ra

ndom

ized

pha

se II

I tri

al o

f af

amel

anot

ide

(Sce

ness

e),

an a

goni

stic

a-

mel

anoc

yte

stim

ulat

ing

horm

one

anal

ogue

in t

he t

reat

men

t of

pro

topo

rphy

ria

indu

ced

phot

otox

icit

y BJ

D ,

201

1 Br

itis

h As

soci

atio

n of

Der

mat

olog

ists

201

1 16

4, p

p112

5–11

76

22

. Sa

fety

and

eff

icac

y of

an

agon

isti

c a-

mel

anoc

yte

stim

ulat

ing

horm

one

anal

ogue

, af

amel

anot

ide

(Sce

ness

e),

in t

reat

ing

pati

ents

w

ith

eryt

hrop

oiet

ic p

roto

porp

hyri

a fo

r 2.

5 co

nsec

utiv

e ye

ars

S. K

reim

, S.

Lau

tens

chla

ger

and

E. M

inde

r

23.

Hay

lett

AK,

Nie

Z,

Brow

nrig

g M

, Ta

ylor

R,

Rhod

es L

E.Sy

stem

ic p

hoto

prot

ecti

on in

sol

ar u

rtic

aria

wit

h α

-mel

anoc

yte-

stim

ulat

ing

horm

one

anal

ogue

[N

le4-

D-P

he7]

-α-M

SH.

Br J

Der

mat

ol.

2011

Feb

;164

(2):

407-

14.

doi:

10.

1111

/j.1

365-

2133

.201

0.10

104.

x 24

. Be

atti

e PE

, D

awe

RS,

Ibbo

tson

SH

et

al.

Char

acte

rist

ics

and

prog

nosi

s of

idio

path

ic s

olar

urt

icar

ia:

a co

hort

of

87 c

ases

. Ar

ch

Der

mat

ol 2

003;

139

:114

9–54

25.

Bern

hard

J,

Jaen

icke

K,

Mom

taz

TK,

Parr

ish

JA.

Ult

ravi

olet

A p

hoto

ther

apy

in t

he p

roph

ylax

is o

f so

lar

urti

cari

a. J

Am

Aca

d D

erm

atol

198

4; 1

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26.

Inte

rnat

iona

l Ass

ocia

tion

for

Res

earc

h on

Can

cer.

IARC

Mon

ogra

phs

on t

he E

valu

atio

n of

Car

cino

geni

c Ri

sks

to H

uman

s. V

olum

e 55

. So

lar

and

Ult

ravi

olet

Rad

iati

on.

Lyon

: In

tern

atio

nal A

ssoc

iati

on f

or R

esea

rch

on C

ance

r, 1

992.

27.

Clin

uvel

to

eval

uate

SCE

NES

SE (

afam

elan

otid

e) a

s th

erap

y in

vit

iligo

. M

elbo

urne

, Au

stra

lia:

Clin

uvel

Pha

rmac

euti

cals

Ltd

. 20

10.

Avai

labl

e fr

om:

http

://w

ww

.clin

uvel

.com

/res

ourc

es/c

msf

iles/

pdf/

2010

0825

CUV0

31Vi

tilig

o.pd

f

An e

arlie

r al

pha-

MSH

ana

logu

e, f

orm

erly

kno

wn

as m

elan

otan

-I (

MT1

), w

as c

hem

ical

ly a

lter

ed a

nd o

ptim

ized

to

its

curr

ent

form

ulat

ion

as a

fam

elan

otid

e.

It w

as f

irst

syn

thes

ized

in 1

980

and

is a

sup

er p

oten

t m

elan

ocor

tin.

Viti

ligo

is a

n ac

quir

ed p

igm

enta

ry d

isor

der

of t

he s

kin

and

muc

ous

mem

bran

es,

and

it is

cha

ract

eriz

ed b

y ci

rcum

scri

bed

depi

gmen

ted

mac

ules

and

pat

ches

. It

is a

pro

gres

sive

dis

orde

r in

whi

ch s

ome

or a

ll of

the

m

elan

ocyt

es i

n th

e af

fect

ed s

kin

are

abse

nt.

A ph

ase

II st

udy

was

con

duct

ed in

the

US

for

the

trea

tmen

t of

vit

iligo

. In

thi

s st

udy,

50%

of

pati

ents

wer

e tr

eate

d w

ith

narr

ow b

and

UVB

and

afa

mel

anot

ide,

whi

le t

he r

emai

ning

50%

wer

e tr

eate

d w

ith

narr

owba

nd U

VB a

lone

. Th

e go

al o

f th

e st

udy

was

to

dete

rmin

e if

afa

mel

anot

ide

decr

ease

d th

e to

tal

dose

of

narr

ow b

and

UVB

exp

osur

e ne

eded

, an

d ti

me

requ

ired

to

reac

tiva

te m

elan

ocyt

es i

n vi

tilig

o le

sion

s. D

ata

was

fav

orab

le in

the

21

pati

ents

rec

eivi

ng 1

6 m

g im

plan

ts.

The

maj

orit

y of

pat

ient

s in

the

stu

dy h

ad s

kin

type

s IV

– V

I and

wer

e di

agno

sed

wit

h N

SV w

ithi

n in

the

la

st 5

yea

rs.

The

data

als

o su

gges

ted

that

afa

mel

anot

ide

incr

ease

s re

pigm

enta

tion

rat

e an

d re

spon

se t

ime

follo

win

g na

rrow

ban

d U

VB e

xpos

ure

in p

atie

nts,

in

the

days

imm

edia

tely

aft

er a

dmin

istr

atio

n.

Furt

her,

afa

mel

anot

ide,

for

th

e tr

eatm

ent

of v

itili

go,

has

rece

ntly

als

o be

en a

ppro

ved

to b

e te

sted

in in

tern

atio

nal

clin

ical

tri

als

(26,

27)

.

The

eryt

hem

al f

lare

and

whe

al f

orm

atio

n ty

pica

l of

sol

ar u

rtic

aria

. It

is a

lso

acco

mpa

nied

by

prur

itus

.

Sola

r ur

tica

ria

SU is

a r

are

form

of

chro

nic

urti

cari

a th

at is

mar

ked

by p

ruri

tus,

ery

them

al f

lare

, an

d w

heal

fo

rmat

ion

wit

hin

min

utes

of

sunl

ight

exp

osur

e an

d re

solu

tion

wit

hin

a fe

w h

ours

. Fo

r th

e m

ost

part

, su

n ex

pose

d ar

eas

are

affe

cted

an

d th

e qu

alit

y of

lif

e in

pat

ient

s su

ffer

ing

from

SU

is v

ery

poor

. Se

vera

l stu

dies

hav

e be

en

cond

ucte

d w

hich

sho

w t

hat

phot

othe

rapy

can

incr

ease

tol

eran

ce in

sol

ar u

rtic

aria

wit

h m

elan

ogen

esis

pro

pose

d as

a

mec

hani

sm.

The

prob

lem

wit

h th

is t

reat

men

t is

tha

t U

V ra

diat

ion

is a

car

cino

gen

whi

ch a

lso

stim

ulat

es m

elan

in t

o re

duce

pen

etra

tion

of

UV

wav

elen

gths

, al

low

ing

for

incr

ease

d pr

otec

tion

in

sola

r ur

tica

ria.

H

ayle

tt e

t al

con

duct

ed a

n op

en l

abel

pha

se II

stu

dy o

n 5

pati

ents

wit

h so

lar

urti

cari

a by

giv

ing

them

16

mg

subc

utan

eous

impl

ant

of a

fam

elan

otid

e du

ring

the

win

ter

as a

pro

phyl

acti

c tr

eatm

ent.

The

stu

dy w

as d

one

in t

he

win

ter

to m

inim

ize

UV

radi

atio

n an

d to

pre

vent

aug

men

tati

on i

n th

e m

elan

ogen

ic r

espo

nse.

All

5 pa

tien

ts s

elec

ted

disp

laye

d po

siti

ve u

rtic

aria

l re

spon

se t

o pr

ovoc

atio

n up

on p

hoto

tes

ting

. Th

e m

elan

in d

ensi

ty in

exp

osed

and

un

expo

sed

site

s w

as a

sses

sed

in a

ll th

e pa

tien

ts o

n da

y 0,

7,

15,

30,

and

60 a

nd t

he r

esul

ts in

dica

te a

red

ucti

on in

so

lar

urti

cari

a re

spon

se o

ver

a br

oad

spec

trum

of

wav

elen

gths

. Th

eir

resu

lts

indi

cate

the

pos

sibi

lity

of

afam

elan

otid

e to

be

a pr

otec

tive

tre

atm

ent

for

pati

ents

suf

feri

ng f

rom

SU

, re

duce

d re

spon

ses

are

due

to t

he

imm

unom

odul

ator

y ef

fect

s of

[N

le4-

D-P

he7]

-alp

ha-M

SH a

nd p

hoto

pro

tect

ion

(22-

25).

Eryt

hrop

oiet

ic p

roto

porp

hyri

a (E

PP)

is c

ause

d by

an

enzy

mat

ic d

efic

ienc

y of

fer

roch

elat

ase,

due

to

an in

heri

ted

defe

ct in

the

last

ste

p of

the

hem

e bi

osyn

thes

is p

athw

ay.

Thi

s ca

uses

an

accu

mul

atio

n of

pho

tose

nsit

izin

g pr

otop

orph

yrin

IX

in t

he d

erm

is w

hich

lea

ds t

o in

crea

sed

sens

itiv

ity

to l

ight

, re

sult

ing

in p

ain

and

inca

paci

tati

ng

phot

o to

xic

reac

tion

s w

hen

expo

sed

to t

he v

isib

le s

pect

rum

. Th

e di

seas

e is

cha

ract

eriz

ed b

y se

vere

into

lera

nce

to

light

.

A ph

ase

II st

udy

was

con

duct

ed o

n 5

pati

ents

suf

feri

ng f

rom

EPP

for

mor

e th

an 4

mon

ths

who

the

n re

ceiv

ed a

su

bcut

aneo

us 2

0 m

g im

plan

t of

afa

mel

anot

ide.

Re

sult

s in

dica

ted

an in

crea

se i

n sk

in p

igm

enta

tion

and

als

o a

sign

ific

ant

incr

ease

in t

oler

ance

to

phot

o pr

ovoc

atio

n.

In a

noth

er p

hase

II t

rial

, 68

pat

ient

s w

ere

trea

ted

for

6 m

onth

s du

ring

pea

k su

nlig

ht s

easo

ns o

f sp

ring

and

sum

mer

, w

here

a s

ubse

t of

pat

ient

s w

ere

expo

sed

to l

ight

on

thei

r ba

ck a

nd h

ands

to

asse

ss t

he t

ime

and

dose

req

uire

d to

cau

se a

rea

ctio

n. P

atie

nts

who

rec

eive

d af

amel

anot

ide

wer

e ab

le t

o sp

end

mor

e ti

me

in d

irec

t su

nlig

ht,

spec

ific

ally

the

mid

dle

of t

he d

ay.

Thes

e pa

tien

ts o

n th

e m

edic

atio

n re

port

ed a

thr

eefo

ld in

crea

se in

the

am

ount

of

tim

e th

ey c

ould

spe

nd in

dir

ect

sunl

ight

.

Rece

ntly

, a

pha

se II

I, r

ando

miz

ed,

doub

le b

lind

cont

rolle

d, a

nd m

ulti

cent

er s

tudy

in E

urop

e an

d Au

stra

lia c

onsi

stin

g of

101

EPP

pat

ient

s to

ok p

lace

ove

r th

e co

urse

of

a ye

ar.

Dat

a fr

om t

he s

tudy

had

bee

n pr

esen

ted

and

dem

onst

rate

d EP

P pa

in in

tens

ity

that

was

sig

nifi

cant

ly l

ower

, an

d su

nlig

ht e

xpos

ure

tim

e th

at w

as s

igni

fica

ntly

hig

her

duri

ng

adm

inis

trat

ion

of a

fam

elan

otid

e. S

ever

al o

ther

pha

se II

I tri

als

have

sho

wn

sim

ilar

resu

lts

(21,

22)

.

ALPH

A M

ELAN

OCY

TE

STIM

ULA

TIN

G H

ORM

ON

E (A

lpha

-MSH

) M

ELAN

OG

ENES

IS

& M

ELAN

OCO

RTIN

1R

Al

pha

mel

anoc

yte

stim

ulat

ing

horm

one

(Alp

ha-M

SH)

is a

tr

idec

apep

tide

pig

men

tary

ho

rmon

e w

hich

is 1

3 am

ino

acid

s in

leng

th a

nd is

sy

nthe

size

d fr

om 2

sou

rces

: th

e pi

tuit

ary

glan

d an

d sk

in

Safe

ty a

nd m

alig

nanc

y

Vitil

igo

Sola

r Urt

icar

ia

Eryt

hrop

oiet

ic p

roto

porp

hyria

Afam

elan

otid

e in

crea

ses

mel

anin

den

sity

, (F

itzp

atri

ck t

ype

1, 2

,3)

. M

edic

atio

n is

re

leas

ed o

ver

10 d

ays,

and

mel

anin

incr

ease

s fo

r 60

day

s.

249

Muir-

Torre

synd

rom

e: A

Case

Asso

ciat

ed w

ith an

Infre

quen

t Gen

etic

Mut

atio

n Ch

ristin

a Fes

er, D

O; Al

exan

dra G

rob,

DO; S

teph

en Ol

sen,

MD; S

teve

n Gre

kin,

DO

Depa

rtmen

t of D

erm

atol

ogy,

Oakw

ood H

ospi

tal H

ealth

care

Syst

em, T

rent

on, M

ichi

gan

Dis

cuss

ion

Mui

r-To

rre

Syn

drom

e (M

TS) i

s a

rare

aut

osom

al d

omin

ant g

enod

erm

atos

is d

efin

ed b

y th

e co

inci

denc

e of

at l

east

one

seb

aceo

us g

land

neo

plas

m a

nd o

ne v

isce

ral m

alig

nanc

y. T

he

seba

ceou

s ne

opla

sms

enco

mpa

ss s

ebac

eous

ade

nom

as, s

ebac

eous

epi

thel

iom

as (s

ebac

eom

a),

and

seba

ceou

s ca

rcin

omas

, as

wel

l as

kera

toac

anth

omas

with

seb

aceo

us d

iffer

entia

tion.

1 The

pr

esen

ce o

f one

of t

hese

tum

ors

may

repr

esen

t a m

arke

r for

MTS

, and

sho

uld

ther

efor

e pr

ompt

a

scre

enin

g fo

r vis

cera

l mal

igna

ncy.

2

Alth

ough

initi

ally

repo

rted

as h

avin

g a

pred

ispo

sitio

n so

lely

to c

olor

ecta

l can

cer,

MTS

pat

ient

s al

so

show

an

incr

ease

d ris

k of

var

ious

mal

igna

ncie

s, in

clud

ing

endo

met

rial,

ovar

ian,

gen

itour

inar

y, a

nd

smal

l bow

el c

ance

rs.2

Col

orec

tal c

arci

nom

a re

mai

ns th

e m

ost f

requ

ently

obs

erve

d ca

rcin

oma,

and

ac

coun

ts fo

r app

roxi

mat

ely

50%

of a

ll pr

imar

y ca

ncer

s in

MTS

. Th

e ch

arac

teris

tic s

kin

lesi

ons

may

oc

cur b

efor

e, c

oncu

rren

tly, o

r afte

r the

dev

elop

men

t of v

isce

ral m

alig

nanc

y.

Seb

aceo

us a

deno

ma

is c

onsi

dere

d th

e m

ost s

peci

fic tu

mor

type

for M

TS, w

ith a

25%

- 60

%

repo

rted

asso

ciat

ion.

The

se c

linic

ally

app

ear a

s ta

n, p

ink,

or y

ello

w n

odul

es o

r pap

ules

, up

to 5

mm

in

gre

ates

t dim

ensi

on, a

nd a

re m

ost c

omm

only

foun

d on

the

head

and

nec

k. T

hese

lesi

ons

may

ra

nge

from

few

in n

umbe

r to

hund

reds

.

Sev

eral

stu

dies

hav

e sh

own

that

the

spec

trum

of i

nter

nal m

alig

nanc

ies

obse

rved

in p

atie

nts

with

M

TS is

sim

ilar t

o th

at o

bser

ved

in H

ered

itary

Non

poly

posi

s C

olor

ecta

l Can

cer (

HN

PCC

), or

Lyn

ch

Syn

drom

e, ra

isin

g th

e po

ssib

ility

that

MTS

, or o

ne o

f its

sub

type

s, re

pres

ents

a p

heno

typi

c va

riant

.4 G

erm

line

mut

atio

ns w

ithin

the

DN

A m

ism

atch

repa

ir (M

MR

) pat

hway

s in

clud

ing

MS

H2

and

MLH

1,

are

the

gene

tic a

nom

aly

resp

onsi

ble

for a

ppro

xim

atel

y 2/

3 of

pat

ient

s di

agno

sed

with

HN

PC

C .5

S

tudi

es h

ave

show

n th

at m

utat

ions

in M

SH

2 oc

cur m

ost f

requ

ently

in M

TS, c

ompr

isin

g ab

out 9

0%

of c

ases

.6

The

early

det

ectio

n of

mal

igna

ncy

is c

ritic

al in

the

care

of M

TS p

atie

nts.

Cur

rent

scr

eeni

ng

reco

mm

enda

tions

for M

TS p

atie

nts

and

thei

r 1st d

egre

e re

lativ

es in

clud

e an

nual

pel

vic/

brea

st

exam

s in

fem

ales

, pro

stat

e/te

stic

ular

exa

ms

in m

ales

, ann

ual c

olon

osco

py fr

om a

ge 2

5 (o

r 5 y

ears

pr

ior t

o th

e yo

unge

st a

ge o

f col

orec

tal c

ance

r dia

gnos

is p

er fa

mily

), an

d la

bora

tory

eva

luat

ion

incl

udin

g a

com

plet

e bl

ood

coun

t, C

EA,

feca

l occ

ult b

lood

, and

urin

alys

is.7

Ref

eren

ces

1. H

adle

y M

E, D

orr R

T. M

elan

ocor

tin p

eptid

e th

erap

eutic

s: h

isto

rical

mile

ston

es, c

linic

al s

tudi

es a

nd c

omm

erci

aliz

atio

n. P

eptid

es 2

006;

27(4

):921

-930

2.

Dor

r RT,

Lin

es R

, Lev

ine

N, e

t al.

Eva

luat

ion

of m

elan

otan

-II, a

sup

erpo

tent

cyc

lic m

elan

otro

pic

pept

ide

in a

pilo

t pha

se-I

clin

ical

stu

dy. L

ife S

ci

1996

;58(

20):1

777-

1784

. 3.

Dor

r RT,

Dvo

rako

va K

, Bro

oks

C, e

t al.

Incr

ease

d eu

mel

anin

exp

ress

ion

and

tann

ing

is in

duce

d by

a s

uper

pote

nt m

elan

otro

pin

[Nle

4-D

-Phe

7]-α

-M

SH

in h

uman

s. P

hoto

chem

Pho

tobi

ol 2

000;

72(4

):526

-532

. 4.

Vira

dor V

M, M

ulle

r J, W

u X

; et a

l. In

fluen

ce o

f a-m

elan

ocyt

e-st

imul

atin

g ho

rmon

e an

d ul

travi

olet

radi

atio

n on

the

trans

fer o

f mel

anos

omes

to

kera

tinoc

ytes

. FA

SE

B J

. 200

2;16

(1):1

05-1

07.

5. R

apos

inho

PD

, Xav

ier C

, Cor

reia

JD

et a

l. M

elan

oma

targ

etin

g w

ith a

lpha

-mel

anoc

yte

stim

ulat

ing

horm

one

anal

ogs

labe

led

with

fac-

[9

9mTv

(CO

)3]+

: ef

fect

of c

ycliz

atio

n on

tum

or-s

eeki

ng p

rope

rties

. J B

iol I

norg

Che

m 2

008;

13:

449-

59.

6. T

hody

AJ.

A-M

SH

and

the

regu

latio

n of

mel

anoc

yte

func

tion.

Ann

N Y

Aca

d S

ci.

1999

;885

:217

-229

. 7.

Jon

es B

, Oh

C, M

ango

ld E

, et a

l. M

uir-

Torre

syn

drom

e: D

iagn

ostic

and

scr

eeni

ng g

uide

lines

. Aus

trala

s J

Der

mat

ol. 2

006;

47(4

):266

-9.

Intr

oduc

tion

M

uir-

Torr

e S

yndr

ome

(MTS

) is

a ra

re, a

utos

omal

do

min

ant g

enod

erm

atos

is c

hara

cter

ized

by

the

pres

ence

of

at l

east

one

seb

aceo

us g

land

neo

plas

m, a

ssoc

iate

d w

ith a

n un

derly

ing

visc

eral

mal

igna

ncy.

Affe

cted

in

divi

dual

s ar

e fo

und

to h

ave

germ

line

mut

atio

ns

pred

omin

antly

in D

NA

mis

mat

ch re

pair

gene

MS

H2,

and

m

uch

less

freq

uent

ly, M

LH1.

We

repo

rt th

e ca

se o

f a 5

5 ye

ar-o

ld fe

mal

e pr

esen

ting

with

mul

tiple

cut

aneo

us

neop

lasm

s in

clud

ing

seba

ceom

a, b

asal

cel

l car

cino

ma,

an

d sq

uam

ous

cell

carc

inom

a; p

erso

nal h

isto

ry o

f co

lore

ctal

and

end

omet

rial c

ance

r; an

d fa

mily

his

tory

of

colo

rect

al c

ance

r; fo

und

to h

ave

a de

letio

n at

mis

mat

ch

repa

ir ge

ne M

LH1.

We

disc

uss

the

clin

ical

pre

sent

atio

n of

MTS

, met

hods

of d

iagn

osis

, and

the

impo

rtanc

e of

re

gula

r med

ical

sur

veilla

nce

to d

etec

t and

pre

vent

di

seas

e pr

ogre

ssio

n in

MTS

pat

ient

s an

d th

eir f

amily

m

embe

rs.

Cas

e R

epor

t H

isto

ry o

f Pre

sent

Illn

ess:

A

55-y

ear-

old

fem

ale

with

a h

isto

ry o

f squ

amou

s ce

ll ca

rcin

oma

(SC

C),

basa

l cel

l car

cino

ma

(BC

C),

hype

rtens

ion,

col

orec

tal c

arci

nom

a an

d en

dom

etria

l ca

rcin

oma,

pre

sent

ed to

the

clin

ic fo

r eva

luat

ion

of a

nas

al

lesi

on, p

rese

nt fo

r an

unkn

own

dura

tion.

The

pat

ient

ad

mitt

ed to

sim

ilar a

ppea

ring

lesi

ons

in th

e pa

st, w

hich

had

be

en tr

eate

d w

ith e

lect

roca

uter

y an

d cr

yoth

erap

y. T

he

patie

nt’s

mot

her w

as d

ecea

sed

at a

ge 6

4 se

cond

ary

to

colo

n ca

ncer

. The

pat

ient

den

ied

a fa

mily

his

tory

of s

kin

canc

er.

Phys

ical

Exa

min

atio

n:

Exa

min

atio

n re

veal

ed a

wel

l-app

earin

g fe

mal

e w

ith a

4-m

m

tend

er, p

early

pap

ule

on th

e rig

ht n

asal

tip.

In

addi

tion,

m

ultip

le, s

catte

red,

0.2

-0.4

cm

, yel

low,

lobu

late

d pa

pule

s w

ere

dens

ely

clus

tere

d on

the

nose

and

bila

tera

l che

eks.

A

shav

e bi

opsy

was

obt

aine

d fro

m th

e rig

ht n

asal

tip,

whi

ch

was

sus

pici

ous

for m

alig

nanc

y.

His

topa

thol

ogy

Mic

rosc

opic

exa

min

atio

n re

veal

ed a

wel

l-ci

rcum

scrib

ed n

odul

ar d

erm

al n

eopl

asm

com

pose

d of

uni

form

bas

aloi

d ce

lls w

ith in

ters

pers

ed

diso

rder

ed a

ggre

gate

s of

mat

ure

sebo

cyte

s an

d tra

nsiti

onal

cel

ls. S

ebac

eous

duc

t for

mat

ion

and

cyst

ic d

ilatio

n w

as p

rese

nt. T

here

was

no

cyto

logi

c at

ypia

or i

nfilt

rativ

e gr

owth

pat

tern

. Th

ese

findi

ngs

wer

e al

l con

sist

ent t

he d

iagn

osis

of a

seb

aceo

ma.

Gen

etic

Ana

lysi

s G

erm

line

anal

ysis

was

pos

itive

reve

alin

g a

dele

tion

in th

e M

LH1

gene

. A

naly

sis

of th

e M

SH

2 ge

ne w

as

unre

mar

kabl

e.

250

re

ma

rk

ab

le m

ed

icin

e. r

em

ar

ka

ble

ca

re

.

Intr

oduc

tion

Loca

lized

scle

rode

rma

(LS)

, or m

orph

ea, i

s an

auto

imm

une

dise

ase

of th

e sk

in a

nd u

nder

lyin

g su

bcut

aneo

us ti

ssue

. T

he le

sion

s var

y in

size

and

ext

ent o

f atr

ophy

and

fibr

osis

. M

any

trea

tmen

t opt

ions

ar

e av

aila

ble,

how

ever

non

e ha

ve b

een

show

n to

pro

vide

defi

niti

ve

reso

luti

on o

f the

lesi

ons.

Ref

eren

ces:

1.

Kur

zins

ki K

, Tor

ok K

S. C

ytok

ine

profi

les i

n lo

caliz

ed sc

lero

derm

a an

d re

lati

onsh

ip to

clin

ical

feat

ures

. C

ytok

ine.

20

11;5

5(2)

:157

-64.

2.

Nis

ticò

SP,

Sar

acen

o R

, Sch

ipan

i C, e

t al.

Diff

eren

t app

licat

ions

of

mon

ochr

omat

ic e

xcim

er li

ght i

n sk

in d

isea

ses.

Phot

omed

Las

er S

urg.

20

09;2

7(4)

:647

-54.

Dis

cuss

ion

Eti

olog

y, P

rese

ntat

ion,

and

Pat

hoge

nesi

s

• L

S of

ten

affe

cts c

hild

ren,

wit

h th

e in

cide

nce

is a

s hig

h as

50

per 1

00,0

00

child

ren.

The

subt

ypes

of L

S in

clud

e de

ep, p

laqu

e, g

ener

aliz

ed, b

ullo

us, a

nd

linea

r var

ient

s. L

inea

r scl

erod

erm

a ca

n be

the

mos

t sev

ere,

cau

sing

join

t co

ntra

ctur

es o

n th

e ex

trem

itie

s. T

he le

sion

s usu

ally

star

t as a

pat

ch o

f ery

them

a or

vio

lace

ous d

isco

lora

tion

, wit

h po

ssib

le a

ssoc

iate

d te

nder

ness

and

war

mth

. T

he le

sion

then

bec

omes

thic

kene

d, h

ard,

and

oft

en h

yper

pigm

ente

d.

• E

arly

LS

appe

ars h

isto

logi

cally

as d

ense

der

mal

and

subc

utan

eous

per

ivas

cula

r ly

mph

ocyt

ic in

filtr

ate

wit

h en

doth

elia

l cel

l sw

ellin

g. L

ater

stag

es d

emon

stra

te

min

imal

infla

mm

atio

n w

ith

dens

ely

pack

ed h

omog

enou

s col

lage

n an

d lo

ss o

f ec

crin

e gl

ands

and

ves

sels

, giv

ing

the

biop

sy a

squa

red-

off a

ppea

ranc

e.

• S

cler

oder

ma

and

mor

phea

shar

e si

mila

r pat

hoph

ysio

logy

att

ribu

ted

to C

D4

T-he

lper

cel

l act

ivit

y. T

h1 a

nd T

h17

infla

mm

atio

n pr

edom

inat

e ea

rly

in th

e pr

oces

s whi

le la

ter fi

bros

is is

Th2

-med

iate

d.

Dia

gnos

tic

Tes

ting

and

Man

agem

ent

• A

utoi

mm

une

mar

kers

such

as a

nti-

nucl

ear a

ntib

ody

(AN

A),

sing

le-s

tran

ded

DN

A (

ss-D

NA

), a

nd a

nti-

hist

one

anti

body

(A

HA

) ca

n be

use

ful f

or d

iagn

osis

an

d m

onit

orin

g of

dis

ease

seve

rity

.

• T

opic

al o

r int

rale

sion

al c

orti

cost

eroi

ds a

re c

onsi

dere

d tr

eatm

ent o

f cho

ice

for

earl

y LS

. M

etho

trex

ate

is u

sefu

l for

the

acut

e an

d de

ep fo

rm o

f the

dis

ease

, de

crea

sing

leve

ls o

f IL-

2, IL

-6, t

enas

cin,

and

mas

t cel

ls. S

yste

mic

cor

tico

ster

oids

ca

n be

add

ed to

the

met

hotr

exat

e re

gim

en fo

r sev

ere,

refr

acto

ry c

ases

.

• T

he e

xcim

er la

ser i

s a n

arro

w b

and

UV

B la

ser e

mit

ting

at 3

08nm

. It

has

bee

n re

port

ed to

effe

ctiv

ely

trea

t a m

ulti

tude

of d

erm

atol

ogic

con

diti

ons i

nclu

ding

pl

aque

pso

rias

is, p

alm

opla

ntar

pus

tulo

sis,

liche

n pl

anus

, alo

peci

a ar

eata

, pat

ch-

stag

e M

F, v

itili

go, a

nd lo

caliz

ed sc

lero

derm

a. I

t is b

elie

ved

to c

ause

dep

leti

on

of T

cel

ls, a

lter

atio

ns in

apo

ptos

is-m

edia

ting

mol

ecul

es, a

nd d

ecre

ased

cyt

okin

e ex

pres

sion

.

• S

urge

ry sh

ould

be

rese

rved

for o

nly

afte

r the

reso

luti

on o

f the

acu

te p

hase

of

the

dise

ase

and

once

the

child

’s gr

owth

is c

ompl

eted

for c

orre

ctio

n of

ass

ocia

ted

cosm

etic

def

ects

.

Lin

ear

Mor

phea

Tre

ated

wit

h M

etho

trex

ate

and

Exc

imer

Las

erA

nne

H. H

anso

n D

O a

nd D

avid

P. F

iven

son

MD

Dep

artm

ent

of D

erm

atol

ogy

• S

t. J

osep

h M

ercy

Liv

ings

ton

Hos

pita

l, H

owel

l, M

ichi

gan

Cas

e P

rese

ntat

ion

His

tory

• A

17-

year

-old

Cau

casi

an fe

mal

e pr

esen

ted

wit

h a

four

yea

r his

tory

of

slow

ly e

xpan

ding

dis

figur

ing

lesi

on o

n he

r lef

t flan

k. T

he

lesi

on st

arte

d as

a re

ticu

lar,

viol

aceo

us p

laqu

e th

at b

ecam

e er

ythe

mat

ous a

nd p

ainf

ul.

The

le

sion

gra

dual

ly p

rogr

esse

d to

a

depr

esse

d an

d ha

rd p

laqu

e. S

he

reca

lled

no tr

aum

a or

inse

ct b

ite

to th

at a

rea.

Lab

orat

ory

• S

erum

che

mis

trie

s, C

BC

, ESR

, an

d C

RP

wer

e al

l nor

mal

.

Cou

rse

and

The

rapy

• T

reat

men

t inc

lude

d in

tral

esio

nal

ster

oid

inje

ctio

ns a

nd to

pica

l ca

lcip

otri

ene

oint

men

t. S

he w

as

also

trea

ted

wit

h m

etho

trex

ate

5mg

wee

kly

and

twic

e w

eekl

y ex

cim

er la

ser f

or a

tota

l of 3

4 tr

eatm

ents

and

a m

axim

um o

f 22

00m

J/tr

eatm

ent.

The

pat

ient

re

spon

ded

wel

l to

trea

tmen

t w

ith

decr

ease

in si

ze o

f the

lesi

on

and

sym

ptom

atic

relie

f by

two

mon

ths.

The

pat

ient

ele

cted

to

unde

rgo

rem

oval

of t

he re

mai

nder

of

the

lesi

on w

ith

plas

tic

surg

ery.

A

n el

lipti

cal e

xcis

ion

was

pe

rfor

med

wit

h 5m

m m

argi

ns.

Figu

re 1

: A

slig

htly

hyp

erpi

gmen

ted,

dep

ress

ed,

indu

rate

d lin

ear p

laqu

e ex

tend

ed fr

om h

er le

ft fla

nk

to th

e le

ft lo

wer

qua

dran

t of h

er a

bdom

en.

Figu

re 2

: Ini

tial b

iops

y re

veal

ed m

ild m

id re

ticul

ar

derm

al s

cler

osis

with

thic

keni

ng o

f col

lage

n bu

ndle

s in

the

mid

retic

ular

der

mis

and

loss

of

peria

ppen

dage

al a

dipo

se ti

ssue

. A s

pars

e su

perfi

cial

pe

rivas

cula

r lym

phoi

d in

filtra

te w

as p

rese

nt

Figu

re 3

: Exc

isio

nal b

iops

y re

veal

ed d

erm

al th

icke

ning

an

d sc

lero

sis

with

sup

erim

pose

d de

rmal

cal

cific

atio

n an

d pe

rfora

tion.

The

cal

cifie

d no

dule

was

ass

ocia

ted

with

col

lect

ions

of n

eutro

phils

and

thic

kene

d co

llage

n bu

ndle

s

3.

Vile

la F

A, C

arne

iro

S, R

amos

-e-S

ilva

M. T

reat

men

t of m

orph

ea o

r lo

caliz

ed sc

lero

derm

a: re

view

of t

he li

tera

ture

. J D

rugs

Der

mat

ol.

2010

;9(1

0):1

213-

9.

4.

Zulia

n F,

Mar

tini

G, V

allo

ngo

C, e

t al.

Met

hotr

exat

e tr

eatm

ent i

n ju

veni

le lo

caliz

ed sc

lero

derm

a: a

rand

omiz

ed, d

oubl

e- b

lind,

pla

cebo

-co

ntro

lled

tria

l.Art

hrit

is R

heum

. 201

1;63

(7):

1998

-200

6.

251

RES

EAR

CH

PO

STER

PR

ESEN

TATI

ON

DES

IGN

© 2

012

ww

w.P

oste

rPre

sent

atio

ns.c

om

Soon

afte

r bi

rth,

a m

ale

neon

ate

was

not

ed t

o ex

hibi

t sk

in f

ragi

lity

resu

lting

in

larg

e er

osio

ns

occu

rrin

g w

ith m

ild t

raum

a su

ch a

s be

ing

hand

led

by h

is p

aren

ts.

His

birt

h w

as o

ther

wis

e un

rem

arka

ble.

He

did

not h

ave

any

fam

ily h

isto

ry o

f unu

sual

ski

n co

nditi

ons.

A s

kin

biop

sy w

as

take

n (F

igur

e 1)

, an

d ro

utin

e pr

oces

sing

w

ith

hem

atox

ylin

an

d eo

sin

reve

aled

co

mpa

ct

hype

rorth

oker

atos

is,

acan

thos

is,

hype

rgra

nulo

sis

with

coa

rse

kera

tohy

alin

e gr

anul

es,

vacu

olar

de

gene

ratio

n, a

nd a

mild

per

ivas

cula

r lym

phoh

istio

cytic

infil

trate

in th

e up

per d

erm

is.

Col

lect

ivel

y th

ese

findi

ngs

take

n to

geth

er w

ith th

e ap

prop

riate

clin

ical

pic

ture

wer

e co

nsis

tent

with

a d

iagn

osis

of

epi

derm

olyt

ic h

yper

kera

tosi

s (E

HK

). W

e ha

ve b

een

follo

win

g th

is p

atie

nt fr

om e

arly

chi

ldho

od

to p

rese

nt.

He

is c

urre

ntly

17

year

s ol

d at

the

time

of th

is w

ritin

g.

Case

Rep

ort

Gen

eral

ized

EH

K, a

lso

know

n as

bul

lous

con

geni

tal i

chth

yosi

form

ery

thro

derm

a, is

a d

isor

der

of

corn

ifica

tion

impa

ctin

g ro

ughl

y 3,

000

Am

eric

ans

with

no

gend

er p

redi

lect

ion.

It i

s in

herit

ed in

an

auto

som

al d

omin

ant

fash

ion

with

com

plet

e pe

netra

nce,

how

ever

hal

f of

the

se p

atie

nts

repr

esen

t sp

orad

ic n

ew m

utat

ions

. O

ur p

atie

nt h

ad n

o fa

mily

his

tory

, lik

ely

indi

catin

g a

new

mut

atio

n. A

lso,

pa

tient

s w

ith e

xten

sive

epi

derm

al n

evi

havi

ng h

isto

logi

c fe

atur

es o

f EH

K,

as s

een

in e

pide

rmal

ne

vus

synd

rom

e (ic

hthy

osis

hys

trix)

, may

be

at r

isk

of h

avin

g ch

ildre

n w

ith g

ener

aliz

ed E

HK

; in

thes

e ca

ses

the

epid

erm

al n

evi r

epre

sent

s a

som

atic

mos

aici

sm, a

nd if

ger

m li

ne c

ells

are

affe

cted

, tra

nsm

issi

on to

offs

prin

g is

pos

sibl

e.

EHK

is

caus

ed b

y lo

ss-o

f-fu

nctio

n m

utat

ions

in

kera

tins

1 an

d 10

whi

ch a

re e

xpre

ssed

in

the

supr

abas

al a

nd g

ranu

lar l

ayer

of

the

epid

erm

is.

Of

note

, EH

K m

ay o

r m

ay n

ot h

ave

palm

opla

ntar

in

volv

emen

t as

kera

tin 1

is e

xpre

ssed

on

the

palm

s an

d so

les,

but k

erat

in 1

0 is

not

. Dys

func

tiona

l ke

ratin

s co

mpr

omis

e no

rmal

ass

embl

y of

the

cyto

skel

eton

whi

ch re

sults

in c

ompr

omis

ed e

pide

rmal

st

reng

th a

nd in

tegr

ity, u

ltim

atel

y m

anife

stin

g in

frag

ility

, blis

terin

g an

d er

osio

ns.

Clin

ical

ly, E

HK

pre

sent

s di

ffere

ntly

in th

e ne

onat

e th

an it

doe

s in

a c

hild

or

adul

t. E

ryth

rode

rma,

fla

ccid

bul

lae

and

eros

ions

resu

lting

from

mild

trau

ma

are

com

mon

ly o

bser

ved

in th

e ne

onat

e. T

he

diffe

rent

ial

diag

nosi

s fo

r th

ese

findi

ngs

wou

ld a

lso

incl

ude

non-

bullo

us c

onge

nita

l ic

hthy

osifo

rm

eryt

hrod

erm

a, e

pide

rmol

ysis

bul

losa

, sta

phyl

ococ

cal

scal

ded

skin

syn

drom

e, a

nd t

oxic

epi

derm

al

necr

olys

is.

Dis

rupt

ed b

arrie

r fun

ctio

n ca

n po

tent

ially

lead

to fl

uid

and

elec

troly

te im

bala

nce

as w

ell

as i

nfec

tion

and

seps

is i

n af

fect

ed n

eona

tes.

For

tuna

tely

our

patient’s

birt

h w

as w

ithou

t th

ese

com

plic

atio

ns.

As

the

child

age

s, th

e er

ythr

oder

ma

is l

ess

prom

inen

t an

d se

vere

hyp

erke

rato

sis

prev

ails

. D

ark,

w

arty

, cor

ruga

ted

scal

es a

re n

oted

to b

e in

crea

sed

at fl

exur

al s

ites

(Fig

ures

2 a

nd 3

), an

d ty

pica

lly

beco

me

less

gen

eral

ized

afte

r pub

erty

. Pa

tient

s co

ntin

ue to

stru

ggle

with

ski

n fr

agili

ty re

sulti

ng in

la

rge

denu

ded

area

s fo

llow

ing

mild

tra

uma.

C

hron

ic r

ecur

ring

blis

terin

g ty

pica

lly r

epre

sent

s se

cond

ary

skin

inf

ectio

ns,

whi

ch t

hese

pat

ient

s ar

e pr

one

to.

The

re i

s al

so a

pun

gent

, so

cial

ly

stig

mat

izin

g bo

dy o

dor.

A

dditi

onal

sig

ns a

nd s

ympt

oms

that

may

be

pres

ent i

n th

e ch

ild o

r ad

ult p

atie

nt in

clud

e al

opec

ia,

angu

lar

chei

litis

, nai

l dys

troph

y, p

alm

opla

ntar

ker

atod

erm

a, m

uscl

e co

ntra

ctur

es, p

ostu

re a

nd g

ait

abno

rmal

ities

, and

var

iabl

e pr

uritu

s an

d pa

in.

Thes

e f

eatu

res

resu

lt in

a tr

emen

dous

psy

chos

ocia

l im

pact

on

the

patie

nt. F

ortu

nate

ly o

ur p

atie

nt o

nly

expe

rienc

es c

hron

ic, s

ever

e ge

nera

lized

pru

ritus

an

d pa

in a

s wel

l as a

n ad

mitt

ed p

rono

unce

d ps

ycho

soci

al im

pact

. N

eona

tes

with

ery

thro

derm

a an

d cu

tane

ous

denu

datio

n re

quire

pla

cem

ent i

n th

e ne

onat

al in

tens

ive

care

uni

t with

pro

tect

ive

isol

atio

n w

ith p

addi

ng a

nd li

bera

l use

of t

opic

al e

mol

lient

s A

ny fl

uid

or

elec

troly

te im

bala

nce

shou

ld b

e co

rrec

ted.

C

utan

eous

infe

ctio

n an

d se

psis

sho

uld

be tr

eate

d w

ith

broa

d-sp

ectru

m a

ntib

iotic

s sho

uld

they

occ

ur.

In th

e ch

ild o

r adu

lt, th

e go

al is

to re

duce

hyp

erke

rato

sis,

rem

ove

scal

e, a

nd so

ften

the

skin

. To

pica

l ke

rato

lytic

s an

d em

ollie

nts

are

effe

ctiv

e bu

t ofte

n no

t wel

l tol

erat

ed (

espe

cial

ly in

chi

ldre

n) d

ue to

bu

rnin

g an

d st

ingi

ng w

ith a

pplic

atio

n.

Our

pat

ient

has

trie

d nu

mer

ous

com

bina

tions

of

topi

cal

prep

arat

ions

ove

r the

yea

rs, a

nd c

ompl

ianc

e ha

s be

en a

con

stan

t stru

ggle

bec

ause

of d

isco

mfo

rt on

ap

plic

atio

n.

He

has

beco

me

mor

e co

mpl

iant

as he

’s g

otte

n ol

der

and

acce

pted

that

ther

e is

initi

al

disc

omfo

rt w

ith a

pplic

atio

n.

Topi

cal r

etin

oids

and

vita

min

D p

repa

ratio

ns m

ay a

lso

be e

ffect

ive.

C

ombi

ned

hydr

atio

n an

d m

echa

nica

l abr

asio

n m

ay a

lso

be u

sed

to re

duce

scal

e.

Disc

ussi

on

Seco

ndar

y ba

cter

ial

skin

inf

ectio

ns a

re c

omm

on i

n EH

K p

atie

nts.

Blis

terin

g in

the

abs

ence

of

fric

tion

sugg

ests

inf

ectio

n.

Our

pat

ient

has

bee

n tre

ated

with

ora

l an

d to

pica

l an

tibio

tics

for

seco

ndar

y st

aphy

loco

ccal

infe

ctio

ns a

bout

eve

ry 3

mon

ths

on a

vera

ge.

Prev

entiv

e pr

actic

es sh

ould

be

tau

ght

to t

hese

pat

ient

s an

d th

eir

fam

ilies

. O

ur p

atie

nt u

ses

antib

acte

rial

bar

clea

nser

s an

d ch

lorh

exid

ine

was

h da

ily. B

leac

h ba

ths

are

also

effe

ctiv

e.

Our

pat

ient

fou

nd t

hat

swim

min

g in

ch

lorin

ated

poo

ls r

egul

arly

has

hel

ped

to d

ecre

ase

mal

odor

and

fre

quen

cy o

f se

cond

ary

infe

ctio

n,

as w

ell

as i

mpr

ove

hype

rker

atos

is.

Loos

e-fit

ting

clot

hing

and

sho

es s

houl

d be

wor

n to

pre

vent

m

echa

nica

l di

srup

tion

of t

he e

pide

rmis

. Av

oid

cont

inuo

us p

roph

ylac

tic t

hera

py w

ith a

ntib

iotic

s du

e to

pot

entia

l for

bac

teria

l res

ista

nce.

Sy

nthe

tic o

ral r

etin

oids

are

ver

y ef

fect

ive

in th

e m

anag

emen

t of

patie

nts

with

EH

K.

Our

pat

ient

w

as s

tarte

d on

ora

l ac

itret

in 1

0mg

twic

e w

eekl

y at

10

year

s of

age

, an

d th

e do

sing

fre

quen

cy

slow

ly ti

trate

d up

ove

r tim

e to

a c

urre

nt d

ose

of 1

0mg

twic

e da

ily. W

e re

com

men

d lo

w in

itial

dos

e w

ith g

radu

al i

ncre

ase

and

care

ful

mon

itorin

g un

til l

owes

t po

ssib

le m

aint

enan

ce d

ose

is r

each

ed.

We

have

fou

nd a

citre

tin h

as p

rovi

ded

the

mos

t be

nefit

in

redu

cing

his

hyp

erke

rato

sis,

but

the

trade

off

is th

at it

has

bee

n sh

own

to in

crea

se e

pide

rmal

fra

gilit

y as

wel

l as

the

risk

of c

utan

eous

in

fect

ions

whi

ch th

ese

patie

nts a

re a

lread

y pr

one

to d

evel

op.

The

wel

l-kno

wn

adve

rse

effe

cts

oral

retin

oids

exh

ibit

with

sho

rt co

urse

s of

trea

tmen

t as

seen

with

ac

ne p

atie

nts

mus

t stil

l be

rout

inel

y m

onito

red

for.

Als

o, th

ere

are

addi

tiona

l ris

ks th

e cl

inic

ian

mus

t be

aw

are

of w

hich

occ

ur o

nly

with

lon

g-te

rm o

ral

retin

oid

use,

as

is o

ften

the

case

whe

n tre

atin

g co

ngen

ital i

chth

yose

s. H

yper

osto

sis

can

occu

r, an

d ap

pear

s si

mila

r to

diff

use

idio

path

ic

skel

etal

hyp

eros

tosi

s (D

ISH

), in

volv

ing

oste

ophy

te f

orm

atio

n an

d ca

lcifi

catio

n of

ten

dons

and

lig

amen

ts.

It

is n

ot r

ecom

men

ded

to r

outin

ely

scre

en f

or h

yper

osto

sis,

but

if su

spec

ted

in a

sy

mpt

omat

ic p

atie

nt, t

his

is b

est a

ccom

plis

hed

with

an

x-ra

y of

the

thor

acic

spi

ne.

How

ever

, mos

t af

fect

ed p

atie

nts

are

asym

ptom

atic

and

cho

ose

not t

o al

ter

thei

r re

tinoi

d th

erap

y du

e to

dra

mat

ic

clin

ical

ben

efit.

Inv

olve

men

t of

the

pos

terio

r lo

ngitu

dina

l lig

amen

t m

ay l

ead

to s

pina

l co

rd

com

pres

sion

and

con

side

ratio

n sh

ould

be

give

n to

dis

cont

inui

ng th

e re

tinoi

d in

this

cas

e.

Prem

atur

e cl

osur

e of

the

epip

hyse

s ha

s als

o be

en ra

rely

repo

rted

at h

ighe

r dos

es.

Rou

tine

pedi

atric

he

ight

mea

sure

men

ts b

efor

e an

d du

ring

ther

apy

are

reco

mm

ende

d to

mon

itor f

or th

is e

ffect

. W

hile

no

t rou

tinel

y pe

rfor

med

, x-r

ays

of th

e fo

rear

m a

nd w

rist c

an b

e do

ne if

this

is su

spec

ted.

O

steo

poro

sis

as a

con

sequ

ence

of

long

-term

ret

inoi

d us

e ha

s be

en s

ugge

sted

; ho

wev

er n

o pr

ospe

ctiv

e st

udie

s ha

ve c

onfir

med

a c

ausa

l rel

atio

nshi

p. W

e fir

st c

heck

ed b

one

dens

ity s

tudi

es in

ou

r pat

ient

1 y

ear f

ollo

win

g in

itiat

ion

of th

erap

y w

ith a

citre

tin, a

nd w

e ha

ve re

chec

ked

year

ly si

nce

then

. H

e w

as in

itial

ly fo

und

to h

ave

Z-sc

ores

in th

e os

teop

enic

and

ost

eopo

rotic

rang

e. H

owev

er,

stan

dard

s fo

r Z-

scor

es a

re s

et u

sing

adu

lt va

lues

, and

are

not

mea

nt f

or d

iagn

osin

g os

teop

enia

in

child

ren.

Fur

ther

mor

e ou

r patient’s

Z-s

core

s ha

ve c

onsi

sten

tly im

prov

ed o

ver t

he y

ears

in s

pite

of

incr

ease

d do

sing

of a

citre

tin.

In th

is c

ase,

his

low

sco

res

are

natu

rally

impr

ovin

g as

he’s

aged

, and

on

ce h

e ha

s re

ache

d ad

ulth

ood

we

can

draw

mor

e de

finiti

ve c

oncl

usio

ns r

egar

ding

his

sco

res.

U

ntil

then

, w

e si

mpl

y no

te a

pos

itive

tre

nd.

Int

eres

tingl

y, o

ur p

atie

nt a

lso

has

a do

cum

ente

d vi

tam

in D

def

icie

ncy

likel

y as

a re

sult

of h

is E

HK

, and

is o

n vi

tam

in D

supp

lem

enta

tion.

Refe

renc

es

1.Sp

itz J

L.

Gen

oder

mat

oses

: A

clin

ical

gui

de to

gen

etic

skin

dis

orde

rs, 2

nd e

ditio

n. L

ippi

ncot

t Will

iam

s & W

ilkin

s;

2004

.

2.E

lsto

n D

M, e

t al.

Req

uisi

tes i

n D

erm

atol

ogy:

Der

mat

opat

holo

gy.

Saun

ders

Els

evie

r; 2

009.

3.B

olog

nia

JL, e

t al.

Der

mat

olog

y, 2

nd e

ditio

n. M

osby

Els

evie

r; 2

008.

4.W

olve

rton

, SE

. C

ompr

ehen

sive

Der

mat

olog

ic D

rug

The

rapy

, 2nd

edi

tion.

Sau

nder

s Els

evie

r; 2

007.

5.N

eshe

r G

, Zuc

kner

J.

Rhe

umat

olog

ic c

ompl

icat

ions

of v

itam

in A

and

ret

inoi

ds.

Sem

in A

rthr

itis R

heum

199

5; 2

4:29

1-6.

6.C

rand

all C

. V

itam

in A

inta

ke a

nd o

steo

poro

sis:

a c

linic

al r

evie

w.

J W

omen

s Hea

lth (L

arch

mt)

200

4; 1

3:93

9-53

.

7.L

ee E

, Koo

J. S

ingl

e-ce

nter

ret

rosp

ectiv

e st

udy

of lo

ng-t

erm

use

of l

ow-d

ose

acitr

etin

(Sor

iata

ne) f

or p

sori

asis

. J

Der

mat

olog

Tre

at 2

004;

15:

18-1

3.

8.

Elli

s CN

, et a

l. L

ong-

term

rad

iogr

aphi

c fo

llow

-up

afte

r is

otre

tinoi

n th

erap

y. J

Am

Aca

d D

erm

atol

198

8; 1

8:12

52-6

1.

9.

DiG

iova

nna

JJ.

Isot

retin

oin

effe

cts o

n bo

ne.

J A

m A

cad

Der

mat

ol 2

001;

45:

S176

-82.

10.

Mar

golis

DJ.

Ost

eopo

rosi

s and

long

-ter

m e

tret

inat

e th

erap

y. A

rch

Der

mat

ol 1

996;

132

:713

-14.

Lew

isGal

e Ho

spita

l Mon

tgom

ery

/ Edw

ard

Via

Colle

ge o

f Ost

eopa

thic

Med

icin

e

Trey

Hau

nson

, DO

and

Dan

iel S

. Hur

d, D

O, F

AOCD

Epid

erm

olyt

ic H

yper

kera

tosis

Figu

res

Figu

re 1

Figu

re 2

Figu

re 3

252

Jare

d He

aton

DO,

Larg

o Med

ical C

ente

r, La

rgo F

lorid

a

CAS

E R

EPO

RT

A 52

-year

-old

HIV

pos

itive

mal

e pre

sent

ed w

ith a

2 m

onth

hist

ory o

f a

mild

ly pr

uriti

c sca

ly er

uptio

n on h

is ch

est,

face

and

uppe

r extr

emiti

es.

He w

as re

cent

ly pr

escr

ibed

hydr

ochl

orot

hiaz

ide f

or hy

perte

nsio

n. H

is ot

her m

edica

tions

inclu

ded

lopi

navir

/rito

navir

, em

tricit

abin

e/

teno

fovir

, lans

opra

zole

, ros

uvas

tatin

, pro

met

hazin

e, a

lpra

zola

m,

dron

abin

ol, r

isper

idon

e and

lisin

opril

. He d

enie

d an

y hist

ory o

f dru

g al

lerg

ies o

r sim

ilar r

ashe

s.

Phys

ical e

xam

inat

ion

reve

aled

larg

e, p

ink,

pol

ycyc

lic, s

caly

plaq

ues o

f th

e che

st an

d up

per e

xtrem

ities

with

pro

min

ent e

ryth

ema

of th

e mal

ar

chee

ks (F

igs 1

and

2). T

he p

roxim

al n

ail f

olds

had

dila

ted,

non-

alte

rnat

ing,

vasc

ular

loop

s.

Due t

o the

mor

phol

ogy a

nd d

istrib

utio

n of t

he p

laqu

es, a

nd th

e rec

ent

addi

tion o

f hyd

roch

loro

thia

zide,

our

pat

ient

was

give

n a w

orkin

g di

agno

sis of

suba

cute

cuta

neou

s lup

us er

ythem

atos

us (S

CLE)

. Ro

utin

e blo

od w

ork a

nd b

iops

y, ho

weve

r, re

veal

ed n

o evid

ence

of

SCLE

or co

nnec

tive t

issue

diso

rder

s. Th

e bio

psy w

as co

nsist

ent w

ith a

psor

iasif

orm

spon

giot

ic de

rmat

itis.

Psor

iasis

is a

com

mon

, rec

urre

nt p

apul

osqu

amou

s ski

n dise

ase t

hat

is th

ough

t to b

e a T-

cell a

nd cy

toki

ne m

edia

ted

auto

imm

une d

isord

er

of ke

ratin

ocyte

hyp

erpr

olife

ratio

n. R

ecog

nizin

g pso

riasis

in p

atie

nts

with

HIV

may

be c

halle

ngin

g. Th

e clin

ical a

ppea

ranc

e may

mim

ic ot

her s

kin d

isord

ers a

ssoc

iate

d wi

th H

IV or

even

the c

utan

eous

ad

vers

e effe

cts f

rom

hig

hly a

ctive

antir

etro

viral

ther

apy (

HAAR

T).1

Near

ly al

l HIV

pat

ient

s will

be a

ffect

ed b

y a d

erm

atol

ogic

cond

ition

. In

fact

, it m

ay b

e the

firs

t sig

n of t

heir

HIV i

nfec

tion.

2 Th

e pre

sent

atio

n of

ps

oria

sis an

d m

any o

ther

der

mat

oses

is of

ten a

typica

l and

mor

e se

vere

in th

ese p

atie

nts.1,

3,4

Furth

erm

ore,

a va

riety

of d

erm

atol

ogic

com

plica

tions

from

HAA

RT ca

n mak

e it d

ifficu

lt to

dist

ingu

ish

psor

iasis

from

a cu

tane

ous a

dver

se ef

fect

of t

hese

med

icatio

ns.5

Psor

iasis

can o

ccur

at an

y sta

ge of

HIV

, but

usua

lly ap

pear

s lat

e in t

he

non-

term

inal

stag

e.1,6 A

dist

ingu

ishin

g fea

ture

of H

IV-a

ssoc

iate

d ps

oria

sis is

that

mul

tiple

form

s, in

cludi

ng gu

ttate

, ery

thro

derm

ic,

inve

rse,

and

acra

l pso

riasis

, can

occu

r sim

ulta

neou

sly in

the s

ame

patie

nt. In

addi

tion,

thes

e pat

ient

s may

hav

e pso

riatic

arth

ritis

which

ha

s a hi

gher

incid

ence

in th

is po

pula

tion.

1,4,

7 In

non-

HIV

indi

vidua

ls, im

mun

osup

pres

sive t

hera

py th

at d

ecre

ases

T-ce

ll cou

nts t

ypica

lly im

prov

es p

soria

sis. Ho

weve

r, wh

en C

D4 T-

cell

coun

ts d

ecre

ase i

n HIV

pat

ient

s pso

riasis

par

adox

ically

wor

sens

. Va

rious

expl

anat

ions

for t

his p

arad

ox ha

ve b

een p

ropo

sed

inclu

ding

an

incr

ease

in th

e CD8

/CD4

T-ce

ll rat

io, a

n alte

ratio

n of

infla

mm

ator

y cy

toki

nes f

rom

the c

lass

ic T h

elpe

r cel

l 1 to

the T

help

er ce

ll 2

path

way,

an in

crea

se in

inte

rfero

n-

and

supe

rant

igen

stim

ulat

ion b

y HI

V, ot

her v

iruse

s or b

acte

ria. 1,

7-9

DIS

CUSS

ION

REF

EREN

CES

1.M

orar

N, W

illis-

Owen

SA, M

aure

r T, e

t al.

HIV-

asso

ciate

d pso

riasis

: pat

hoge

nesis

, clin

ical fe

atur

es, a

nd m

anag

emen

t.

Lanc

et In

fect

Dis.

201

0;10

:470

-478

2.

Garm

an M

E, Ty

ring S

K. T

he cu

tane

ous m

anife

stat

ions

of H

IV in

fect

ion.

Der

mat

ol C

lin. 2

002;

20:1

93-2

08

3.M

orar

N, D

lova

NC,

Mos

am A

, et a

l. Cu

tane

ous m

anife

stat

ions

of H

IV in

Kwa

-Zul

u Nat

al, S

outh

Afri

ca. I

nter

natio

nal

Jour

nal o

f Der

mat

olog

y. 2

006;

45:1

006-

1007

4.

Men

on K

, Van

Voor

hees

AS,

Beb

o BF J

r, et

al.

Psor

iasis

in p

atie

nts w

ith H

IV in

fect

ion:

From

the m

edica

l boa

rd of

the

Natio

nal P

soria

sis Fo

unda

tion.

J Am

Aca

d De

rmat

ol. 2

010;

62(2

):291

-299

5.

Kong

HH,

Mye

rs S

A. C

utan

eous

effe

cts o

f hig

hly a

ctive

ant

iretro

viral

ther

apy i

n HIV

-infe

cted

patie

nts.

Der

mat

olog

ic Th

erap

y . 2

005;

18:5

8-66

6.

Mah

ajan

VK, S

harm

a NL,

Sarin

S, e

t al.

Tripl

e ant

iretro

viral

ther

apy i

mpr

oves

pso

riasis

asso

ciate

d hu

man

im

mun

odef

icien

cy vi

rus i

nfec

tion:

a cli

nico

-ther

apeu

tic ex

perie

nce.

JEA

DV. 2

008;

22:1

017-

1018

7.

Mal

lon E

, Bun

ker C

B. H

IV-A

ssoc

iate

d Pso

riasis

. AID

S PA

TIENT

CAR

E an

d STD

s. 2

000;

14(5

):239

-246

8.

Fife D

J, W

alle

r JM

, Jef

fes E

W, e

t al.

Unra

velin

g the

par

adox

es of

HIV

-ass

ocia

ted p

soria

sis: a

revie

w of

T-ce

ll sub

sets

an

d cyto

kine p

rofil

es. D

erm

atol

ogy O

nlin

e Jou

rnal

. 200

7;13

(2):4

9.

Nam

azi M

R. P

arad

oxica

l Exa

cerb

atio

n of P

soria

sis in

AID

S: P

ropo

sed E

xpla

natio

ns In

cludi

ng th

e Pot

entia

l Rol

es o

f Su

bsta

nce P

and

Gram

-Neg

ative

Bac

teria

. Aut

oim

mun

ity. 2

004;

37(1

):67-

71

FIG

URES

The m

anag

emen

t of p

soria

sis in

HIV

pos

itive

pat

ient

s can

be

chal

leng

ing a

s it t

ends

to b

e mor

e sev

ere a

nd re

calci

trant

to

treat

men

t. Th

e Nat

iona

l Pso

riasis

Foun

datio

n rec

ently

pub

lishe

d gu

idel

ines

for t

reat

men

t of p

soria

sis in

HIV

pat

ient

s. Th

e aut

hors

re

com

men

d to

pica

ls as

firs

t-lin

e the

rapy

in m

ild to

mod

erat

e di

seas

e, fo

llowe

d by

antir

etro

viral

s and

ultr

avio

let l

ight

for

mod

erat

e to s

ever

e pso

riasis

. Ora

l ret

inoi

ds sh

ould

be c

onsid

ered

se

cond

-line

for m

oder

ate t

o sev

ere d

iseas

e. Im

mun

osup

pres

sive

agen

ts in

cludi

ng hy

drox

yure

a, cy

closp

orin

e, m

etho

trexa

te a

nd

tum

or ne

cros

is fa

ctor

-α in

hibi

tors

may

be c

onsid

ered

for s

ever

e an

d re

fract

ory d

iseas

e. T

he au

thor

s rec

omm

end

close

mon

itorin

g fo

r adv

erse

even

ts es

pecia

lly w

hen u

sing i

mm

unos

uppr

essiv

e th

erap

y. M

onito

ring o

f CD4

T-ce

ll cou

nts a

nd vi

ral lo

ad in

co

ordi

natio

n with

an in

fect

ious

dise

ase s

pecia

list i

s also

ad

vised

.4

1 2

253

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ICK

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port

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oste

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he F

B ic

on.

23 ye

ar ol

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an A

meric

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ale w

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story

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or 2

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uppe

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area

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painf

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month

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wise

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ns w

ere a

symp

tomati

c •

Past

medic

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tory:

acne

vulga

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. No h

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TN

•Pa

st su

rgica

l hist

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•

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story:

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story

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E or

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s smo

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IVDA

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gies:

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nt Me

dicati

ons:

napr

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, plaq

uenil

•

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No f

ever

s, my

algias

, arth

ralgi

as, w

eight

loss,

fatigu

e, ab

domi

nal p

ain, o

r pre

cedin

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bs: C

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NL, S

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Ultra

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Daps

one

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0 Na

prox

en 5

00mg

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: 11/2

011-

curre

nt Pl

aque

nil 2

00mg

BID

: 2/20

12 –

curre

nt

Hist

ory

Phys

ical

find

ings

12/6/

2010

Hist

olog

y Br

ief O

verv

iew o

f Sys

tem

ic Po

lyarte

ritis

Nodo

sa

Multis

ystem

ic va

sculi

tis

pred

omina

ntly m

edium

-size

d ve

ssel

disea

se

•Co

ntrov

ersy

on re

quire

ment

for ab

senc

e of

small

vess

el dis

ease

(ie g

lomer

ulone

phriti

s) An

y age

, but

typica

lly 40

-60;

Asso

ciated

with

HBV

, infla

mmato

ry bo

wel d

iseas

e, SL

E, F

amilia

l Med

iterra

nean

feve

r, Ha

iry ce

ll leu

kemi

a Cl

inica

l: Cuta

neou

s find

ings:

50%

with

syste

mic P

AN (L

ivedo

retic

ularis

, “pu

nche

d-ou

t” ulc

ers,

painf

ul su

bcuta

neou

s nod

ules a

nd di

gital

infar

cts)

Extra

cutan

eous

symp

toms:

weigh

t loss

, feve

r, abd

omina

l pain

, arth

ralgi

as, m

yalgi

as, m

onon

euriti

s mult

iplex

, co

nges

tive

hear

t fail

ure,

kidne

y inv

olvem

ent,

orch

itis, C

VA ar

e rar

e

Cuta

neou

s Pol

yarte

ritis

Nodo

sa (C

PAN)

: Firs

t des

cribe

d in

1931

by L

indbe

rg

Repr

esen

ts 10

% o

f PAN

case

s; Re

porte

d av

erag

e ag

e: 43

(6-7

2); M

ild sy

stemi

c sym

ptoms

: feve

r, mya

lgias

, ar

thralg

ias, p

eriph

eral

neur

opath

y Cl

inica

l: live

do re

ticula

ris, te

nder

subc

utane

ous n

odule

s, cu

taneo

us u

lcera

tions

; Othe

r find

ings:

petec

hiae,

purp

ura,

cutan

eous

nec

rosis

; Mos

t com

monly

on le

gs (9

7% le

gs, 3

3% a

rms,

8% tr

unk);

Chr

onic,

relap

sing

and

remi

tting

benig

n co

urse

; mon

ths to

year

s; wi

th sp

ontan

eous

remi

ssion

or in

duce

d by

ster

oid th

erap

y

Diag

nosis

: No s

pecif

ic tes

ting

for C

PAN

After

histo

logica

l con

firmati

on o

f pre

senc

e of

vasc

ulitis

, CPA

N dia

gnos

is ca

n only

be m

ade

follow

ing e

xclus

ion o

f sy

stem

ic PA

N –Ch

eck a

rteria

l BP,

CBC,

ESR

, live

r and

rena

l func

tion

tests,

cryo

globu

lins,

ANA,

ANC

A, R

F an

d co

mplem

ent le

vels

–Th

en e

valua

te ba

sed

on sy

mptom

s:

•ele

ctrom

yogr

am a

nd m

uscle

enzy

mes f

or m

yalgi

as or

mus

cle w

eakn

ess

•ne

rve co

nduc

tion

studie

s for

pare

sthes

ias

•gu

aiac s

tool +

/- co

lonos

copy

for

abdo

mina

l pain

•

rena

l ang

iogra

m for

pts w

ith re

nal d

ysfun

ction

and

/or H

TN

–Al

so co

nside

r ASO

titer

if pt

repo

rts re

cent

illnes

s –

Evalu

ation

of IB

D, in

fectio

n, me

dicati

on h

istor

y

Lab

Find

ings

–

Mild

Anem

ia –

Mode

rate

leuko

cytos

is –

ESR

eleva

ted (6

0%)

–AS

O tite

rs (e

spec

ially

in kid

s) –

pANC

A (u

suall

y mino

cylci

ne in

duce

d CP

AN)

Hist

olog

y: Fib

rin de

posit

ion in

arter

iolar

wall

s and

junc

tion

of re

ticula

r der

mis a

nd th

e fat,

neu

troph

ilic d

ebris

, mixe

d inf

lamma

tory i

nfiltra

te

Et

iolo

gy: U

nkno

wn

- View

ed as

an im

mune

comp

lex-m

ediat

ed d

iseas

e 1)

DIF

show

s IgM

and

C3 de

posit

ion in

vess

el wa

lls in

9/10

pts

(Diaz

-Per

ez e

t al, 1

980)

2)

16 pt

s – 78

% Ig

M an

ti-pho

spha

tidyls

erine

-pro

throm

bin co

mplex

antib

odies

?

Activ

ate cl

assic

al co

mplem

ent p

athwa

y to c

ause

CPA

N (K

awak

ami e

t al, 2

007)

- G

roup

A- b

eta h

emoly

tic st

repto

cocc

al inf

ectio

n –

URI (

Fath

alla

et a

l, 200

5)

–On

e cas

e afte

r nec

rotiz

ing fa

ciitis

(Ste

in et

al, 2

001)

- A

ssoc

iated

w/ H

ep B

infec

tion

–4/9

pts w

ith C

PAN

had

Hep B

infec

tion

- A

ssoc

iated

with

IBD

–5/7

9 pts

with

CPA

N ha

d IB

D (D

aoud

et a

l, 199

7)

- Cas

e rep

orts

of CP

AN as

socia

ted w

ith H

ep C

, Par

vo B

-19,

myco

bater

ium tu

bercu

losis

Mino

cycli

ne in

duce

d CP

AN

Does

CPA

N pr

ogre

ss to

syst

emic

PAN?

Da

oud

et a

l, 199

7:

–79

patie

nts fo

llowe

d an

aver

age

of 7 y

ears

had

no pr

ogre

ssion

to sy

stemi

c PAN

Ch

en, 1

989:

–2 o

f 20 p

atien

ts pr

ogre

ssed

to sy

stemi

c PAN

in 18

year

s Fa

thall

a et

al, 2

005:

–

4 chil

dren

follo

wed

for an

aver

age

of 5 y

ears

– no o

rgan

invo

lveme

nt M

inkow

itz e

t al,1

991:

–

7 of 9

patie

nts in

a re

trosp

ectiv

e stud

y inv

olved

at le

ast o

ne o

rgan

othe

r tha

n the

skin

Fo

llow

Up:

•Fo

llow

up Q

6mon

ths to

Q ye

ar w

ith fu

ll eva

luatio

n for

syste

mic P

AN

•Hi

story,

phys

ical, v

itals,

ESR

, CBC

, com

pleme

nt lev

els, li

ver a

nd re

nal fu

nctio

n stu

dies

Trea

tmen

t Opt

ions

•A

numb

er o

f trea

tmen

t opti

ons h

ave b

een

used

in th

e tre

atmen

t of th

is sk

in dis

orde

r •N

SAID

S or

colch

icine

•P

ts mo

re re

fracto

ry to

cons

erva

tive t

reatm

ent a

nd h

ave e

xtra-

cutan

eous

symp

toms

syste

mic s

teroid

s •

Then

ster

oid sp

aring

agen

ts: N

SAID

s, co

lchici

ne, h

ydro

xych

loroq

uine,

daps

one,

azoth

ioprin

e, cy

cloph

osph

amide

, meth

otrex

ate

•Pen

icillin

for a

ntece

dent

strep

tococ

cal in

fectio

n

Disc

ussi

on

Min

ocyc

line

indu

ced

CPAN

Be

awar

e of p

ossib

le mi

nocy

cline

indu

ced C

PAN

Th

is ma

y or m

ay no

t be t

he ca

se fo

r this

patie

nt as

it wa

s hist

orica

lly un

clear

if the

patie

nts ha

d the

ra

sh be

fore s

tartin

g the

mino

cycli

ne.

Pr

opos

ed di

agno

sitc c

riteria

for m

inocy

cline

indu

ced C

PAN

(Culv

er e

t al, 2

005)

–

Cons

ider t

his co

nditio

n if p

t has

6 of

the 7

criter

ia •

1) m

inocy

cline

use >

12 m

onths

**

•2)

skin

manif

estat

ions i

nclud

ing liv

edo r

eticu

laris

and/o

r sub

cutan

eous

nodu

les **

•

3) ar

thritis

and/o

r mya

lgias

and/o

r neu

ropa

thy in

the d

istrib

ution

of th

e ras

h •

4) la

ck of

syste

mic i

nvolv

emen

t **

•5)

skin

biops

y with

necro

tizing

vasc

ulitis

of m

edium

size

d ves

sels

** •

6) pA

NCA

posit

ivity

•7)

impr

ovem

ent a

fter d

iscon

tinua

tion o

f mino

cycli

ne

Refe

renc

es

Lin

dber

g K. E

in be

itrag z

ur ke

nntni

s der

peria

rteriti

s nod

osa.

Acta

Med

Sca

nd 19

31; 7

6: 18

3.

Mor

gan A

, Scw

artz

RA. C

utan

eous

polua

rterit

is no

dosa

: a co

mpr

ehen

sive r

eivew

. Int

J of

Der

mat

ol 20

10; 4

9:75

0-75

6

Fatha

lla B

M, M

iller L

, Bra

dy S

, et a

l. Cut

aneo

us po

lyarte

ritis

nodo

sa in

child

ren.

J Am

Aca

d De

rmat

ol 20

05; 5

3: 72

4–72

8.

Daou

d MS,

Hutt

on K

P, Gi

bson

LE. C

utane

ous p

eriar

teritis

nodo

sa: a

clini

copa

tholog

ical s

tudy o

f 79 c

ases

. Br J

Der

mat

ol 19

97;

136:

706–

713.

Di

az-P

erez

JL, W

inkelm

ann R

K. C

utane

ous p

eriar

teritis

nodo

sa. A

rch

Derm

atol

1974

; 110

: 407

–414

.

Kawa

kami

T, Y

amaz

aki M

, Mizo

guch

i M, e

t al. H

igh tit

er o

f ant

i-pho

spha

tidyls

erine

–pro

thro

mbin

com

plex a

ntibo

dies i

n pa

tient

s wi

th cu

tane

ous p

olyar

terit

is no

dosa

. Arth

ritis

Rheu

m 20

07; 5

7: 15

07–1

Diaz

-Per

ez JL

, Sch

roete

r AL,

Wink

elman

n RK.

Cuta

neou

s per

iarter

itis no

dosa

: immu

noflu

ores

cenc

e stud

ies. A

rch

Derm

atol

1980

; 116

: 56–

58.

St

ein R

H, P

helps

RG,

Sap

adin

AN. C

utane

ous p

olyar

teritis

nodo

sa af

ter st

repto

cocc

al ne

crotiz

ing fa

sciiti

s. M

t Sina

i J M

ed 20

01;

68: 3

36–3

38.

Mi

nkow

itz G

, Smo

ller B

R, M

cNutt

NS.

Ben

ign cu

taneo

us po

lyarte

ritis n

odos

a. Re

lation

ship

to sy

stemi

c poly

arter

itis no

dosa

and

to he

patiti

s B in

fectio

n. Ar

ch D

erm

atol

1991

; 127

: 152

0–15

23.

Ch

en K

R. C

utane

ous p

olyar

teritis

nodo

sa: a

clini

cal a

nd hi

stopa

tholog

ical s

tudy o

f 20 c

ases

. J D

erm

atol

1989

; 16:

429–

442.

Ma

gnan

t J, L

homm

et C,

Mac

het L

, et a

l. Cut

aneo

us po

lyarte

ritis

nodo

sa an

d Cro

hn’s

disea

se: a

n as

socia

tion n

ot to

be i

gnor

ed.

Rev M

ed In

tern

e 200

9; 30

: 345

–348

.

Durst

R, G

oldsc

hmidt

N, B

en Ye

huda

A. P

arvo

virus

B19

infec

tion a

ssoc

iated

with

mye

losup

pres

sion a

nd cu

taneo

us po

lyarte

ritis

nodo

sa. R

heum

atolo

gy (O

xford

) 200

2; 41

: 121

0–12

12

Na

ouri M

, Bac

q Y, M

ache

t MC,

et a

l. Int

erfe

ron-

alpha

and r

ibavir

in tre

atm

ent in

a p

atien

t with

hep

atitis

C vi

rus-

asso

ciate

d cu

tane

ous p

eriar

terit

is no

dosa

. Ann

Der

mat

ol Ve

nere

ol 20

06; 1

33: 6

79–6

82

Mo

relan

d LW

, Ball

GV.

Cuta

neou

s poly

arter

itis no

dosa

. Am

J M

ed 19

90; 8

8: 42

6–43

0.

Culve

r B, It

kin A

, Pisc

hel K

. Cas

e rep

ort a

nd re

view

of mi

nocy

cline

-indu

ced c

utane

ous p

olyar

teritis

nodo

sa. A

rthrit

is Rh

eum

20

05; 5

3: 46

8–47

0.

Abad

S, K

ambo

uchn

er M

, Nejj

ari M

, et a

l. Add

itiona

l cas

e of

mino

cycli

ne-in

duce

d cut

aneo

us po

lyarte

ritis

nodo

sa: c

omm

ent o

n th

e arti

cle b

y Culv

er e

t al..

Arth

ritis

Rheu

m 20

06; 5

5: 83

1; au

thor

repl

y 2

Pe

lletie

r F, P

uzen

at E,

Blan

c D, e

t al. M

inocy

cline

-indu

ced c

utan

eous

polya

rterit

is no

dosa

with

ant

ineut

roph

il cyto

plasm

ic an

tibod

ies. E

ur J

Derm

atol

2003

; 13:

396–

398.

Sc

haffe

r JV,

Dav

idson

DM,

McN

iff JM

, et a

l. Per

inucle

ar an

tineu

troph

ilic cy

topla

smic

antib

ody-

posit

ive cu

tane

ous p

olyar

terit

is no

dosa

asso

ciate

d with

mino

cycli

ne th

erap

y for

acn

e vu

lgaris

. J A

m A

cad

Derm

atol

2001

; 44:

198–

206.

Te

hran

i R, N

ash-

Goeli

tz A,

Ada

ms E

, et a

l. Mino

cycli

ne-in

duce

d cu

tane

ous p

olyar

terit

is no

dosa

. J C

lin R

heum

atol

2007

; 13:

14

6–14

9

•“S

tarbu

rst” h

yper

pigme

nted

to vio

laceo

us li

vido r

eticu

laris

patte

rn o

n dist

al leg

s and

arms

•

No no

dules

, no u

lcera

tions

.

Wes

tern

Uni

vers

ity/P

acifi

c Ho

spita

l of L

ong

Beac

h

Te

resa

Isha

k, D

O

Cuta

neou

s Pol

yart

eriti

s Nod

osa

8/22

/11

254

Tabl

e 1:

Pat

ient

Dem

ogra

phic

s

Abs

trac

t R

esul

ts

Bac

kgro

und:

Pri

mar

y de

rmal

mel

anom

a (P

DM

) has

bee

n do

cum

ente

d an

d de

scri

bed

to r

epre

sent

a fo

rm o

f mel

anom

a th

at is

con

fined

to th

e de

rmis

with

out a

n ep

ider

mal

com

pone

nt

or m

etas

tatic

dis

ease

from

a p

rim

ary

canc

er.1,

2 O

ur g

oal w

as to

ev

alua

te tu

mor

cha

ract

eris

tics,

dem

ogra

phic

s, an

d st

atis

tical

ly e

valu

ate

thos

e w

ith P

DM

who

als

o po

sses

sed

a pr

evio

us d

iagn

osis

of c

onve

ntio

nal m

elan

oma.

M

etho

ds: A

ret

rosp

ectiv

e re

view

of a

pro

spec

tive

sent

inel

ly

mph

nod

e (S

LN

) dat

abas

e, w

hich

incl

uded

569

pat

ient

s, w

as

perf

orm

ed to

iden

tify

mel

anom

a pa

tient

s pre

sent

ing

with

so

litar

y de

rmal

mel

anom

a be

twee

n Fe

brua

ry 1

997

and

June

20

06 a

t the

May

o C

linic

in A

rizo

na.

R

esul

ts: A

tota

l of 2

3 pa

tient

s wer

e id

entif

ied

that

met

the

stud

y

crite

ria

of p

osse

ssin

g PD

M.

3 pa

tient

s (13

%) p

osse

ssed

a

hist

ory

of a

pre

viou

sly

diag

nose

d m

elan

oma

rang

ing

15 m

onth

s to

10

year

s pri

or to

the

deve

lopm

ent o

f PD

M.

Age

and

Bre

slow

th

ickn

ess

wer

e st

atis

tical

ly s

igni

fican

t fac

tors

bet

wee

n th

e PD

M a

nd u

sual

cut

aneo

us m

elan

oma

grou

p (p

=.00

2, p

=0.0

001,

re

spec

tivel

y).

The

re w

as n

o di

ffer

ence

in d

isea

se-f

ree

or o

vera

ll su

rviv

al b

etw

een

PDM

and

con

vent

iona

l mel

anom

a (p

=1.0

, p=

0.64

), an

d re

curr

ence

rat

es w

ere

not a

ltere

d (p

=0.5

8).

C

oncl

usio

n: P

DM

pat

ient

s wer

e ol

der

(p<0

.000

1), h

ad g

reat

er

Bre

slow

thic

knes

s (p

<0.0

02),

and

dise

ase-

free

and

ove

rall

surv

ival

was

sim

ilar,

sugg

estin

g a

mor

e fa

vora

ble

prog

nosi

s co

mpa

red

to c

utan

eous

mel

anom

as o

f con

vent

iona

l sub

type

s.

The

re w

as n

o as

soci

atio

n w

ith p

osse

ssin

g a

hist

ory

of

mel

anom

a an

d de

velo

ping

PD

M, s

igni

fyin

g th

ese

lesi

ons a

re

prop

erly

nam

ed a

s “pr

imar

y”.

PDM

, how

ever

, may

mim

ic

met

asta

tic d

isea

se a

nd e

xten

sive

rad

iogr

aphi

c w

orku

p is

re

com

men

ded

befo

re a

fina

l dia

gnos

is o

f PD

M is

mad

e.

Intr

oduc

tion

•Pr

imar

y de

rmal

mel

anom

a (P

DM

) is a

m

elan

oma

conf

ined

to th

e de

rmis

or

subc

utan

eous

tiss

ue, l

acki

ng a

n ep

ider

mal

co

mpo

nent

.3 •

Sim

ilar s

urvi

val r

ates

of P

DM

com

pare

d to

co

nven

tiona

l mel

anom

a4 pr

ompt

ed th

is st

udy

to e

xam

ine

patie

nts w

ith c

onve

ntio

nal

mel

anom

a w

ho a

lso

deve

lope

d PD

M, a

nd to

co

mpa

re th

eir d

isea

se-f

ree

surv

ival

, re

curr

ence

rate

s, an

d B

resl

ow d

epth

. •

Kno

win

g th

e pa

tient

pop

ulat

ion

and

tum

or

char

acte

ristic

s hel

p to

furth

er d

efin

e th

is

subt

ype

of m

elan

oma.

Met

hods

Dat

a C

olle

ctio

n

•Ret

rosp

ectiv

e re

view

of p

rosp

ectiv

e SL

N d

atab

ase

cont

aini

ng fr

om F

ebru

ary

1997

thro

ugh

Dec

embe

r 200

8 at

May

o C

linic

.

•Fou

r crit

eria

wer

e re

quire

d fo

r his

tolo

gic

cons

ider

atio

n as

a P

DM

: in

volv

emen

t of t

he d

erm

is, n

o de

rmal

-epi

derm

al ju

nctio

nal c

ompo

nent

, no

dire

ct c

onne

ctio

n to

adn

exal

stru

ctur

es, a

nd n

o as

soci

ated

ben

ign

nevu

s. (F

igur

e 1,

2)

•No

hist

opat

holo

gic

evid

ence

of u

lcer

atio

n or

regr

essi

on a

ssoc

iate

d w

ith th

e le

sion

.

Figu

re 1

. D

erm

al m

elan

oma.

Mel

anoc

ytic

nes

ts (a

rrow

) are

con

fined

to th

e de

rmis

. Hem

atox

ylin

-eos

in; o

rigin

al m

agni

ficat

ion

x 10

0.

Figu

re 2

. C

onve

ntio

nal m

elan

oma.

Mel

anoc

ytic

nes

ts in

volv

e th

e de

rmal

-ep

ider

mal

junc

tion

(arr

owhe

ad) a

nd d

erm

is (a

rrow

). H

emat

oxyl

in-e

osin

; or

igin

al m

agni

ficat

ion

x 10

0.

1

2

Stat

istic

al c

onsi

dera

tion

•Diff

eren

ces b

etw

een

patie

nts w

ith P

DM

and

pat

ient

s with

all

othe

r mel

anom

a w

ere

com

pare

d.

•For

cat

egor

ical

var

iabl

es, t

he F

ishe

r’s e

xact

test

and

the

Chi

-squ

are

test

for

inde

pend

ence

wer

e us

ed to

det

erm

ine

diffe

renc

es b

etw

een

the

two

popu

latio

ns.

Unp

aire

d t-t

est w

as u

sed

to c

ompa

re m

eans

of t

he tw

o po

pula

tions

. •O

vera

ll su

rviv

al w

as th

e tim

e in

terv

al fr

om d

iagn

osis

to d

eath

from

any

cau

se.

Dis

ease

free

surv

ival

was

the

time

inte

rval

to fi

rst l

ocor

egio

nal r

ecur

renc

e,

dist

ance

recu

rren

ce, o

r dea

th fr

om a

ny c

ause

. •K

apla

n-M

eier

met

hod

was

use

d to

cal

cula

te su

rviv

al c

urve

s for

x-y

ear d

isea

se-

free

surv

ival

and

ove

rall

surv

ival

. Log

-ran

k te

sts w

ere

used

to c

ompa

re ti

me

to

even

t cur

ves.

•569

pat

ient

s und

erw

ent w

ide

loca

l exc

isio

n an

d se

ntin

el n

ode

diss

ectio

n af

ter a

di

agno

sis o

f mel

anom

a

•23

(4.0

%) p

atie

nts w

ere

diag

nose

d w

ith P

DM

(Tab

le 1

)

•Pat

ient

s dia

gnos

ed w

ith P

DM

wer

e si

gnifi

cant

ly o

lder

(72

vs. 6

1, P

= 0

.002

)

•Pat

ient

tum

or c

hara

cter

istic

s wer

e si

gnifi

cant

ly d

iffer

ent i

n re

fere

nce

to B

resl

ow

thic

knes

s and

did

not

reve

al d

iffer

ence

s in

recu

rren

ce. (

Tabl

e 2)

PDM

C

utan

eous

m

elan

oma

P va

lue

Age

: Med

ian,

(mea

n)

L

ess t

han

50

5

0-59

60-

69

7

0-79

Gre

ater

than

79

72, (

72.1

) 0

1

(4

%)

8

(35%

) 1

0 (4

3%)

4

(17%

)

65, (

61.3

) 1

30 (2

4%)

82

(15

%)

127

(23%

) 1

43 (2

6%)

62

(11

%)

0.00

2 0.

002

Sex

M

ale

F

emal

e

17 (7

4%)

6 (2

6%)

326

(60%

) 22

0 (4

0%)

0.20

Ethn

icity

Whi

te

A

fric

an-A

mer

ican

His

pani

c

Oth

er

23 (1

00%

) 0 0 0

529

(98%

) 1

(0.2

%)

7 (1

.3%

) 3

(0.5

%)

1.0

Prev

ious

his

tory

of

mel

anom

a 3

(13%

) 41

(8%

) 0.

41

Tabl

e 2:

Pri

mar

y D

erm

al M

elan

oma

PDM

C

utan

eous

m

elan

oma

P valu

e

Loca

tion

H

ead

and

Nec

k

Tru

nk

U

pper

Ext

Low

er E

xt

10 (4

3%)

5 (2

2%)

4 (1

7%)

4 (1

7%)

134

(25%

) 17

0 (3

1%)

116

(21%

) 12

1 (2

2%)

0.25

Thic

knes

s

< 1

mm

1-4

mm

> 4

mm

Unk

now

n

3, 3

.86

2 (9

%)

11 (4

9%)

8 (3

5%)

2 (9

%)

1.37

, 1.9

8 15

0 (2

9%)

341

(63%

) 48

(9%

)

0.00

01

Lym

ph n

ode

posi

tivity

(4

%)

73 (1

3%)

0.50

Rec

urre

nce

L

ocal

/Intra

nsit

In

trans

it/R

egio

nal

R

egio

nal

D

ista

nt

1 2 0 2

33

7 18

37

0.58

Dea

th

M

elan

oma

O

ther

2 0

32

21

1.0

0.64

1.

0

Con

clus

ions

•Pat

ient

s with

PD

M re

quire

a th

orou

gh m

etas

tatic

wor

k-up

to ru

le-o

ut sy

stem

ic m

etas

tasi

s

•Dep

th-f

or-d

epth

, PD

M h

as b

ette

r sur

viva

l tha

n co

nven

tiona

l mel

anom

a

•A h

isto

ry o

f mel

anom

a do

es n

ot p

redi

spos

e on

e to

dev

elop

ing

PDM

•PD

M p

atie

nts a

re si

gnifi

cant

ly o

lder

•Loc

al, r

egio

nal,

and

dist

ant m

etas

tase

s are

not

sign

ifica

ntly

diff

eren

t fro

m c

onve

ntio

nal m

elan

oma

Ref

eren

ces

1 Sc

hlag

enha

uff B

, Stro

ebel

W, E

lwan

ger U

, et.

al.

Met

asta

tic M

elan

oma

of U

nkno

wn

Prim

ary

Orig

in S

how

s Pro

gnos

tic S

imila

ritie

s to

Reg

iona

l Met

asta

tic M

elan

oma.

Can

cer.

199

7;80

:60-

65.

2 B

owen

GM

, Cha

ng A

E, L

owe

L, H

amilt

on T

, Pat

el R

, Joh

snon

TM

. So

litar

y M

elan

oma

Con

fined

to th

e D

erm

al a

nd/o

r Sub

cuta

neou

s Tis

sue:

Evi

denc

e fo

r Rev

isiti

ng th

e St

agin

g C

lass

ifica

tion.

Arc

h D

erm

atol

. 200

0;13

6:13

97-1

399.

3 C

assa

rino

DS,

Cab

ral E

S, K

arth

a RV

, Sw

ette

r SM

. Pr

imar

y D

erm

al M

elan

oma:

Dis

tinct

Imm

unoh

isto

chem

ical

Fin

ding

s and

Clin

ical

Out

com

e C

ompa

red

with

Nod

ular

and

Met

asta

tic M

elan

oma.

Arc

h D

erm

atol

. 200

8;14

4(1)

49-5

6.

4 Le

e C

C, F

arie

s MB

, Xin

g Y,

Mor

ton

DL.

Sol

itary

Der

mal

Mel

anom

a: B

egin

ning

or E

nd o

f the

Met

asta

tic P

roce

ss?

Ann

Sur

g O

ncol

. 200

9;16

:578

-584

.

Prim

ary

Der

mal

Mel

anom

a: D

iffer

ing

Cha

ract

eris

tics f

rom

C

onve

ntio

nal M

elan

oma?

1 J

ense

n JD

, 2 Gra

y R

J, 2 W

asif

N, 2 C

asey

III W

J, 2 K

reym

erm

an P

, 3 DiC

audo

DJ,

3 Lam

an S

D, 3 S

ekul

ic A

, 2 Poc

kaj B

A

1 McL

aren

Oak

land

Hos

pita

l, M

ayo

Clin

ic A

rizon

a—2 D

ept.

of S

urge

ry, 3 D

ept.

of D

erm

atol

ogy

255

Iatr

ogen

ic K

apos

i’s S

arco

ma

Ari

sing

A3

er R

enal

Tra

nspl

ant I

mm

unos

uppr

essi

on

Kath

erin

e Jo

hnso

n D

O*,

How

ard

D. L

ipki

n D

O**

*

Der

mat

olog

y Re

side

nt, P

GY-‐

III B

otsf

ord

Hos

pita

l, Fa

rmin

gton

Hill

s, M

I **

Der

mat

olog

y A

Men

ding

, Bot

sfor

d/M

cLar

en O

akla

nd D

erm

atol

ogy

Resi

denc

y Pr

ogra

m, F

arm

ingt

on H

ills/

PonO

ac, M

I

CASE

REP

ORT

H

isto

ry

A 67 year-‐old Caucasian male presented to clinic with a

chief complaint of lower extremity swelling, pruritus,

pain and discolora<on over a one-‐month dura<on. He

also complained of dark patches on his right arm and

axillae.. Laboratory studies, radiographs, and an EKG

were all found to be normal. The pa<ent’s past medical

history included a renal transplanta<on in October 2010,

and he was maintained on mycophenolate mofe<l 1g PO

BID, tacrolimus 3mg PO BID, and prednisone 10 mg PO

daily.

Exam

inaO

on

Physical examina<on revealed violaceous papules and

plaques over the extensor surfaces of the right upper

and lower extremi<es. In addi<on, there were violaceous

plaques on the bilateral plantar surfaces and 2-‐4 mm

erythematous macules on the bilateral dorsal feet and

anterior lower legs (See Figures 1 and 2). The right lower

extremity had piWng edema and pain upon palpa<on.

Labo

rato

ry

An HIV screen was nega<ve.

Figure 3: low power magnifica<on

DER

MAT

OH

ISTO

PATH

OLO

GY

Punch biopsies of the right upper extremity and right plantar

foot were performed, which demonstrated a prolifera<on of

endothelial cells forming bizarre-‐shaped, thin-‐walled vessels

that followed pre-‐exis<ng vascular plexuses (see Figures 3 and

4). A CD31 stain was performed, highligh<ng the vascular

prolifera<ve changes and an HHV-‐8 stain decorated many

spindle cells that were associated with the vessels (See Figure

5).

Figure 4: vascular prolifera<on

Figure 1: KS lesions on toes

Figure 2:

Lesions on

plantar surface

of right foot

Figure 5: HHV-‐8 stain

COU

RSE

AN

D T

HER

APY

In light of the histopathology results

and in conjunc<on with approval of

his renal transplant team,

mycophenolate mofe<l was

discon<nued and tacrolimus was

maintained at the same dose. The

pa<ent began showing regression of

his lesions shortly a_er discon<nuing

the mycophenolate mofe<l.

CON

CLU

SIO

N

Iatrogenic Kaposi’s sarcoma most commonly

occurs in solid organ transplant recipients due to

post-‐transplant immunosuppression and

associa<on of HHV-‐8. Treatment is aimed at

decreasing and/or changing immunosuppressive

medica<ons when possible.

REFE

REN

CES:

1. Jan MM, Laskas JW, Griffin TD. Erup<ve Kaposi sarcoma: an unusual presenta<on in an HIV-‐

nega<ve pa<ent. Cu#

s. 2011 Jan; 87(1): 34-‐38.

2. Johari Y, Nicholson ML. Complete resolu<on of oral Kaposi’s sarcoma achieved by changing

immunosuppression: a case report. A

nn R Coll Surg Engl. 2010; March; (92).

3. Zwald, Fiona O’Reilly, Brown M. Skin Cancer in solid organ transplant recipients: Advances in

therapy and management. J Am Acad Dermatol. 2011 Aug; 65: 253-‐261.

4. Jakob, Lena et al. Non-‐AIDS associated Kaposi’s sarcoma: clinical features and treatment

outcome. PLoS One. 2011; 6(4): e18397.

256

RES

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7 Fo

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Str

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Uni

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erke

ley

CA 9

4710

pos

terp

rese

nter

@gm

ail.c

om

Stud

ent

disc

ount

s ar

e av

aila

ble

on o

ur F

aceb

ook

page

. G

o to

Pos

terP

rese

ntat

ions

.com

and

clic

k on

the

FB

icon

.

Exag

gera

ted

reac

tion

to

inse

ct b

ites

is a

rar

e ph

enom

enon

see

n in

pat

ient

s w

ith

chro

nic

lym

phoc

ytic

leuk

emia

. S

kin

lesi

ons

usua

lly a

ppea

r m

onth

s to

yea

rs a

fter

the

dia

gnos

is o

f le

ukem

ia a

nd a

re u

nrel

ated

to

the

cour

se o

f th

e di

seas

e.

We

repo

rt a

pat

ient

wit

h ch

roni

c ly

mph

ocyt

ic le

ukem

ia (

CLL)

who

pre

sent

ed w

ith

a re

curr

ent

prur

itic

pap

ulov

esic

ular

and

bu

llous

eru

ptio

n th

at w

as h

isto

logi

cally

con

sist

ent

wit

h an

exa

gger

ated

res

pons

e to

an

inse

ct b

ite.

Her

ein,

we

desc

ribe

wha

t is

kno

wn

abou

t th

is p

heno

men

on in

clud

ing

its

pres

enta

tion

, pr

opos

ed p

atho

gene

sis,

and

opt

ions

for

tre

atm

ent.

Intr

oduc

tion

A 71

yea

r-ol

d H

ispa

nic

mal

e pr

esen

ted

to t

he d

erm

atol

ogy

clin

ic w

ith

a re

curr

ent

gene

raliz

ed p

ruri

tic

erup

tion

tha

t he

bel

ieve

d to

be

the

resu

lt o

f in

sect

bit

es.

The

pat

ient

ha

d a

hist

ory

of B

-cel

l chr

onic

lym

phoc

ytic

leuk

emia

(CL

L) t

hat

was

dia

gnos

ed a

nd t

reat

ed

in 2

006

wit

h 5

cycl

es o

f ch

emot

hera

py w

ith

flud

arab

ine.

The

pat

ient

was

als

o di

agno

sed

wit

h pr

imar

y cu

tane

ous

CD30

+ an

apla

stic

lar

ge-c

ell

lym

phom

a (A

LCL)

of

the

left

thi

gh in

20

07,

for

whi

ch h

e un

derw

ent

CHO

P ch

emot

hera

py a

long

wit

h ex

cisi

on a

nd lo

cal r

adia

tion

th

erap

y w

ith

com

plet

e re

solu

tion

. A

ddit

iona

l med

ical

his

tory

incl

udes

a d

eep

vein

th

rom

bosi

s of

the

left

low

er e

xtre

mit

y fo

r w

hich

an

IVC

filt

er w

as p

lace

d. T

he p

atie

nt w

as

taki

ng n

o m

edic

atio

ns a

nd r

epor

ted

no a

llerg

ies.

So

cial

his

tory

was

non

-con

trib

utor

y.

Revi

ew o

f sy

stem

s w

as n

egat

ive

othe

r th

an t

he p

ruri

tus

asso

ciat

ed w

ith

the

rash

. T

he

pati

ent

was

und

ergo

ing

regu

lar

mon

itor

ing

by H

emat

olog

y/O

ncol

ogy

and

all r

ecen

t la

bora

tory

stu

dies

wer

e no

rmal

.

On

phys

ical

exa

min

atio

n, m

ulti

ple

papu

love

sicl

es w

ere

pres

ent

on t

he u

pper

and

low

er

extr

emit

ies.

Se

vera

l les

ions

on

the

low

er l

egs

cont

aine

d te

nse

hem

orrh

agic

bul

lae,

som

e of

w

hich

wer

e un

roof

ed,

bear

ing

an e

rode

d su

rfac

e. (

Figu

re 1

) N

ikol

sky

sign

and

Asb

oe-

Han

sen

sign

wer

e ne

gati

ve.

H

isto

path

olog

ical

exa

min

atio

n of

lesi

onal

ski

n re

veal

ed e

pide

rmal

spo

ngio

sis

and

vesi

cula

tion

wit

h su

perf

icia

l an

d de

ep p

eriv

ascu

lar

and

inte

rsti

tial

mix

ed c

ell i

nfilt

rate

wit

h ly

mph

ocyt

es a

nd e

osin

ophi

ls.

(Fig

ure

2) N

o at

ypic

al c

ells

wer

e pr

esen

t.

Dir

ect

imm

unof

luor

esce

nt s

tudi

es o

f pe

rile

sion

al s

kin

wer

e ne

gati

ve.

Tre

atm

ent

wit

h po

tent

to

pica

l ste

roid

s re

sult

ed in

sig

nifi

cant

impr

ovem

ent.

Figu

re 2

: Hist

opat

holo

gy

Figu

re 1

: Clin

ical

pre

sent

atio

n Di

scus

sion

(con

t)

Refe

renc

es

1.

Cerr

oni L

, Ze

nahl

ik P

, H

ofle

r G

, Ka

ddu

S, S

mol

le J

, Ke

rl H

. Sp

ecif

ic c

utan

eous

infi

ltra

tes

of B

-cel

l chr

onic

lym

phoc

ytic

leuk

emia

: a

clin

icop

atho

logi

c an

d pr

ogno

stic

stu

dy o

f 42

pat

ient

s. A

m J

Sur

g Pa

thol

. Au

g 19

96;2

0(8)

:100

0-10

10.

2.

Agne

w K

L, R

uchl

emer

R,

Cato

vsky

D,

Mat

utes

E,

Bunk

er C

B. C

utan

eous

fin

ding

s in

chr

onic

lym

phoc

ytic

leuk

aem

ia.

Br J

Der

mat

ol.

Jun

2004

;150

(6):

1129

-113

5.

3.

Roba

k E,

Rob

ak T

. Sk

in le

sion

s in

chr

onic

lym

phoc

ytic

leuk

emia

. Le

uk L

ymph

oma.

May

200

7;48

(5):

855-

865.

4.

W

eed

RI.

Exag

gera

ted

Del

ayed

Hyp

erse

nsit

ivit

y to

Mos

quit

o Bi

tes

in C

hron

ic L

ymph

ocyt

ic L

euke

mia

. Bl

ood.

Sep

196

5;26

:257

-268

. 5.

U

lmer

A,

Met

zler

G,

Scha

nz S

, Fi

erlb

eck

G.

Dap

sone

in t

he m

anag

emen

t of

"in

sect

bit

e-lik

e re

acti

on"

in a

pat

ient

wit

h ch

roni

c ly

mph

ocyt

ic l

euka

emia

. Br

J

Der

mat

ol.

Jan

2007

;156

(1):

172-

174.

6.

D

avis

MD

, Pe

rnic

iaro

C,

Dah

l PR,

Ran

dle

HW

, M

cEvo

y M

T, L

eife

rman

KM

. Ex

agge

rate

d ar

thro

pod-

bite

lesi

ons

in p

atie

nts

wit

h ch

roni

c ly

mph

ocyt

ic le

ukem

ia:

a cl

inic

al,

hist

opat

holo

gic,

and

imm

unop

atho

logi

c st

udy

of e

ight

pat

ient

s. J

Am

Aca

d D

erm

atol

. Ju

l 199

8;39

(1):

27-3

5.

7.

Blum

RR,

Phe

lps

RG,

Wei

H. A

rthr

opod

bit

es m

anif

esti

ng a

s re

curr

ent

bulla

e in

a p

atie

nt w

ith

chro

nic

lym

phoc

ytic

leuk

emia

. J

Cuta

n M

ed S

urg.

Jul

-Aug

20

01;5

(4):

312-

314.

8.

Co

curo

ccia

B,

Gis

ondi

P,

Gub

inel

li E,

Gir

olom

oni G

. An

itch

y ve

sicu

lobu

llous

eru

ptio

n in

a p

atie

nt w

ith

chro

nic

lym

phoc

ytic

leuk

aem

ia.

Int

J Cl

in P

ract

. D

ec

2004

;58(

12):

1177

-117

9.

9.

Smit

h KJ

, Sk

elto

n H

G,

3rd,

Vog

el P

, Ye

ager

J,

Baxt

er D

, W

agne

r KF

. Ex

agge

rate

d in

sect

bit

e re

acti

ons

in p

atie

nts

posi

tive

for

HIV

. M

ilita

ry M

edic

al C

onso

rtiu

m

for

the

Adva

ncem

ent

of R

etro

vira

l Re

sear

ch.

J A

m A

cad

Der

mat

ol.

Aug

1993

;29(

2 Pt

1):

269-

272.

10

. Ba

rzila

i A,

Shpi

ro D

, G

oldb

erg

I, e

t al

. In

sect

bit

e-lik

e re

acti

on in

pat

ient

s w

ith

hem

atol

ogic

mal

igna

nt n

eopl

asm

s. A

rch

Der

mat

ol.

Dec

199

9;13

5(12

):15

03-1

507.

11

. Ab

erer

W,

Konr

ad K

, W

olff

K.

Wel

ls' s

yndr

ome

is a

dis

tinc

tive

dis

ease

ent

ity

and

not

a hi

stol

ogic

dia

gnos

is.

J A

m A

cad

Der

mat

ol.

Jan

1988

;18(

1 Pt

1):

105-

114.

12

. Ze

eli T

, Fe

inm

esse

r M

, Se

gal R

, D

avid

M.

Inse

ct-b

ite-

like

Wel

ls' s

yndr

ome

in a

ssoc

iati

on w

ith

man

tle-

zone

lym

phom

a. B

r J

Der

mat

ol.

Sep

2006

;155

(3):

614-

616.

13

. Li

ndel

of B

, Is

lam

N,

Eklu

nd G

, Arf

ors

L. P

emph

igoi

d an

d ca

ncer

. A

rch

Der

mat

ol.

Jan

1990

;126

(1):

66-6

8.

14.

Bolo

gnia

J,

ed D

erm

atol

ogy.

2 e

d. S

t. L

ouis

: M

osby

Els

evie

r; 2

008.

15

. Te

ffer

i A,

Vard

iman

JW

. Cl

assi

fica

tion

and

dia

gnos

is o

f m

yelo

prol

ifer

ativ

e ne

opla

sms:

the

200

8 W

orld

Hea

lth

Org

aniz

atio

n cr

iter

ia a

nd p

oint

-of-

care

dia

gnos

tic

algo

rith

ms.

Leu

kem

ia.

Jan

2008

;22(

1):1

4-22

. 16

. Va

ssal

lo C

, Pa

ssam

onti

F,

Cana

nzi R

, et

al.

Exa

gger

ated

inse

ct b

ite-

like

reac

tion

in p

atie

nts

affe

cted

by

onco

haem

atol

ogic

al d

isea

ses.

Act

a D

erm

Ven

ereo

l.

2005

;85(

1):7

6-77

. 17

. W

alke

r P,

Lon

g D

, Ja

mes

C,

Mar

shm

an G

. Ex

agge

rate

d in

sect

bit

e re

acti

on e

xace

rbat

ed b

y a

pyog

enic

infe

ctio

n in

a p

atie

nt w

ith

chro

nic

lym

phoc

ytic

le

ukae

mia

. A

ustr

alas

J D

erm

atol

. Au

g 20

07;4

8(3)

:165

-169

.

Exag

gera

ted

inse

ct b

ite-

like

reac

tion

in

a p

atie

nt w

ith

chro

nic

lym

phoc

ytic

leuk

emia

St.

Barn

abas

Hos

pita

l, De

part

men

t of D

erm

atol

ogy,

Bron

x, N

Y 10

457

Pati

ents

wit

h he

mop

rolif

erat

ive

diso

rder

s, p

arti

cula

rly

CLL,

may

pre

sent

wit

h an

exa

gger

ated

re

acti

on t

o in

sect

bit

es,

and

this

dia

gnos

is s

houl

d be

con

side

red

in s

uch

pati

ents

who

pre

sent

w

ith

a no

nspe

cifi

c ra

sh.

Phy

sici

ans

shou

ld b

e co

gniz

ant

of t

he f

act

that

the

eru

ptio

n m

ay

occu

r pr

ior

to t

he d

iagn

osis

of

the

hem

atol

ogic

dis

orde

r, a

nd f

urth

er e

valu

atio

n of

the

se

pati

ents

may

be

war

rant

ed.

Skin

eru

ptio

ns a

re s

een

in a

ppro

xim

atel

y 25

% of

pat

ient

s w

ith

CLL

and

are

cate

gori

zed

as

eith

er s

peci

fic

or n

onsp

ecif

ic.

Spe

cifi

c le

sion

s ar

e de

fine

d as

tho

se w

ith

lym

phom

atou

s m

alig

nant

infi

ltra

tion

of

the

skin

, i.

e. le

ukem

ia c

utis

. N

onsp

ecif

ic le

sion

s in

clud

e th

ose

due

to a

bnor

mal

hem

atop

oies

is (

typi

cally

pre

sent

ing

as e

cchy

mos

es o

r pu

rpur

a),

infe

ctio

ns,

drug

eru

ptio

ns,

vasc

ulit

is,

graf

t ve

rsus

hos

t di

seas

e (G

VHD

), im

mun

obul

lous

dis

ease

s in

clud

ing

bullo

us p

emph

igoi

d (B

P) a

nd p

aran

eopl

asti

c pe

mph

igus

(PN

P),

and

EIBL

R.1-

3 In

ad

diti

on,

pyod

erm

a ga

ngen

osum

, er

ythe

ma

nodo

sum

, an

d Sw

eets

syn

drom

e m

ay o

ccur

as

para

neop

last

ic p

heno

men

a.3

H

eigh

tene

d re

acti

ons

to in

sect

bit

es in

ass

ocia

tion

wit

h he

mop

rolif

erat

ive

dise

ase

was

fir

st

repo

rted

by

Wee

d in

196

5 in

a p

atie

nt w

ith

CLL.

4 S

ince

the

n, t

here

hav

e be

en s

ever

al

othe

r re

port

s of

thi

s ph

enom

enon

des

crib

ed in

ass

ocia

tion

wit

h CL

L, a

s w

ell a

s in

pat

ient

s w

ith

ALL,

man

tle-

cell

and

larg

e-ce

ll ly

mph

oma,

HIV

infe

ctio

n an

d co

ngen

ital

ag

amm

agol

ubul

inem

ia.

5-9

In W

eeds

ori

gina

l des

crip

tion

, th

e re

acti

on w

as d

efin

ed b

y le

sion

s gr

eate

r th

an 2

0mm

in d

iam

eter

, ch

arac

teri

zed

by in

dura

tion

, ed

ema,

ery

them

a an

d pr

urit

us a

t th

e si

te o

f a

know

n m

osqu

ito

bite

or

evid

ence

the

reof

.4

Lesi

ons

coul

d pr

esen

t w

ith

vari

ous

mor

phol

ogie

s, in

clud

ing

mac

ules

, pa

pule

s, n

odul

es,

vesi

cles

, an

d bu

llae

up t

o 10

cm,

and

leav

e no

res

idua

l pos

t in

flam

mat

ory

hype

rpig

men

tati

on.4

, 6-

7 T

hey

are

typi

cally

re

curr

ent

and

tend

to

pers

ist.

Cl

inic

al d

iagn

osis

is o

ften

cha

lleng

ing

sinc

e m

ost

pati

ents

do

not

reca

ll an

ant

eced

ent

inse

ct b

ite.

8 T

he e

rupt

ion

can

pres

ent

any

tim

e fr

om m

onth

s to

ye

ars

afte

r th

e di

agno

sis

of le

ukem

ia,

and

in s

ome

case

s ye

ars

prio

r.8,

10

It is

not

rel

ated

to

the

cour

se o

f di

seas

e, la

bora

tory

val

ues,

or

trea

tmen

t.4,

6,

10 T

here

is s

ome

evid

ence

tha

t th

e pr

esen

ce o

f EI

BLR

in p

atie

nts

wit

h CL

L po

rten

ds a

mor

e di

smal

pro

gnos

is.

In a

stu

dy

cond

ucte

d by

Bar

zila

i et

al,

3 pa

tien

ts w

ith

CLL

and

EIBL

R de

mon

stra

ted

rapi

d pr

ogre

ssio

n of

the

ir C

LL.1

0 F

urth

erm

ore,

fat

al c

ompl

icat

ions

dev

elop

ed in

3 o

f th

e 8

pati

ents

wit

h CL

L an

d EI

BLR

desc

ribe

d by

Dav

is e

t al

.6 T

here

are

sev

eral

rep

orts

in t

he li

tera

ture

of

vesi

culo

bullo

us W

ells

syn

drom

e oc

curr

ing

in a

ssoc

iati

on w

ith

B-ce

ll ly

mph

omas

. W

hile

so

me

cons

ider

Wel

ls’

synd

rom

e a

dist

inct

clin

ical

ent

ity,

11 w

e re

gard

it a

s a

derm

al

hype

rsen

siti

vity

rea

ctio

n to

som

e tr

igge

ring

eve

nt t

hat

resu

lts

in d

egra

nula

tion

of

a la

rge

num

ber

of d

erm

al e

osin

ophi

ls.

Pot

enti

al t

rigg

ers

incl

ude

arth

ropo

d bi

tes,

vir

al in

fect

ions

, pa

rasi

tic

infe

ctio

ns,

mal

igna

ncy,

mye

lopr

olif

erat

ive

diso

rder

s, d

rugs

and

vac

cina

tion

s.12

It

is

our

bel

ief

that

rep

orts

of

Wel

ls’

synd

rom

e in

the

set

ting

of

hem

atol

ogic

mal

igna

ncy

repr

esen

t an

alt

erna

te d

escr

ipti

on o

f th

e sa

me

phen

omen

on o

bser

ved

in E

IBLR

.

Case

Pre

sent

atio

n

Holly

Kan

avy,

DO, K

asha

Toul

oei,

MSI

V, C

harle

s Gro

pper

, MD,

Dam

ian

DiCo

stan

zo, M

D, C

indy

Hof

fman

, DO

b

Disc

ussi

on

Disc

ussi

on (c

ont)

Conc

lusi

on

Disc

ussi

on (c

ont)

A B

In t

he d

iffe

rent

ial

diag

nosi

s of

ves

icul

obul

lous

eru

ptio

ns in

pat

ient

s w

ith

an u

nder

lyin

g m

alig

nanc

y, im

mun

obul

lous

dis

ease

mus

t be

con

side

red.

13

Bullo

us p

emph

igoi

d is

com

mon

ly

seen

in t

he e

lder

ly a

nd in

volv

es s

kin

of t

he g

roin

, ax

illae

, an

d fl

exor

sur

face

s of

the

for

earm

s.

Dir

ect

imm

unof

luor

esce

nce

typi

cally

rev

eals

lin

ear

depo

sits

of

IgG

and

/or

C3 a

long

the

ba

sem

ent

mem

bran

e.14

PN

P is

com

mon

ly a

ssoc

iate

d w

ith

B-ce

ll ly

mph

opro

lifer

ativ

e di

sord

ers

and

is c

hara

cter

ized

by

pain

ful

muc

osal

ulc

erat

ions

alo

ng w

ith

a po

lym

orph

ic e

rupt

ion

of t

he

trun

k, p

alm

s, a

nd s

oles

.3

Dia

gnos

is o

f PN

P re

sts

upon

dem

onst

rati

on o

f Ig

G a

nd C

3 w

ithi

n in

terc

ellu

lar

spac

es a

nd a

long

the

bas

emen

t m

embr

ane

zone

on

dire

ct im

mun

oflu

ores

cent

st

udie

s of

per

ilesi

onal

ski

n.14

Le

ukem

ia c

utis

is m

ost

com

mon

ly s

een

in m

yelo

id l

euke

mia

s an

d m

anif

ests

as

disc

rete

gro

uped

or

gene

raliz

ed,

firm

, de

ep,

red-

brow

n pa

pule

s, p

laqu

es,

or

nodu

les

that

can

man

ifes

t on

any

par

t of

the

bod

y, m

ost

com

mon

ly t

he h

ead.

H

isto

logi

c ex

amin

atio

n an

d im

mun

ohis

toch

emis

try

assa

ys c

an b

e us

ed t

o ex

clud

e th

e di

agno

sis.

Sk

in

lesi

ons

freq

uent

ly r

esol

ve w

ith

trea

tmen

t of

the

und

erly

ing

leuk

emia

.15

Cu

tane

ous

infe

ctio

ns a

re a

fre

quen

t oc

curr

ence

in p

atie

nts

wit

h CL

L du

e to

imm

unol

ogic

su

ppre

ssio

n, a

nd in

clud

e bo

th c

omm

on a

nd o

ppor

tuni

stic

pat

hoge

ns.

The

mos

t co

mm

on

infe

ctio

ns s

een

are

due

to h

erpe

s si

mpl

ex v

irus

and

her

pes

zost

er.1

M

anif

esta

tion

s of

the

se

may

be

seve

re,

diss

emin

ated

or

recu

rren

t. A

ddit

iona

lly,

papu

lar

and

nodu

lar

lesi

ons

can

occu

r at

the

sit

e of

her

pes

sim

plex

or

herp

es z

oste

r sc

ars.

1 O

ther

cut

aneo

us in

fect

ions

incl

ude

diss

emin

ated

mol

lusc

um c

onta

gios

um,

baci

llary

ang

iom

atos

is,

and

atyp

ical

myc

obac

teri

al

infe

ctio

ns.3

Sk

in s

wab

s ca

n be

con

duct

ed t

o ru

le o

ut b

acte

rial

and

fun

gal

infe

ctio

n.

The

path

ogen

esis

of

EIBL

R is

poo

rly

unde

rsto

od.

Bar

zila

i et

al p

ropo

se t

hat

sinc

e m

any

of t

he

hem

atol

ogic

mal

igna

ncie

s in

the

se p

atie

nts

are

of B

cel

l ori

gin,

the

phe

nom

enon

may

be

due

to a

cyt

okin

e im

bala

nce,

wit

h an

exc

ess

of in

terl

euki

ns 4

and

5 le

adin

g to

pro

lifer

atio

n of

m

alig

nant

B c

ells

and

alt

ered

imm

une

resp

onse

cha

ract

eriz

ed b

y eo

sino

phili

c in

filt

rati

on o

f th

e sk

in.

Bec

ause

hei

ghte

ned

inse

ct b

ite

reac

tion

s ha

ve b

een

docu

men

ted

in H

IV in

fect

ion

and

cong

enit

al a

gam

mag

olub

ulin

emia

, an

d pr

esen

t si

mila

rly

to t

hose

wit

h he

mat

olog

ic m

alig

nanc

y,

the

path

ogen

esis

may

be

attr

ibut

able

to

imm

unod

efic

ienc

y pl

us a

n im

mun

olog

ic s

tim

ulus

suc

h as

inse

ct b

ites

or

vira

l inf

ecti

on.1

0 V

assa

lo e

t al

pro

pose

an

imm

uno-

alle

rgic

mec

hani

sm,

spec

ific

ally

, an

alle

rgic

rea

ctio

n to

the

inse

ct b

ite

and

an im

pair

ed im

mun

e re

spon

se.1

6

A re

view

of

the

liter

atur

e in

dica

tes

that

EIB

LR is

res

ista

nt t

o m

ost

trea

tmen

ts.7

Alt

houg

h ou

r pa

tien

t re

spon

ded

favo

rabl

y to

top

ical

ste

roid

s, t

his

trea

tmen

t is

usu

ally

inef

fect

ive.

10

Sim

ilarl

y, t

opic

al a

nti-

prur

itic

s an

d U

VB p

hoto

ther

apy

are

rare

ly o

f an

y be

nefi

t.10

Pr

edni

sone

40

mg/

day

may

pro

vide

tra

nsie

nt r

elie

f, b

ut t

he e

rupt

ion

recu

rs o

nce

the

med

icat

ion

is

tape

red.

7-8,

10

Oth

er t

reat

men

ts t

hat

have

bee

n at

tem

pted

wit

h in

adeq

uate

res

pons

e in

clud

e an

tibi

otic

s, s

yste

mic

ant

ihis

tam

ines

, in

trav

enou

s im

mun

oglo

bulin

, ch

lora

mbu

cil,

and

in

terf

eron

alp

ha.1

0 V

aryi

ng d

egre

es o

f im

prov

emen

t ha

ve b

een

repo

rted

in p

atie

nts

wit

h CL

L un

derg

oing

che

mot

hera

py,

and

in o

ne r

epor

t, t

he e

rupt

ion

reso

lved

com

plet

ely

afte

r ef

fect

ive

trea

tmen

t of

the

und

erly

ing

ALL.

6, 1

7 T

here

is a

rep

ort

of p

atie

nt r

espo

ndin

g to

Dea

d Se

a ph

otot

hera

py i

ndic

atin

g th

e ps

oral

en U

VA t

hera

py m

ay p

rove

ben

efic

ial.

10

Dai

ly o

ral

daps

one

may

als

o be

a p

rom

isin

g tr

eatm

ent

opti

on a

s tw

o ca

se r

epor

ts h

ave

docu

men

ted

mar

ked

impr

ovem

ent.

5, 7

257

Q U I C K T I P S ( - - T H I S S E C T I O N D O E S N O T P R I N T - - ) T h i s P o w e r P o i n t t e m p l a t e r e q u i r e s b a s i c P o w e r P o i n t ( v e r s i o n 2 0 0 7 o r n e w e r ) s k i l l s . B e l o w i s a l i s t o f c o m m o n l y a s k e d q u e s t i o n s s p e c i f i c t o t h i s t e m p l a t e . I f y o u a r e u s i n g a n o l d e r v e r s i o n o f P o w e r P o i n t s o m e t e m p l a t e f e a t u r e s m a y n o t w o r k p r o p e r l y . U s i n g t h e t e m p l a t e V e r i f y i n g t h e q u a l i t y o f y o u r g r a p h i c s G o t o t h e V I E W m e n u a n d c l i c k o n Z O O M t o s e t y o u r p r e f e r r e d m a g n i f i c a t i o n . T h i s t e m p l a t e i s a t 1 0 0 % t h e s i z e o f t h e f i n a l p o s t e r . A l l t e x t a n d g r a p h i c s w i l l b e p r i n t e d a t 1 0 0 % t h e i r s i z e . T o s e e w h a t y o u r p o s t e r w i l l l o o k l i k e w h e n p r i n t e d , s e t t h e z o o m t o 1 0 0 % a n d e v a l u a t e t h e q u a l i t y o f a l l y o u r g r a p h i c s b e f o r e y o u s u b m i t y o u r p o s t e r f o r p r i n t i n g . U s i n g t h e p l a c e h o l d e r s T o a d d t e x t t o t h i s t e m p l a t e c l i c k i n s i d e a p l a c e h o l d e r a n d t y p e i n o r p a s t e y o u r t e x t . T o m o v e a p l a c e h o l d e r , c l i c k o n i t o n c e ( t o s e l e c t i t ) , p l a c e y o u r c u r s o r o n i t s f r a m e a n d y o u r c u r s o r w i l l c h a n g e t o t h i s s y m b o l :

T h e n , c l i c k o n c e a n d d r a g i t t o i t s n e w l o c a t i o n w h e r e y o u c a n r e s i z e i t a s n e e d e d . A d d i t i o n a l p l a c e h o l d e r s c a n b e f o u n d o n t h e l e f t s i d e o f t h i s t e m p l a t e . M o d i f y i n g t h e l a y o u t T h i s t e m p l a t e h a s f o u r d i f f e r e n t c o l u m n l a y o u t s . R i g h t - c l i c k y o u r m o u s e o n t h e b a c k g r o u n d a n d c l i c k o n “ L a y o u t ” t o s e e t h e l a y o u t o p t i o n s . T h e c o l u m n s i n t h e p r o v i d e d l a y o u t s a r e f i x e d a n d c a n n o t b e m o v e d b u t a d v a n c e d u s e r s c a n m o d i f y a n y l a y o u t b y g o i n g t o V I E W a n d t h e n S L I D E M A S T E R . I m p o r t i n g t e x t a n d g r a p h i c s f r o m e x t e r n a l s o u r c e s T E X T : P a s t e o r t y p e y o u r t e x t i n t o a p r e - e x i s t i n g p l a c e h o l d e r o r d r a g i n a n e w p l a c e h o l d e r f r o m t h e l e f t s i d e o f t h e t e m p l a t e . M o v e i t a n y w h e r e a s n e e d e d . P H O T O S : D r a g i n a p i c t u r e p l a c e h o l d e r , s i z e i t f i r s t , c l i c k i n i t a n d i n s e r t a p h o t o f r o m t h e m e n u . T A B L E S : Y o u c a n c o p y a n d p a s t e a t a b l e f r o m a n e x t e r n a l d o c u m e n t o n t o t h i s p o s t e r t e m p l a t e . T o a d j u s t t h e w a y t h e t e x t f i t s w i t h i n t h e c e l l s o f a t a b l e t h a t h a s b e e n p a s t e d , r i g h t - c l i c k o n t h e t a b l e , c l i c k F O R M A T S H A P E t h e n c l i c k o n T E X T B O X a n d c h a n g e t h e I N T E R N A L M A R G I N v a l u e s t o 0 . 2 5 M o d i f y i n g t h e c o l o r s c h e m e T o c h a n g e t h e c o l o r s c h e m e o f t h i s t e m p l a t e g o t o t h e “ D e s i g n ” m e n u a n d c l i c k o n “ C o l o r s ” . Y o u c a n c h o o s e f r o m t h e p r o v i d e c o l o r c o m b i n a t i o n s o r y o u c a n c r e a t e y o u r o w n .

QU

ICK

DES

IGN

GU

IDE

(--T

HIS

SEC

TIO

N D

OES

NO

T PR

INT-

-)

Th

is P

ower

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t 20

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uces

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2 1 1 7 F o u r t h S t r e e t , U n i t C

B e r k e l e y C A 9 4 7 1 0

p o s t e r p r e s e n t e r @ g m a i l . c o m

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aceb

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A 7

5 ye

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ispa

nic

mal

e w

ith a

n ex

tens

ive

hist

ory

of c

oron

ary

arte

ry d

isea

se w

as a

dmitt

ed to

th

e Ve

tera

ns A

dmin

istra

tion

Hos

pita

l with

a se

vera

l ho

ur h

isto

ry o

f cru

shin

g ch

est p

ain

and

was

un

resp

onsi

ve to

subl

ingu

al n

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lyce

rin.

On

adm

issi

on, h

e w

as n

oted

to h

ave

an a

sym

ptom

atic

pe

tech

ial r

ash

on h

is a

bdom

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roxi

mal

ex

trem

ities

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e re

porte

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ticin

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o th

e de

velo

pmen

t of a

ngin

a. T

he p

atie

nt’s

onl

y cu

rren

t m

edic

atio

n w

as F

uros

imid

e 40

mg

BID

.

Case

Pre

sent

atio

n

Ove

r the

ens

uing

few

day

s, th

e ra

sh p

rogr

esse

d an

d be

cam

e m

ore

verr

ucou

s on

his e

xten

sor f

orea

rms;

ho

wev

er, t

he c

utan

eous

find

ings

rem

aine

d pe

tech

ial

on h

is tr

unk.

The

pat

ient

was

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erw

ise

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rile

thro

ugho

ut h

is h

ospi

tal c

ours

e.

Seve

ral a

reas

of t

he v

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cous

, cru

sted

and

pu

stul

ar p

laqu

es o

n hi

s for

earm

s wer

e sw

abbe

d fo

r ba

cter

ial c

ultu

re, a

nd w

ere

nega

tive.

Pun

ch

biop

sies

wer

e pe

rfor

med

on

two

thic

ker p

apul

es

on th

e rig

ht fo

rear

m, o

ne o

f whi

ch w

as su

bmitt

ed

for t

issu

e cu

lture

and

the

othe

r for

rout

ine

hist

oche

mis

try.

Bio

psie

s per

form

ed w

ere

subm

itted

for r

outin

e H

&E.

Seve

re S

T el

evat

ion

MI w

hich

pro

gres

sed

to

cong

estiv

e he

art f

ailu

re th

at w

as c

ompl

icat

ed b

y ac

ute

rena

l fai

lure

Sy

stem

ic c

ortic

oste

roid

s to

addr

ess t

he S

wee

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e w

ere

held

giv

en th

e ac

ute

situ

atio

n an

d hi

s exh

aust

ive

com

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ditie

s.

Patie

nt re

fuse

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mod

ialy

sis a

nd u

ltim

atel

y ex

pire

d on

hos

pita

l day

12

Hist

opat

holo

gy

Con

clus

ion

•The

dia

gnos

tic c

riter

ia fo

r dru

g-in

duce

d Sw

eet s

yndr

ome

prop

osed

by

Wal

ker e

t al.

are

the

follo

win

g: a

brup

t ons

et

of p

ainf

ul e

ryth

emat

ous p

laqu

es o

r nod

ules

, hi

stop

atho

logi

c ev

iden

ce o

f a d

ense

neu

troph

ilic

infil

trate

w

ithou

t evi

denc

e of

leuk

ocyt

ocla

stic

vas

culit

is, p

yrex

ia

(380 C

), te

mpo

ral r

elat

ions

hip

betw

een

drug

inge

stio

n an

d cl

inic

al p

rese

ntat

ion

or te

mpo

rally

rela

ted

recu

rren

ce a

fter

oral

cha

lleng

e, a

nd te

mpo

rally

rela

ted

reso

lutio

n of

lesi

ons

afte

r dru

g w

ithdr

awal

or t

reat

men

t with

syst

emic

co

rtico

ster

oids

.

• Unu

sual

of S

wee

t’s sy

ndro

me,

our

pat

ient

was

afe

brile

on

pre

sent

atio

n an

d in

the

deve

lopm

ent o

f his

lesi

ons.

The

clas

sic

hist

opat

holo

gic

findi

ngs o

f acu

te fe

brile

ne

utro

phili

c de

rmat

osis

are

den

se, d

iffus

e ne

utro

phili

c in

filtra

te in

a b

and-

like

dist

ribut

ion

with

in th

e up

per a

nd

mid

-der

mis

with

leuk

ocyt

ocla

stic

nuc

lear

deb

ris

inte

rstit

ially

, and

freq

uent

ly p

apill

ary

derm

al e

dem

a.

•Tru

e va

scul

itic

chan

ges a

re o

ften

abse

nt.

•W

hile

non

spec

ific

findi

ngs,

such

as s

pong

iosi

s and

su

bcor

neal

pus

tule

form

atio

n m

ay b

e ob

serv

ed in

the

epid

erm

is, i

t usu

ally

is sp

ared

. M

anag

emen

t of S

wee

t’s sy

ndro

me

varie

s dep

endi

ng o

n th

e un

derly

ing

etio

logy

. In

the

abse

nce

of a

ny th

erap

eutic

in

terv

entio

n, c

utan

eous

lesi

ons a

nd d

erm

atos

is-r

elat

ed

sym

ptom

s may

reso

lve

spon

tane

ousl

y in

som

e pa

tient

s w

ith c

lass

ical

Sw

eet’s

synd

rom

e

•Sw

eet’s

synd

rom

e as

soci

ated

with

mal

igna

ncy

typi

cally

re

mits

follo

win

g tre

atm

ent o

r cur

e of

the

unde

rlyin

g ca

rcin

oma,

whi

le d

rug-

indu

ced

Swee

t’s sy

ndro

me

impr

oves

spon

tane

ousl

y su

bseq

uent

to c

essa

tion

of th

e of

fend

ing

agen

t. In

mos

t cas

es o

f acu

te fe

brile

neu

troph

ilic

derm

atos

is, p

redn

ison

e is

ver

y ef

fect

ive

at a

dos

e of

1

mg/

kg/d

. Add

ition

ally

, hig

h po

tenc

y to

pica

l or

intra

lesi

onal

ster

oids

may

be

used

to tr

eat f

ocal

lesi

ons

Disc

ussi

on

Swee

t’s S

yndr

ome

(Acu

te F

ebril

e N

eutro

phili

c D

erm

atos

is) i

s typ

ical

ly c

hara

cter

ized

by

rais

ed a

nd

pain

ful e

ryth

emat

ous p

apul

es, p

laqu

es a

nd n

odul

es o

f ra

pid

onse

t, th

ey a

re m

ost c

omm

only

loca

ted

on th

e fa

ce,

neck

and

upp

er e

xtre

miti

es

Cla

ssic

ally

acc

ompa

nied

by

feve

r, le

ukoc

ytos

is a

nd

neut

roph

ilia

•Sw

eet’s

Syn

drom

e is

a re

activ

e ph

enom

enon

that

shou

ld

be c

onsi

dere

d a

cuta

neou

s mar

ker f

or sy

stem

ic d

isea

se

•Firs

t des

crib

ed in

196

4 in

refe

renc

e to

eig

ht m

iddl

e ag

ed

wom

en w

ho h

ad a

n ac

ute

onse

t of f

ever

and

ery

them

atou

s pl

aque

s ass

ocia

ted

with

resp

irato

ry a

nd G

I inf

ectio

ns.

•Stre

ptoc

occa

l pne

umon

ia is

the

mos

t com

mon

ly re

porte

d in

fect

ion.

•Oth

er re

porte

d as

soci

ated

bac

teria

l inf

ectio

ns in

clud

e Sa

lmon

ella

, Sta

phyl

ococ

cus s

peci

es, Y

ersi

nia

ente

roco

litic

a, E

ntam

oeba

col

i, H

elic

obac

ter p

ylor

i, Bo

rrel

ia b

urgd

orfe

ri, T

uber

culo

sis m

ycob

acte

ria,

and

M

ycob

acte

rium

che

lona

e.

•Hep

atiti

s A a

nd B

, cyt

omeg

alov

irus (

CM

V),

and

HIV

are

vi

ral a

gent

s tha

t hav

e al

so b

een

repo

rtedl

y as

soci

ated

•A

ppro

xim

atel

y 16

% o

f pat

ient

s with

the

so-te

rmed

id

iopa

thic

var

iant

hav

e an

ass

ocia

ted

unde

rlyin

g in

flam

mat

ory

cond

ition

•C

rohn

’s d

isea

se a

nd u

lcer

ativ

e co

litis

are

the

mos

t co

mm

only

ass

ocia

ted

dise

ases

, how

ever

, rhe

umat

oid

arth

ritis

, lup

us e

ryth

emat

osus

, Sjo

gren

’s sy

ndro

me

and

Beh

çet d

isea

se h

ave

also

bee

n re

porte

d in

ass

ocia

tion.

•R

elev

ant t

o th

e pr

esen

t cas

e, R

odrig

uez-

de la

Ser

na

desc

ribed

a c

ase

of S

wee

t’s sy

ndro

me

that

occ

urre

d in

a

patie

nt w

ith p

ost-m

yoca

rdia

l inf

arct

ion

synd

rom

e (D

ress

ler’s

synd

rom

e).

•Hem

atol

ogic

or s

olid

tum

or m

alig

nanc

y w

as fo

und

to

repr

esen

t 21

perc

ent o

f pat

ient

s with

Sw

eet’s

synd

rom

e in

a

retro

spec

tive

revi

ew o

f 15

stud

ies d

one

by C

ohen

and

K

urzr

ock

in 1

993.

AM

L m

ost c

omm

only

ass

ocia

ted,

als

o so

lid tu

mor

car

cino

mas

incl

udin

g G

U, B

reas

t and

G

•Whi

le re

pres

entin

g le

ss th

an 5

% o

f cas

es, m

edic

atio

ns

have

bee

n as

soci

ated

with

the

deve

lopm

ent o

f dru

g-in

duce

d Sw

eet’s

synd

rom

e. M

ost c

omm

only

, the

ad

min

istra

tion

of g

ranu

locy

te-c

olon

y st

imul

atin

g fa

ctor

ca

uses

this

var

iant

of t

he d

erm

atos

is

•Oth

er d

rug

reac

tions

that

hav

e ap

pear

ed in

mor

e th

an 1

ca

se re

port

incl

ude

trim

etho

prim

-sul

fam

etho

xazo

le, a

ll-tr

ans r

etin

oic

acid

and

min

ocyc

line

•Alth

ough

our

pat

ient

had

not

bee

n ex

pose

d to

thes

e m

edic

atio

ns, h

e ha

d be

en re

ceiv

ing

furo

sem

ide

40 m

g B

ID, w

hich

has

bee

n re

porte

d on

ly tw

ice

in th

e lit

erat

ure

as a

ttrib

utin

g to

Sw

eet’s

synd

rom

e

•Our

pat

ient

repr

esen

ts a

uni

que

pres

enta

tion

of

Swee

t’s sy

ndro

me

yet t

o be

repo

rted

in th

e lit

erat

ure.

Fi

rst,

he w

as a

febr

ile th

roug

hout

his

hos

pita

l cou

rse

desp

ite p

rogr

essi

on o

f the

rash

, aty

pica

l for

Sw

eet’s

sy

ndro

me,

whi

ch is

oth

erw

ise

know

n as

acu

te

neut

roph

ilic

febr

ile d

erm

atos

is.

Seco

ndly

, with

rega

rd to

th

e te

mpo

ral r

elat

ions

hip,

the

cuta

neou

s eru

ptio

n co

inci

ded

with

his

acu

te m

yoca

rdia

l inf

arct

ion

sugg

estin

g th

at it

was

eith

er re

activ

e to

or p

ossi

bly

prec

ipita

ted

the

coro

nary

eve

nt g

iven

his

ext

ensi

ve

unde

rlyin

g he

art d

isea

se, a

lso

not y

et d

escr

ibed

in th

e lit

erat

ure.

•W

ith a

ll of

the

feat

ures

of t

he p

rese

nt c

ase

take

n to

geth

er, w

e fe

el it

to re

pres

ent a

n at

ypic

al a

febr

ile

Swee

t’s sy

ndro

me

reac

tive

to o

r pot

entia

lly p

reci

pita

ting

an a

cute

myo

card

ial i

nfar

ctio

n.

Diff

use

neut

roph

ilic

infil

trate

in a

ban

d-lik

e di

strib

utio

n in

upp

er a

nd m

id d

erm

is w

ith m

arke

d de

rmal

ede

ma,

con

sist

ent w

ith S

wee

t’s sy

ndro

me

Wes

tern

Uni

vers

ity o

f Hea

lth S

cien

ces /

Pac

ific

Hosp

ital o

f Lon

g Be

ach

Mic

hael

Kas

sard

jian

D.O

.

Swee

t’s S

yndr

ome

in C

onco

rdan

ce w

ith A

cute

Cor

onar

y Sy

ndro

me

258

rrr

Wha

t is L

iche

n Pl

anus

Pe

mph

igoi

des?

L

iche

n pl

anus

pem

phig

oide

s (LP

P) is

a ra

re a

utoi

mm

une

sube

pide

rmal

bl

iste

ring

dise

ase.

It is

con

side

red

to b

e a

clin

ical

var

iatio

n of

bul

lous

pe

mph

igoi

d (B

P) o

r a c

oexi

sten

ce o

f lic

hen

plan

us (L

P) a

nd B

P3,4 .

It i

s cha

ract

eriz

ed b

y bu

llous

lesi

ons d

evel

opin

g on

LP

papu

les a

s wel

l as

on

clin

ical

ly u

ninv

olve

d ar

eas o

f the

skin

. The

dis

ease

may

pro

gres

s to

eros

ive

muc

osal

dis

ease

to in

volv

e th

e m

outh

, eso

phag

us, a

nd v

agin

al

tract

in w

omen

. E

pide

mio

logy

L

iche

n Pl

anus

Pem

phig

oide

s is a

rare

chr

onic

skin

dis

orde

r with

less

th

en 1

00 c

ases

repo

rted

in th

e lit

erat

ure.

C

ompa

red

to B

P, L

PP is

bel

ieve

d to

affe

ct a

you

nger

age

gro

up a

nd

have

a le

ss se

rious

clin

ical

cou

rse.

Tw

o re

view

s of t

he li

tera

ture

reve

aled

th

e m

ean

age

of o

nset

of L

PP to

be

in th

e th

ird to

four

th d

ecad

es, w

hile

B

P ty

pica

lly p

rese

nts i

n th

e si

xth

deca

de o

f life

5 . Th

e di

seas

e oc

curs

in

all r

aces

and

affe

cts t

he se

xes e

qual

ly.

Et

iolo

gy a

nd p

atho

gene

sis o

f LPP

is p

oorly

und

erst

ood.

Ack

now

ledg

men

ts

I wou

ld li

ke to

than

k A

ngel

o A

. Pet

ropo

lis, M

.D a

nd V

erno

n T.

Mac

key,

D.O

. for

thei

r su

ppor

t and

reco

mm

enda

tions

with

this

pat

ient

and

in th

is p

roje

ct.

Cas

e R

epor

t- P

atie

nt C

A 7

1 ye

ar o

ld H

ispa

nic

fem

ale

pres

ente

d to

the

derm

atol

ogy

clin

ic w

ith a

pr

uriti

c pa

pulo

squa

mou

s eru

ptio

n of

3 y

ears

dur

atio

n.

Pa

tient

des

crib

ed a

n in

sidi

ous o

nset

initi

ally

on

her l

egs w

hich

pro

gres

sed

to

her v

olar

wris

ts a

nd e

xten

sor e

lbow

s.

Pat

ient

den

ied

any

cons

titut

iona

l sym

ptom

s pre

cedi

ng d

evel

opm

ent o

f ras

h.

She

repo

rted

good

ove

rall

heal

th w

ith a

his

tory

of d

iabe

tes a

nd h

yper

tens

ion.

H

er m

edic

atio

ns in

clud

ed ri

sedr

onat

e an

d at

enol

ol.

Pat

ient

den

ied

smok

ing,

alc

ohol

or d

rug

use.

S

he d

enie

d an

y co

nstit

utio

nal s

ympt

oms i

nclu

ding

: mal

aise

, fev

er, c

hills

, di

arrh

ea, o

r wei

ght l

oss.

Prio

r tre

atm

ents

incl

uded

topi

cal c

ortic

oste

roid

s with

out r

esol

utio

n.

So w

hat a

bout

pat

ient

C?

Pa

tient

show

ed li

ttle

clin

ical

impr

ovem

ent w

ith in

itial

trea

tmen

t of p

redn

ison

e,

tetra

cycl

ine

and

nico

tinam

ide.

Add

ition

ally

, pat

ient

was

usi

ng c

lobe

taso

l oin

tmen

t bid

to

the

lesi

ons o

n he

r ski

n.

D

apso

ne 1

00m

g bi

d w

as a

dded

, how

ever

the

patie

nt d

evel

oped

ane

mia

and

it w

as

disc

ontin

ued.

Sh

e w

as th

en p

lace

d on

aza

thio

prin

e bu

t it c

ause

d na

usea

and

vom

iting

and

the

patie

nt

stop

ped

taki

ng it

. N

ext,

myc

ophe

nola

te m

ofiti

l was

add

ed. S

he se

emed

to b

e im

prov

ing

afte

r tw

o m

onth

s of t

hera

py, h

owev

er, r

ash

star

ted

to fl

are.

B

iolo

gic

med

icat

ions

wer

e co

nsid

ered

ow

ing

to th

eir e

ffica

cy a

nd sa

fety

pro

file

in

treat

ing

psor

iasi

s pat

ient

s as w

ell a

s lite

ratu

re w

ritte

n on

thei

r use

in o

ral l

iche

n pl

anus

. W

e ch

ose

to u

se u

stek

inum

ab b

ecau

se it

had

a b

road

er sp

ectru

m o

f inh

ibiti

ng m

any

infla

mm

ator

y pa

thw

ays,

not j

ust T

NF.

Tr

eatm

ent w

as st

arte

d w

ith a

n in

itial

intra

mus

cula

r dos

e of

45

mg

follo

wed

by

a 45

m

g in

tram

uscu

lar d

ose

four

wee

ks la

ter.

Afte

r jus

t the

initi

al tw

o do

ses,

the

patie

nt

dem

onst

rate

d a

redu

ctio

n in

the

papu

les a

nd p

rurit

is. S

he w

ill b

e co

ntin

ued

on 4

5 m

g do

ses a

t 12

wee

k in

terv

als.

Ray

mon

d R

. Kni

sley

, D.O

. A

dvan

ced

Des

ert D

erm

atol

ogy/

Mid

wes

tern

Uni

vers

ity. P

eoria

, AZ

For

furt

her

info

rmat

ion

Plea

se c

onta

ct rk

nisl

ey@

coch

isede

rmat

olog

y.com

for q

uest

ions

or s

ugge

stio

ns.

Phys

ical

Fin

ding

s O

n ph

ysic

al e

xam

the

patie

nt h

ad p

ink

to v

iola

ceou

s, fla

t top

ped,

pol

ygon

al

papu

les c

onsi

sten

t with

Lic

hen

Plan

us c

over

ing

her v

olar

wris

ts, e

xten

sor

elbo

ws,

and

bila

tera

l low

er le

gs.

Fu

rther

mor

e, sh

e ha

d er

ythe

mat

ous,

viol

aceo

us, i

nfilt

rate

d pl

aque

s with

m

icro

-ves

iclu

latio

n on

her

bila

tera

l thi

ghs.

Sh

e ha

d al

so st

arte

d de

velo

ping

hai

r los

s, dy

spha

gia

and

vagi

nal i

rrita

tion.

LIC

HE

N P

LA

NU

S PE

MPH

IGO

IDE

S:

RE

VIE

W O

F T

RE

ATM

EN

T O

PTIO

NS

Man

agem

ent B

eyon

d th

e M

edic

ine

Ofte

n ov

erlo

oked

in th

e m

edic

al li

tera

ture

on

LPP

is th

e im

porta

nce

of m

anag

ing

patie

nt

sequ

elae

per

tain

ing

to e

xtra

cuta

neou

s man

ifest

atio

ns in

clud

ing

the

psyc

hoso

cial

asp

ect.

Muc

osal

invo

lvem

ent c

an e

volv

e an

d ca

use

the

patie

nt d

iffic

ultie

s with

eat

ing

and

sexu

al

rela

tions

. Th

e ps

ycho

soci

al st

igm

a as

soci

ated

with

the

look

of t

he le

sion

s on

the

skin

and

hai

r los

s sh

ould

als

o be

add

ress

ed. W

ell k

now

n is

the

impa

ct p

soria

sis p

atie

nts f

eel w

ith re

gard

s to

the

way

they

see

them

selv

es a

nd th

e w

ay th

ey a

re p

erce

ived

by

othe

rs.

Ps

oria

sis i

s lin

ked

with

soci

al st

igm

atiz

atio

n, p

ain,

dis

com

fort,

and

psy

chol

ogic

al d

istre

ss.11

It

is c

lear

that

LPP

pat

ient

s may

suffe

r fro

m th

e sa

me

type

s of i

ssue

s inc

ludi

ng p

sych

olog

ical

di

stre

ss a

nd st

igm

atiz

atio

n.

Due

to th

e im

mun

osup

pres

sion

ass

ocia

ted

with

her

trea

tmen

t, th

e pa

tient

will

hav

e to

avo

id

plac

es w

here

she

may

enc

ount

er il

lnes

ses.

The

nee

d fo

r fre

quen

t blo

od te

sts a

nd d

octo

rs v

isits

can

be

taki

ng o

n th

e pa

tient

’s e

mpl

oyer

m

akin

g he

r mis

s day

s at w

ork.

D

epre

ssio

n m

ay b

ecom

e an

issu

e fo

r eve

n th

e m

ost s

toic

, and

pat

ient

s sho

uld

be a

ppro

pria

tely

sc

reen

ed. P

atie

nts s

houl

d be

enc

oura

ged

to b

ecom

e fa

mili

ar w

ith th

eir c

ondi

tion

and

acqu

aint

ed w

ith a

ny su

ppor

t gro

ups a

vaila

ble.

La

stly

, eve

ry e

ffort

shou

ld b

e m

ade

to e

nsur

e th

at th

e do

ctor

-pat

ient

rela

tions

hip

be o

ne o

f av

aila

bilit

y, u

nder

stan

ding

, and

em

path

y.

Trea

tmen

t C

lass

ical

ly, L

PP re

spon

ds w

ell t

o tra

ditio

nal t

hera

pies

, with

syst

emic

ster

oids

bei

ng th

e m

ost e

ffica

ciou

s tre

atm

ent f

or e

xten

sive

dis

ease

6,7 .

O

ther

trea

tmen

t opt

ions

repo

rted

incl

ude

tetra

cycl

ine

and

nico

tinam

ide,

isot

retin

oin,

ac

itret

in, d

apso

ne, a

nd im

mun

osup

pres

sive

dru

gs, s

uch

as o

ral c

ortic

oste

roid

s.6

Syst

emic

Cor

ticos

tero

ids

Sys

tem

ic st

eroi

ds h

ave

tradi

tiona

lly b

een

the

mai

nsta

y of

trea

tmen

t for

LPP

6,7 .

They

are

kn

own

to h

ave

an e

xten

sive

side

effe

ct p

rofil

e to

incl

ude

supp

ress

ion

of th

e pa

tient

’s

HPA

axi

s, os

teop

oros

is, g

astri

c ul

cers

, Cus

hing

oid

feat

ures

and

wei

ght g

ain.

Thi

s wou

ld

not b

e ac

cept

able

long

term

trea

tmen

t. Te

trac

yclin

e T

he te

tracy

clin

e fa

mily

has

bee

n us

ed fo

r man

y ye

ars f

or it

s ant

i-inf

lam

mat

ory

effe

ct

and

to h

alt n

eutro

phil

chem

otax

is. W

ith c

hron

ic u

se, p

atie

nts m

ay d

evel

op re

sist

ance

to

the

who

le c

lass

and

man

y w

omen

dev

elop

vag

inal

yea

st in

fect

ions

. R

etin

oids

S

yste

mic

retin

oids

app

eare

d to

be

an e

ffect

ive

ther

apeu

tic o

ptio

n. A

n ex

tens

ive

side

ef

fect

pro

file

of th

e or

al re

tinoi

ds in

clud

ing

xero

tic sk

in, h

yper

lipid

emia

, ocu

lar s

icca

, an

d te

rato

geni

c po

tent

ial

has p

rovi

ded

an im

petu

s in

findi

ng a

safe

r, m

ore

conv

enie

nt

treat

men

t opt

ion.

D

apso

ne

Dap

sone

is k

now

n to

inhi

bit n

eurtr

ophi

l che

mot

axis

. It i

s pru

dent

to a

lway

s che

ck a

pa

tient

’s G

6PD

leve

l prio

r to

star

ting

them

on

this

med

icat

ion

to a

void

the

poss

ibili

ty o

f he

mol

ytic

ane

mia

in d

efic

ient

pat

ient

s. Lo

ng te

rm u

se o

f dap

sone

is a

ssoc

iate

d w

ith

anap

last

ic a

nem

ia, a

gran

uloc

ytos

is, h

epat

otox

icity

, and

met

hem

oglo

bine

mia

. H

ydro

xych

loro

quin

e H

ydro

xych

loro

quin

e is

an

antim

alar

ial a

ntib

iotic

use

d in

the

treat

men

t of c

erta

in

dise

ases

such

cut

aneo

us lu

pus e

ryth

emat

osus

, sys

tem

ic lu

pus e

rtyhe

mat

osus

, po

lym

orph

ous l

ight

eru

ptio

n. It

’s e

xact

mec

hani

sm o

f act

ion

is n

ot k

now

n bu

t it s

eem

s to

inhi

bit r

heum

atoi

d fa

ctor

, acu

te p

hase

reac

tant

s, an

d ot

her c

ytok

ines

of i

nfla

mm

atio

n.

Long

term

use

can

be

asso

ciat

ed w

ith re

tinop

athy

, apl

astic

ane

mia

, thr

ombo

cyto

peni

a an

d he

pato

toxi

city

. Yea

rly e

ye e

xam

s and

rout

ine

labs

are

requ

ired.

M

ycop

heno

late

Mof

etil

Myc

ophe

nola

te m

ofet

il is

an

imm

unos

upre

ssio

n m

edic

atio

n th

at in

hibi

ts T

-cel

l and

B-

cell

lym

phoc

yte

prol

ifera

tion.

Typ

ical

ly u

sed

in tr

ansp

lant

pat

ient

s to

prev

ent r

ejec

tion

of

thei

r tra

nspl

ante

d or

gan,

it is

use

d in

oth

er ly

mph

ocyt

e-dr

iven

dis

orde

rs. I

t has

a se

rious

si

de e

ffect

pro

file

to in

clud

e op

portu

nist

ic in

fect

ions

, hyp

erte

nsio

n, re

nal f

ailu

re, a

nem

ia

and

inte

rstit

ial l

ung

dise

ase.

B

iolo

gic

The

rapy

N

ewer

bio

logi

c th

erap

y ha

s sho

wn

prom

ise

in th

e tre

atm

ent o

f pso

riasi

s and

rh

eum

atol

ogic

dis

orde

rs. T

umor

nec

rosi

s fac

tor (

TNF)

-alp

ha in

hibi

tors

, firs

t lic

ense

d fo

r cl

inic

al u

se in

199

8, is

one

cla

ss o

f bio

logi

c ag

ent.

T

NF

repr

esen

ts a

n im

porta

nt c

ytok

ine

invo

lved

in n

orm

al in

flam

mat

ory

and

imm

une

resp

onse

s.

The

re a

re re

ports

in th

e lit

erat

ure

of tr

eatin

g cu

tane

ous,

nail,

and

ora

l LP

with

TN

F-α

inhi

bito

rs (a

dalim

umab

and

eta

nerc

ept)

with

goo

d re

sults

8,9,

10. H

owev

er, w

e ha

ve n

ot

been

abl

e to

find

any

repo

rts o

f tre

atin

g LP

P w

ith b

iolo

gic

med

icat

ions

. G

iven

the

fact

that

TN

F-α

and

othe

r inf

lam

mat

ory

cyto

kine

s are

invo

lved

in th

e pa

thog

enes

is o

f BP

and

LP, i

t is f

easi

ble

that

they

may

als

o be

invo

lved

in th

e pa

thog

enes

is o

f LPP

. U

stek

inum

ab is

a b

iolo

gic

agen

t dire

cted

at I

L-12

and

IL-2

3. It

indi

rect

ly in

hibi

ts T

NF-

α, in

terf

eron

-γ, I

L-23

and

oth

er c

ytok

ines

to d

ecre

ase

infla

mm

atio

n an

d T-

cell

prol

ifera

tion.

His

topa

thol

ogy

H

isto

path

olog

ic e

xam

inat

ion

rem

ains

an

esse

ntia

l dia

gnos

tic c

riter

ion.

The

hist

opat

holo

gy o

f the

bul

lous

lesi

on o

f LPP

dep

icts

a su

bepi

derm

al

bulla

with

var

iabl

e di

ffuse

or s

pars

e ly

mph

ohis

tiocy

tic in

filtra

te, f

requ

ent

eosi

noph

ils w

ith o

r with

out n

eutro

phils

in u

pper

der

mis

1 .

The

exi

sten

ce o

f C3

alon

e or

with

IgG

alo

ng th

e de

rmoe

pide

rmal

junc

tion

give

s con

firm

atio

n on

DIF

. The

exp

ress

ion

of Ig

G a

uto-

antib

odie

s dire

cted

ag

ains

t the

bas

emen

t mem

bran

e zo

ne d

istin

guis

hes L

PP fr

om b

ullo

us L

P2 .

Ref

eren

ces

1.Zi

llike

ns D

, Cau

x F,

Mas

caro

JM, W

esse

lman

n U

, Sch

mid

t E, P

rost

C, C

alle

n JP

, Brö

cker

EB

, Dia

z LA

, Giu

dice

GJ.

Aut

oant

ibod

ies

in

liche

n pl

anus

pem

phig

oide

s rea

ct w

ith a

nov

el e

pito

pe w

ithin

the

C-te

rmin

al N

C16

A d

omai

n of

BP1

80. J

Inve

st D

erm

atol

. 199

9 Ju

l;113

(1):1

17-2

1.

2.O

koch

i H, N

ashi

ro K

, Tsu

chid

a T,

et a

l. Li

chen

pla

nus p

emph

igoi

des:

Cas

e re

ports

and

resu

lts o

f im

mun

oflo

ures

cenc

e an

d im

mun

oele

ctro

n m

icro

scop

ic s

tudy

. J A

m A

cad

Der

mat

ol 1

990;

22:6

26-3

1.

3.H

artin

g M

S, H

su S

. Lic

hen

plan

us p

emph

igoi

des:

a c

ase

repo

rt an

d re

view

of t

he li

tera

ture

. Der

mat

olog

y O

nlin

e Jo

urna

l 200

6, M

ay 3

0;

12(4

):10.

4.

Swal

e, B

lack

, Bho

gal.

Lich

en p

lanu

s pem

phig

oide

s: tw

o ca

se re

ports

. Clin

Exp

er D

erm

atol

199

8;23

(3):1

32-1

35.

5.D

emirc

ay Z

, Bay

kal C

, Dem

irkes

en C

. Lic

hen

plan

us p

emph

igoi

des:

repo

rt of

two

case

s. In

t J D

erm

atol

200

1;40

(12)

:757

-760

. 6.

Saku

ma-

Oya

ma

Y, P

owel

l AM

, Alb

ert S

, Oya

ma

N, B

hoga

l BS,

Bla

ck N

M. L

iche

n pl

anus

pem

phig

oide

s ev

olvi

ng in

to p

emph

igoi

d no

dula

ris. C

lin E

xper

Der

mat

ol 2

004

;28(

6):6

13-6

16.

7.H

olló

P, S

zako

nyi J

, Kis

s D, J

okai

H, H

orvá

th A

, Kár

páti

S. S

ucce

ssfu

l Tre

atm

ent o

f Lic

hen

Plan

us w

ith A

dalim

umab

, Dep

artm

ent o

f D

erm

atov

ener

eolo

gy a

nd D

erm

atoo

ncol

ogy,

Sem

mel

wei

s U

nive

rsity

, Már

ia st

r. 41

, HU

-108

5 B

udap

est,

Hun

gary

. 8.

Yaro

m N

. Eta

nerc

ept f

or th

e m

anag

emen

t of o

ral l

iche

n pl

anus

. Am

J C

lin D

erm

atol

200

7; 8

: 121

. 9.

Cha

o TJ

. Ada

limum

ab in

the

man

agem

ent o

f cut

aneo

us a

nd o

ral l

iche

n pl

anus

. Cut

is 2

009;

84:

352

–358

. 10

.Ir

la N

, Sch

neite

r T, H

anek

e E,

Yaw

alka

r N. N

ail l

iche

n pl

anus

: suc

cess

ful t

reat

men

t with

eta

nerc

ept.

Cas

e R

ep D

erm

atol

201

0; 2

: 173

–17

6.

11.

Bho

sle

MJ,

Kul

karn

i A, F

eldm

an S

R, e

t al.

Hea

lth Q

ual L

ife O

utco

mes

. 200

6; 4

: 35.

Pub

lishe

d on

line

2006

June

6. d

oi: 1

0.11

86/1

477-

7525

-4-3

5.

259

Pers

iste

nt R

ash

in a

75

Year

Old

Mal

eC.

Kog

er1 , D

. Kal

lgre

n2 , C. P

acoc

ha2 , L

.J. C

leav

er3 , N

orth

east

Reg

iona

l Med

ical

Cen

ter1 , K

irksv

ille,

MO

. Kal

lgre

n D

erm

atol

ogy2 , B

ould

er, C

O.,

Clea

ver D

erm

atol

ogy3 , K

irksv

ille,

MO

.

CASE

PRE

SEN

TATI

ON

FIG

URE

1

FIG

URE

3

FIG

URE

5

FIG

URE

4

FIG

URE

6

FIG

URE

2

A 7

5-ye

ar-o

ld C

auca

sian

mal

e pr

esen

ted

with

a y

ear-

long

his

tory

of a

no

n-pr

uriti

c ra

sh o

n hi

s up

per b

ody.

He

clai

med

he

has

had

the

rash

for r

ough

ly

a ye

ar, a

nd th

at it

�rs

t app

eare

d on

his

righ

t arm

aft

er a

rout

ine

bloo

d dr

aw. T

he

patie

nt d

enie

d as

soci

ated

fatig

ue, w

eigh

t los

s, or

oth

er s

yste

mic

sym

ptom

s. H

is

regu

lar p

hysi

cian

dia

gnos

ed th

e ra

sh a

s tin

ea v

ersi

colo

r and

adv

ised

Sel

sun

Blue

fo

r tre

atm

ent.

The

Sels

un B

lue

had

not h

elpe

d, a

nd th

e ra

sh s

ubse

quen

tly s

prea

d to

the

patie

nt’s

trun

k an

d ex

trem

ities

. The

pat

ient

’s pa

st m

edic

al h

isto

ry in

clud

ed

Hep

atiti

s B

and

arth

ritis

. He

was

on

daily

asp

irin

and

pota

ssiu

m a

nd h

ad n

o dr

ug

alle

rgie

s. H

e ha

d liv

ed a

s a

mon

k fo

r mos

t of h

is li

fe a

nd th

us h

ad n

o kn

own

risk

fact

ors

for h

uman

imm

unod

e�ci

ency

viru

s (H

IV) i

nfec

tion.

His

last

trav

el o

vers

eas

had

been

to In

dia

3 ye

ars

ago.

He

deni

ed a

ny k

now

n ex

posu

res

and

clai

med

to

have

bee

n ba

ck in

the

Uni

ted

Stat

es fo

r ove

r a y

ear p

rior t

o th

e on

set o

f his

skin

lesi

ons.

Phys

ical

exa

min

atio

n re

veal

ed m

ultip

le, r

ed-b

row

n, in

dura

ted

2-3c

m p

laqu

es

and

patc

hes

disp

erse

d on

the

patie

nt’s

ches

t, ba

ck, a

nd u

pper

ext

rem

ities

(F

igur

e 1,

2),

spar

ing

the

face

. The

pat

ient

als

o ha

d se

vera

l reg

ular

app

earin

g ne

vi a

nd h

eman

giom

as. O

ther

wis

e hi

s sk

in e

xam

was

nor

mal

. He

had

no a

xilla

ry,

cerv

ical

or i

ngui

nal l

ymph

aden

opat

hy, w

as n

egat

ivel

y de

rmat

ogra

phic

, and

had

in

tact

per

iphe

ral s

ensa

tion.

A p

unch

bio

psy

of th

e ab

dom

en w

as p

erfo

rmed

and

sen

t with

a d

i�er

entia

l di

agno

sis

of ly

mph

oma,

lepr

osy,

or s

yphi

lis. T

he re

turn

dia

gnos

is b

y th

e de

rmat

opat

holo

gist

cam

e ba

ck in

itial

ly a

s su

per�

cial

and

inte

rstit

ial d

erm

atiti

s w

ith fe

atur

es s

ugge

stin

g gr

anul

oma

annu

lare

. H

owev

er, g

iven

the

back

grou

nd

of a

per

sist

ent r

ash

and

the

patie

nt’s

trav

el h

isto

ry, a

n ad

ditio

nal p

unch

bio

psy

was

take

n fr

om th

e pa

tient

’s le

ft a

rm a

nd s

ent b

ack

for f

urth

er e

valu

atio

nan

d st

aini

ng.

HIS

TOPA

THO

LOG

YLo

w p

ower

(200

x) h

emat

oxyl

in a

nd e

osin

sta

inin

g of

the

punc

h bi

opsy

spe

cim

en s

how

ed a

rela

tivel

y un

rem

arka

ble,

slig

htly

att

enua

ted

epid

erm

is. T

he e

pide

rmis

w

as s

epar

ated

from

the

derm

is b

y a

Gre

nz z

one,

and

the

papi

llary

der

mis

dis

play

ed p

oorly

-form

ed g

ranu

lom

as a

s w

ell a

s sc

atte

red

lym

phoc

ytes

(Fi

gure

3).

Hig

her

pow

er (6

00x)

exa

min

atio

n sh

owed

that

the

in�a

mm

ator

y in

�ltr

ate

of th

e de

rmis

ext

ende

d do

wn

to in

volv

e ne

rves

and

adn

exal

str

uctu

res

(Fig

ure

4).

Fite

sta

inin

g of

th

e tis

sue

reve

aled

glo

bi c

onta

inin

g nu

mer

ous

smal

l, �l

amen

tous

, aci

d fa

st o

rgan

ism

s co

nsis

tent

with

lepr

osy

baci

lli (F

igur

e 5,

6). T

he c

ombi

ned

clin

ical

pre

sent

atio

n an

d hi

stio

logi

c �n

ding

s co

n�rm

ed a

dia

gnos

is o

f lep

rom

atou

s le

pros

y.

DIS

CUSS

ION

Lepr

osy

is a

chr

onic

, non

fata

l, in

fect

ious

dis

ease

cau

sed

by M

ycob

acte

rium

le

prae

. M. l

epra

e is

an

oblig

ate

intr

acel

lula

r aci

d-fa

st b

acill

us th

at is

idea

lly

dete

cted

usi

ng a

Fite

sta

in o

n tis

sue

sect

ions

.1 Myc

obac

teriu

m le

prae

tr

ansm

issi

on is

bel

ieve

d to

occ

ur a

lmos

t exc

lusi

vely

by

inha

latio

n of

nas

al

drop

lets

and

less

com

mon

ly th

roug

h br

eaks

in th

e sk

in b

arrie

r.3,4 L

epro

sy h

as a

va

riabl

e in

cuba

tion

perio

d of

mon

ths

to 3

0 ye

ars,

with

an

aver

age

of 5

-7 y

ears

pr

ior t

o di

seas

e m

anife

stat

ion.

2

Lepr

omat

ous

lepr

osy

(LL)

is o

ne o

f the

two

stab

le p

olar

form

s of

the

dise

ase,

with

tu

berc

uloi

d le

pros

y (T

T) b

eing

the

othe

r. LL

pat

ient

s ha

ve d

epre

ssed

ce

ll-m

edia

ted

imm

unity

with

a p

redo

min

ant T

H2

resp

onse

, whe

reas

TT

patie

nts

have

inta

ct c

ell-m

edia

ted

imm

unity

with

a p

redo

min

ant T

H1

resp

onse

.5 As

a re

sult,

LL

ofte

n pr

esen

ts c

linic

ally

with

mul

tiple

, poo

rly d

e�ne

d, h

ypop

igm

ente

d,

sym

met

rical

mac

ules

but

min

imal

-to-

no s

enso

ry lo

sses

.1,5 If

unt

reat

ed, L

L w

ill

even

tual

ly le

ad to

ner

ve e

nlar

gem

ents

and

sev

ere

neur

opat

hic

chan

ges

alon

g w

ith th

e de

velo

pmen

t of l

eoni

ne fa

cies

, mad

aros

is, a

nd s

addl

e no

se

defo

rmiti

es.1,

5,8

The

diag

nosi

s of

lepr

omat

ous

lepr

osy

is u

sual

ly a

com

bine

d cl

inic

al a

nd

hist

opat

holo

gic

one.

1,5

His

tolo

gica

lly, t

he g

ranu

lom

as o

f LL

cont

ain

mac

roph

ages

w

ith n

umer

ous

baci

lli a

nd li

pid

drop

lets

in th

eir c

ytop

lasm

.5 Th

is d

i�us

e de

rmal

in

�ltr

ate

is s

epar

ated

from

the

epid

erm

is b

y a

wel

l-de�

ned

Gre

nz z

one.

In

cont

rast

, the

wel

l-for

med

gra

nulo

mas

of T

T co

ntai

n no

n-lip

idiz

ed e

pith

elio

d ce

lls

with

litt

le to

no

baci

lli a

nd n

o di

stin

guis

habl

e G

renz

zon

e.8

The

Wor

ld H

ealth

Org

aniz

atio

n (W

HO

) dev

elop

ed a

sim

pli�

ed le

pros

y cl

assi

�cat

ion

syst

em fr

om w

hich

the

curr

ent t

reat

men

t reg

imen

is b

ased

. Pa

tient

s w

ith m

ore

than

�ve

ski

n le

sion

s (L

L pa

tient

s) a

re la

bele

d m

ultib

acill

ary,

w

here

as p

atie

nts

with

one

to �

ve s

kin

lesi

ons

(TT

patie

nts)

are

labe

led

pauc

ibac

illar

y.2,

6 The

cur

rent

ly re

com

men

ded

mul

tibac

illar

y tr

eatm

ent f

or L

L pa

tient

s is

a 1

2-24

mon

th m

ultid

rug

ther

apy

(MD

T) c

onsi

stin

g of

dai

ly d

apso

ne

(100

mg)

and

clo

fazi

min

e (5

0mg)

, with

mon

thly

sup

ervi

sed

rifam

pin

(600

mg)

and

cl

ofaz

imin

e (3

00m

g).2,

4,5 A

rece

nt s

tudy

sug

gest

ed th

e ad

ditio

n of

mon

thly

m

inoc

yclin

e (1

00m

g) h

as a

syn

ergi

stic

e�e

ct a

long

with

MD

T in

the

trea

tmen

t of

lepr

omat

ous

lepr

osy

in th

at it

sig

ni�c

antly

redu

ces

angi

ogen

esis

and

rapi

dly

elim

inat

es le

pra

baci

lli fr

om th

e sk

in.9

Eryt

hem

a no

dosu

m le

pros

um (E

NL)

is a

n in

�am

mat

ory

reac

tion

occa

sion

ally

de

velo

ping

with

in a

few

yea

rs o

f sta

rtin

g an

tibio

tic tr

eatm

ent f

or L

L or

dur

ing

preg

nanc

y.8 E

NL

is d

ue to

circ

ulat

ing

imm

une

com

plex

es a

nd c

an le

ad to

m

ultis

yste

m in

volv

emen

t. Th

alid

omid

e is

the

drug

of c

hoic

e to

trea

t EN

L bu

t is

used

cau

tious

ly d

ue to

its

tera

toge

nici

ty.7 L

epro

mat

ous

lepr

osy

is n

ow

cons

ider

ed a

larg

ely

cura

ble

dise

ase

with

a g

ood

prog

nosi

s if

diag

nose

d an

d tr

eate

d ea

rly, t

hus

prev

entin

g th

e lo

ng te

rm in

capa

cita

ting

sequ

elae

.6

REFE

REN

CES

1. G

elbe

r R. L

epro

sy (H

anse

n’s

Dis

ease

). In

: Kas

per D

L, B

raun

wal

d E,

Fau

ci A

S, H

ause

r SL,

Lon

go D

L, Ja

mes

on JL

. Har

rison

’s Pr

inci

ples

of I

nter

nal M

edic

ine,

16th

ed.

McG

raw

-Hill

; 200

5:96

6-97

2.

2. K

umar

B. D

egra

S. L

epro

sy.

In: B

ope

ET, R

akel

RE,

Kel

lerm

an R

D. C

onn’

s Cu

rren

t The

rapy

201

0, 1

st e

d. S

aund

ers-

Else

vier

; 20

09:9

5-10

1.

3. C

zerk

asij

V. D

iagn

osin

g an

d tr

eatin

g H

anse

n’s

dise

ase:

Clin

icia

n Re

view

s. 20

09;7

3(12

):15-

19.

4) B

ritto

n W

, Loc

kwoo

d D

. Lep

rosy

: The

Lan

cet.

2004

;363

(941

6):1

209-

1219

.

5) R

amos

-e-S

ilva

M, R

ibei

ro d

e Ca

stro

MC.

Myc

obac

teria

l Inf

ectio

ns.

In: B

olog

nia

JL, J

oriz

zo JL

, Rap

ini R

P. D

erm

atol

ogy,

2nd

ed

. Mos

by E

lsev

ier;

2008

:110

7-11

26.

6) M

osch

ella

SL.

An

upda

te o

n th

e di

agno

sis

and

trea

tmen

t of l

epro

sy:

J Am

Aca

d D

erm

atol

. 200

4; 5

1(3)

:417

-426

.

7) T

seng

S, P

ak G

, Was

heni

k K,

Pom

eran

z M

K, S

hupa

ck JL

. Red

isco

verin

g th

alid

omid

e: A

revi

ew o

f its

mec

hani

sm o

f act

ion,

si

de e

�ect

s, an

d po

tent

ial u

ses:

J A

m A

cad

Der

mat

ol. 1

996;

35(

6):9

69-9

79.

8) Ja

mes

WD

, Ber

ger T

G, E

lsto

n D

M. H

anse

n’s

Dis

ease

. In

: And

rew

’s D

isea

ses

of th

e Sk

in: C

linic

al D

erm

atol

ogy.

10th

ed.

Ph

ilade

lphi

a, P

A: S

aund

ers

Else

vier

. 200

6:34

3-35

2.

9) E

l-Kha

law

any

M, S

haab

an D

, Sul

tan

M, A

lsal

am F

. Inh

ibiti

on o

f ang

ioge

nesi

s as

a n

ew th

erap

eutic

targ

et in

the

trea

tmen

t of l

epro

mat

ous

lepr

osy:

Clin

ical

, Cos

met

ic, a

nd In

vest

igat

ive

Der

mat

olog

y. 2

012;

5:1-

6.Ep

ub 2

011

Dec

29.

260

Inva

sive

Duc

tal B

reas

t Car

cino

ma

Pres

entin

g as

Lip

oma

in a

Mal

e: A

Cas

e R

epor

t and

a

Rev

iew

of t

he L

itera

ture

Ja

mes

Lan

dero

, DO

W

ellin

gton

Reg

iona

l Med

ical

Cen

ter

Abs

trac

t D

iscu

ssio

n

App

roac

h

Cas

e R

epor

t

Pres

ente

d at

the

2012

ann

ual m

eetin

g of

the

Am

eric

an O

steo

path

ic C

olle

ge o

f Der

mat

olog

y in

San

Die

go, C

A

Bre

ast C

A in

Mal

es

Con

clus

ion

Ref

eren

ces

Mal

e br

east

can

cer,

alth

ough

a ra

re m

alig

nanc

y th

at a

ccou

nts

for

less

than

1%

of a

ll ca

ncer

s in

men

is e

asily

trea

ted

whe

n ca

ught

in

the

early

sta

ges.

We

desc

ribe

the

case

of a

76

year

old

Cau

casi

an

mal

e pa

tient

with

inva

sive

duc

tal b

reas

t car

cino

ma

who

pre

sent

ed

with

a s

impl

e br

east

lum

p co

nsis

tent

with

a c

omm

on li

pom

a ov

erly

ing

the

mal

igna

nt tu

mor

. Thi

s pa

per w

ill re

view

the

curr

ent

liter

atur

e on

epi

dem

iolo

gy, r

isk

fact

ors,

etio

logy

, diff

eren

t typ

es o

f br

east

can

cer,

clin

ical

pre

sent

atio

n, im

agin

g, d

iagn

ostic

wor

kup

and

treat

men

t. W

e st

ress

the

impo

rtanc

e of

a th

orou

gh e

valu

atio

n of

a

brea

st lu

mp

in a

ny p

erso

n, m

ale

or fe

mal

e to

avo

id u

nder

-dia

gnos

is.

We

also

sup

port

a lo

wer

thre

shol

d fo

r bio

psy

of a

ny b

reas

t lum

p,

espe

cial

ly w

ith a

his

tory

of r

ecen

t dis

cove

ry o

r gro

wth

.

Epid

emio

logy

C

urre

ntly,

mal

e br

east

car

cino

ma

acco

unts

for l

ess

than

1%

of a

ll ca

ncer

s in

men

and

is o

nly

0.7%

of a

ll br

east

can

cers

(2, 3

). M

ale

brea

st

canc

er c

ompr

ises

1%

of a

ll m

alig

nant

bre

ast c

ance

r and

lead

s to

less

than

0.1

% o

f can

cer r

elat

ed d

eath

s in

men

(14)

. The

mal

e to

fem

ale

ratio

fo

r bre

ast c

ance

r is

1:10

0 (1

). Th

e pe

ak in

cide

nce

at w

hich

age

bre

ast c

ance

r affe

cts

men

is 7

1 (6

8) a

nd u

sual

ly d

evel

ops

afte

r the

age

of 6

0 (1

6). T

he m

edia

n ag

e of

dia

gnos

is in

men

is 6

5 ye

ars

old

(23)

. Men

are

dia

gnos

ed w

ith b

reas

t can

cer l

ater

than

wom

en (6

8) b

y 5

to 1

0 ye

ars

(4).

Ther

e ha

ve b

een

case

s of

bre

ast c

ance

r occ

urrin

g in

mal

es b

etw

een

the

ages

of 1

3 an

d 32

(2, 6

8, 2

5, 2

4). M

iao

et a

l's d

ata

show

s th

at

mal

e br

east

can

cer h

as re

mai

ned

stab

le o

ver t

he la

st 3

8 ye

ars

inte

rnat

iona

lly. T

he c

urre

nt li

tera

ture

sta

tes

that

the

inci

denc

e of

bre

ast c

ance

r in

men

is 1

cas

e in

eve

ry 1

00,0

00 m

en (6

8). I

n 20

10, 1

970

case

s w

ere

diag

nose

d in

the

US

, with

390

pre

dict

ed to

die

(41)

. In

2009

, the

Uni

ted

Sta

tes

had

1900

new

dia

gnos

ed c

ases

of m

ale

brea

st c

ance

r and

440

dea

ths

(18)

. Ash

kena

zi J

ews

(57)

and

Afri

can

Am

eric

an m

en h

ave

a hi

gher

pre

vale

nce

com

pare

d to

Cau

casi

an m

en (4

3).

Wor

kup/

Imag

ing

Imag

ing

that

can

be

carr

ied

out i

nclu

de m

amm

ogra

phy,

whi

ch c

an d

etec

t if t

he le

sion

is m

alig

nant

or b

enig

n (1

,2).

Bec

ause

of t

he ra

rity

of th

e di

seas

e,

mam

mog

raph

y is

not

nee

ded

for s

cree

ning

pur

pose

s (4)

. Men

who

hav

e an

incr

ease

d ris

k of

bre

ast c

ance

r inc

ludi

ng s

trong

fam

ily h

isto

ry, B

RC

A2

posi

tive,

K

linef

elte

r syn

drom

e ar

e re

com

men

ded

to u

nder

go b

ase-

line

mam

mog

raph

y, fo

llow

ed b

y an

nual

mam

mog

raph

y an

d se

mia

nnua

l bre

ast e

xam

inat

ion(

92).

M

amm

ogra

phy

has a

sens

itivi

ty a

nd sp

ecifi

city

of 9

2% a

nd 9

0% in

mal

e br

east

can

cer,

resp

ectiv

ely

(60)

. It c

an a

lso

be u

sed

to d

iffer

entia

te b

etw

een

mal

igna

ncy

and

gyne

com

astia

(74)

. Mic

roca

lcifi

catio

ns a

re le

ss c

omm

on o

n m

amm

ogra

phy

in m

ale

brea

st c

ance

r whe

n co

mpa

red

to fe

mal

e br

east

can

cer

(74)

. Ultr

asou

nd c

an b

e us

ed fo

r nod

al in

volv

emen

t (61

). C

ore

biop

sy is

use

d fo

r def

initi

ve d

iagn

osis

(42

or 2

1), w

hich

mea

ns th

at fi

ne n

eedl

e as

pira

tion

can

also

be

used

in m

ales

as i

t is v

ery

sens

itive

and

spec

ific.

Onc

e a

lesi

on h

as b

een

conf

irmed

to b

e m

alig

nant

, the

tum

or st

age

shou

ld b

e as

sess

ed a

nd th

e tis

sue

shou

ld a

lso

be e

valu

ated

for h

orm

one

rece

ptor

sta

tus.

The

tum

or st

agin

g sh

ould

follo

w th

e Am

eric

an J

oint

Com

mitt

ee o

n C

ance

r cla

ssifi

catio

n sy

stem

, w

hich

incl

udes

tum

or si

ze, n

odal

invo

lvem

ent,

and

dist

ant m

etas

tase

s (6

3). H

isto

logi

cal t

umor

gra

ding

sho

uld

be a

sses

sed

usin

g th

e Sc

arff

Blo

om a

nd

Ric

hard

son

hist

olog

ical

sys

tem

. Im

mun

ohis

toch

emic

al a

naly

sis

shou

ld b

e do

ne a

t thi

s tim

e to

ass

ess h

orm

one

rece

ptor

sta

tus o

f est

roge

n (E

R) a

nd

prog

este

rone

rece

ptor

(PR

). M

etas

tase

s ar

e ex

amin

ed th

e sa

me

way

they

are

don

e in

fem

ale

brea

st c

ance

r: th

roug

h la

b w

ork,

che

st x

-ray

, bon

e sc

an, a

nd C

T sc

an o

f the

abd

omen

and

pel

vis (

62).

The

liter

atur

e do

es n

ot h

ave

any

reco

mm

enda

tion

for f

ollo

w u

p im

agin

g af

ter d

iagn

osis

. Our

reco

mm

enda

tions

wou

ld

be to

follo

w th

e sa

me

guid

elin

es fo

r fem

ale

brea

st c

ance

r.

We

pres

ent a

76-

year

-old

Cau

casi

an g

entle

man

who

pre

sent

ed to

our

clin

ic fo

r ev

alua

tion

of a

pai

nles

s lum

p on

his

left

brea

st th

at h

ad b

een

pres

ent f

or 6

yea

rs

with

rece

nt g

row

th o

ver t

he la

st 6

mon

ths.

The

patie

nt's

past

med

ical

his

tory

was

si

gnifi

cant

for b

asal

cel

l car

cino

ma,

hyp

erte

nsio

n an

d hy

perc

hole

ster

olem

ia. H

is

med

icat

ions

incl

ude

aten

olol

, lov

asta

tin a

nd h

ydro

chlo

roth

iazi

de. T

he p

atie

nt

repo

rted

no a

llerg

ies.

He

deni

ed sm

okin

g bu

t adm

itted

to a

lcoh

ol u

se. R

evie

w o

f sy

stem

s was

unr

emar

kabl

e. P

atie

nt d

enie

d ni

pple

retra

ctio

n, d

isch

arge

, or

ulce

ratio

n. P

hysi

cal e

xam

inat

ion

reve

aled

a w

ell-d

evel

oped

, wel

l-nou

rishe

d m

ale.

Upo

n co

mpl

ete

skin

exa

min

atio

n, th

e le

ft lo

wer

qua

dran

t of h

is le

ft br

east

re

veal

ed a

soft,

rubb

ery,

mob

ile, w

ell c

ircum

scrib

ed m

ass a

bout

2.5

cm X

2cm

in

diam

eter

. An

exci

sion

al b

iops

y of

this

mas

s was

per

form

ed w

hich

was

wel

l co

nsis

tent

clin

ical

ly w

ith a

lipo

ma.

How

ever

upo

n fu

rther

insp

ectio

n an

d pa

lpat

ion

of th

e ar

ea, a

firm

mas

s was

felt

in d

eepe

r tis

sue.

The

dec

isio

n w

as

mad

e ex

plor

e de

eper

und

erne

ath

the

fat.

We

foun

d an

irre

gula

r mas

s abo

ut 2

X

3 cm

in d

iam

eter

, ver

y fir

m a

nd n

oted

to h

ave

a gr

ay c

olor

. Th

is m

ass w

as a

lso

sent

for h

isto

logi

cal e

xam

inat

ion

and

reve

aled

a 0

.7cm

gra

de II

inva

sive

duc

tal

carc

inom

a w

ith m

icro

calc

ifica

tions

. Th

e pa

tient

did

not

exh

ibit

any

axill

ary

lym

phad

enop

athy

and

did

not

hav

e an

y br

east

dis

char

ge. T

here

wer

e no

ab

norm

aliti

es o

r mas

ses n

oted

in th

e co

ntra

late

ral c

hest

wal

l or c

ontra

late

ral

axill

a. F

ollo

win

g re

view

of t

he h

isto

path

olog

y, th

e pa

tient

was

dia

gnos

ed w

ith

brea

st d

ucta

l car

cino

ma.

A c

ompu

ted

tom

ogra

phy

was

com

plet

ed o

f his

che

st

and

abdo

men

whi

ch d

emon

stra

ted

no m

etas

tasi

s. Si

nce

his i

nitia

l vis

it, th

ere

has

been

no

evid

ence

of r

ecur

renc

e ba

sed

on m

amm

ogra

phy

take

n 3

mon

ths p

ost-

biop

sy. T

he p

atie

nt is

cur

rent

ly u

nder

stric

t sur

veill

ance

with

regu

lar c

ompl

ete

cuta

neou

s exa

ms a

nd m

amm

ogra

phy

ever

y 6

mon

ths.

This

cas

e re

port

serv

es to

ra

ise

awar

enes

s of a

ny g

row

ths p

rese

ntin

g in

the

brea

sts o

f bot

h m

ale

and

fem

ale

to e

xclu

de b

reas

t car

cino

ma

as a

n un

derly

ing

path

olog

y. W

e ex

amin

e th

e cu

rren

t lite

ratu

re su

rrou

ndin

g m

ale

brea

st c

arci

nom

a.

The

grea

test

risk

fact

or fo

r mal

e br

east

can

cer i

s Klin

efel

ter’s

syn

drom

e w

hich

incr

ease

s m

ale

brea

st c

ance

r ris

k by

50

fold

(24,

69)

. Klin

efel

ter

patie

nts h

ave

a lif

etim

e ris

k of

mal

e br

east

can

cer o

f 5%

(44)

. A fa

mily

his

tory

of b

reas

t can

cer i

n m

en h

ave

an e

stim

ated

odd

s rad

io o

f 3.9

8 fo

r de

velo

ping

bre

ast c

ance

r (49

) and

a re

lativ

e ris

k of

2.5

(59)

. G

enet

ic a

nd h

orm

onal

imba

lanc

es p

lay

a m

ajor

role

in m

ale

brea

st c

ance

r. B

RC

A2

(17)

is a

stro

ng ri

sk fa

ctor

, alth

ough

BR

CA

1 ha

s als

o be

en

repo

rted

(26-

28);

so m

en w

ho p

rese

nt w

ith b

reas

t can

cer s

houl

d ha

ve g

enet

ic c

ouns

elin

g an

d te

stin

g do

ne (7

1). C

urre

ntly

the

Nat

iona

l C

ompr

ehen

sive

Can

cer N

etw

ork

reco

mm

ends

that

pat

ient

s w

ith B

RC

A1/

2 m

utat

ions

shou

ld b

e ta

ught

how

to u

nder

go b

reas

t sel

f-ex

amin

atio

n (7

1). M

utat

ions

in C

HEK

2 (1

100d

elC

) als

o in

crea

se th

e ris

k of

mal

e br

east

can

cer b

y 10

fold

(55)

and

gen

etic

var

iant

s at

chr

omos

omes

2q3

5, 5

p12,

6q

25.1

,10q

26.1

3, a

nd 1

6q12

(70)

hav

e be

en a

ssoc

iate

d w

ith m

ale

brea

st c

ance

r.

A p

ossi

ble

etio

logy

for m

ale

brea

st c

ance

r is d

isea

se s

econ

dary

to h

orm

onal

abn

orm

aliti

es (6

8), l

ack

of a

ndro

gen(

58) i

ncre

ased

est

roge

n ex

posu

re

(3, 5

,6),

estro

gen

adm

inis

tratio

n (7

1),

or e

stro

gen

rela

ted

dise

ase

incl

udin

g bu

t not

lim

ited

to: g

ynec

omas

tia (1

5), c

irrho

sis (

29),

and

obes

ity. T

he

incr

ease

in b

reas

t can

cer i

n m

en h

as b

een

attri

bute

d to

a p

ossi

ble

incr

ease

d es

troge

n co

nver

sion

in a

dipo

se ti

ssue

(6).

Als

o, te

stic

ular

trau

ma

(68)

, co

ngen

ital i

ngui

nal h

erni

a (7

2), o

rchi

tis, o

rchi

dect

omy

(72)

Cow

den’

s dis

ease

(21)

, rad

iatio

n(68

), fa

mily

his

tory

of b

reas

t or o

varia

n ca

ncer

(44)

pr

edis

pose

to th

e pa

thol

ogy.

A

n in

crea

sed

risk

of b

reas

t can

cer h

as a

lso

been

not

ed in

pat

ient

s who

hav

e a

hist

ory

of o

ccup

atio

nal e

xpos

ure

to b

last

furn

aces

, rol

ling

mill

s, m

otor

veh

icle

man

ufac

turin

g an

d st

eel w

orks

(7).

). O

ur p

atie

nt d

id n

ot h

ave

a hi

stor

y of

pre

viou

s occ

upat

iona

l exp

osur

e. O

ther

risk

fact

ors

incl

ude

low

leve

l of p

hysi

cal a

ctiv

ity(5

6), h

isto

ry o

f bon

e fr

actu

re a

fter a

ge 4

5 (5

6).

1. T

emm

im L

, Luq

man

i YA

, Jar

alla

h M

, et a

l. E

valu

atio

n of

pro

gnos

tic fa

ctor

s in

mal

e br

east

can

cer.

Bre

ast.

2001

;10:

166–

175.

2.

Bre

ast e

nlar

gem

ent i

n yo

ung

men

not

alw

aysg

ynae

com

astia

: Bre

ast c

ance

r in

a 22

-yea

r-ol

d m

an. A

NZ

J S

urg.

200

5;75

:914

–916

. 3.

Gio

rdan

o S

H. A

revi

ew o

f the

dia

gnos

is a

nd m

anag

emen

t of m

ale

brea

st c

ance

r. O

ncol

ogis

t. 20

05; 1

0:47

1–47

9.

4. G

iord

ano

SH

, Coh

en D

S, B

uzda

r AU

, et a

l. B

reas

t car

cino

ma

in m

en: A

pop

ulat

ion-

base

d st

udy.

Can

cer.

2004

;101

:51–

57.

5. H

sing

AW

, McL

augh

lin J

K, C

occo

P, e

t al.

Ris

k fa

ctor

s fo

r mal

e br

east

can

cer (

Uni

ted

Sta

tes)

. Can

cer C

ause

s C

ontro

l. 19

98;9

:269

–275

. 6.

Gio

rdan

o S

H, B

uzda

r AU

, Hor

toba

gyi G

N. B

reas

t can

cer i

n m

en. A

nn In

tern

Med

. 200

2;13

7:67

8–68

7.

7. C

occo

P, F

iggs

L, D

osem

eci M

, et a

l. C

ase-

cont

rol s

tudy

of o

ccup

atio

nal e

xpos

ures

and

mal

e br

east

can

cer.

Occ

up E

nviro

n M

ed. 1

998;

55:5

99–6

04.

8. G

iord

ano

SH

, Per

kins

G, B

rogl

io K

, et a

l. A

djuv

ant s

yste

mic

ther

apy

for m

ale

brea

st c

arci

nom

a. C

ance

r. 20

05;1

04:2

359–

2364

. 9.

Spe

nce

RA

, Mac

Ken

zie

G, A

nder

son

JR, e

t al.

Long

-term

sur

viva

l fol

low

ing

canc

er o

f the

mal

e br

east

in N

orth

ern

Irela

nd. A

repo

rt of

81

case

s. C

ance

r. 19

85;5

5:64

8–65

2.

10. G

oss

PE

, Rei

d C

, Pin

tilie

M, e

t al.

Mal

e br

east

car

cino

ma:

A re

view

of 2

29 p

atie

nts

who

pre

sent

ed to

the

Prin

cess

Mar

gare

t Hos

pita

l dur

ing

40 y

ears

: 195

5–19

96. C

ance

r. 19

99;8

5:62

9–63

9.

11. R

ibei

ro G

G, S

win

dell

R, H

arris

M, e

t al.

A re

view

of t

he m

anag

emen

t of t

he m

ale

brea

st c

arci

nom

a ba

sed

on a

n an

alys

is o

f 420

trea

ted

case

s. B

reas

t. 19

96;5

:141

–146

. 12

. Gos

s P

E, R

eid

C, P

intil

ie M

, et a

l. M

ale

brea

st c

arci

nom

a: A

revi

ew o

f 229

pat

ient

s w

ho p

rese

nted

to th

e P

rince

ss M

arga

ret H

ospi

tal d

urin

g 40

yea

rs:1

955–

1996

. Can

cer.

1999

;85:

629–

639.

13

. Rib

eiro

G, S

win

dell

R. A

djuv

ant t

amox

ifen

for m

ale

brea

st c

ance

r (M

BC

). B

r J C

ance

r. 19

92;6

5:25

2–25

4.

14. W

iess

JR

, Moy

isch

KB

, Sw

ede

H. E

pide

myo

logy

of m

ale

brea

st c

ance

r. C

ance

r Epd

emio

l Bbi

omar

kers

Pre

v 20

05l 1

4: 2

0 - 2

6.

15. K

ahla

PB

, Cas

saro

S V

ladi

mir,

Fg

Way

ne M

G, C

amm

arat

a. B

ilate

ral s

ynch

rono

us b

reas

t can

cer i

n a

mal

e. M

s S

inai

J M

ed 2

005l

72:

120

-123

. 16

. bey

rout

e M

I, B

eyro

uti R

, Rey

rout

i R e

t al.

Bre

ast c

ance

r in

men

. Pre

sse

Med

200

7: 1

919

-192

4.

17. s

tratto

n M

R, F

ord

D, N

euha

sen

S e

t al.

Fam

ilial

mal

e br

east

can

cer i

s no

t lin

ed to

the

BR

CA

1 lo

cus

on c

hrom

osom

e 17

q. N

at G

enet

199

4l 7

: 103

-7

18. J

emal

A, S

iege

l R, W

ard

E, H

ao Y

, Xu

J, T

hun

MJ:

Can

cer s

tatis

tics.

CA

Can

cer J

Clin

200

9, 5

9:22

5-24

9.

19. G

enna

ri R

, Cur

iglia

no G

, Jer

ecze

k-Fo

ssa

BA

, Zur

rida

S, R

enne

G, I

ntra

M, G

alim

berti

V, L

uini

A, O

recc

hia

R, V

iale

G, G

oldh

risch

A, V

eron

esi U

: Mal

e br

east

can

cer:

a sp

ecia

l the

rape

utic

pro

blem

. Any

thin

g ne

w?

(Rev

iew

). In

t J

Onc

ol 2

004,

24:

663-

670.

20

. Gio

rdan

o S

H, C

ohen

DS

, Buz

dar A

U, P

erki

ns G

, Hor

toba

gyi G

N: B

reas

t car

cino

ma

in m

en: a

pop

ulat

ion-

base

d st

udy.

Can

cer 2

004,

101

:51-

57.

21. F

entim

an IS

, Fou

rque

t A, H

orto

bagy

i GN

: Mal

e br

east

can

cer.

Lanc

et 2

006,

367

:595

-604

. 22

. Cze

ne K

, Ber

gqvi

st J

, Hal

l P, B

ergh

J: H

ow to

trea

t mal

e br

east

can

cer.

Bre

ast 2

007,

16(

Sup

pl 2

):S14

7-15

4.

23. S

AM

E A

S 4

5 C

utul

i B: S

trate

gies

in tr

eatin

g m

ale

brea

st c

ance

r. E

xper

t Opi

n P

harm

acot

her

2007

, 8:1

93-2

02.

24. A

hmad

R, L

ewis

S, M

ahar

aj D

: A m

ale

patie

nt fr

om th

e W

est I

ndie

s w

ith

inva

sive

duc

tal c

arci

nom

a in

the

right

bre

ast:

A c

ase

repo

rt an

d lit

erat

ure

revi

ew. G

end

Med

201

0, 7

:179

-183

. 25

. Cha

ng H

L, K

ish

JB, S

mith

BL,

Gol

dste

in A

M: A

16-

year

-old

mal

e w

ith g

ynec

omas

tia a

nd d

ucta

l car

cino

ma

in s

itu. P

edia

tr S

urg

Int 2

008,

24:

1251

-125

3.

26. F

rank

TS

, Def

fenb

augh

AM

, Rei

d JE

, Hul

ick

M, W

ard

BE

, Lin

genf

elte

r B

, Gum

pper

KL,

Sch

oll T

, Tav

tigia

n S

V, P

russ

DR

, Crit

chfie

ld G

C: C

linic

al c

hara

cter

istic

s of

indi

vidu

als

with

ger

mlin

e m

utat

ions

in B

RC

A1

and

BR

CA

2:

anal

ysis

of 1

0,00

0 in

divi

dual

s. J

Clin

Onc

ol 2

002,

20:

1480

-149

0.

27. F

riedm

an L

S, G

ayth

er S

A, K

uros

aki T

, Gor

don

D, N

oble

B, C

asey

G, P

onde

r BA

, Ant

on-C

ulve

r H: M

utat

ion

anal

ysis

of B

RC

A1

and

BR

CA

2 in

a m

ale

brea

st c

ance

r pop

ulat

ion.

Am

J H

um G

enet

199

7, 6

0:31

3-31

9.

28. H

aral

dsso

n K

, Lom

an N

, Zha

ng Q

X, J

ohan

nsso

n O

, Ols

son

H, B

org

A: B

RC

A2

germ

-line

mut

atio

ns a

re fr

eque

nt in

mal

e br

east

can

cer p

atie

nts

with

out a

fam

ily h

isto

ry o

f the

dis

ease

. Can

cer R

es 1

998,

58:

1367

-137

1.

29. G

anly

I, T

aylo

r EW

: Bre

ast c

ance

r in

a tra

ns-s

exua

l man

rece

ivin

g ho

rmon

e re

plac

emen

t the

rapy

. Br J

Sur

g 19

95, 8

2:34

1.

30. C

olom

bo-B

enkm

ann

M, S

tern

J, H

erfa

rth C

: On

the

negl

ecte

d en

tity

of u

nila

tera

l gyn

ecom

astia

. Ann

Pla

st S

urg

2006

, 56:

346.

31

. Gom

ez-R

apos

o C

, Zam

bran

a Te

var F

, Ser

eno

Moy

ano

M, L

opez

Gom

ez M

, Cas

ado

E: M

ale

brea

st c

ance

r. C

ance

r Tre

at R

ev 2

010.

32

. Auv

inen

A, C

urtis

RE

, Ron

E: R

isk

of s

ubse

quen

t can

cer f

ollo

win

g br

east

can

cer i

n m

en. J

Nat

l Can

cer I

nst 2

002,

94:

1330

-133

2.

33. B

ruce

DM

, Hey

s S

D, P

ayne

S, M

iller

ID, E

rem

in O

: Mal

e br

east

can

cer:

clin

ico-

path

olog

ical

feat

ures

, im

mun

ocyt

oche

mic

al c

hara

cter

istic

s an

d pr

ogno

sis.

Eur

J S

urg

Onc

ol 1

996,

22:

42-4

6.

34. B

en D

hiab

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cino

ma.

Can

cer 2

005;

104:

2359

. 88

. Jai

yesi

mi I

A, B

uzda

r AU

, Sah

in A

A, e

t al.

Car

cino

ma

of th

e m

ale

brea

st. A

nn

Inte

rn M

ed 1

992;

117:

771–

7.

89. L

opez

M, D

i Lau

ro L

, Laz

zaro

B, e

t al.

Hor

mon

al tr

eatm

ent o

f dis

sem

inat

ed

mal

e br

east

can

cer.

Onc

olog

y 19

85;4

2:34

5–9.

90

. Kilu

k JV

, Lee

MC

, Par

k C

K, M

eade

T, M

into

n S

, Har

ris E

, Kim

J, L

aron

ga C

.Mal

e br

east

can

cer:

man

agem

ent a

nd fo

llow

-up

reco

mm

enda

tions

. Bre

ast J

. 201

1 S

ep-O

ct;1

7(5)

:503

-9. d

oi: 1

0.11

11/j.

1524

-474

1.20

11.0

1148

.x.

Epu

b 20

11 A

ug 2

9.

91. M

iao

H, V

erko

oije

n H

M, C

hia

KS

, Bou

char

dy C

, Puk

kala

E, L

arøn

ning

en S

, Mel

lem

kjæ

r L, C

zene

K, H

artm

an M

. In

cide

nce

and

Out

com

e of

Mal

e B

reas

t Can

cer:

An

Inte

rnat

iona

l Pop

ulat

ion-

Bas

ed S

tudy

. J C

lin O

ncol

. 201

1 O

ct 3

. [E

pub

ahea

d of

prin

t] 92

. Joh

anse

n Ta

ber J

A, M

oris

y LR

, Osb

ahr

AJ,

Dic

kins

on B

D. M

ale

brea

st c

ance

r: ris

k fa

ctor

s, d

iagn

osis

, and

man

agem

ent (

revi

ew).

Onc

ol R

ep 2

010;

24:1

115−

20

The

prog

nosi

s for

mal

e br

east

can

cer i

s sim

ilar t

o w

omen

, with

lym

ph n

ode

invo

lvem

ent a

nd tu

mor

size

bei

ng th

e m

ost d

eter

min

ant

prog

nost

ic fa

ctor

(4).

Sim

ilar t

o w

omen

, pro

gnos

is is

det

erm

ined

by

stag

ing

of th

e tu

mor

, alth

ough

in m

en it

is ty

pica

lly d

etec

ted

late

r in

dire

ctly

.

Mor

talit

y in

crea

ses b

y 50

% w

ith ly

mph

nod

e in

volv

emen

t (71

). If

the

tum

or m

easu

res b

etw

een

2 an

d 5

cm, m

orta

lity

incr

ease

s by

40%

(7

1). M

orta

lity

is a

lso

incr

ease

d if

the

patie

nt is

gre

ater

than

65

year

s old

(71)

, but

mal

e se

x is

a fa

vora

ble

prog

nost

ic fa

ctor

(81)

. B

ourh

afou

r et a

l's st

udy

of 1

27 c

ases

of m

ale

brea

st c

ance

r rev

eale

d m

etas

tase

s in

41 c

ases

(32%

), w

ith th

e bo

ne b

eing

the

mos

t com

mon

si

te fo

r met

asta

sis.

Cur

rent

ly, t

he 5

yea

r sur

viva

l rat

e fo

r mal

e br

east

can

cer s

tand

s at 6

0% a

nd th

e 10

yea

r sur

viva

l rat

e at

40%

(38)

. The

5

year

surv

ival

rate

bas

ed o

n st

age

is a

s fol

low

s: S

tage

I 78

%; S

tage

II 6

7%; S

tage

III 4

0%; a

nd S

tage

IV 1

9% (4

). O

f all

ethn

iciti

es,

Afr

ican

Am

eric

an m

en te

nd to

hav

e a

wor

se p

rogn

osis

(44)

. Unf

ortu

nate

ly, l

ater

det

ectio

n in

men

is a

lso

due

to m

en n

ot h

avin

g ch

ange

s in

sym

ptom

s in

brea

sts s

imila

r to

how

fem

ales

typi

cally

do

(71)

. How

ever

, mal

e pa

tient

s with

bre

ast c

ance

r hav

e a

low

er ri

sk o

f dea

th

from

bre

ast c

ance

r whe

n co

mpa

red

to fe

mal

es w

hen

adju

stin

g fo

r hig

her a

ge a

t dia

gnos

is, d

iffer

ent s

tand

ard

of tr

eatm

ent a

nd m

ore

adva

nced

stag

e at

dia

gnos

is (8

1).

Nea

rly h

alf o

f new

ly d

iagn

osed

bre

ast c

ance

rs in

men

are

dia

gnos

ed a

t sta

ge II

I or I

V (2

1), e

ven

thou

gh B

ourh

afou

r et a

l sho

wed

that

82

% o

f cas

es w

ere

diag

nose

d at

stag

e II

or I

II. T

his f

urth

er a

dds t

o th

e re

ason

why

mas

ses o

n th

e m

ale

brea

st a

re n

ot a

ggre

ssiv

ely

soug

ht

afte

r. Ea

rlier

dia

gnos

is le

ads t

o st

rong

er su

cces

s with

trea

tmen

t (68

), bu

t men

are

typi

cally

dia

gnos

ed in

itial

ly w

ith g

ynec

omas

tia c

ausi

ng

treat

men

t to

be d

elay

ed.

Th

e la

ter d

etec

tion

is m

ost l

ikel

y du

e to

bet

ter a

nd m

ore

freq

uent

scre

enin

g in

wom

en, b

ut a

lso

the

lack

of a

war

enes

s of m

ale

brea

st

canc

er c

ontri

bute

s to

it be

ing

igno

red

in m

any

case

s or b

eing

mis

take

n w

ith g

ynec

omas

tia. S

ympt

oms o

f mal

e br

east

can

cer t

ypic

ally

pr

esen

t lat

er w

hen

com

pare

d to

wom

en, w

hich

als

o ca

uses

men

to h

ave

a la

ter d

iagn

osis

and

wor

se p

rogn

osis

(5).

Ris

k Fa

ctor

s/Et

iolo

gy

Trea

tmen

t

Type

s of B

reas

t Can

cer

in M

en

90%

of m

ale

brea

st c

arci

nom

as a

re o

f an

inva

sive

type

with

the

mos

t com

mon

bei

ng in

filtra

ting

duct

al c

arci

nom

a, w

hich

acc

ount

s fo

r gre

ater

than

65

to 9

5% (1

9,20

). Pa

pilla

ry c

arci

nom

as re

pres

ents

2.6

% (6

4) o

f cas

es a

nd m

ucin

ous 1

.8%

of c

ases

(64)

. Lob

ular

car

cino

mas

repr

esen

t 1.5

% o

f ca

ses (

4). O

ther

subt

ype

incl

udin

g m

edul

lary

, muc

inou

s, tu

bula

r, an

d sq

uam

ous c

arci

nom

as h

ave

been

repo

rted

in is

olat

ed c

ase

repo

rts w

ith le

ss

freq

uenc

y in

men

com

pare

d to

wom

en. P

aget

's di

seas

e an

d in

flam

mat

ory

carc

inom

a pr

esen

t equ

ally

in m

ales

and

fem

ales

but

hav

e ra

rely

bee

n re

porte

d in

men

(34)

. M

ales

tend

to h

ave

a hi

gher

exp

ress

ion

of h

orm

one

rece

ptor

, spe

cific

ally

90%

of m

ale

brea

st c

ance

rs e

xpre

ss e

stro

gen

rece

ptor

pos

itivi

ty a

nd 8

0%

expr

ess p

roge

ster

one

rece

ptor

pos

itivi

ty (4

). Th

e de

gree

of H

er2-

neu

over

expr

essi

on in

men

is le

ss th

an w

omen

(2–1

5%) a

nd h

as b

een

docu

men

ted

in

(65-

67).

•C

linic

al P

rese

ntat

ion

The

mos

t com

mon

pre

sent

atio

n of

a m

ale

with

bre

ast c

ance

r is a

pai

nles

s pal

pabl

e lu

mp

loca

ted

suba

reol

arly

(1,2

). M

ale

patie

nts a

lso

som

etim

es

pres

ent w

ith o

ther

sym

ptom

s, in

clud

ing

nipp

le p

ain,

ble

edin

g, re

tract

ion,

ulc

erat

ion

or d

isch

arge

(21)

. Lym

phad

enop

athy

may

als

o be

pre

sent

(73)

. G

ynec

omas

tia is

pre

sent

in 6

to 3

8% o

f cas

es o

f mal

e br

east

can

cer (

30).

Mal

e br

east

can

cer t

ypic

ally

affe

cts

the

right

bre

ast w

hich

is si

mila

r to

fem

ales

(1,2

). Th

e po

ssib

ility

of a

con

trala

tera

l bre

ast c

ance

r dev

elop

ing

in m

en is

hig

her t

han

wom

en(3

1), s

peci

fical

ly 3

0 fo

ld p

ossi

bilit

y in

men

(3

2) b

ut th

e ab

solu

te ri

sk is

0.1

% p

er y

ear (

53, 5

4). T

he d

iffer

entia

l dia

gnos

is fo

r mal

e br

east

can

cer i

nclu

des b

reas

t abs

cess

, lip

oma,

gyn

ecom

astia

, m

etas

tase

s to

the

brea

st, a

nd sa

rcom

as (7

4).

Ove

rall,

the

mos

t eff

ectiv

e tre

atm

ent s

houl

d be

targ

eted

tow

ard

the

stag

e of

the

dise

ase,

the

patie

nt's

over

all h

ealth

, the

age

of d

iagn

osis

, the

pr

esen

ce o

f hor

mon

e re

cept

or H

ER2,

and

BR

CA

(71)

. C

urre

nt tr

eatm

ent r

ecom

men

datio

ns a

re n

ot b

ased

on

data

from

clin

ical

stud

ies i

n m

en b

ut

the

mos

t agr

eed

upon

stan

dard

trea

tmen

t in

the

liter

atur

e is

mod

ified

radi

cal m

aste

ctom

y w

ith a

xilla

ry ly

mph

nod

e di

ssec

tion

or se

ntin

el n

ode

lym

ph b

iops

y (S

LNB

). M

ale

patie

nts w

ho p

rese

nt w

ith a

solit

ary

tum

or w

ith n

o m

etas

tasi

s sho

uld

have

a m

odifi

ed ra

dica

l mas

tect

omy

with

ax

illar

y ly

mph

nod

e di

ssec

tion

(3, 3

5).

Sent

inel

lym

ph n

ode

biop

sy c

an b

e do

ne in

pat

ient

s with

a c

linic

ally

neg

ativ

e ax

illa

to a

void

inva

sive

ax

illar

y di

ssec

tion

(40)

. Mal

es w

ho h

ave

DC

IS sh

ould

und

ergo

lum

pect

omy

follo

wed

by

brea

st ir

radi

atio

n (7

1), w

hile

smal

ler i

nvas

ive

tum

ors

can

be tr

eate

d w

ith lu

mpe

ctom

y an

d se

ntin

el n

ode

biop

sy fo

llow

ed b

y ad

juva

nt ra

diat

ion

ther

apy

(71)

. For

loca

lly a

dvan

ced

tum

ors,

loco

re

gion

al ra

diat

ion

to c

hest

wal

l and

lym

ph n

odes

shou

ld b

e do

ne (7

1). O

vera

ll, se

ntin

el n

ode

biop

sy is

one

of t

he m

ost e

ffec

tive

way

s of

as

sess

ing

noda

l inv

olve

men

t (50

-52)

. D

ue to

the

high

pre

vale

nce

of e

stro

gen

rece

ptor

pos

itivi

ty in

mal

e br

east

can

cers

, firs

t lin

e st

anda

rd a

djuv

ant t

hera

py is

tam

oxife

n (8

). Ta

mox

ifen

has s

how

n to

impr

ove

surv

ival

and

recu

rren

ce in

mal

e br

east

can

cer a

ssoc

iate

d w

ith e

stro

gen

rece

ptor

pos

itivi

ty (4

2) a

nd m

en w

ho a

re tr

eate

d w

ith ta

mox

ifen

have

bet

ter p

rogn

osis

and

surv

ival

rate

s(9-

11).

Gos

s et a

l con

duct

ed a

stud

y of

57

patie

nts w

ho h

ad si

gnifi

cant

impr

ovem

ent w

ith

tam

oxife

n (1

2). T

amox

ifen

has b

een

effe

ctiv

e in

trea

ting

met

asta

tic m

ale

brea

st c

ance

r, w

hich

Cut

tie e

t al d

emon

stra

ted

in th

eir s

tudy

of 2

43 n

ode

posi

tive

men

and

saw

can

cer r

ates

redu

ced

from

62%

to 2

8% (2

3 or

45)

. Thi

s is a

lso

cons

iste

nt w

ith o

ther

stud

ies (

89,9

0). T

amox

ifen

com

plia

nce

in m

en h

as b

een

chal

leng

ing

due

to th

e dr

ug n

ot b

eing

tole

rate

d (4

7,48

). Fi

ve y

ears

of a

djuv

ant t

amox

ifen

is re

com

men

ded

for m

en w

ith H

R-

posi

tive

brea

st c

ance

r afte

r mas

tect

omy

is p

erfo

rmed

(75)

. Th

ere

is c

onfli

ctin

g in

form

atio

n in

term

s of w

hen

radi

atio

n sh

ould

be

give

n. M

ale

patie

nts t

ypic

ally

rece

ive

radi

atio

n m

ore

ofte

n th

an fe

mal

es,

due

to m

ore

adva

nced

stag

e w

hen

diag

nose

d (7

6,21

or 4

2). I

ndic

atio

n fo

r rad

iatio

n th

erap

y co

mes

from

the

data

from

fem

ale

brea

st c

ance

rs

whi

ch in

clud

es la

rge

tum

ors,

axill

ary

node

invo

lvem

ent,

and

an a

dvan

ced

tum

or st

age

(45)

. Som

e of

the

mor

e re

cent

lite

ratu

re is

adv

ocat

ing

for a

m

odifi

ed ra

dica

l or s

impl

e m

aste

ctom

y in

add

ition

to ra

diat

ion

ther

apy.

If a

lum

pect

omy

is p

erfo

rmed

, adj

uvan

t rad

iatio

n sh

ould

als

o be

incl

uded

(7

1), i

nclu

ding

che

st w

all r

adia

tion

(24)

. How

ever

, if l

ymph

nod

e or

pec

tora

l mus

cle

inva

sion

is p

rese

nt, r

adio

ther

apy

follo

win

g m

aste

ctom

y sh

ould

be

perf

orm

ed (7

3).

Ther

e is

als

o co

nflic

ting

info

rmat

ion

in te

rms o

f how

radi

atio

n af

fect

s mal

e br

east

can

cer.

One

stud

y sh

ows t

hat p

osto

pera

tive

radi

atio

n pr

even

ts

recu

rren

ce b

ut h

as n

o ef

fect

on

patie

nt su

rviv

al (4

6). A

djuv

ant r

adio

ther

apy

appe

ars t

o be

eff

ectiv

e in

pre

vent

ing

recu

rren

ces i

n m

ale

brea

st

canc

er, b

ut d

iffer

ence

s in

mor

talit

y ha

ve n

ot b

een

iden

tifie

d (7

7-81

). A

djuv

ant r

adio

ther

apy

is a

dvis

ed in

men

with

pos

itive

lym

ph n

odes

or

tum

or >

5 cm

or m

argi

ns p

ositi

ve (8

2).

Som

e of

the

liter

atur

e st

ates

that

adj

uvan

t che

mot

hera

py s

houl

d be

add

ed w

hen

dise

ase

is a

dvan

ced

or th

ere

is a

xilla

ry n

ode

invo

lvem

ent (

71).

Som

e ch

emot

hera

py o

ptio

ns u

sed

incl

ude

CM

F (c

yclo

phos

pham

ide,

met

hotre

xate

, and

fluo

rour

acil)

, FEC

and

EC

(37)

. Thu

s far

, no

curr

ent d

ata

exis

ts o

n th

e us

e of

tras

tuzu

mab

in m

ale

brea

st c

ance

r. A

djuv

ant c

hem

othe

rapy

is re

com

men

ded

in th

e yo

unge

r pat

ient

pop

ulat

ion,

pat

ient

s with

la

rger

tum

ors,

and

patie

nts w

ho h

ave

axill

ary

node

invo

lvem

ent (

71).

To

date

, onl

y on

e pr

ospe

ctiv

e st

udy

of a

djuv

ant c

hem

othe

rapy

has

bee

n pu

blis

hed

in p

atie

nts w

ith m

ale

brea

st c

ance

r (83

). C

hem

othe

rapy

has

bee

n sh

own

in re

trosp

ectiv

e da

ta to

dec

reas

e re

curr

ence

and

impr

ove

mor

talit

y (8

4-86

) and

it h

as b

een

show

n to

incr

ease

bot

h, 5

yea

r and

10

year

sur

viva

l rat

es (8

3, 8

7). M

en w

ith in

term

edia

te o

r hig

h ris

k br

east

ca

ncer

and

hor

mon

e re

cept

or n

egat

ive

tum

ors (

74) o

r pat

ient

s who

bec

ome

refr

acto

ry to

hor

mon

e th

erap

y sh

ould

rece

ive

adju

vant

che

mot

hera

py.

The

best

follo

w u

p is

clin

ical

ass

essm

ent a

nd se

lf-br

east

exa

min

atio

n si

nce

mos

t mal

e br

east

can

cers

pre

sent

with

a p

alpa

ble

mas

s (90

). Yo

u ca

n pl

ace

your

org

aniz

atio

ns lo

gos o

n ei

ther

side

of t

he ti

tle o

f the

pos

ter.

Inse

rt yo

ur te

xt h

ere.

Prog

nosi

s

Mal

e br

east

can

cer,

alth

ough

a ra

re c

ondi

tion

is li

kely

und

er d

iagn

osed

freq

uent

ly.

Der

mat

olog

ists

can

pl

ay a

cru

cial

role

in th

e di

agno

sis o

f thi

s tre

atab

le d

isea

se.

Der

mat

olog

ists

shou

ld in

clud

e br

east

ca

rcin

oma

in th

eir d

iffer

entia

l dia

gnos

es o

f a lu

mp

in th

e br

east

of b

oth

mal

es a

nd fe

mal

es a

like.

Cur

rent

ly

the

liter

atur

e is

lack

ing

in c

linic

al ra

ndom

ized

tria

ls o

n m

ale

brea

st c

ance

r pat

ient

s in

term

s of t

he b

est

treat

men

t and

man

agem

ent a

nd fu

rther

, the

pat

hoph

ysio

logy

of m

ale

brea

st c

ance

r is n

ot c

lear

ly u

nder

stoo

d at

pre

sent

. Man

agem

ent o

f bre

ast c

ance

r may

not

be

sole

ly in

the

hand

s of d

erm

atol

ogis

ts, t

here

fore

we

stre

ss th

e im

porta

nce

of m

aking

the

diag

nosi

s. T

his i

nclu

des s

ampl

ing

with

his

topa

thol

ogy

and

imag

ing

stud

ies a

s a m

eans

to b

ette

r pre

pare

the

patie

nt f

or sp

ecia

lists

in su

rger

y an

d on

colo

gy fo

r def

initi

ve

treat

men

t.

261

prin

ted

by

ww

w.po

ster

sess

ion.

com

Met

achr

onou

s C

lass

ical

Kap

osi S

arco

ma

in a

His

pani

c M

ale

Tang

D. L

e, D

.O1 ;

Alp

esh

Des

ai, D

.O, F

AO

CD

2 ; R

ick

Lin,

D.O

, FA

OC

D3

1.So

uth

Texa

s Der

mat

olog

y R

esid

ent

2.Pr

ogra

m D

irect

or, S

outh

Tex

as D

erm

atol

ogy

Res

iden

cy P

rogr

am

3. A

ttend

ing

Phys

icia

n, O

asis

Der

mat

olog

y G

roup

, PLL

C

“N

odul

es …

brow

n-re

d to

blu

e-re

d in

col

our d

evel

op in

the

skin

with

out a

kno

wn

gene

ral o

r loc

al c

ause

…”

is th

e de

scrip

tion

for “

idio

path

ic m

ultip

le p

igm

ente

d sa

rcom

a of

skin

”1 firs

t de

scrib

ed b

y D

r. M

oritz

K. K

apos

i in

his p

ublic

atio

n in

187

2. T

his

entit

y is

con

side

red

to b

e a

rela

tivel

y ra

re, s

low

-gro

win

g m

alig

nanc

y, m

ost c

omm

only

seen

in p

atie

nts w

ith H

IV a

nd a

lso

in

imm

unoc

ompe

tent

eld

erly

Med

iterr

anea

n an

d Ea

ster

n Eu

rope

an

mal

es a

s Cla

ssic

al K

apos

i sar

com

a. I

n 19

81, D

r. A

lvin

Frie

dman

-K

ein

repo

rted

wha

t eve

ntua

lly p

rove

d to

be

HIV

-ass

ocia

ted

(epi

dem

ic) K

apos

i’s sa

rcom

a2 . It

was

not

unt

il 19

96 th

at C

hang

et

al. d

isco

vere

d hu

man

her

pes v

irus 8

, (H

HV

8),

also

kno

wn

as

Kap

osi s

arco

ma

asso

ciat

ed h

erpe

s viru

s, w

hich

is st

rong

ly

impl

icat

ed in

the

path

ogen

esis

of a

ll ty

pes o

f Kap

osi s

arco

ma3 .

This

mal

igna

nt e

ntity

is n

ow d

ivid

ed c

hron

olog

ical

ly in

to fo

ur

type

s: (1

) mid

dle

aged

and

eld

erly

mal

es o

f Med

iterr

anea

n an

d Ea

ster

n Eu

rope

an li

neag

e pr

esen

ting

with

an

indo

lent

form

; (2)

ch

ildre

n an

d ad

ults

from

equ

ator

ial A

fric

a w

ith fl

orid

and

mor

e ag

gres

sive

form

, firs

t des

crib

ed in

195

0s; (

3) ia

troge

nica

lly

imm

unoc

ompr

omis

ed w

ith tr

ansp

lant

or r

ecei

ving

im

mun

osup

pres

sive

ther

apy,

firs

t des

crib

ed in

197

0s; (

4) H

IV

asso

ciat

ed K

apos

i sar

com

a.

A

lthou

gh th

ere

are

four

form

s of K

apos

i sar

com

a w

ith

diffe

rent

clin

ical

pre

sent

atio

n an

d di

ffere

nt c

ours

es o

f dis

ease

, the

de

rmat

ohis

tolo

gica

l app

eara

nce

in a

ll fo

rms o

f Kap

osis

sarc

oma

is

sim

ilar.

On

mic

rosc

opy,

ther

e ar

e pr

olife

ratio

ns o

f spi

ndle

cel

ls a

nd

of sm

all b

lood

ves

sels

, for

mat

ion

of v

ascu

lar s

lits f

illed

with

er

ythr

ocyt

es, h

emor

rhag

e an

d de

posi

tion

of h

emos

ider

in5 .

H

isto

logi

cal d

iagn

osis

is in

mos

t cas

es c

ompl

eted

by

imm

unoh

isto

chem

ical

test

s suc

h as

HH

V-8

stai

ning

, or

imm

unos

tain

ing

with

ant

ibod

ies a

gain

st e

ndot

helia

l mar

kers

D2-

40, C

D31

and

CD

34.

Tr

eatm

ent m

odal

ities

incl

ude

loca

l and

syst

emic

ther

apy.

Lo

cal t

hera

py in

clud

es si

mpl

e ex

cisi

on, c

ryot

hera

py, l

aser

tre

atm

ent a

nd in

trale

sion

al c

hem

othe

rapy

. Sys

tem

ther

apy

is o

ften

indi

cate

d w

ith se

vere

dis

ease

incl

udin

g in

tern

al in

volv

emen

t, co

mm

only

with

in th

e lu

ngs,

lym

ph n

odes

, and

GI t

ract

and

ge

nera

lly in

volv

es th

e us

e of

dox

orub

icin

or t

axol

. Oth

er tr

eatm

ents

in

clud

e su

bcut

aneo

us in

ject

ions

with

low

-dos

e in

tefe

ron

alfa

, vin

ca

alka

loid

s dru

gs (v

inbl

astin

e an

d vi

ncris

tine)

, act

inom

ycin

D,

adria

myc

in, a

nd d

ecar

bazi

ne. T

his i

s a v

ery

radi

ores

pons

ive

tum

or.

Afte

r the

adm

inis

tratio

n of

radi

othe

rapy

, les

ions

regr

ess a

t var

iabl

e ra

te.

A

54

year

-old

His

pani

c m

ale

pres

ente

d to

clin

ic i

n 20

07 w

ith a

se

vera

l mon

th h

isto

ry o

f a “

bum

p” o

n th

e rig

ht fo

rear

m .

Pat

ient

de

nied

any

oth

er sy

mpt

oms.

The

patie

nt d

enie

d an

y pr

evio

us e

piso

des

or p

revi

ous i

njur

y to

the

site

. He

deni

ed a

per

sona

l or f

amily

his

tory

of

skin

can

cer a

nd p

rese

nted

sole

ly fo

r rem

oval

of t

he le

sion

.

Phys

ical

exa

min

atio

n re

veal

ed a

6m

m p

urpl

e-br

own

nodu

le w

ith

cent

ral u

lcer

atio

n on

the

prox

imal

righ

t for

earm

(Exh

ibit

1).

A sh

ave

biop

sy w

as p

erfo

rmed

. Int

erde

partm

enta

l rev

iew

con

clud

ed th

at th

ere

was

a n

eopl

astic

pro

cess

cha

ract

eriz

ed b

y no

dula

r agg

rega

tes o

f sp

indl

e ce

lls w

ith v

ascu

lar d

iffer

entia

tion.

The

re w

as a

lso

extra

vasa

ted

eryt

hroc

ytes

, sid

erop

hage

s and

pla

sma

cells

. By

imm

unoh

isto

chem

ical

met

hod,

the

mal

igna

nt c

ells

of c

once

rn sh

owed

m

ultif

ocal

stro

ng c

ytop

lasm

ic p

ositi

vely

for C

D34

and

mul

tifoc

al

deco

ratio

n in

a n

ucle

ar p

atte

rn fo

r hum

an h

erpe

sviru

s-8

(Exh

ibit

1).

Mal

igna

nt c

ells

wer

e ne

gativ

e fo

r pan

cyto

kera

tin, C

K-p

an, M

elan

A,

34EB

12, a

nd S

100,

CK

5/6.

The

patie

nt w

as d

iagn

osed

with

Kap

osi s

arco

ma,

nod

ular

type

. H

is H

IV1/

2 EI

A a

ntib

ody

scre

en w

ith re

flex

was

neg

ativ

e.

Abs

trac

t

Cas

e Pr

esen

tatio

n

Dis

cuss

ion

D

urin

g th

e on

e ye

ar fo

llow

-up,

the

pat

ient

com

plai

ned

of a

sim

ilar “

bum

p” o

n hi

s lef

t arm

. Th

e le

sion

was

a 6

-mm

blu

e-re

d, sm

ooth

, nod

ule

on h

is d

ista

l lef

t arm

. A

shav

e bi

opsy

was

pe

rfor

med

. Dia

gnos

is w

as m

ade

hist

olog

ical

ly a

s nod

ular

stag

e, K

apos

i sar

com

a. (

Exhi

bit 2

)

Exhi

bit 1

: Clin

ical

and

der

mat

ohis

tolo

gy o

f ini

tial K

apos

i sar

com

a le

sion

– H

HV-

8 po

sitiv

e

Exhi

bit2

: Clin

ical

and

der

mat

ohis

tolo

gy o

f sec

ond

Kap

osi s

arco

ma

– C

D34

pos

itive

imm

unoh

isto

chem

istry

Th

e pa

tient

com

plai

ned

abou

t a “

pim

ple”

on

the

tip o

f his

nos

e in

201

1. O

n ph

ysic

al

exam

inat

ion,

ther

e w

as a

3-m

m b

row

n-re

d no

dule

with

cen

tral u

lcer

atio

n on

the

right

nos

tril.

A

biop

sy w

as p

erfo

rmed

, and

Kap

osi’s

sarc

oma,

nod

ular

stag

e w

as m

ade.

(Exh

ibit

3)

In

201

2, th

is p

atie

nt p

rese

nted

with

ano

ther

“pi

mpl

e” o

n th

e br

idge

of h

is n

ose

for a

ppea

ring

one

mon

th p

revi

ous.

The

lesi

on w

as a

3-m

m b

row

n-re

d no

dule

with

tela

ngie

ctas

ias.

Clin

ical

di

agno

sis o

f a h

eman

giom

a w

as m

ade.

How

ever

, tis

sue

biop

sy w

as o

btai

ned

due

to th

e pa

tient

’s

hist

ory

and

Kap

osi s

arco

ma,

nod

ular

stag

e, w

as m

ade

by p

atho

logy

lab

with

inte

rdep

artm

ent

revi

ew.

(Exh

ibit

3)

Exhi

bit 3

: Kap

osi s

arco

ma

in 2

011

and

2012

– C

D10

pos

itive

imm

unoh

isto

chem

istry

Th

e pa

tient

und

erw

ent r

adia

tion

ther

apy

with

4-6

MeV

ele

ctro

n be

ams f

or e

ach

epis

ode.

Loc

al fi

eld

radi

othe

rapy

was

del

iver

ed to

th

e tu

mor

with

its m

argi

n of

2-c

m n

orm

al ti

ssue

. The

pat

ient

had

co

mpl

ete

resp

onse

at f

irst r

adia

tion

cour

se.

The

rapy

1. K

apos

i M. I

diop

athi

sche

s mul

tiple

s pi

gmen

tsar

kom

der

Hau

t. Ar

chiv

e fu

r Der

mat

olog

ie u

nd S

yphi

lis 1

872;

4:2

65-7

3 (tr

ansl

ated

CA

19

82;3

2:34

2-7)

. 2.

Ste

rnba

ch G

, Var

on J.

Mor

itz K

apos

i: Id

iopa

thic

Pig

men

ted

Sarc

oma

of th

e Sk

in. T

he J

ourn

al o

f Em

erge

ncy

Med

icin

e 19

95; 1

3:67

1-17

4.

3. C

hang

Y, M

oore

PS.

Kap

osi’s

Sar

com

a (K

S)-a

ssoc

iate

d he

rpes

viru

s and

its r

ole

in K

S. In

fect

Age

nt D

is 1

996;

5:2

15-2

22.

4. R

.A. S

hiel

s. A

his

tory

of K

apos

i’s sa

rcom

a. J

ourn

al o

f the

Roy

al S

ocie

ty o

f Med

icin

e 19

86; 7

9:53

2-53

4.

5. S

afai

B.,

Goo

d R

a. K

apos

i’s S

arco

ma:

a re

view

and

rece

nt d

evel

opm

ents

. Clin

ical

Bul

letin

198

0; 1

0:62

-69.

A 5

4-ye

ar-o

ld i

mm

unoc

ompe

tent

His

pani

c m

ale

pres

ente

d w

ith a

pur

ple

brow

n no

dule

, bio

psy

prov

en to

be

Kap

osi s

arco

ma,

an

d w

as s

ubse

quen

tly d

iagn

osed

with

fou

r ad

ditio

nal

lesi

ons

at

diffe

rent

site

s w

ithin

a f

ive

year

per

iod.

The

firs

t no

dule

was

co

nfirm

ed to

be

Kap

osi

sarc

oma

on th

e pr

oxim

al r

ight

for

earm

in

2007

. Th

e se

cond

bro

wn-

red

nodu

le p

rese

nted

on

the

left

arm

in

2008

and

was

dia

gnos

ed a

s nod

ular

stag

e K

apos

i sar

com

a. T

he th

ird

and

four

th n

odul

ar s

tage

Kap

osi s

arco

ma

lesi

ons

wer

e di

agno

sed

in

2011

and

201

2 re

spec

tivel

y. A

ll fo

ur l

esio

ns w

ere

conf

irmed

by

biop

sies

. T

he p

atie

nt u

nder

wen

t ra

diat

ion

ther

apy

with

com

plet

e re

mis

sion

. B

iops

ies

reve

aled

a

vasc

ular

ne

opla

stic

pr

oces

s ch

arac

teriz

ed b

y bi

zarr

e sh

aped

ves

sels

sur

roun

ding

pre

-exi

stin

g ve

ssel

s lin

ed b

y th

in e

ndot

helia

l cel

ls. I

mm

unos

tain

for H

HV

8 w

as

stro

ngly

pos

itive

with

in th

e sp

indl

e ce

ll nu

clei

. The

CD

10 a

nd S

MA

sh

owed

foc

al p

ositi

ve s

tain

ing.

Ki6

7 ha

d a

high

pro

lifer

atio

n ra

te.

CK

5/6,

CK

-pan

, Mel

an A

, 34E

B12

, and

S10

0 im

mun

osta

ins

wer

e ne

gativ

e. W

hen

pres

entin

g in

im

mun

ocom

pete

nt p

atie

nts,

it is

kn

own

as C

lass

ical

Kap

osi s

arco

ma,

how

ever

, thi

s en

tity

typi

cally

oc

curs

prim

arily

in

elde

rly m

en o

f M

edite

rran

ean

and

East

ern

Euro

pean

dec

ent.

Her

e w

e pr

esen

t th

e ca

se o

f a

mid

dle

aged

, he

tero

sexu

al, H

ispa

nic

mal

e pr

esen

ting

with

met

achr

onou

s K

apos

i sa

rcom

a.

Ref

eren

ces:

262

Carc

inoi

d Tu

mor

s an

d Ca

rcin

oid

Synd

rom

eA

Rev

iew

Fro

m A

Tw

o-Po

int P

ersp

ectiv

e

Katy

Mat

thew

s, D

.O.,

Robi

n Sh

ecte

r, D

.O.,

PBCG

ME/

Der

mat

olog

y, C

olum

bia

Hos

pita

l

Palm

Bea

ch C

entr

e fo

r Gra

duat

e M

edic

al E

duca

tion

Thro

ugh

the

eyes

of a

n in

tern

ist..

..Ca

rcin

oid

tum

ors

are

low

-gra

de m

alig

nant

gas

troi

ntes

tinal

and

pul

mon

ary

neur

oend

ocrin

e tu

mor

s w

hich

con

-ta

in n

euro

secr

etor

y gr

anul

es [1

]. Th

e tu

mor

s ar

e cl

assi

�ed

acco

rdin

g to

site

of o

rigin

, and

the

secr

etor

y pr

od-

ucts

var

y ac

cord

ing

to lo

catio

n [1

]. 1.

For

egut

(eso

phag

us, s

tom

ach,

duo

denu

m, p

ancr

eas,

gallb

ladd

er, b

ronc

hus/

lung

/tra

chea

)= lo

w s

erot

onin

-se

cret

ing;

thus

rare

for c

arci

noid

syn

drom

e to

dev

elop

[1].

2. M

idgu

t (je

junu

m, i

leum

, app

endi

x, m

ecke

l's d

iver

ticul

um, a

scen

ding

/ tra

nsve

rse/

desc

endi

ng c

olon

, liv

er,

ovar

ies,

test

es)=

hig

h se

roto

nin-

secr

etin

g; th

us v

ery

com

mon

ly c

ause

car

cino

id s

yndr

ome,

esp

ecia

lly w

hen

tum

ors

met

asta

size

to li

ver [

1].

3. H

indg

ut (r

ectu

m)=

low

ser

oton

in-s

ecre

ting;

thus

rare

ly c

ause

car

cino

id s

yndr

ome

[1].

INCR

EASE

D #

OF

NEU

ROSE

CRET

ORY

GRA

NU

LES

= IN

CREA

SED

RIS

K O

F CA

RCIN

OID

SYN

DRO

ME

SO W

HAT

EXA

CTL

Y IS

CA

RCIN

OID

SYN

DRO

ME?

FLU

SHIN

G

DIA

RRH

EA

MID

GU

T CA

RCIN

OID

TU

MO

RS

(+)

WH

EEZI

NG

, PEL

LAG

RA, R

IGH

T H

EART

PU

LMO

NIC

STEN

OSI

S, T

R, C

ON

DU

CTI

ON

DEF

ECTS

[1,2

].

Carc

inoi

d tu

mor

s ca

n oc

cur i

n th

e ab

senc

e of

car

cino

id s

yndr

ome,

and

the

mea

n ag

e fo

r tum

ors

is a

ge 6

3 [1

].

The

smal

l int

estin

e, lu

ng, a

nd b

ronc

hus

are

the

mor

e co

mm

on s

ites

curr

ently

, with

the

smal

l int

estin

e (il

eum

) by

far w

inni

ng th

e #1

spo

t [1]

.

DIA

GN

OSI

S:

1. S

ERU

M C

HRO

MO

GRA

NIN

A(A

LSO

SEE

N IN

PH

EO, R

ENA

L IN

SUFF

I-CI

ENCY

, LIV

ER F

AIL

URE

, IBD

, PPI

S [4

,6})

2. U

RIN

ARY

5-H

IAA

3. U

RIN

ARY

5-H

T

4. U

RIN

ARY

5-H

TP(fo

r pat

ient

s w

ith d

opa

deca

rbox

ylas

e de

fect

{1}

5. O

CTR

EOTI

DE

SCIN

TIG

RAPH

Y

INTE

RNA

L SY

MPT

OM

S O

F CA

RCIN

OID

TU

MO

RS:

COU

GH

WH

EEZI

NG

HEM

OPT

YSIS

BRO

NCH

IAL

OBS

TRU

CTI

ON

RECU

RREN

T PN

AA

NTE

RIO

R M

EDIA

STIN

AL

THYM

IC M

ASS

GI B

LEED

ING

HSM

WIT

H N

ORM

AL

LFTS

ABD

OM

INA

L PA

INSB

O

Thro

ugh

the

eyes

of a

der

mat

olog

ist..

.1.

Cla

ssic

car

cino

id �

ush:

rapi

d on

set f

acia

l and

che

st d

eep

eryt

hem

a, fo

llow

ed b

y a

cyan

otic

hue

, som

etim

es

asso

ciat

ed w

ith p

rurit

is/e

dem

a/ la

crim

atio

n/di

arrh

ea. T

his

is s

een

in 1

0% o

f car

cino

id s

yndr

ome

with

live

r m

ets,

but i

s al

so s

een

in m

idgu

t tum

ors

(app

endi

x, s

mal

l int

estin

e, a

nd p

roxi

mal

col

on) [

1,2,

5,6]

.2.

Brig

ht s

alm

on-p

ink

red

�ush

rese

mbl

ing

phys

iolo

gic

�ush

ing:

Thi

s is

see

n in

fore

gut t

umor

s [5

,6].

3. B

right

red

prur

itic

and

patc

hy �

ush

with

whi

te p

atch

es in

term

ixed

on

face

and

nec

k: T

his

is s

een

in g

astr

ic

carc

inoi

d tu

mor

s [1

,2].

4. R

ed-p

urpl

e �u

sh, l

astin

g ho

urs-

days

, ass

ocia

ted

with

sal

ivat

ion/

la

crim

atio

n/di

apho

resi

s/di

arrh

ea/h

ypot

ensi

on: S

een

in b

ronc

hial

car

cino

id tu

mor

s [1

,2].

5. H

indg

ut tu

mor

s ar

e N

OT

usua

lly a

ssoc

iate

d w

ith �

ushi

ng [2

].

DER

MAT

OLO

GIC

MA

NIF

ESTA

TIO

NS:

FLU

SHIN

G H

YPER

HID

ROSI

SPE

LLAG

RASC

LERO

DER

MA

PHO

TOD

ERM

ATO

SIS

ACU

TE-O

NSE

T RO

SACE

A W

ITH

TEL

AN

GEC

TASI

AS

AN

D R

HIN

OPH

YMA

HYP

ERPI

GM

ENTA

TIO

NRA

YNAU

D’S

NF1

MEN

1

TREA

TMEN

T:Fi

rst l

ine

ther

apy

invo

lves

loca

lizat

ion

of tu

mor

and

sur

gica

l res

ectio

n; fo

r non

-met

asta

tic tu

mor

s, su

rger

y is

us

ually

cur

ativ

e[1]

. Pr

e-op

erat

ive

man

agem

ent i

nvol

ves

avoi

ding

pre

cipi

tant

s of

�us

hing

suc

h as

alc

ohol

, sp

icy

food

s, st

ress

, SSR

Is a

nd c

hees

e [1

]. T

here

are

a v

arie

ty o

f "sy

mpt

om re

lievi

ng" m

edic

atio

ns th

at a

re d

i-re

cted

at t

he m

ain

unde

rlyin

g sy

mpt

omat

olog

y lik

e an

ti-di

arrh

ea a

gent

s (lo

pera

mid

e), c

ombi

natio

n H

1 an

d H

2 an

tago

nist

s (d

iphe

nhyd

ram

ine,

cim

etid

ine,

and

rani

tidin

e) a

nd b

ronc

hodi

lato

rs [1

]. S

erot

onin

rece

ptor

an

tago

nist

s (m

ethy

serg

ide,

cyp

rohe

pata

dine

, and

ket

anse

rin) a

re a

lso

occa

sion

ally

use

d [1

]. C

uren

tly, t

he

mos

t com

mon

sys

tem

ic tr

eatm

ent u

tiliz

ed (e

spec

ially

with

the

synd

rom

e) a

re th

e so

mat

osta

tin a

nalo

gues

oc

treo

tide

and

lanr

eotid

e [1

]. If

met

asta

tic d

isea

se is

pre

sent

in th

e liv

er, a

com

bina

tion

of h

epat

ic a

rter

y em

boliz

atio

n (w

ith o

r with

out c

hem

othe

rape

utic

age

nts

5-FU

, adr

iam

ycin

, cis

plat

in, m

itom

ycin

) and

in

terf

eron

-alp

ha is

use

d [1

.]

THE

ROLE

OF

CHRO

MO

GRA

NIN

A IN

FO

RMAT

ION

OF

NEU

ROSE

CRET

ORY

G

RAN

ULE

S N

EJM

200

3; 3

48: F

IGU

RE 4

HA

RRIS

ON

’S P

RIN

CIPL

ES O

F IN

TERN

AL

MED

ICIN

E 16

TH E

DIT

ION

, 20

05; F

IGU

RE 3

29-1

Refe

renc

es

1.Ka

sper

DL,

Har

rison

TR.

Har

rison

's Pr

inci

ples

of I

nter

nal M

edic

ine.

ebo

ok, 1

6th

editi

on, 2

005,

222

0-22

26.

Acce

ssed

via

Nov

a So

uthe

aste

rn U

nive

rsity

libr

arie

s EB

SCO

hos

t on

4/12

/12.

2.Bo

logn

ia JL

, Jor

izzo

JL, R

apin

i RP.

Der

mat

olog

y. 2

nd e

ditio

n; v

olum

es 1

,2. E

lsev

ier 2

008.

3.W

ol�

K, G

olds

mith

LA

, Kat

z SI

, Gilc

hres

t BA

, Pal

ler A

S, L

e�el

l DJ.

Fitz

patr

ick'

s D

erm

atol

ogy

in G

ener

al M

edic

ine.

7th

edi

tion;

vol

umes

1,2

. McG

raw

Hill

200

8.4.

Taup

enot

L, H

arpe

r KL,

O'C

onne

r D. T

he C

hrom

ogra

nin-

Secr

etog

rani

n Fa

mily

. The

New

Eng

land

Jour

nal o

f Med

icin

e 20

03; 3

48: 1

134-

1149

.5.

Bell

HK,

Pos

ton

GJ,

Vora

J, W

ilson

NJE

. Cu

tane

ous

man

ifest

atio

ns o

f the

mal

igna

nt c

arci

noid

syn

drom

e. C

linic

al a

nd la

bora

tory

inve

stig

atio

ns, B

ritis

h Jo

urna

l of D

erm

atol

ogy

2005

; 152

: 71-

75.

6.Ja

bbou

r SA

. Sk

in m

anife

stat

ions

of h

orm

one-

secr

etin

g tu

mor

s. D

erm

atol

ogic

The

rapy

201

0; 2

3: 6

43-6

50.

Ther

e ar

e se

vera

l oth

er n

otew

orth

y cu

tane

ous

man

ifest

atio

ns. A

cute

-ons

et ro

sace

a, in

the

sett

ing

of th

e "3

H's:

HO

T (d

iaph

ores

is),

HTN

, HR

(tac

hyca

rdia

)" (+

) dia

rrhe

a, s

houl

d pr

ompt

one

to in

vest

igat

e fo

r car

cino

id

synd

rom

e [1

,2].

Sero

toni

n, b

eing

a v

asoa

ctiv

e su

bsta

nce,

dire

ctly

con

trib

utes

to th

e ro

sace

a [2

]. It

has

also

bee

n sh

own

that

long

-ter

m re

peat

ed �

ushi

ng c

ause

s ro

sace

a, te

lang

iect

asia

s, �x

ed e

ryth

ema,

and

ear

ly rh

i-no

phym

a [2

,5].

Patie

nts

can

also

dev

elop

scl

erod

erm

a/sc

lero

derm

oid

skin

cha

nges

, but

thes

e pr

edom

inat

ely

a�ec

t the

bila

tera

l low

er e

xtre

miti

es (r

athe

r tha

n up

per e

xtre

miti

es) w

ith a

n ab

senc

e of

rayn

aud'

s ph

e-no

men

on [2

, 5].

Di�

use

hype

rpig

men

tatio

n (d

ue to

MSH

pro

duct

ion

from

tum

or),

hype

rhid

rosi

s, an

d pr

esen

tatio

n as

a p

hoto

aggr

avat

ed d

erm

atos

is c

an a

lso

occu

r [2,

3]. N

euro

�bro

mat

osis

type

1 h

as b

een

asso

ciat

ed

with

duo

dena

l car

cino

ids,

and

up to

12%

of N

F1 p

atie

nts

deve

lop

an u

pper

GI c

arci

noid

tum

or, c

hara

cter

istic

ally

at t

he p

eri-a

mpu

lla [1

,2,7

]. Ra

rely

, pat

ient

s w

ith M

EN1

deve

lop

carc

inoi

d tu

mor

s; s

peci

�cal

ly 8

% o

f M

EN1

patie

nts

deve

lop

bron

chia

l car

cino

ids,

8% th

ymic

car

cino

ids,

and

13-3

0% o

f pat

ient

s w

ith Z

ollin

ger-

Ellis

on S

yndr

ome

and

MEN

1 ha

ve g

astr

ic c

arci

noid

s! [1

,2].

Col

umbi

a H

ospi

tal

Palm

s Wes

t Hos

pita

lSt

. Luc

ie M

edic

al C

ente

rU

nive

rsity

Hos

pita

l &

Med

ical

Cen

ter

PELL

AGRA

DER

MAT

ITIS

DEM

ENTI

A

DIA

RRH

EA

DEA

TH

TRYP

TOPH

AN

NIA

CIN

(VIT

B3)

**C

ERA

MID

ES**

SERO

TON

IN

263

Tem

plat

e pr

ovid

ed b

y: “p

oste

rs4r

esea

rch.

com

”

EPID

EMIO

LOG

Y

•Sw

eet’s

synd

rom

e is

an

unco

mm

on d

isea

se, a

bout

500

repo

rted

case

s •

Wor

ldw

ide

dist

ribut

ion,

slig

htly

hig

her i

ncid

ence

in Ja

pan

•Fe

mal

e: m

ale

ratio

= 4

:1

•Av

erag

e ag

e of

ons

et 3

0-60

yea

rs

•In

fant

s, ch

ildre

n an

d el

derly

may

als

o be

affe

cted

•

Up

to 2

0% m

ay h

ave

an in

tern

al m

alig

nanc

y (n

o se

x pr

efer

ence

in

thes

e ca

ses)

•

Dru

g-in

duce

d sw

eet’s

synd

rom

e is

mor

e co

mm

on in

wom

en (1

) ET

IOLO

GY

AN

D P

ATH

OG

ENES

IS

•Pa

thog

enes

is u

nkno

wn,

thou

ght t

o be

a h

yper

sens

itivi

ty re

actio

n.

•C

an b

e as

soci

ated

with

infe

ctio

ns, a

utoi

mm

une

dise

ases

, IB

D,

mal

igna

ncie

s (e.

g. m

yelo

geno

us le

ukem

ia),

drug

-rea

ctio

ns a

nd

preg

nanc

y, h

owev

er 5

0% o

f cas

es a

re id

iopa

thic

. (1,

2)

•So

me

of th

e dr

ugs t

hat h

ave

foun

d to

be

asso

ciat

ed in

clud

e ab

acav

ir, tr

imet

hopr

im/s

ulfa

met

hoxa

zole

, min

ocyc

line,

tetra

cycl

ine,

Al

l-tra

ns re

tinoi

c ac

id, g

ranu

locy

te c

olon

y-st

imul

atin

g fa

ctor

, le

vono

rges

trel/e

thin

yl e

stra

diol

, and

cel

ecox

ib (3

,4,5

,6).

•O

rigin

ally

swee

t’s sy

ndro

me

was

thou

ght t

o be

an

imm

une

com

plex

va

scul

itis w

ith a

ltere

d ne

utro

phil

func

tion,

how

ever

cur

rent

rese

arch

no

long

er su

ppor

ts th

is.

•A

new

theo

ry is

that

cyt

okin

es su

ch a

s IL-

1, g

ranu

locy

te c

olon

y-st

imul

atin

g fa

ctor

(G-C

SF),

gran

uloc

yte-

mac

roph

age

colo

ny-

stim

ulat

ing

fact

or (G

M-C

SF),

and

IFN

-gam

ma

are

dysr

egul

ated

ei

ther

loca

lly o

r sys

tem

ical

ly. (

1)

•A

50

year

-old

His

pani

c fe

mal

e w

as a

dmitt

ed to

the

hosp

ital w

ith

a ch

ief c

ompl

aint

of a

diff

use

pain

ful r

ash.

•

PMH

: HIV

, Gen

ital H

erpe

s •

Med

s: N

orvi

r, Ep

zico

m, R

eyat

az, B

enad

ryl,

Perc

ocet

, Pep

cid,

C

olac

e an

d C

linda

myc

in

•A

ll: N

iasp

an, P

CN

•

Surg

: Den

tal p

roce

dure

2-3

wee

ks p

rior

•Fa

m: n

onco

ntrib

utor

y •

Soc:

Occ

asio

nal E

TOH

, den

ies d

rug

abus

e, d

enie

s sm

okin

g,

perio

ds re

gula

r •

Hos

pita

l Cou

rse:

The

pat

ient

was

initi

ally

susp

ecte

d to

hav

e di

ssem

inat

ed h

erpe

s zos

ter d

ue to

a v

esic

ular

rash

not

ed b

y th

e

med

ical

team

and

her

imm

unoc

ompr

omis

ed st

atus

. Sh

e w

as

plac

ed o

n is

olat

ion

and

treat

ed w

ith a

cycl

ovir.

•

Upo

n de

rmat

olog

ic c

onsu

ltatio

n, w

e w

ere

able

to e

luci

date

a

rece

nt h

isto

ry o

f a d

enta

l pro

cedu

re fo

r whi

ch sh

e w

as

pres

crib

ed C

linda

myc

in.

In a

dditi

on, s

he c

ompl

aine

d of

feve

rs,

coug

hing

, mya

lgia

and

dia

rrhe

a fo

r one

wee

k pr

ior t

o th

e ra

sh.

She

repo

rts th

at h

er P

MD

susp

ecte

d an

influ

enza

infe

ctio

n,

pres

crib

ed o

selta

miv

ir an

d ad

min

iste

red

the

influ

enza

vac

cine

.

•O

n sk

in e

xam

ther

e w

ere

diffu

se e

ryth

emat

ous,

edem

atou

s, te

nder

pap

ules

and

pla

ques

ove

r her

che

st, b

ack,

abd

omen

, arm

s an

d le

gs.

Som

e le

sion

s had

pse

udov

esic

les a

t the

per

iphe

ry d

ue

to th

e ex

tens

ive

edem

a, e

xpla

inin

g th

e he

rpes

zos

ter d

iffer

entia

l.

(See

Fig

ures

I-II

I)

•La

bora

tory

eva

luat

ion

show

ed a

mild

ly in

crea

sed

WB

C (1

0.9)

, m

ild a

nem

ia, n

orm

al e

lect

roly

tes,

norm

al c

oagu

latio

n pr

ofile

, C

D4

coun

t of 1

90, n

egat

ive

hepa

titis

pan

el, n

onre

activ

e R

PR,

nega

tive

C.d

iff to

xin,

neg

ativ

e bl

ood

cultu

res,

elev

ated

VZV

Ig

G b

ut n

egat

ive

VZV

IgM

.

•U

pon

furth

er q

uest

ioni

ng, t

he p

atie

nt a

dmitt

ed to

a c

hild

hood

ch

icke

n po

x in

fect

ion,

con

sist

ent w

ith th

e V

ZV Ig

G.

The

nega

tive

IgM

pro

vide

d ev

iden

ce a

gain

st th

e di

agno

sis o

f di

ssem

inat

ed h

erpe

s zos

ter.

•

A p

unch

bio

psy

of th

e sk

in w

as o

btai

ned

and

the

path

olog

y w

as

cons

iste

nt w

ith S

wee

t’s sy

ndro

me.

She

was

dis

char

ged

hom

e or

al p

redn

ison

e an

d to

pica

l cor

ticos

tero

id o

intm

ent a

nd th

e co

nditi

on re

solv

ed w

ithin

6 w

eeks

.

AB

STR

AC

T

CA

SE D

ESC

RIP

TIO

N

CO

NC

LU

SIO

N

RE

FER

EN

CE

S

Swee

t’s S

yndr

ome

Mas

quer

adin

g as

Dis

sem

inat

ed H

erpe

s Zos

ter

in a

n H

IV P

ositi

ve P

atie

nt

Cha

riss

e M

cCal

l, D

O, O

GM

E-I

I D

epar

tmen

t of D

erm

atol

ogy,

St.

John

’s E

psic

opal

Hos

pita

l, Fa

r Roc

kaw

ay, N

Y

Pr

ogra

m D

irec

tor:

Mar

vin

Wat

sky,

DO

- A

ssis

tant

Pro

gram

Dir

ecto

r: S

uzan

ne S

irot

a R

ozen

berg

, DO

- D

ME

: Alb

ert S

troj

an, D

O

Logo

H

ere

We

desc

ribe

a pa

tient

with

an

unus

ual

pres

enta

tion

of a

rare

synd

rom

e in

the

setti

ng o

f a

com

plic

ated

med

ical

his

tory

. The

se fa

ctor

s lea

d to

an

initi

al m

isdi

agno

sis a

nd a

del

ay in

ap

prop

riate

trea

tmen

t. T

his c

ase

serv

es to

in

crea

se a

war

enes

s of t

his u

ncom

mon

skin

di

seas

e an

d hi

ghlig

hts t

he n

eed

for p

rom

pt

derm

atol

ogic

con

sulta

tion

in th

e ho

spita

lized

pa

tient

with

an

unus

ual r

ash,

incl

udin

g sk

in

biop

sy if

indi

cate

d.

DIS

CU

SSIO

N

1) JL

Bol

ogni

a, JL

Joriz

zo, R

P R

apin

i. D

erm

atol

ogy.

2nd

Ed.

Spa

in:

Else

vier

, 200

3. p

p 38

0-3.

2)

Rap

ini R

P. P

ract

ical

Der

mat

opat

holo

gy. 1

st E

d. P

hila

delp

hia,

PA

: El

sevi

er In

c, 2

005.

p 1

32.

3) D

el G

iudi

ce P

, Van

denb

os F

, Per

rin C

, Ber

nard

E, M

arq

L,

Del

lam

onic

a P.

Sw

eet’s

synd

rom

e fo

llow

ing

abac

avir

ther

apy.

Jour

nal o

f th

e Am

eric

an A

cade

my

of D

erm

atol

ogy.

200

4;Vo

l 51,

No

3:47

4-47

5.

4) K

han

Dur

ani B

, Jap

pe U

. Dru

g-in

duce

d Sw

eet’s

synd

rom

e in

acn

e ca

used

by

diffe

rent

tetra

cycl

ines

: cas

e re

port

and

revi

ew o

f the

lite

ratu

re.

Br J

Der

mat

ol 2

002;

147:

558-

62.

5) D

enis

e C

. Wal

ker,

MD

, Phi

lip R

. Coh

en, M

D. T

rimet

hopr

im-

sulfa

met

hoxa

zole

-ass

ocia

ted

acut

e fe

brile

neu

troph

ilic

derm

atos

is: C

ase

repo

rt an

d re

view

of d

rug-

indu

ced

Swee

t's sy

ndro

me.

Jour

nal o

f the

A

mer

ican

Aca

dem

y of

Der

mat

olog

y. 1

996;

Vol 3

4,N

o 5,

Part

2:91

8-92

3.

6) K

enne

th H

. Fye

, MD

, Eile

en C

row

ley,

MD

, PhD

, Tim

othy

G. B

erge

r, M

D, P

hilip

E. L

eBoi

t, M

D, M

. Kar

i Con

nolly

, MD

. Cel

ecox

ib-in

duce

d Sw

eet’s

synd

rom

e. J

Am

Aca

d D

erm

atol

200

1;45

:300

-2.

7) W

olff

K, J

ohns

on R

A. F

itzpa

trick

’s C

olor

Atla

s & S

ynop

sis o

f Clin

ical

D

erm

atol

ogy.

6th

Ed.

The

McG

raw

-Hill

Com

pani

es, 2

009.

pp

160-

162.

Sw

eet’s

synd

rom

e, a

lso

know

n as

acu

te fe

brile

neu

troph

ilic

derm

atos

is,

has a

n un

know

n pa

thog

enes

is.

It is

ofte

n id

iopa

thic

but

has

bee

n re

porte

d in

ass

ocia

tion

with

acu

te u

pper

resp

irato

ry in

fect

ion,

gas

troin

test

inal

in

fect

ion,

HIV

, vac

cina

tions

, med

icat

ions

, aut

oim

mun

e di

seas

es a

nd

mal

igna

ncie

s. O

ur c

ase

is in

tere

stin

g in

that

man

y of

thes

e et

iolo

gic

fact

ors w

ere

pres

ent i

mm

edia

tely

pre

cedi

ng h

er ra

sh. T

he e

xact

cau

se o

f he

r eru

ptio

n is

unk

now

n an

d m

ay h

ave

been

bro

ught

on

by th

e H

IV

infe

ctio

n, re

cent

flu-

like

illne

ss, i

nflu

enza

vac

cine

, rec

ent d

enta

l inf

ectio

n,

the

antib

iotic

s use

d to

trea

t the

den

tal i

nfec

tion

or a

com

bina

tion

of

fact

ors.

Ther

e is

a n

eed

for m

ore

rese

arch

on

the

mec

hani

sm o

f thi

s di

seas

e. T

he tw

o th

eorie

s tha

t are

cur

rent

ly b

eing

stud

ied

are

hype

rsen

sitiv

ity re

actio

n an

d dy

sreg

ulat

ion

of c

ytok

ine

secr

etio

n. T

he

pseu

dove

sicu

lar f

eatu

res o

f the

pat

ient

’s le

sion

s are

als

o a

rare

pr

esen

tatio

n, a

nd le

ad to

the

initi

al m

isdi

agno

sis a

s a d

isse

min

ated

her

pes

zost

er in

fect

ion.

Thi

s del

ay o

f acc

urat

e di

agno

sis a

nd tr

eatm

ent r

einf

orce

s th

e ne

ed fo

r ear

ly d

erm

atol

ogic

con

sulta

tion

in th

e in

patie

nt se

tting

. T

he

case

als

o re

min

ds u

s tha

t the

re sh

ould

be

a ve

ry lo

w th

resh

old

for s

kin

biop

sy, a

s it i

s min

imal

ly in

vasi

ve a

nd o

ften

inva

luab

le in

mak

ing

the

corr

ect d

iagn

osis

.

Figu

re II

I

CLI

NIC

AL

FEAT

UR

ES

•R

apid

ons

et o

f pai

nful

, brig

ht re

d, sm

ooth

, ten

der p

apul

es (2

-4m

m

in d

iam

eter

) tha

t coa

lesc

e to

form

irre

gula

r, sh

arpl

y bo

rder

ed,

edem

atou

s pla

ques

. •

The

bord

er o

f the

pla

que

may

look

as i

f com

pose

d of

ves

icle

s, m

imic

king

dis

sem

inat

ed z

oste

r inf

ectio

n as

in o

ur c

ase.

How

ever

pa

lpat

ion

reve

als t

hat t

he le

sion

s are

solid

, als

o kn

own

as

pseu

dove

sicu

latio

n, in

whi

ch in

tens

e ed

ema

give

s the

app

eara

nce

of

vesi

cula

tion.

•

Lesi

ons m

ost c

omm

only

pre

sent

on

face

, nec

k an

d up

per e

xtre

miti

es

but a

lso

on lo

wer

ext

rem

ities

whe

re le

sion

s may

be

deep

in th

e fa

t an

d m

imic

pan

nicu

litis

or e

ryth

ema

nodo

sum

. •

As t

he le

sion

s evo

lve,

cen

tral c

lear

ing

may

lead

to a

rcua

te o

r an

nula

r pat

tern

s. Ti

ny, s

uper

ficia

l pus

tule

s may

occ

ur.

•If

ass

ocia

ted

with

leuk

emia

, bul

lous

lesi

ons m

ay o

ccur

and

lesi

ons

may

mim

ic p

yode

rma

gang

reno

sum

. •

May

be

acco

mpa

nied

by

feve

r, ar

thra

lgia

and

per

iphe

ral

leuk

ocyt

osis

. (1,

7)

•D

iagn

osis

is m

ade

afte

r exc

ludi

ng in

fect

ion

in th

e sk

in le

sion

s with

sp

ecia

l sta

ins a

nd c

ultu

res.

(2)

DIA

GN

OST

IC C

RIT

ERIA

M

ajor

•

Sudd

en o

nset

of p

laqu

es, o

r ery

them

atou

s to

viol

aceo

us a

nd p

ainf

ul

nodu

les

•D

erm

al n

eutro

phili

c in

filtra

te w

ithou

t leu

kocy

tocl

astic

vas

culit

is

Min

or

•Pr

eced

ing

infe

ctio

n, v

acci

natio

n, in

flam

mat

ion

(or)

ass

ocia

ted

with

in

flam

mat

ion,

hem

opro

lifer

ativ

e di

sord

er, s

olid

tum

or o

r pre

gnan

cy

•Fe

ver a

bove

38

degr

ees C

elsi

us

•Le

ukoc

ytos

is w

ith n

eutro

phili

a, in

crea

sed

CR

P an

d ES

R

•Ex

celle

nt re

spon

se to

syst

emic

cor

ticos

tero

ids (

1)

HIS

TOPA

THO

LOG

Y (S

ee F

igur

e IV

) •

Epid

erm

al c

hang

es v

aria

ble,

som

etim

es e

pide

rmal

nec

rosi

s •

Supe

rfic

ial d

erm

al e

dem

a •

Diff

use

derm

al n

eutro

phils

, but

als

o ly

mph

ocyt

es, h

istio

cyte

s and

a

few

eos

inop

hils

•

No

true

vasc

uliti

s (no

ves

sel w

all n

ecro

sis)

•

Som

etim

es e

xtra

vasa

ted

eryt

hroc

ytes

(2)

PRO

GN

OSI

S A

ND

TR

EATM

ENT

•Sw

eet’s

synd

rom

e is

a b

enig

n co

nditi

on w

hich

, if l

eft u

ntre

ated

, may

pe

rsis

t for

wee

ks to

mon

ths.

•

Cut

aneo

us le

sion

s inv

olut

e sp

onta

neou

sly,

leav

ing

no sc

ars.

•

Rec

urre

nces

occ

ur in

app

roxi

mat

ely

30%

of p

atie

nts,

and

occu

r m

ore

ofte

n in

thos

e w

ith h

emat

olog

ic d

isor

ders

. •

The

mos

t effe

ctiv

e th

erap

y fo

r Sw

eet’s

Syn

drom

e is

ora

l pre

dnis

one

(0.5

-1m

g/kg

/day

) for

4-6

wee

ks. T

here

is p

rom

pt re

lief o

f cut

aneo

us

and

extra

cuta

neou

s man

ifest

atio

ns. I

n so

me

patie

nts,

prol

onge

d lo

w

dose

pre

dnis

one

for a

n ad

ditio

nal 2

-3 m

onth

s may

be

nece

ssar

y to

su

ppre

ss re

curr

ence

s. (1

) •

Whe

n th

e le

sion

s are

few

and

loca

lized

, top

ical

supe

rpot

ent o

r in

trale

sion

al c

ortic

oste

roid

s and

/or t

opic

al c

alci

neur

in in

hibi

tors

m

ay h

elp.

•

Maj

or a

ltern

ativ

e st

eroi

d-sp

arin

g dr

ugs a

re p

otas

sium

iodi

de,

daps

one

and

colc

hici

ne. N

on-s

tero

idal

ant

i-inf

lam

mat

ory

(e.g

. in

dom

etha

cin,

nap

roxe

n, su

linda

c) c

lofa

zim

ine,

cyc

losp

orin

e,

thal

idom

ide

and

inte

rfer

on-a

lpha

hav

e al

so b

een

repo

rted

to le

ad to

im

prov

emen

t of S

wee

t’s sy

ndro

me.

(1)

Figu

re II

Figu

re IV

264

Car

cin

oma

Ery

sipe

loid

esM

orga

n M

cCar

ty D

O, J

enn

y C

otto

n P

hD

, MD

, An

n L

aFon

d M

D

St. J

osep

h M

ercy

Hos

pita

l •

Ann

Arb

or, M

ichi

gan

REM

AR

KA

BLE

MED

ICIN

E. R

EMA

RK

AB

LE C

AR

E.

Phy

sica

lE

xam

inat

ion

The

re i

s a

shar

ply

mar

ked

bord

er o

f ery

them

a ov

erly

-in

g th

e en

tire

rig

ht b

reas

t in

to t

he t

ail

of S

penc

er

and

exte

ndin

g to

th

e po

ster

ior

shou

lder

(Fi

gure

1,

2). T

here

was

slig

ht d

is-

com

fort

of

the

brea

st o

n ex

amin

atio

n. T

he s

urgi

cal

scar

s w

ere

wel

l hea

led.

No

lym

phad

enop

athy

, m

ass,

crus

t, ex

udat

e,

vesi

cles

, no

r bu

llae

wer

e ap

prec

i-at

ed.

Der

mat

opat

holo

gyT

he p

unch

bio

psy

of t

he

back

re

veal

ed

neop

las-

tic

cells

ide

ntifi

ed w

ithi

n de

rmal

lym

phat

ic v

esse

ls

cons

iste

nt w

ith

met

asta

t-ic

bre

ast

carc

inom

a (F

ig-

ure

3).

Rep

eat

horm

onal

m

arke

rs r

evea

led

posi

tive

pr

oges

tero

ne m

arke

rs.

Dia

gnos

isC

arci

nom

a Er

ysip

eloi

des

Tabl

e 1.

Cut

aneo

us M

etas

tatic

Bre

ast C

arci

nom

a su

btyp

es c

linic

al fe

atur

es a

nd d

erm

atop

atho

logy

1,3,

6,7,

8

His

tory

A 7

8-ye

ar-o

ld C

auca

sian

fem

ale

pres

ente

d to

her

pla

stic

surg

eon

for

prog

ress

ive

eryt

hem

a, t

ende

rnes

s an

d pr

urit

us o

f he

r ri

ght

brea

st s

even

mon

ths

afte

r br

east

rec

onst

ruct

ion.

The

pat

ient

ha

d a

past

med

ical

his

tory

of

inva

sive

duc

tal

carc

inom

a w

ith

estr

ogen

, pr

oges

tero

ne,

HER

-2/n

eu n

egat

ive

mar

kers

. Tw

o of

th

e th

ree

righ

t axi

llary

lym

ph n

odes

wer

e po

siti

ve fo

r met

asta

sis.

The

pat

ient

und

erw

ent

chem

othe

rapy

wit

h cy

clop

hosp

ham

ide,

do

xoru

bici

n, a

nd 5

-fluo

rour

acil

in a

ddit

ion

to s

urge

ry. I

n M

arch

20

11, t

he p

atie

nt h

ad a

tis

sue

expa

nder

pla

ced

for

futu

re b

reas

t re

cons

truc

tion

. She

had

no

hist

ory

of fe

ver,

chill

s, di

scha

rge,

nor

ul

cera

tion

. The

are

a w

as c

ultu

re n

egat

ive.

She

was

giv

en a

mox

-ic

illin

-cla

vula

nate

, ce

phal

exin

, ci

profl

oxac

in,

and

clin

dam

ycin

ov

er t

wo

mon

ths

wit

h no

impr

ovem

ent.

The

pat

ient

was

tak

en

to t

he o

pera

ting

roo

m t

o cu

ltur

e th

e im

plan

t m

atri

x an

d su

r-ro

undi

ng fl

uid

whi

ch w

ere

nega

tive

. T

he p

atie

nt w

as s

een

by

derm

atol

ogy

and

a bi

opsy

of

the

invo

lved

ski

n of

the

bac

k w

as

obta

ined

.

Ref

eren

ces

1. R

Sch

war

tz. C

utan

eous

met

asta

tic

dise

ase.

J A

m A

cad

Der

mat

ol. 1

995

Aug

;33(

2 Pt

1):

161-

82; q

uiz 1

83-6

.2.

Loo

king

bill,

D. P

., N

. Spa

ngle

r, et

al.

Cut

aneo

us m

etas

tase

s in

pati

ents

wit

h m

etas

tati

c ca

rcin

oma:

a re

tros

pect

ive

stud

y of

402

0 pa

tien

ts. 1

993

J Am

Aca

d

Der

mat

ol 2

9(2

Pt 1

): 2

28-2

36.

3. V

De

Gio

rgi,

M G

razz

ini,

B A

lfaio

li, e

t al.

Cut

aneo

us m

anife

stat

ions

of b

reas

t car

cino

ma.

Der

mat

ol T

her.

2010

Nov

-Dec

;23(

6):5

81-9

.4.

B A

bdul

lGaf

far ,

A A

lmua

lla, F

Al-

Mar

zooq

i. Po

st-m

aste

ctom

y br

east

rash

. Car

cino

ma

erys

ipel

atoi

des.

Int J

Der

mat

ol. 2

010

Aug

;49(

8):8

55-7

.5.

L L

ever

, P H

olt.

Car

cino

ma

erys

ipel

atoi

des.

Br J

Der

mat

ol. 1

991

Mar

;124

(3):

279-

82.

6. B

Tan

, J M

arsd

en, D

San

ders

: Mel

anom

a er

ysip

eloi

des:

infla

mm

ator

y m

etas

tati

c m

elan

oma

of th

e sk

in, T

he B

riti

sh jo

urna

l of d

erm

atol

ogy

1993

, 129

:327

-329

.7.

Tom

asin

i, C

., E.

Sor

o, e

t al.

(200

2). E

yelid

swel

ling:

thin

k of

met

asta

sis o

f his

tioc

ytoi

d br

east

car

cino

ma.

Der

mat

olog

y 20

5(1)

: 63-

66.

8. 8

. Soy

er, H

. P.,

L. C

erro

ni, e

t al.

(199

0). C

low

n no

se--

skin

met

asta

sis o

f bre

ast c

ance

r. Z

Hau

tkr 6

5(10

): 9

29-9

31.

Dis

cuss

ion

Cut

aneo

us m

etas

tase

s oc

cur

in 0

.7-0

.9%

of

all

canc

er t

ypes

. A

ret

rosp

ecti

ve a

naly

sis

of 4

020

pati

ents

, bo

th m

ale

and

fem

ale,

exa

min

ed c

utan

eous

met

asta

sis

of w

hich

23.

9% w

ere

brea

st

carc

inom

a in

ori

gin.

The

refo

re,

emph

asis

of

com

mon

cut

aneo

us m

etas

tati

c pa

tter

ns a

re r

ele-

vant

to

the

clin

icia

n.1,

2 Fi

rst

desc

ribe

d by

Hut

chin

son

in 1

893,

car

cino

ma

erys

ipel

oide

s (C

E) o

r in

flam

mat

ory

carc

inom

a, r

epre

sent

s 1-

2% o

f cut

aneo

us b

reas

t ca

rcin

oma

met

asta

ses.1 S

kin

met

as-

tase

s m

ay b

e th

e fir

st i

ndic

ator

of

brea

st c

ance

r re

curr

ence

. Dia

gnos

is o

f C

E is

a p

oor

prog

nost

ic

indi

cato

r an

d su

rger

y is

not

adv

ised

. CE

is r

esis

tant

to

radi

atio

n th

erap

y bu

t m

ay b

e re

spon

sive

to

chem

othe

rapy

or

horm

one

ther

apy.

3 CE

is a

lmos

t ex

clus

ivel

y as

soci

ated

wit

h in

vasi

ve d

ucta

l car

-ci

nom

a bu

t ha

s be

en d

ocum

ente

d in

met

asta

tic

mel

anom

a, lu

ng, c

olon

, ute

rine

, ova

rian

, gas

tric

, to

nsill

ar,

rect

al,

paro

tid

glan

d an

d pa

ncre

atic

can

cers

. 3,

4,5,

6 T

he m

ain

diffe

rent

ial

diag

nose

s fo

r C

E ar

e er

ythe

ma

annu

lare

cen

trifu

gum

(EA

C)

and

reti

cula

r er

ythe

mat

ous

muc

inos

is (

REM

).

How

ever

, cas

es o

f bre

ast c

arci

nom

a in

con

junc

tion

wit

h R

EM a

nd E

AC

hav

e be

en re

port

ed.1,

4

Num

erou

s cl

inic

al v

aria

nts

of c

utan

eous

bre

ast

carc

inom

a ex

ist

incl

udin

g: t

elan

giec

tati

c ca

rci-

nom

a, n

odul

ar c

arci

nom

a, c

arci

nom

a en

cui

rass

e, z

oste

rifo

rm m

etas

tasi

s, cl

own

nose

, al

ope-

cia

neop

last

ica,

bre

ast

carc

inom

a of

the

inf

ram

amm

ary

crea

se,

and

met

asta

tic

mam

mar

y ca

rci-

nom

a of

the

eye

lid w

ith

hist

iocy

toid

his

tolo

gy (

Tabl

e 1)

.1 D

ue t

o th

e hi

gh i

ncid

ence

of

brea

st

carc

inom

a in

the

fem

ale

popu

lati

on c

utan

eous

met

asta

sis

of b

reas

t ca

rcin

oma

is m

ore

likel

y to

be

enco

unte

red

by th

e cl

inic

ian.

. Em

phas

is is

pla

ced

upon

pra

ctit

ione

rs to

reco

gniz

e th

ese

clin

ical

sign

s ea

rly

and

to re

peat

hor

mon

al m

arke

rs fo

r opt

imal

out

com

e an

d m

anag

emen

t of t

hese

pat

ient

s.Fi

g. 1

Fig.

2 Fig.

3.

Tela

ngie

ctat

icum

C

arci

nom

a

Nod

ular

C

arci

nom

a

Car

cino

ma

En C

uira

sse

Car

cino

ma

Er

ysip

eloi

des

Zost

erifo

rm

met

asta

sis

Sim

ilar t

o ly

mph

angi

oma

ci

rcum

scrip

tum

but

vio

lace

ous

clin

ical

ly m

ay fo

llow

sur

gica

l in

cisi

on li

ne; h

isto

path

olog

y of

co

nges

ted

vasc

ulat

ure

w

ith tu

mor

cel

ls

Nod

ules

whi

ch m

ay b

e

num

erou

s or

sol

itary

Beg

in w

ith n

odul

es a

nd th

en

diffu

se in

dura

tion

of th

e sk

in;

hist

opat

holo

gy o

f fibr

osis

with

tu

mor

cel

ls re

sem

blin

g fib

ro-

blas

ts li

ning

up

in s

ingl

e fil

e

No

syst

emic

sym

ptom

s

desp

ite e

ryth

ema;

tum

or

cells

with

in d

ilate

d ly

mph

atic

ve

ssel

s no

infla

mm

ator

y

infil

trate

.

Varia

tions

in p

rese

ntat

ion:

ve

sicu

lar,

nodu

lar,

papu

lar;

neop

last

ic c

ells

in e

pide

rmis

w

ith s

ubep

ider

mal

ves

icle

s

Met

asta

tic

mam

mar

y

carc

inom

a

of th

e ey

elid

Page

t’s D

isea

se

Alo

peci

a

neop

last

ica

Bre

ast c

arci

nom

a of

th

e in

fram

amm

ary

crea

se

Clo

wn

nose

Rar

e on

ly 1

% o

f cut

aneo

us m

e-ta

stas

is b

ut h

alf o

f cas

e as

soci

-at

ed w

ith b

reas

t can

cer;

eyel

id

swel

ling

or n

odul

e; h

istio

cytic

in

filtra

te w

ith tu

mor

cel

ls in

an

Indi

an fi

le p

atte

rn

May

occ

ur w

ith n

odul

ar o

r en

cuira

sse

type

s; p

aget

oid

spre

ad

in th

e ep

ider

mis

84%

of c

ases

ass

ocia

ted

with

br

east

can

cer h

emat

ogen

ous

spre

ad to

the

scal

p w

ith s

moo

th

plaq

ues;

his

topa

thol

ogy

of fi

bro-

sis

and

sing

le fi

le tu

mor

cel

ls.

Mim

ics

inte

rtrig

o or

BC

C

Ery

them

atou

s na

sal t

ip n

odul

e

265

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ICK

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IS S

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plat

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sion

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new

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skill

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elow

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list

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ly a

sked

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peci

fic

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his

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e.

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ou a

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n of

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erPo

int

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ate

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plat

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ste

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m a

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eboo

k pa

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to P

oste

rPre

sent

atio

ns.c

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lick

on t

he F

B ic

on.

Met

asta

tic a

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cally

adv

ance

d ba

sal c

ell c

arci

nom

a ha

ve tr

aditi

onal

ly

been

ext

rem

ely

diffi

cult

to tr

eat.

Tho

se c

ases

that

are

resi

stan

t to

treat

men

t or

thos

e pa

tient

s who

are

not

can

dida

tes

for s

urge

ry o

r rad

iatio

n m

ay

sign

ifica

ntly

ben

efit

from

vis

mod

egib

, a n

ewly

app

rove

d dr

ug th

at in

hibi

ts

the

Hed

geho

g pa

thw

ay.

We

repo

rt a

case

of a

n el

derly

gen

tlem

an w

ith

recu

rren

t loc

ally

inva

sive

bas

al c

ell c

arci

nom

a w

ho d

emon

stra

ted

favo

rabl

e re

sults

follo

win

g 2

mon

ths

of tr

eatm

ent w

ith v

ism

odeg

ib.

INTR

ODU

CTIO

N

CASE

Vis

mod

egib

, app

rove

d in

Janu

ary

2012

, is s

peci

fical

ly in

dica

ted

for

“adu

lts w

ith m

etas

tatic

bas

al c

ell c

arci

nom

a, o

r with

loca

lly a

dvan

ced

basa

l cel

l car

cino

ma

that

has

recu

rred

follo

win

g su

rger

y or

who

are

not

ca

ndid

ates

for s

urge

ry, a

nd w

ho a

re n

ot c

andi

date

s for

radi

atio

n.”1

Vis

mod

egib

exe

rts it

s act

ion

by a

ffect

ing

the

Hed

geho

g pa

thw

ay.

In th

e pr

esen

ce o

f son

ic h

edge

hog

ligan

d, th

e PT

CH

gen

e’s n

orm

al in

hibi

tion

of

smoo

then

ed, a

tran

smem

bran

e re

cept

or p

rote

in in

volv

ed in

sign

al

trans

duct

ion,

is d

eact

ivat

ed.

The

subs

eque

nt a

ctiv

atio

n of

smoo

then

ed

stim

ulat

es G

LI1

expr

essi

on c

ontro

lling

the

trans

crip

tion

of h

edge

hog

targ

et

gene

s.2 A

wel

l kno

wn

caus

e of

spor

adic

as w

ell a

s her

edita

ry b

asal

cel

l ca

rcin

omas

is a

mut

atio

n in

the

PTC

H g

ene,

thus

allo

win

g fo

r con

tinue

d ac

tivat

ion

of sm

ooth

ened

.3 V

ism

odeg

ib in

hibi

ts th

e H

edge

hog

path

way

by

bind

ing

to a

nd in

hibi

ting

smoo

then

ed.

The

pha

se I

trial

incl

uded

68

patie

nts,

33 o

f the

m w

ith a

dvan

ced

basa

l ce

ll ca

rcin

oma

and

the

rem

aini

ng 3

5 pa

tient

s with

var

ious

oth

er ty

pes o

f so

lid c

ance

rous

tum

ors.

Pha

rmac

odyn

amic

ass

essm

ent w

as m

easu

red

by

GLI

1 ex

pres

sion

. A

dditi

onal

ly, p

harm

acok

inet

ic, d

osin

g, a

nd sa

fety

in

form

atio

n w

ere

also

gat

here

d. A

t lea

st 5

8% o

f the

BC

C p

atie

nts h

ad

parti

al o

r com

plet

e re

spon

se a

s ass

esse

d by

phy

sica

l exa

min

atio

n, a

nd a

t th

e tim

e of

the

stud

y, th

e m

ean

dura

tion

of tr

eatm

ent w

as 1

2.8

mon

ths.

V

ism

odeg

ib w

as g

ener

ally

wel

l-tol

erat

ed.

Adv

erse

eve

nts m

ore

com

mon

ly

repo

rted

incl

uded

mus

cle

spas

m, d

ysge

usia

, fat

igue

, alo

peci

a, a

nd n

ause

a.4

The

opt

imal

dos

ing

sche

dule

of v

ism

odeg

ib w

as d

eter

min

ed to

be

150m

g da

ily.

This

sche

dule

was

com

pare

d to

wee

kly

dosi

ng a

nd th

ree

dose

s per

wee

k, a

ll af

ter a

load

ing

perio

d of

11

days

with

dai

ly d

osin

g, fo

r a

tota

l of 5

7 da

ys.

Patie

nts w

ere

stra

tifie

d ac

cord

ing

to a

lpha

1-a

cid

glyc

opro

tein

leve

ls, a

s the

se le

vels

wer

e no

ted

to h

ave

corr

espo

ndin

g flu

ctua

tions

to d

rug

conc

entra

ion,

and

tota

l and

unb

ound

pla

sma

leve

ls o

f th

e dr

ug w

ere

mea

sure

d. A

new

vis

mod

egib

con

cent

ratio

n st

eady

stat

e w

as

reac

hed

in th

e Q

W a

nd T

IW d

osin

g gr

oups

afte

r 29

days

, and

by

day

57,

the

stea

dy-s

tate

con

cent

ratio

n ha

d de

crea

sed

by a

t lea

st 2

4% a

nd 4

6% fo

r th

e Q

W a

nd T

IW g

roup

s, re

spec

tivel

y.5

Thus

, dai

ly d

osin

g w

as

dete

rmin

ed to

be

mos

t effe

ctiv

e w

hile

als

o m

aint

aini

ng a

tole

rabl

e si

e ef

fect

pro

file.

Tan

g et

al.

perf

orm

ed a

rand

omiz

ed, d

oubl

e-bl

ind,

pla

cebo

-con

trolle

d tri

al w

hich

stud

ied

the

effe

ctiv

enes

s of

vis

mod

egib

in p

atie

nts a

ffect

ed b

y G

orlin

Syn

drom

e (b

asal

cel

l nev

us sy

ndro

me)

- a

cond

ition

mar

ked

by a

de

fect

in th

e PT

CH

1 ge

ne.

This

mut

atio

n m

ay c

ause

a p

atie

nt to

dev

elop

hu

ndre

ds o

r eve

n th

ousa

nds o

f bas

al c

ell c

arci

nom

as, a

mon

g ot

her c

linic

al

feat

ures

. Th

is st

udy

prim

arily

exa

min

ed th

e ra

te o

f app

eara

nce

of n

ew

basa

l cel

l car

cino

mas

elig

ible

for s

urgi

cal r

esec

tion

in 4

1 pa

tient

s. R

esul

ts

indi

cate

d a

sign

ifica

nt d

ecre

ase

in th

is ra

te w

ith v

ism

odeg

ib tr

eatm

ent w

ith

a m

ean

per-p

atie

nt ra

te o

f 2 v

s. 29

new

surg

ical

ly e

ligib

le b

asal

cel

l ca

rcin

omas

per

yea

r in

the

vism

odeg

ib a

nd p

lace

bo g

roup

s, re

spec

tivel

y.

Add

ition

ally

, the

size

of e

xist

ing

surg

ical

ly e

ligib

le b

asal

cel

l car

cino

mas

w

as si

gnifi

cant

ly re

duce

d in

the

vism

odeg

ib g

roup

(-65

% v

s. -1

1% in

the

plac

ebo

grou

p as

per

cent

cha

nge

from

bas

elin

e in

the

sum

of t

he lo

nges

t di

amet

ers)

.6

DISC

USS

ION

CO

NCL

USI

ON

V

ism

odeg

ib h

as p

rove

n to

be

safe

and

effe

ctiv

e in

the

clin

ical

setti

ng

for t

reat

ing

met

asta

tic a

nd a

dvan

ced

basa

l cel

l car

cino

ma.

Our

pat

ient

has

ha

d si

mila

r res

ults

and

effe

cts

as th

e cl

inic

al tr

ial s

ubje

cts,

and,

pen

ding

co

ntin

ued

effic

acy,

we

hope

to e

vent

ually

shi

ft fo

cus f

rom

tum

or c

lear

ance

to

reco

nstru

ctio

n ef

forts

. W

e lo

ok fo

rwar

d to

futu

re re

ports

of s

ucce

ss w

ith

this

med

icat

ion,

as w

ell a

s lon

g-te

rm tr

eatm

ent d

ata.

REFE

REN

CES

1 Sou

th S

an F

ranc

isco

, CA

: Gen

etec

h U

SA, I

nc, A

mem

ber o

f the

Roc

he

Gro

up; 2

012.

Vis

mod

egib

[pac

kage

inse

rt]

2 Kas

per M

, Sch

nida

r H, N

eill

GW

, Han

nede

r M, K

lingl

er S

, Bla

as L

, Sc

hmid

C, H

ause

r-Kro

nber

ger C

, Reg

l G, P

hilp

ott M

P, A

berg

er F

. Se

lect

ive

mod

ulat

ion

of H

edge

hog/

GLI

targ

et g

ene

expr

essi

on b

y ep

ider

mal

gro

wth

fact

or s

igna

ling

in h

uman

ker

atin

ocyt

es. M

ol C

ell B

iol.

2006

;26(

16):6

283-

6298

. 3 B

ale A

E, Y

u K

P. T

he h

edge

hog

path

way

and

bas

al c

ell c

arci

nom

as. H

um

Mol

Gen

et. 2

001

Apr

;10(

7):7

57-6

2.

4 LoR

usso

PM

, Rud

in C

M, R

eddy

JC, T

ibes

R, W

eiss

GJ,

Bor

ad M

J, H

ann

CL,

Bra

hmer

JR

, C

hang

I, D

arbo

nne

WC

, Gra

ham

RA

, Zer

ivitz

KL,

Low

JA

, Von

Hof

f DD

. Pha

se I

Tria

l of H

edge

hog

Path

way

Inhi

bito

r V

ism

odeg

ib (G

DC

-044

9) in

Pat

ient

s with

Ref

ract

ory,

Loc

ally

Adv

ance

d or

M

etas

tatic

Sol

id T

umor

s. C

lin C

ance

r Res

. 201

1;17

(8):2

502-

2511

. 5 L

oRus

so P

M, J

imen

o A

, Dy

G, e

t al.

Phar

mac

okin

etic

Dos

e-Sc

hedu

ling

Stud

y of

Hed

geho

g Pa

thw

ay In

hibi

tor V

ism

odeg

ib (G

DC

-044

9) in

Pat

ient

s w

ith L

ocal

ly A

dvan

ced

or M

etas

tatic

Sol

id T

umor

s. C

lin C

ance

r Res

20

11;1

7:57

74-5

782.

6 T

ang

JY, M

acka

y-W

igga

n JM

, Asz

terb

aum

M, Y

auch

RL,

Lin

dgre

n J,

Cha

ng K

, Cop

pola

C, C

hana

na A

M, M

arji

J, B

icke

rs D

R, E

pste

in E

H Jr

. In

hibi

ting

the

hedg

ehog

pat

hway

in p

atie

nts w

ith th

e ba

sal-c

ell n

evus

sy

ndro

me.

N E

ngl J

Med

. 201

2 Ju

n 7;

366(

23):2

180-

8.

A

n 85

y/o

His

pani

c m

ale

with

a h

isto

ry o

f inv

asiv

e ba

sal c

ell c

arci

nom

a of

the

nose

dia

gnos

ed 1

8 ye

ars p

rior,

stat

us p

ost s

urgi

cal d

ebul

king

with

su

bseq

uent

radi

atio

n th

erap

y an

d re

cons

truct

ive

surg

ery,

pre

sent

ed w

ith

ulce

ratio

n an

d de

nuda

tion

of th

e pr

evio

usly

trea

ted

area

. O

n ph

ysic

al

exam

, the

pat

ient

had

loss

of t

he c

artil

agin

ous

nasa

l stru

ctur

e as

wel

l as t

he

uppe

r cut

aneo

us li

p an

d pa

rtial

loss

of t

he ri

ght c

heek

seco

ndar

y to

surg

ery.

Et

hmoi

d an

d rig

ht m

axill

ary

sinu

ses w

ere

also

exp

osed

. A

dditi

onal

ly,

ther

e w

as si

gnifi

cant

ulc

erat

ion,

as w

ell a

s sm

all a

reas

of a

ctiv

e bl

eedi

ng

and

drai

nage

. [FI

GU

RE

1] A

t thi

s vis

it, th

e re

gion

was

cle

anse

d an

d th

ree

2.0m

m p

unch

bio

psie

s wer

e pe

rfor

med

of t

he u

lcer

ativ

e ar

eas:

the

right

lo

wer

lip,

righ

t che

ek, a

nd le

ft na

sola

bial

regi

on.

Two

of th

ese

biop

sies

(th

e rig

ht lo

wer

lip

and

left

naso

labi

al re

gion

) wer

e de

term

ined

to b

e po

sitiv

e fo

r mor

phea

form

bas

al c

ell c

arci

nom

a, w

hile

the

right

che

ek

reve

aled

hyp

erke

rato

sis.

We

imm

edia

tely

beg

an th

e pr

oces

s of a

ppro

ving

vi

smod

egib

ther

apy

for t

his p

atie

nt.

He

was

enr

olle

d in

an

assi

stan

ce

prog

ram

, and

app

roxi

mat

ely

one

mon

th la

ter,

he b

egan

ora

l vis

mod

egib

15

0mg

daily

.

Figu

re 3

C

linic

al

pres

enta

tion

follo

win

g 3

½

mon

ths

of d

aily

V

ism

odeg

ib

ther

apy

S

ubse

quen

t fol

low

-up

3 ½

mon

ths f

ollo

win

g in

itiat

ion

of v

ism

odeg

ib

reve

aled

furth

er c

linic

al im

prov

emen

t; ho

wev

er, t

he p

atie

nt a

t thi

s poi

nt

had

com

plai

nts

of c

onst

ipat

ion

and

thin

ning

of h

air.

Phy

sica

l exa

m a

t thi

s tim

e re

veal

ed c

ompl

ete

re-e

pith

elia

lizat

ion

of th

e af

fect

ed a

rea

and

no

ulce

ratio

n, b

leed

ing,

nor

dra

inag

e. [F

IGU

RE

3] C

ontin

ued

treat

men

t with

vi

smod

egib

was

reco

mm

ende

d, w

ith o

ver-t

he-c

ount

er s

tool

softe

ners

and

ad

equa

te h

ydra

tion

sugg

este

d to

com

bat h

is m

ild m

edic

atio

n-re

late

d ad

vers

e ef

fect

. Th

is p

atie

nt is

cur

rent

ly st

ill u

nder

goin

g tre

atm

ent w

ith

vism

odeg

ib, a

nd c

ontin

ued

ther

apy

is p

lann

ed u

ntil

he n

o lo

nger

ach

ieve

s fa

vora

ble

resu

lts o

r unt

il po

tent

ial a

dver

se e

vent

s bec

ome

into

lera

ble.

Figu

re 2

C

linic

al

pres

enta

tion

follo

win

g 2

mon

ths

of d

aily

V

ism

odeg

ib

ther

apy

T

he p

atie

nt w

as se

en fo

r fol

low

-up

2 m

onth

s lat

er, a

nd n

oted

sign

ifica

nt

impr

ovem

ent i

n th

e ap

pear

ance

of t

he a

ffect

ed a

rea.

Phy

sica

l exa

m

reve

aled

no

blee

ding

or d

rain

age.

The

re w

as a

lso

cons

ider

able

im

prov

emen

t in

ulce

ratio

n, a

lthou

gh fe

w sm

all a

reas

still

rem

aine

d.

[FIG

UR

E 2]

Figu

re 1

Pa

tient

on

initi

al p

rese

ntat

ion,

prio

r to

initi

atio

n of

ther

apy

*Der

mat

olog

y Re

siden

t, PG

Y-3,

Wel

lingt

on R

egio

nal M

edic

al C

ente

r, W

ellin

gton

, Flo

rida;

**U

nive

rsity

of M

iam

i, De

part

men

t of

Derm

atol

ogy,

Mia

mi,

Flor

ida;

Cha

irman

of t

he D

epar

tmen

t of D

erm

atol

ogy,

Flor

ida

Inte

rnat

iona

l Uni

vers

ity, F

lorid

a

Suza

nne

M. H

orw

itz D

O*,

Mar

tin Z

aiac

MD*

*

Succ

essf

ul T

reat

men

t of A

dvan

ced

Inop

erab

le B

asal

Cel

l Car

cino

ma

with

Vism

odeg

ib

266

TEM

PLAT

E D

ESIG

N ©

200

8

ww

w.P

oste

rPre

sent

atio

ns.c

om

Cas

e of

a P

ecul

iar

Fung

atin

g N

ose

Lesi

on

Pana

giot

is M

itrop

oulo

s D

O1 ,

Just

in R

ubin

DO

1 , A

ngel

a C

ombs

DO

2 , Tr

acy

Favr

eau

DO

2

1 Der

mat

olog

y R

esid

ent.

Nov

a So

uthe

aste

rn U

nive

rsity

Col

lege

of O

steo

path

ic M

edic

ine/

Bro

war

d G

ener

al M

edic

al C

ente

r; In

terim

Pro

gram

Dire

ctor

. Nov

a So

uthe

aste

rn U

nive

rsity

Col

lege

of O

steo

path

ic M

edic

ine/

Bro

war

d G

ener

al M

edic

al C

ente

r Der

mat

olog

y R

esid

ency

, For

t Lau

derd

ale,

Flo

rida

INT

RO

DU

CT

ION

D

IFFE

RE

NT

IAL

DIA

GN

OS

ES

D

ISC

US

SIO

N

Refe

renc

es

Rhino

scler

oma i

s a ch

ronic

, gra

nulom

atous

cond

ition t

hat m

ost

frequ

ently

affec

ts the

resp

irator

y muc

osa,

espe

cially

the n

asal

cavit

y, wi

th po

tentia

l exte

nsion

to th

e low

er re

spira

tory t

ract.

1 Th

e con

dition

is

the re

sult o

f infec

tion b

y the

bacte

rium

Kleb

siella

rhino

scler

omat

is.2

Altho

ugh r

are i

n the

USA

the i

ncide

nce o

f rhin

oscle

roma

has b

een

incre

asing

.3 Mo

st of

the ca

ses a

ppea

r in im

migr

ants

from

less

deve

loped

coun

tries.

The

dise

ase i

s end

emic

in Ce

ntral

Amer

ica,

Indon

esia,

India

, and

some

coun

tries i

n Afric

a.4

Most

often

, the p

rese

ntatio

n is n

onsp

ecific

. Bec

ause

of its

mun

dane

cli

nical

pres

entat

ion re

semb

ling c

hron

ic rh

initis

, it of

ten go

es

unre

cogn

ized.

We e

xplor

e a ca

se of

a 73

-year

-old

Afric

an A

meric

an w

ho up

on

admi

ssion

to th

e hos

pital

for a

sync

opal

episo

de w

as in

ciden

tally

found

to ha

ve an

unus

ual a

ppea

ring

lesion

on th

e tip

of his

nose

. He

repo

rted t

hat th

e les

ion ha

s bee

n pre

sent

for 3

year

s, ha

s be

en la

rgely

asym

ptoma

tic, a

nd he

nce n

ever

soug

ht me

dical

atten

tion

for it.

We i

nves

tigate

poss

ible d

iffere

ntial

diagn

oses

and

deter

mine

the

diagn

osis

of rh

inosc

lerom

a ba

sed o

n the

histo

logica

l find

ings a

nd

clinic

al ap

pear

ance

. Rhin

oscle

roma

is a

rare

cond

ition t

hat m

ay el

ude

the cl

inicia

n for

year

s. W

e disc

uss e

tiolog

ies, d

iagno

sis, a

nd av

ailab

le tre

atmen

t opti

ons.

CA

SE

RE

PO

RT

Our D

erma

tolog

y tea

m wa

s con

sulte

d to e

valua

te wh

at wa

s des

cribe

d to

us as

a “fu

ngati

ng le

sion”

on th

e nos

e of a

73yo

Afric

an A

meric

an

male

who w

as ad

mitte

d at th

e hos

pital

for ev

aluati

on of

a sy

ncop

al ep

isode

. The

patie

nt sta

ted th

at the

lesio

n has

been

pres

ent fo

r ove

r 3 y

ears

and d

enied

any p

ain, it

ching

, blee

ding,

or an

y othe

r tro

ubles

ome s

ympto

ms re

lated

to it.

The p

atien

t des

cribe

d him

self a

s gen

erall

y hea

lthy w

ith no

rece

nt me

dical

conc

erns

. His

past

medic

al his

tory w

as si

gnific

ant fo

r gas

tric

ulcer

s, an

d dive

rticulo

sis. P

atien

t indic

ated t

hat h

e was

home

less a

t the

pres

ent ti

me, a

nd de

nied t

obac

co, a

lcoho

l, or r

ecre

ation

al dr

ug

abus

e. H

e also

denie

d any

pres

ent u

se of

pres

cribe

d med

icatio

ns.

On ph

ysica

l exa

m the

patie

nt wa

s well

-nou

rishe

d, ale

rt, an

d co

oper

ative

. Vita

l sign

s inc

luded

oral

tempe

ratur

e of 9

8.1, p

ulse r

ate

85, r

espir

atory

rate

17 br

eaths

/min,

bloo

d pre

ssur

e 129

/78 m

mHg,

oxyg

en sa

turati

on 98

% at

room

air.

Cutan

eous

exam

reve

aled a

1 cm

verru

cifor

m, cr

ustin

g plaq

ue

involv

ing th

e dor

sal ti

p and

left b

ulbou

s por

tion o

f the n

ose.

(pict

ures

1,

2, 3)

. Exa

mina

tion t

he of

rest

of the

body

was

unre

marka

ble.

CU

TAN

EO

US

PH

YS

ICA

L E

XA

M

Imag

e 1

Imag

e 2

Imag

e 3

•Sq

uamo

us C

ell C

arcin

oma

•Ba

sal C

ell C

arcin

oma

•Ma

jocch

i gra

nulom

a/Dee

p fun

gal in

fectio

n •

Weg

ener

’s Gr

anulo

matos

is •

Sarco

idosis

•

Syph

ilis

•Le

pros

y •

Tube

rculos

is Ve

rruco

sa C

utis

•Le

ishma

niasis

•

Rhino

scler

oma

Rhino

scler

oma i

s an u

nusu

al ch

ronic

gran

uloma

tous d

iseas

e of th

e up

per a

irway

s.1 It c

ommo

nly af

fects

the na

sal c

avity

(95%

to 10

0%),

the

naso

phar

ynx (

18%

to 43

%),

laryn

x (15

% to

40%

), tra

chea

(12%

), an

d br

onch

i (2%

to 7%

). Th

e etio

logic

agen

t is a

gram

-neg

ative

diplo

bacil

lus,

Kleb

siella

rhino

scler

omat

is.2

It is n

ot hig

hly co

ntagio

us an

d risk

of tr

ansm

ission

is in

creas

ed w

ith po

or

hygie

ne, c

rowd

ed liv

ing co

nditio

ns, a

nd m

alnutr

ition.

Thre

e clin

ical s

tages

have

been

desc

ribed

:4 1.

C ATA

RRHA

L STA

GE no

nspe

cific

rhini

tis, w

hich e

volve

s into

puru

lent,

fetid

rhino

rrhea

and c

rusti

ng, la

sting

for w

eeks

or m

onths

. 2.

G RAN

ULOM

ATOU

S ST

AGE –

the n

asal

muco

sal ti

ssue

beco

mes b

luish

-re

d, an

d rub

bery

nodu

les fo

rm. A

s the

se gr

anulo

matou

s swe

llings

grow

, the

y can

caus

e nas

al en

large

ment

and d

eform

ity. S

ympto

ms in

clude

ep

istax

is, re

spira

tory t

ract

obstr

uctio

n, an

osmi

a, ho

arse

ness

, and

thi

cken

ing or

numb

ing of

the s

oft pa

late.

3.

S CLE

ROTI

C PH

ASE –

the g

ranu

lation

tissu

e is r

eplac

ed by

fibro

tic sc

ars,

which

can o

ccas

ionall

y res

ult in

bloc

ked a

irway

s.

Diag

nosti

c hist

ologic

al fea

tures

are f

ound

in th

e gra

nulom

atous

stag

e an

d inc

lude c

hron

ic inf

lamma

tory c

ells,

Russ

ell bo

dies,

and

pseu

doep

itheli

omato

us h

yper

plasia

, gro

ups o

f larg

e vac

uolat

ed

histio

cytes

conta

ining

the K

lebsie

lla rh

inosc

lerom

atis (

Miku

licz c

ells).

4,5

If num

erou

s, the

y can

be se

en w

ith he

matox

ylin-

eosin

stain

s, bu

t may

re

quire

perio

dic ac

id–Sc

hiff, s

ilver

impr

egna

tion,

or im

muno

histoc

hemi

cal

stains

for c

onfirm

ation

and i

denti

ficati

on.

A po

sitive

cultu

re in

Mac

Conk

ey

agar

is di

agno

stic o

f rhin

oscle

roma

, but

cultu

res a

re po

sitive

in on

ly 50

% to

60

% of

case

s.

Rhino

scler

oma i

s rar

ely le

thal u

nless

it ob

struc

ts the

airw

ays.

MRI

and

bron

chos

copy

may

be w

arra

nted f

or ev

aluati

on of

the e

xtend

of th

e dise

ase

involv

emen

t. Be

caus

e of th

e high

incid

ence

of re

curre

nce,

prolo

nged

an

tibiot

ic the

rapy

over

mon

ths to

year

s may

is ne

cess

ary.6

The c

hoice

of

long-

term

antib

iotic

thera

py sh

ould

be gu

ided b

y the

patie

nt's a

ge an

d sex

. Re

peat

biops

y can

be pe

rform

ed to

help

deter

mine

the a

ppro

priat

e dur

ation

of

the an

tibiot

ic the

rapy

Tetra

cycli

ne is

the d

rug o

f cho

ice.2,6

Othe

r anti

biotic

s inc

lude

cipro

floxa

cin an

d rifa

mpin.

Bac

terial

supe

rinfec

tion r

espo

nds t

o tre

atmen

t with

clind

amyc

in an

d thir

d-ge

nera

tion c

epha

lospo

rins.

Sc

leroti

c les

ions r

espo

nd w

ell to

trea

tmen

t with

cipr

oflox

acin.

6

Desp

ite an

tibiot

ic the

rapy

relap

ses d

o occ

ur an

d clos

e obs

erva

tion i

s the

ke

y to t

he lo

ng-te

rm fo

llow-

up ca

re of

the p

atien

t.6

PAT

HO

LOG

Y

Skin

Biop

sy, n

asal

tip:

De

nse p

lasma

cell i

nfiltra

te of

the de

rmis

with

over

lying

pseu

doep

itheli

omato

us h

yper

plasia

. The

se fin

dings

could

be

se

en in

asso

ciatio

n with

rhino

scler

oma.

Ma

ligna

ncy n

ot ide

ntifie

d. P

AS st

ain ne

gativ

e for

patho

genic

fungi.

Fea

tures

char

acter

istic

of sa

rcoido

sis, W

egen

er’s

gr

anulo

matos

is, sy

philis

, tube

rculos

is ve

rruco

sa cu

tis, o

r

leish

mania

sis w

ere n

ot ob

serve

d. T

issue

cultu

re, n

asal

tip:

no

orga

nisms

on th

e sub

mitte

d spe

cimen

wer

e

seen

with

Stei

ner o

r Gra

m sta

in.

P

ictur

e 3

Pictu

re 2

Pictu

re 1

RE

FER

EN

CE

S

1. H

art C

A, R

ao S

K. R

hinos

clero

ma. J

Med

Micr

obiol

2000

; 49:3

95-6

. 2

. Sch

wartz

DA,

Gey

er S

J. Kl

ebsie

lla an

d rhin

oscle

roma

. In: C

orno

r DH,

Cha

ndler

FW

, Sc

hwar

tz DA

, et a

l, eds

. Path

ology

of In

fectio

us D

iseas

es. N

Y: M

cGra

w-Hi

ll Pro

fessio

nal,

1998

:589-

95

3. A

mar M

E, R

osen

A. R

hinos

clero

ma m

imick

ing na

sal p

olypo

sis. A

nn O

tol R

hinol

Lary

ngol.

2001

Mar

;110(

3):29

0-2.

4. A

balkh

ail A

, Satt

i MB,

Uthm

an M

A, A

l Hilli

F, D

arwi

sh A

, Sati

r A. R

hicos

clero

ma: a

cli

nicop

atholo

gical

study

from

the G

ulf re

gion.

Sing

apor

e M

ed J.

2007

Feb

;48(2

)148

-51.

5. T

an S

L, Ne

oh C

Y, Ta

n HH.

Rhin

oscle

roma

: a ca

se se

ries.

Sing

apor

e Med

J. 20

12

Feb;5

3(2)

;e24-

7 6

. Gaa

far H

A, G

aafar

AH,

Nou

r YA.

Rhin

oscle

roma

; an u

pdate

d exp

erien

ce th

roug

h the

last

10 ye

ars.

Acta

Oto

laryn

gol. 2

011 A

pr;13

1(4)

440-

6. Ep

ub 20

11 Ja

n 3.

Figu

re 2

Figu

re 1

267

Mu

ltip

le S

ebac

eou

s T

rich

ofol

licu

lom

as

on t

he

Face

Meg

an M

orri

son

, DO

, Rya

n S

. Jaw

itz,

DO

, A

nn

LaF

ond,

MD

, Dan

iel S

tew

art,

DO

, Bri

an S

chap

iro,

MD

St. J

osep

h M

ercy

Hos

pita

l •

Ann

Arb

or, M

ichi

gan

REM

AR

KA

BLE

MED

ICIN

E. R

EMA

RK

AB

LE C

AR

E.

Ref

eren

ces

1.

Bad

r A, L

aksh

mia

h G

R. F

ollic

ulos

ebac

eous

cy

stic

ham

arto

ma

of th

e ni

pple

: a c

ase

repo

rt.

J Cut

anPa

thol

. 200

9;36

:597

-600

.

2.

Nom

ura

M, H

ata

S. S

ebac

eous

Tri

chfo

llicu

-lo

ma

on S

crot

um a

nd P

enis

. Der

mat

olog

ica.

19

90;1

81:6

8-70

.

3.

Plew

ig G

. Seb

aceo

us T

rich

ofol

licul

oma.

J C

utan

Path

ol. 1

980;

7:39

4-40

3.

4.

Wu

YH

. Fol

licul

oseb

aceo

us c

ysti

c ha

mar

tom

a or

tric

hofo

llicu

lom

a? A

spec

trum

of h

amar

to-

mat

ous c

hang

es in

duct

ed b

y pe

rifo

llicu

lars

trom

a in

the

folli

cula

r epi

thel

ium

. J C

utan

Path

ol.

2008

;35:

843-

848.

Dis

cuss

ion

Seba

ceou

s tri

chof

ollic

ulom

as a

re a

rare

app

enda

geal

tu

mor

and

a v

aria

nt o

f tri

chof

olli

culo

ma

firs

t

desc

ribe

d in

198

0. T

hey

appe

ar a

s slo

w g

row

ing

no

dule

s in

seba

ceou

s ric

h ar

eas a

nd a

re c

lass

ical

ly

seen

as a

solit

ary

lesi

on o

n th

e no

se. T

hese

lesi

ons

aris

e cl

inic

ally

wit

h a

cent

ral p

ore

like

open

ing

that

ex

hibi

t pro

trud

ing

hair

s in

vari

ous s

tage

s of d

evel

op-

men

t. U

sual

ly th

ey a

re a

sym

ptom

atic

, but

can

som

e-ti

mes

ext

rude

seba

ceou

s mat

eria

l.

The

diff

eren

tial

dia

gnos

is in

clud

es o

ther

folli

cula

r ne

opla

sms s

uch

as c

onve

ntio

nal t

rich

ofol

licul

oma

and

foll

icul

oseb

aceo

us c

ysti

c ha

mar

tom

a, w

hich

ar

e di

ffere

ntia

ted

by h

isto

logi

c ex

amin

atio

n.

Trea

tmen

t fo

r th

ese

lesi

ons

is li

mit

ed, a

nd u

sual

ly

cons

ists

of l

ocal

des

truc

tion

or e

xcis

ion.

We

have

just

de

scri

bed

the

first

repo

rted

cas

e of

mul

tipl

e se

bace

ous

tric

hofo

llicu

lom

as o

n th

e fa

ce.

Rev

iew

of t

he li

tera

ture

reve

aled

one

cas

e fr

om Ja

pan

of m

ulti

ple

seba

ceou

s tr

ich

ofol

licu

lom

as o

n t

he

sc

rotu

m a

nd p

enis

. Clin

icia

ns sh

ould

be

awar

e of

this

ra

re e

ntit

y w

hen

eval

uati

ng m

ulti

ple

faci

al n

odul

es

wit

h a

cent

ral k

erat

in p

lug.

Rep

ort

of a

Cas

eA

59

year

-old

mal

e pr

esen

ted

to th

e cl

inic

wit

h a

seve

ral

year

his

tory

of 3

slow

gro

w-

ing,

asy

mpt

omat

ic n

odul

es o

n hi

s lef

t fac

e. H

e ha

d a

hist

ory

of a

cne

vulg

aris

wit

h sc

arri

ng.

The

lesi

ons w

ere

trea

ted

wit

h cl

inda

myc

in so

luti

on, b

enzo

yl

pero

xide

an

d in

tral

esio

nal

in

ject

ion

of 2

.5m

g tr

iam

cino

-lo

ne, w

itho

ut im

prov

emen

t.

Phy

sica

l Exa

mT

here

wer

e 3

skin

col

ored

fir

m d

erm

al n

odul

es in

a li

n-ea

r arr

ange

men

t wit

h a

cen-

tral

ker

atin

plu

g on

his

left

la

tera

l che

ek (

Figu

re 1

).

Tre

atm

ent

Due

to u

nres

pons

iven

ess t

o pr

evio

us tr

eatm

ents

, the

3

cyst

-lik

e le

sion

s w

ere

su

rgic

ally

exc

ised

und

er

loca

l ane

sthe

sia.

His

topa

thol

ogic

Exa

mLe

sion

al e

xcis

ions

reve

aled

a

dila

ted

kera

tin

plu

gged

fo

llicl

e w

ith

cord

s rad

iati

ng

from

the

folli

cle.

Em

anat

ing

from

the

cord

s wer

e pr

omi-

nent

seba

ceou

s gla

nds (

Figu

re

2). O

n hi

gher

pow

er a

fibr

ous

stro

ma

wit

h nu

mer

ous s

mal

l bl

ood

vess

els w

ereo

bser

ved

(Fig

ure

3).

Figu

re 1 Fi

gure

2

Figu

re 3

268

Julia

n M

. Ngo

, DO,

Larg

o Med

ical C

ente

r, La

rgo,

Flor

ida

4707

CAS

E R

EPO

RT

A 39

year

old

heal

thy m

ale p

rese

nted

with

a 3-

4 ye

ar hi

stor

y of a

pr

ogre

ssive

ly en

larg

ing g

rowt

h on

the r

ight

ear.

Pas

t med

ical h

istor

y is

signi

fican

t for

dep

ress

ion,

anxie

ty. H

e den

ies a

fam

ily or

per

sona

l hi

stor

y of m

elan

oma

or no

n-m

elan

oma

skin

canc

ers.

Soc

ial h

istor

y is

posit

ive fo

r sm

okin

g for

man

y yea

rs. R

evie

w of

syst

ems i

s neg

ative

for

pain

, ten

dern

ess ,

or b

leed

ing o

f the

righ

t ear

. He d

enie

s any

co

nstit

utio

nal s

ympt

oms.

Exam

inat

ion

of th

e rig

ht ea

r rev

eals

a lar

ge 2

.7cm

X 1.

2cm

, exo

phyti

c, hy

perk

erat

otic,

ill-d

efin

ed, i

ndur

ated

pla

que (

Fig. 1

). N

o reg

iona

l lym

phad

enop

athy

is no

ted.

Hist

opat

holo

gy o

f thi

s les

ion

is

cons

isten

t with

inva

sive,

wel

l diff

eren

tiate

d sq

uam

ous c

ell

carc

inom

a.

Com

plet

e exc

ision

of th

e SCC

was

per

form

ed u

sing M

ohs

micr

ogra

phic

surg

ery.

The p

atie

nt w

as se

en m

onth

ly po

st-o

pera

tivel

y fo

r fol

low-

up an

d ha

d no

com

plica

tions

dur

ing t

he in

itial

mon

ths.

Ho

weve

r, he

miss

ed tw

o fol

low-

up ap

poin

tmen

ts 4

mon

ths a

fter h

is su

rger

y and

upo

n ret

urn,

2 cy

stic

nodu

les i

n the

pos

t-aur

icula

r reg

ion

were

note

d (F

ig. 2

). A

deno

path

y in

all o

ther

regi

ons w

ere n

egat

ive.

Hist

opat

holo

gic e

xam

inat

ion

of th

is le

sion w

as co

nsist

ent w

ith

met

asta

tic S

CC. T

he p

atie

nt w

as re

ferre

d fo

r che

mor

adio

ther

apy

follo

wed

by ri

ght n

eck d

issec

tion.

Cuta

neou

s Squ

amou

s Cel

l Car

cinom

a (C

SCC)

is th

e sec

ond

mos

t co

mm

on ty

pe of

skin

canc

er a

nd e

ach y

ear m

ore t

han

3,00

0,00

0 ca

ses a

re d

iagn

osed

wor

ldwi

de. 1 Al

thou

gh m

ost c

ases

can b

e cur

ed, a

sm

all p

erce

ntag

e can

caus

e sig

nific

ant m

orbi

dity

and

mor

talit

y.

Appr

oxim

atel

y 4%

can r

esul

t in n

odal

met

asta

sis a

nd 1

.5%

in d

eath

.1,

Give

n the

sign

ifica

nt im

pact

met

asta

tic C

SCC

can h

ave o

n pat

ient

s, it’

s im

porta

nt fo

r clin

ician

s to i

dent

ify hi

gh-ri

sk ca

ses e

arly

so

man

agem

ent c

an b

e opt

imize

d wi

th a

redu

ctio

n in m

orbi

dity

and

mor

talit

y for

thes

e pat

ient

s.

Ther

e are

no st

anda

rdize

d de

finiti

ons o

f hig

h-ris

k cut

aneo

us

squa

mou

s cel

l car

cinom

a (H

RCSC

C). D

iffer

ent s

tudi

es an

d gu

idel

ines

us

e diff

eren

t par

amet

ers i

n det

erm

inin

g HRC

SCC1,

2,4 .

Howe

ver,

amon

g the

diff

eren

t gui

delin

es in

the l

itera

ture

ther

e are

som

e wid

ely

acce

pted

par

amet

ers t

hat w

ould

aid

in id

entif

ying

high

-risk

pat

ient

s.

Thes

e fea

ture

s are

dim

ensio

ns la

rger

than

2 cm

in d

iam

eter

, thi

ckne

ss

grea

ter t

han 4

mm

, rec

urre

nt le

sion,

poo

rly d

iffer

entia

ted

tum

ors,

pres

ence

of p

erin

eura

l inva

sion,

lym

phov

ascu

lar i

nvas

ion,

loca

tion

(muc

osal

surfa

ces,

geni

talia

, “m

ask a

reas

” of

face

–ey

elid

s and

br

ows,

perio

rbita

l, lip

s, ea

rs, n

ose,

tem

ple,

pre

and

post

auric

ular

, ch

in),

imm

unos

uppr

essio

n, an

d or

gan

trans

plan

t pat

ient

s. As

you c

an

see f

rom

our

case

mul

tiple

high

-risk

feat

ures

wer

e pre

sent

in ou

r pa

tient

. On

ce it

’s de

term

ined

that

a pa

tient

has a

high

-risk

CSC

C , a

thor

ough

ph

ysica

l exa

min

atio

n sh

ould

be p

erfo

rmed

inclu

ding

dra

inin

g nod

al

basin

s1 . If n

o clin

ically

pal

pabl

e nod

es ar

e pre

sent

addi

tiona

l im

agin

g (CT

, MRI

) stu

dies

may

be p

erfo

rmed

in or

der t

o aid

in

eval

uatin

g fo

r pos

sible

subc

linica

l nod

al in

volve

men

t1 .

DIS

CUSS

ION

REF

EREN

CES

1.Le

Boeu

f NR,

Sch

mul

ts C

D. U

pdat

e on

the

Man

agem

ent o

f Hig

h-Ri

sk S

quam

ous C

ell C

arin

oma.

Se

min

Cut

an M

ed S

urg.

201

1 M

ar;3

0(1)

:26-

34

2.Pu

glia

no-M

auro

M, G

oldm

an G

. Moh

s sur

gery

is e

ffect

ive

for h

igh-

risk

cuta

neou

s squ

amou

s ce

ll ca

rcin

oma.

Der

mat

ol S

urg.

201

0 O

ct;3

6(10

):154

4-53

. 3.

Kwon

S, D

ong

ZM, W

u PC

. Sen

tinel

lym

ph n

ode

biop

sy fo

r hig

h-ris

k cu

tane

ous s

quam

ous c

ell

carc

inom

a: cl

inic

al e

xper

ienc

e an

d re

view

of l

itera

ture

. Wor

ld J

Surg

Onc

ol. 2

011

Jul 1

9;9:

80.

Revi

ew.

4.Ja

mbu

saria

-Pah

laja

ni A

, Hes

s SD,

Kat

z KA,

Ber

g D,

Sch

mul

ts C

D. U

ncer

tain

ty in

the

perio

pera

tive

man

agem

ent o

f hig

h-ris

k cu

tane

ous s

quam

ous c

ell c

arci

nom

a am

ong

Moh

s sur

geon

s. A

rch

Derm

atol

. 201

0 N

ov;1

46(1

1):1

225-

31.

5.Ve

ness

MJ,

Mor

gan

GJ, P

alm

e CE

, Geb

ski V

. Sur

gery

and

adj

uvan

t rad

ioth

erap

y in

pat

ient

s with

cu

tane

ous h

ead

and

neck

squa

mou

s cel

l car

cino

ma

met

asta

tic to

lym

ph n

odes

: com

bine

d tr

eatm

ent s

houl

d be

con

sider

ed b

est p

ract

ice.

Lar

yngo

scop

e. 2

005

May

;115

(5):8

70-5

. 6.

Mou

rouz

is C,

Boy

nton

A, G

rant

J, U

mar

T, W

ilson

A, M

acph

eson

D, P

ratt

C. C

utan

eous

hea

d an

d ne

ck S

CCs a

nd ri

sk o

f nod

al m

etas

tasis

- U

K ex

perie

nce.

J Cr

anio

max

illof

ac S

urg.

200

9 De

c;37

(8):4

43-7

. Epu

b 20

09 A

ug 2

7.

7.D'

Souz

a J,

Clar

k J.

Man

agem

ent o

f the

nec

k in

met

asta

tic c

utan

eous

squa

mou

s cel

l car

cino

ma

of

the

head

and

nec

k. C

urr O

pin

Oto

lary

ngol

Hea

d N

eck

Surg

. 201

1 Ap

r;19(

2):9

9-10

5. R

evie

w

FIG

URES

Howe

ver,

ther

e is n

o gol

d st

anda

rd fo

r rad

iolo

gic s

tagi

ng o

f CSC

C an

d se

nsiti

vity a

nd sp

ecifi

city a

re la

ckin

g1 . The

role

of se

ntin

el

lymph

node

bio

psy i

n nod

e neg

ative

HRC

SCC

patie

nts r

emai

n in

vest

igat

iona

l and

is cu

rrent

ly no

t a st

anda

rd

reco

mm

enda

tion1,

3 . How

ever

, it m

ay b

e a us

eful

tool

in th

e fut

ure

give

n ear

ly de

tect

ion

of no

dal d

iseas

e res

ults

in a

high

-cur

e rat

e (7

3%)1 .

Moh

s sur

gery

is th

e rec

omm

ende

d th

erap

y for

all H

RCSC

C an

d is

an ef

fect

ive m

onot

hera

py w

ith lo

w re

curre

nce r

ates

2 . The

re is

lim

ited

date

rega

rdin

g adj

uvan

t rad

ioth

erap

y, ex

cept

in p

atie

nts

with

per

ineu

ral in

vasio

n. In

case

of m

etas

tatic

CSC

C su

rger

y with

ad

juva

nt ra

diot

hera

py is

reco

mm

ende

d. C

hem

othe

rapy

is al

so an

op

tion.

Pa

tient

s sho

uld

be fo

llowe

d clo

sely

afte

r tre

atm

ent,

espe

cially

du

ring t

he fi

rst 2

year

s as m

ost m

etas

tasis

occ

ur d

urin

g thi

s tim

e.

1 2

269

Aty

pic

al V

ascu

lar

Les

ion A

risi

ng

in a

n A

rea

of P

revi

ous

Rad

iati

on T

reat

men

t on

the

Bre

ast

Leh

igh V

alle

y H

ealt

h N

etw

ork,

Allen

tow

n,

Pen

nsy

lvan

ia a

nd P

hilad

elphia

Col

lege

of

Ost

eopat

hic

Med

icin

e, P

hilad

elphia

, P

ennsy

lvan

iaSte

phen

M. Pur

cell, DO a

nd C

hris

tian

W. Ora

m, DO R

efer

ence

s:1

Bre

nn T

, Fle

tche

r C

. Rad

iatio

n-as

soci

ated

cut

aneo

us a

typ

ical

vas

cula

r le

sio

ns a

nd a

ngio

sarc

om

a: c

linic

op

atho

log

ic a

naly

sis

of

42 c

ases

. Am

. J. S

urg

. Pat

hol.

2005

;29:

983-

966.

2 B

renn

T, F

letc

her.

Po

stra

dia

tion

vasc

ular

pro

lifer

atio

ns: a

n in

crea

sing

pro

ble

m. H

isto

pat

holo

gy.

200

6;48

:106

-114

.3

Pat

ton

K, D

eyru

p A

, Wei

ss S

. Aty

pic

al v

ascu

lar

lesi

ons

aft

er s

urg

ery

and

rad

iatio

n o

f th

e b

reas

t: a

clin

ico

pat

holo

gic

stu

dy

of

32

case

s an

alyz

ing

his

tolo

gic

hee

rog

enei

ty a

nd a

sso

ciat

ion

with

ang

iosa

rco

ma.

Am

. J .

Pat

hol.

2008

;32:

943-

950.

4 F

erna

ndez

A, S

un Y

, Tub

bs

R, G

old

blu

m J

, Bill

ing

s S

. FIS

H f

or

myc

am

plif

icat

ion

and

ant

i-m

yc im

mun

ohi

sto

chem

istr

y: u

sefu

l d

iag

nost

ic t

oo

ls in

the

ass

essm

ent

of

seco

ndar

y an

gio

sarc

om

a an

d a

typ

ical

vas

cula

r le

sio

n p

rolif

erat

ions

. J C

utan

Pat

hol.

2012

;29:

234-

242.

Pa

tie

nt:

A.B

. is

an 8

2 y.

o. C

ausa

sian

fem

ale.

His

tory

of

Pre

se

nt

Illn

ess:

Pat

ient

pre

sent

ed in

Oct

ob

er 2

010

with

a

pin

k to

pur

ple

asy

mp

tom

atic

pla

que

on

the

rig

ht m

edia

l bre

ast.

Thi

s ha

d

dev

elo

ped

in a

n ar

ea o

f p

revi

ous

rad

iatio

n tr

eatm

ent

for

bre

ast

canc

er.

Sin

ce t

he le

sio

n ar

ose

in a

n ar

ea o

f p

revi

ous

rad

iatio

n tr

eatm

ent,

a b

iop

sy

was

ob

tain

ed.

The

lesi

on

rem

aine

d a

sym

pto

mat

ic a

nd s

tab

le in

siz

e fo

r ap

pro

xim

atel

y o

ne y

ear.

No

tre

atm

ent

was

pur

sued

and

wat

chfu

l wai

ting

w

as im

ple

men

ted

, with

the

inte

nt t

o b

iop

sy a

ny n

ew o

r ch

ang

ing

are

as.

At

app

roxi

mat

ely

twel

ve m

ont

hs, w

ithin

the

sp

an o

f tw

o w

eeks

, the

lesi

on

gre

w

four

tim

es in

siz

e an

d b

ecam

e te

nder

. T

his

pro

mp

ted

re-

bio

psy

due

to

the

ag

gre

ssiv

e cl

inic

al n

atur

e o

f th

e le

sio

n.

M

ed

ica

l H

isto

ry:

Dem

entia

, mal

igna

nt m

elan

om

a, b

reas

t ca

ncer

, o

steo

po

rosi

s, a

nem

iaS

urg

ica

l H

isto

ry:

Bila

tera

l lum

pec

tom

y (r

ight

bre

ast

stag

e T

2 N

0 w

ith

rad

iatio

n tr

eatm

ent,

to

tal r

adia

tion

do

se 6

2.40

Gy,

last

rad

iatio

n d

ose

200

5, le

ft

bre

ast

T0)

, hip

rep

lace

men

tM

ed

ica

tio

ns:

Asp

irin

, do

nep

ezil,

cal

cium

plu

s vi

tam

in D

, iro

n P

hysic

al E

xa

min

atio

n:

Oct

ob

er 2

010:

2.0

x 3

.0 c

m p

ink

to p

urp

le p

laq

ue

on

the

rig

ht b

reas

t. D

ecem

ber

201

1: 1

0.0

x 14

.0 c

m p

ink

to p

urp

le, i

ndur

ated

p

laq

ue o

n th

e ri

ght

bre

ast

B

iop

sy:

Ad

vanc

ed D

erm

ato

log

y A

sso

ciat

es, L

TD

. (A

D10

-107

99, 1

0/04

/201

0) R

ight

m

edia

l bre

ast:

“In

the

sup

erfic

ial h

alf

of

an e

dem

ato

us d

erm

is is

a s

ubtle

p

op

ulat

ion

of

ecta

tic v

esse

ls w

ith p

lum

p, b

ut s

mal

l, en

do

thel

ial c

ells

. T

his

is s

om

ewha

t o

bsc

ured

by

a p

atch

y m

ixed

cel

l inf

lam

mat

ory

infil

trat

e th

at

incl

udes

lym

pho

cyte

s, h

istio

cyte

s, a

nd a

rar

e eo

sino

phi

l. T

here

are

als

o

extr

avas

ated

ery

thro

cyte

s. A

PA

S s

tain

is n

egat

ive

for

fung

us.”

Ad

vanc

ed D

erm

ato

log

y A

sso

ciat

es, L

TD

. (A

D11

-134

64, 1

2/15

/201

1) R

ight

m

edia

l and

late

ral b

reas

t: “

Bo

th s

pec

imen

s co

ntai

n a

pro

lifer

atio

n o

f ir

reg

ular

, er

ythr

ocy

te-c

ont

aini

ng, v

ascu

lar

chan

nels

tha

t ar

e lin

ed b

y a

sing

le la

yer

of

flatt

ened

end

oth

elia

l cel

ls.

The

se v

ary

in s

ize

and

sha

pe

with

sm

all j

agg

ed

chan

nels

sub

tly in

terc

alat

ed b

etw

een

colla

gen

bun

dle

s ad

mix

ed w

ith la

rge

ecta

tic o

nes.

Thi

s p

roce

ss is

mo

st p

rom

inen

t in

the

sup

erfic

ial h

alf

of

the

der

mis

tho

ugh

it is

ful

l thi

ckne

ss, o

vera

ll, w

ith in

volv

emen

t o

f th

e su

bcu

tis

(rig

ht b

reas

t m

edia

l). E

ndo

thel

ial m

orp

holo

gy

is m

ono

mo

rphi

c w

ith n

o

cyto

log

ic a

typ

ia a

nd n

o m

itose

s. S

uper

imp

ose

d o

n th

is, a

nd a

lso

mo

st

pro

min

ent

is a

co

nsp

icuo

us p

op

ulat

ion

of

lym

pho

cyte

s th

at a

re c

lust

ered

w

ithin

, and

aro

und

, the

ves

sels

.”A

dd

itio

na

l S

tud

ies:

D2-

40 n

egat

ive,

FIS

H f

or

MY

C a

mp

lific

atio

n p

end

ing

Tre

atm

en

t: In

tere

st a

nd t

reat

men

t re

com

men

dat

ions

Cas

e P

rese

nta

tion

:

Dis

cuss

ion

:O

ver

the

pas

t d

ecad

e, a

dire

ct li

nk h

as b

een

esta

blis

hed

bet

wee

n th

e d

evel

op

men

t o

f an

gio

sarc

om

a an

d r

adia

tion

trea

tmen

t, s

pec

ifica

lly o

n th

e b

reas

t. A

ltho

ugh

the

rela

tive

risk

is a

bo

ut 1

0-fo

ld, t

he o

vera

ll in

cid

ence

of

ang

iosa

rco

ma

aris

ing

in a

bre

ast

rad

iatio

n fie

ld f

alls

with

in a

n es

timat

ed r

ang

e o

f 0.

09 t

o 0

.16%

. T

he s

pec

ific

inci

ting

req

uire

men

ts a

re s

pec

ulat

ed t

o b

e a

resu

lt o

f b

reas

t-co

nser

ving

sur

ger

y, c

hem

oth

erap

y, a

nd p

ost

lum

pec

tom

y ra

dia

tion

trea

tmen

t. I

nter

estin

gly

, aty

pic

al, b

ut n

ot

out

war

dly

mal

igna

nt

vasc

ular

lesi

ons

hav

e b

een

rep

ort

ed t

o d

evel

op

in r

adia

tion

field

s fo

llow

ing

b

reas

t-co

nser

ving

sur

ger

y as

wel

l. C

linic

al a

nd h

isto

log

ic o

verl

ap, c

om

bin

ed

with

an

unp

red

icta

ble

long

ter

m c

linic

al c

our

se, m

ay c

ause

diff

icul

ty in

Fig

ure

1A:

Oct

ob

er 2

010:

2.0

x 3

.0 c

m p

ink

to

pur

ple

pla

que

on

the

rig

ht b

reas

t.

Fig

ure

1B:

Dec

emb

er 2

011:

10.

0 x

14.0

cm

pin

k to

pur

ple

, ind

urat

ed p

laq

ue o

n th

e ri

ght

bre

ast.

Fig

ure

2A:

H&

E O

cto

ber

201

0: T

here

are

a

num

ber

of

ecta

tic

vess

els

wit

h p

lum

p s

mal

l en

do

thel

ial c

ells

sur

roun

ded

by

a p

atch

y m

ixed

ce

ll in

filt

rate

. T

he in

filt

rate

is c

om

po

sed

of

lym

pho

cyte

s, h

isti

oct

yes,

and

a r

are

eosi

nop

hil.

E

xtra

vasa

ted

ery

thro

cyte

s ar

e p

rese

nt.

Fig

ure

2B:

H&

E D

ecem

ber

201

1:

Mo

nom

orp

hic

end

oth

elia

l cel

ls w

ith

no

cyto

log

ic a

typ

ia a

nd n

o m

ito

ses.

The

re is

a

cons

pic

uous

po

pul

atio

n o

f ly

mp

hocy

tes

clus

tere

d w

ithi

n an

d a

roun

d t

he v

esse

ls.

dis

ting

uish

ing

aty

pic

al v

ascu

lar

lesi

ons

(AV

Ls) f

rom

ear

ly a

ngio

sarc

om

a. A

n es

tab

lishe

d t

reat

men

t p

roto

col i

s ne

eded

fo

r p

atie

nts

that

fal

l int

o t

his

cate

go

ry.

AV

Ls t

ypic

ally

pre

sent

in w

om

en in

the

ir 5

0s t

hat

have

rec

eive

d b

reas

t-co

nser

ving

sur

ger

y, in

co

njun

ctio

n w

ith a

n av

erag

e tr

eatm

ent

of

40-6

0 G

y cu

mul

ativ

e ra

dia

tion

do

se.

Clin

ical

ly, t

hese

lesi

ons

ten

d t

o b

e sm

alle

r, w

ell c

ircum

scri

bed

, and

sym

met

rica

l. T

he p

ost

rad

iatio

n in

terv

al f

or

the

dev

elo

pm

ent

of

AV

Ls is

no

tab

ly s

hort

er c

om

par

ed t

o f

rank

ang

iosa

rco

ma.

T

he t

ime

to p

rese

ntat

ion

for

AV

Ls is

ap

pro

xim

atel

y 3

year

s co

mp

ared

to

an

gio

sarc

om

a, w

hich

is a

pp

roxi

mat

ely

6 ye

ars.

Thi

s ha

s le

d t

o t

he h

ypo

thes

is

that

AV

Ls a

nd a

ngio

sarc

om

a ar

e p

art

of

a co

ntin

uous

sp

ectr

um o

f va

scul

ar

lesi

ons

, and

tha

t A

VLs

rep

rese

nt a

pre

curs

or

lesi

on.

H

isto

pat

holo

gic

ana

lysi

s o

f A

VLs

ver

sus

ang

iosa

rco

ma

can

be

diff

icul

t d

ue

to m

any

diff

eren

t o

verl

app

ing

fea

ture

s. T

o d

ate,

ang

iosa

rco

ma

has

bee

n hi

sto

pat

holo

gic

ally

iden

tifie

d b

y an

asto

mo

sing

vas

cula

r ch

anne

ls li

ned

by

pro

min

ent

end

oth

elia

l cel

ls w

ith n

ucle

ar h

yper

chro

mas

ia a

nd h

ob

naili

ng.

Dis

sect

ion

of

der

mal

co

llag

en a

nd in

volv

emen

t o

f th

e su

bcu

tane

ous

tis

sue

can

occ

ur in

co

njun

ctio

n w

ith n

ecro

sis

or

“blo

od

lake

s”.

AV

Ls, i

n co

ntra

st, a

pp

ear

wel

l circ

umsc

rib

ed, w

edg

e-sh

aped

, and

ten

d t

o in

volv

e o

nly

the

sup

erfic

ial t

o

mid

der

mis

. R

ecen

tly, f

luo

resc

ence

in s

itu h

ybri

diz

atio

n (F

ISH

) has

bee

n ab

le

to d

istin

gui

sh A

VLs

fro

m a

ngio

sarc

om

a b

y th

e p

rese

nce

of

MY

C a

mp

lific

atio

n,

alth

oug

h re

pea

t te

stin

g o

n m

ultip

le b

iop

sy s

ites

may

be

need

ed f

or

cons

iste

nt

resu

lts.

N

o d

efin

itive

cri

teri

a ar

e av

aila

ble

to

ad

equa

tely

pre

dic

t w

heth

er A

VLs

will

d

evel

op

into

ang

iosa

rco

ma

or

may

co

ntin

ue t

o f

ollo

w a

ben

ign

cour

se.

Rec

ent

atte

mp

ts a

t su

b-c

lass

ifyin

g le

sio

ns w

ith s

imila

r hi

sto

pat

holo

gic

fin

din

gs

into

tw

o c

ateg

ori

es (i

.e. l

ymp

hatic

ap

pea

ring

ver

sus

cap

illar

y ap

pea

ring

lesi

ons

) ha

s no

t b

een

foun

d t

o b

e a

def

initi

ve m

eans

of

dis

ting

uish

ing

AV

Ls o

f a

mo

re

agg

ress

ive

natu

re, o

r th

ose

tha

t m

ay d

evel

op

into

ang

iosa

rco

ma.

Ana

lysi

s o

f ne

w c

ases

with

long

ter

m f

ollo

w-u

p is

nee

ded

to

fur

ther

ana

lyze

the

sp

ectr

um o

f th

ese

lesi

ons

, lea

din

g t

o a

n ap

pro

pri

ate

and

acc

epte

d t

reat

men

t al

go

rith

m in

the

fu

ture

.

40x

10x

270

A

Cas

e of

Per

sist

ent

Aca

ntho

lyti

c D

erm

atos

is

Sita

l Pat

el, D

O1 ,

Nita

Koh

li, M

D1 ,

Bla

kely

Ric

hard

son,

DO

1 , K

evin

Coo

per,

MD

2 , K

ord

Hon

da, M

D2

1 Der

mat

olog

y R

esid

ent,

Uni

vers

ity H

ospi

tals

Cas

e M

ed C

tr, C

leve

land

, OH

, 2U

nive

rsity

Hos

pita

ls C

ase

Med

Ctr,

Cle

vela

nd, O

H

Bac

kgro

und

Per

sist

ent a

cant

holy

tic d

erm

atos

is w

as fi

rst d

escr

ibed

in 1

976

as p

ersi

sten

t sca

ly p

apul

es o

n th

e tru

nk a

nd e

xtre

miti

es, c

linic

ally

rese

mbl

ing

trans

ient

aca

ntho

lytic

der

mat

osis

. S

ince

then

ther

e ha

ve b

een

addi

tiona

l cas

es o

f per

sist

ent a

cant

holy

tic d

erm

atos

is

and

it is

thou

ght t

o be

mor

e pr

eval

ent i

n th

e po

pula

tion

and

larg

ely

unde

rdia

gnos

ed.1,

2

Mor

e re

cent

ly, p

ersi

sten

t aca

ntho

lytic

der

mat

osis

has

bee

n as

soci

ated

with

lent

igin

es.3

Figu

res

1 an

d 2.

Red

dish

bro

wn

papu

les

with

sca

le a

nd b

row

n m

acul

es o

n th

e lo

wer

and

upp

er e

xtre

miti

es.

Ref

eren

ces

1.S

imon

RS,

Blo

om D

, Ack

erm

an A

B. P

ersi

sten

t aca

ntho

lytic

der

mat

osis

. A v

aria

nt o

f tra

nsie

nt a

cant

holy

tic d

erm

atos

is (G

rove

r dis

ease

). A

rchi

ves

of D

erm

atol

ogy.

197

6;11

2,

1429

-143

1

2.Fa

wce

tt H

A an

d M

iller J

A.

Per

sist

ent a

cant

holy

tic d

erm

atos

is re

late

d to

act

inic

dam

age.

B

ritis

h Jo

urna

l of D

erm

atol

ogy.

198

3;10

9:34

9-35

4.

3.C

oope

r SM

, Dhi

ttava

t J, M

illard

P, B

urge

S.

Ext

ensi

ve G

rove

r’s-li

ke e

rupt

ion

with

le

ntig

inou

s ‘fr

eckl

ing’

: rep

ort o

f tw

o ca

ses.

Brit

ish

Jour

nal o

f Der

mat

olog

y. 2

004;

150:

350-

352.

4.

Gira

rd C

, Dur

and

L, G

uillo

t B, G

ildho

u JJ

, Bes

sis

D.

Per

sist

ent a

cant

holy

tic d

erm

atos

is

and

exte

nsiv

e le

ntig

inou

s ‘fr

eckl

ing’

: a n

ew e

ntity

? B

ritis

h Jo

urna

l of D

erm

atol

ogy.

20

05;1

53:2

17-2

18.

5. D

odd

HJ

and

Sar

kany

I. P

ersi

sten

t aca

ntho

lytic

der

mat

osis

. Clin

ical

and

exp

erim

enta

l

der

mat

olog

y. 1

984;

9:43

1-43

4.

Ack

now

ledg

men

ts

I wis

h to

than

k ou

r pat

ient

and

her

fam

ily fo

r the

ir tim

e an

d gr

acio

usne

ss

Dis

cuss

ion

Per

sist

ent a

cant

holy

tic d

erm

atos

is, f

irst d

escr

ibed

as

a va

riant

of t

rans

ient

aca

ntho

lytic

der

mat

osis

, is

char

acte

rized

by

pers

iste

nt p

rurit

ic p

apul

es a

nd v

esic

les

with

clin

ical

feat

ures

sim

ilar t

o G

rove

r’s d

isea

se, b

ut w

ith h

isto

logi

c fin

ding

s si

mul

atin

g D

arie

r’s d

isea

se.1,

2 T

hese

find

ings

wer

e in

itial

ly o

bser

ved

in m

ales

and

thou

ght t

o be

rela

ted

to a

ctin

ic d

amag

e. I

n 20

04, C

oope

r et a

l re

porte

d tw

o no

vel c

ases

of p

ersi

sten

t aca

ntho

lytic

der

mat

osis

ass

ocia

ted

with

sun

-indu

ced

lent

igin

es o

n th

e tru

nk a

nd le

gs in

two

fem

ale

patie

nts.

No

mut

atio

ns in

the

ATP

2A2

gene

wer

e fo

und

in th

e pa

tient

s. B

iops

y of

thes

e le

sion

s re

veal

ed a

cant

holy

tic d

yske

rato

sis,

sim

ilar t

o w

hat w

as s

een

in o

ur p

atie

nt.3

Two

addi

tiona

l cas

es, i

n bo

th s

exes

, hav

e be

en d

escr

ibed

in th

e lit

erat

ure,

whe

re th

e fre

cklin

g w

as in

sun

-pro

tect

ed a

reas

. Th

e pr

edom

inan

t ide

a in

thes

e ca

ses

was

the

pres

ence

of l

entig

ines

was

a re

sult

of p

ost i

nfla

mm

ator

y pi

gmen

tatio

n of

the

acan

thol

ytic

pap

ules

.4 T

reat

men

t of p

ersi

sten

t aca

ntho

lytic

der

mat

osis

has

bee

n m

ostly

uns

ucce

ssfu

l. T

opic

al tr

eatm

ents

suc

h as

retin

oids

, cal

cipo

triol

, 5-fl

uoro

urac

il, to

pica

l ste

roid

s, a

nd

cryo

ther

apy

have

sho

wn

eith

er n

o re

spon

se o

r min

imal

impr

ovem

ent o

f sho

rt du

ratio

n.2,

3,4 E

mol

lient

s ha

ve b

een

used

in th

e ba

th a

nd in

aqu

eous

cre

am to

con

trol p

rurit

us.3,

5 S

yste

mic

retin

oids

(a

citre

tin, e

tretin

ate)

hav

e sh

own

clea

ranc

e in

4 c

ases

, at d

oses

of 0

.25-

0.5

mg/

kg/d

ay w

ith d

urat

ion

rang

ing

from

6 w

eeks

to 6

mon

ths.

2,4,

5 Thi

s ef

ficac

y is

sim

ilar t

o th

at u

sed

in th

e tre

atm

ent o

f cl

assi

cal D

arie

r’s d

isea

se. O

ur p

atie

nt w

ill b

e tre

ated

with

topi

cal s

tero

ids

and

inte

nse

puls

ed li

ght t

hera

py d

irect

ed to

war

ds th

e le

ntig

ines

. S

eria

l pho

togr

aphs

will

be

take

n to

det

erm

ine

if th

e le

ntig

ines

follo

w, p

rece

de o

r are

inde

pend

ent o

f the

aca

ntho

lytic

pap

ular

lesi

ons.

Cas

e R

epor

t A

37-y

ear-o

ld w

oman

pre

sent

ed w

ith a

10-

year

his

tory

of m

ildly

pru

ritic

hyp

erpi

gmen

ted

mac

ules

and

ery

them

atou

s pa

pule

s th

at in

itial

ly s

tarte

d on

the

bila

tera

l leg

s an

d th

en p

rogr

esse

d to

her

arm

s, c

hest

, and

bac

k ov

er a

thre

e-m

onth

per

iod,

with

spa

ring

of th

e fa

ce a

nd n

eck.

The

pat

ient

den

ied

any

oral

lesi

ons.

She

repo

rted

that

the

lesi

ons

neve

r res

olve

com

plet

ely

but d

o lig

hten

on

occa

sion

. H

er p

ast m

edic

al h

isto

ry re

veal

ed c

hild

hood

lupu

s an

d ar

thrit

is.

Rev

iew

of s

yste

ms

was

pos

itive

for j

oint

pai

n bu

t oth

erw

ise

nega

tive.

Fam

ily h

isto

ry is

unk

now

n as

the

patie

nt is

ado

pted

. P

hysi

cal e

xam

inat

ion

reve

aled

redd

ish-

brow

n pa

pule

s w

ith s

cale

and

bro

wn

mac

ules

on

the

ches

t, ba

ck, a

rms

and

legs

with

spa

ring

of th

e fa

ce a

nd n

eck.

(Fig

ures

1 a

nd 2

) D

arie

r’s s

ign

was

ne

gativ

e an

d he

r nai

ls w

ere

norm

al.

The

rest

of t

he p

hysi

cal e

xam

inat

ion

was

unr

emar

kabl

e. L

abor

ator

y w

orku

p co

nsis

ting

of C

BC

, LFT

s, E

SR

, AN

A pa

nel,

BUN

and

cre

atin

ine

wer

e no

rmal

. A

biop

sy s

peci

men

was

take

n fro

m th

e rig

ht b

reas

t and

righ

t kne

e.

His

tolo

gic

exam

inat

ion

of th

e bi

opsy

spe

cim

ens

reve

aled

cen

tral p

arak

erat

osis

with

sup

raba

sila

r aca

ntho

lysi

s w

ith fo

rmat

ion

of o

ccas

iona

l cor

ps ro

nds

and

grai

ns a

nd c

entra

l par

aker

atos

is w

ith o

ccas

iona

l dys

kera

tosi

s re

spec

tivel

y. A

mild

sup

erfic

ial p

eriv

ascu

lar

lym

phoc

ytic

infil

trate

with

mel

anop

hage

s w

as a

lso

note

d (F

igur

es 3

a an

d 3b

).

.

Figu

res

3a a

nd 3

b. A

. Cen

tral p

arak

erat

osis

with

sup

raba

sala

r aca

ntho

lysi

s an

d su

perfi

cial

per

ivas

cula

r lym

phoc

ytic

in

filtra

te (h

emat

oxyl

in-e

osin

, orig

inal

mag

nific

atio

n x

10) B

. Sup

raba

sala

r aca

ntho

lysi

s (h

emat

oxyl

in-e

osin

, orig

inal

mag

nific

atio

n x

20)

271

QU

ICK

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(-

-TH

IS S

ECTI

ON

DO

ES N

OT

PRIN

T--)

This

Pow

erPo

int

tem

plat

e re

quir

es b

asic

Pow

erPo

int

(ver

sion

200

7 or

new

er)

skill

s. B

elow

is a

list

of

com

mon

ly a

sked

que

stio

ns s

peci

fic

to t

his

tem

plat

e.

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ou a

re u

sing

an

olde

r ve

rsio

n of

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erPo

int

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e te

mpl

ate

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ures

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k pr

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ly.

U

sing

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plat

e

Veri

fyin

g th

e qu

alit

y of

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r gr

aphi

cs

Go

to t

he V

IEW

men

u an

d cl

ick

on Z

OO

M t

o se

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ur

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erre

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agni

fica

tion

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is t

empl

ate

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the

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ill

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rint

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heir

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e. T

o se

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oom

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alit

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ntin

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Usi

ng t

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lace

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ers

To a

dd t

ext

to t

his

tem

plat

e cl

ick

insi

de a

pl

aceh

olde

r an

d ty

pe in

or

past

e yo

ur t

ext.

To

mov

e a

plac

ehol

der,

clic

k on

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nce

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ct it

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lace

yo

ur c

urso

r on

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e an

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urso

r w

ill c

hang

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s sy

mbo

l:

Then

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ick

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and

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g it

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tion

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ou c

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esiz

e it

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Addi

tion

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lace

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ers

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ound

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f th

is t

empl

ate.

M

odif

ying

the

layo

ut

This

tem

plat

e w

as s

peci

fica

lly d

esig

ned

for

a 48

x36

tri-

fold

pre

sent

atio

n. It

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yout

sho

uld

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chan

ged

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a st

anda

rd b

oard

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has

a

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umn

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ft,

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e m

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IEW

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Im

port

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phic

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ourc

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TEXT

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ste

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ype

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t in

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-exi

stin

g pl

aceh

olde

r or

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ew p

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er f

rom

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le

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ide

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he t

empl

ate.

Mov

e it

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whe

re a

s ne

eded

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OTO

S: D

rag

in a

pic

ture

pla

ceho

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st,

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k in

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nd in

sert

a p

hoto

fro

m t

he m

enu.

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BLES

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u ca

n co

py a

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aste

a t

able

fro

m a

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tern

al d

ocum

ent

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tem

plat

e. T

o ad

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e w

ay t

he t

ext

fits

wit

hin

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cells

of

a ta

ble

that

has

bee

n pa

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Four

th S

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t , U

nit C

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St

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our

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eboo

k pa

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Go

to P

oste

rPre

sent

atio

ns.c

om a

nd c

lick

on t

he F

B ic

on.

Infl

amm

ator

y lin

ear

verr

ucou

s ep

ider

mal

nev

us (

ILVE

N)

is a

n un

com

mon

con

diti

on t

hat

has

been

tre

ated

wit

h a

plet

hora

of

trea

tmen

ts.

This

incl

udes

top

ical

cor

tico

ster

oids

, da

pson

e,

cryo

surg

ery,

exc

isio

n, a

nd 5

-flu

orou

raci

l wit

h tr

etin

oin.

Res

ults

ha

ve b

een

mix

ed w

ith

no t

reat

men

t pr

otoc

ol o

r re

com

men

dati

ons.

W

e pr

esen

t a

case

of

ILVE

N in

a p

edia

tric

pat

ient

tha

t de

mon

stra

ted

clin

ical

impr

ovem

ent

whi

le o

n m

onot

hera

py o

f tr

etin

oin.

Ano

ther

im

port

ant

aspe

ct w

as t

hat

the

tret

inoi

n w

as a

t lo

w d

ose;

whi

ch

mak

es f

or s

afer

use

in p

edia

tric

pat

ient

s. W

ith

succ

ess

in o

ur

pati

ent,

mor

e cl

inic

ian

wou

ld c

onsi

der

trea

ting

oth

er IL

VEN

pat

ient

s w

ith

tret

inoi

n of

var

ying

str

engt

hs d

epen

ding

on

the

pati

ent’

s ag

e an

d ar

ea o

f in

volv

emen

t.

ABST

RACT

CASE

A s

have

bio

psy

was

per

form

ed o

n th

e su

peri

or a

spec

t of

the

for

ehea

d pl

aque

wit

hin

the

hair

line

. Th

e lo

cati

on w

as p

icke

d fo

r co

smet

ic r

easo

ns.

Pa

thol

ogy

repo

rt c

ame

back

as

hype

rker

atos

is,

para

kera

tosi

s al

tern

atin

g w

ith

orth

oker

atos

is,

psor

iasi

form

aca

ntho

sis,

wit

h pa

pillo

mat

osis

co

mpa

tibl

e w

ith

ILVE

N.

The

repo

rted

dia

gnos

is c

orre

late

d w

ith

the

pati

ent’

s hi

stor

y an

d ph

ysic

al e

xam

. Th

ese

plaq

ues

have

bee

n pr

evio

usly

di

agno

sed

as li

near

pso

rias

is,

atop

ic d

erm

atit

is,

tine

a in

fect

ion,

and

eve

n ep

ider

mal

nev

us.

Thes

e en

titi

es a

re c

omm

on d

iffe

rent

ial

diag

nose

s fo

r IL

VEN

. M

ost

freq

uent

ly,

the

his

tory

giv

en f

or t

hese

cas

es is

a le

sion

tha

t ha

s be

en r

esis

tant

to

typi

cal t

reat

men

ts r

esul

ting

in t

issu

e bi

opsy

yie

ldin

g th

e di

agno

sis

of IL

VEN

.

Nei

ther

the

pat

ient

or

the

pati

ent’

s m

othe

r co

uld

rem

embe

r th

e ex

act

nam

es o

f pr

evio

usly

use

d to

pica

l the

rapi

es,

so a

cla

ss V

(lo

w m

id s

tren

gth)

to

pica

l ste

roid

was

sta

rted

. H

e is

to

use

it t

wic

e da

ily o

n w

eekd

ays

and

hold

on

wee

kend

s to

red

uce

the

pote

ntia

l for

sid

e ef

fect

s. O

n on

e m

onth

fo

llow

up,

no

noti

ceab

le c

hang

e co

uld

be a

ppre

ciat

ed o

n ei

ther

lesi

ons.

Not

ing

that

bot

h pl

aque

s w

ere

still

hyp

erke

rato

tic

and

not

the

firs

t ti

me

faili

ng o

n co

rtic

oste

roid

the

rapy

, w

e co

nsid

ered

sta

rtin

g hi

m o

n a

topi

cal r

etin

oid.

Aft

er d

etai

led

disc

ussi

on w

ith

the

pati

ent

and

his

mot

her

rega

rdin

g ri

sks

and

bene

fits

of

ther

apy,

a t

rial

of

low

dos

e to

pica

l tre

tino

in (

0.02

5%)

once

dai

ly a

t be

dtim

e w

as s

tart

ed.

Alon

g w

ith

this

, th

e to

pica

l ste

roid

is t

o be

sto

pped

imm

edia

tely

. H

e w

as s

een

back

in c

linic

fou

r w

eeks

aft

er s

tart

ing

tret

inoi

n an

d th

ere

was

muc

h im

prov

emen

t in

th

e te

xtur

e of

the

pla

ques

. Al

so t

here

was

a

redu

ctio

n in

ery

them

a le

adin

g to

an

over

all d

ecre

ase

in n

otic

eabi

lity

of t

he le

sion

s, b

ut n

o ch

ange

in

size

. H

e w

as t

oler

atin

g th

is r

egim

en w

ell w

itho

ut a

ny s

ide

effe

cts.

He

was

to

cont

inue

wit

h th

is t

reat

men

t pl

an a

nd r

etur

n to

clin

ic in

thr

ee

mon

ths.

On

this

fol

low

up

, th

e le

sion

on

the

righ

t ch

eek

was

no

long

er p

alpa

ble

and

only

res

idua

l pos

t in

flam

mat

ory

hypo

pigm

enta

tion

(PI

H)

was

no

ted.

Whi

le t

he f

oreh

ead

lesi

on d

ecre

ased

in s

ize

to o

nly

6 cm

by

1.5

cm.

The

pati

ent’

s m

othe

r re

late

d th

at t

he r

etin

oid

was

cau

sing

the

tre

ated

ar

ea t

o be

ver

y dr

y .

They

wer

e ad

vise

d to

moi

stur

ize

the

affe

cted

are

a th

ree

tim

es d

aily

wit

h ge

ntle

ove

r th

e co

unte

r em

ollie

nts.

Pat

ient

will

co

ntin

ue t

o be

mon

itor

ed f

or f

urth

er im

prov

emen

t an

d an

y ad

vers

e ef

fect

s th

at m

ight

be

enco

unte

red.

TREA

MEN

T

Prio

r to

tre

atm

ent:

A

fter

fou

r m

onth

s tr

eatm

ent:

RESU

LTS

DISC

USS

ION

REFE

REN

CES

1. A

ltm

an J

, M

ehre

gan

AH.

Infl

amm

ator

y lin

ear

verr

ucou

s ep

ider

mal

nev

us.

Arc

h D

erm

atol

. O

ct

1971

;104

(4):

385-

9 2.

Kaw

aguc

hi H

, et

al.

Adu

lt o

nset

of

infl

amm

ator

y lin

ear

verr

ucou

s ep

ider

mal

nev

us.

J D

erm

atol

19

99;2

6:59

9.

3. H

amm

H,

Hap

ple

R. In

flam

mat

ory

linea

r ve

rruc

ous

epid

erm

al n

evus

(IL

VEN

) in

a m

othe

r an

d he

r da

ught

er.

Am J

Med

Gen

et.

1986

Aug

;24(

4):6

85-9

0.

4. D

ereu

re O

, et

al.

Infl

amm

ator

y lin

ear

verr

ucou

s ep

ider

mal

nae

vus

wit

h au

to-i

mm

une

thyr

oidi

tis:

Co

exis

tenc

e of

tw

o au

to-i

mm

une

epit

helia

l in

flam

mat

ions

? Ac

ta D

erm

Ven

ereo

l (S

tock

h) 1

994;

74:2

08.

5. A

l-En

ezi

S, e

t al

. In

flam

mat

ory

linea

r ve

rruc

ous

epid

erm

al n

evus

and

art

hrit

is:

a ne

w a

ssoc

iati

on.

J Pe

diat

r 20

01;1

38:6

02.

6. Z

huan

g L,

Wen

yuan

Z.

Infl

amm

ator

y lin

ear

verr

ucou

s ep

ider

mal

nev

us c

oexi

stin

g w

ith

liche

n am

yloi

dosi

s. J

Der

mat

ol 1

996;

23:4

15.

7. J

ong

E, R

ulo

HF,

Ker

khof

PC.

Infl

amm

ator

y lin

ear

verr

ucou

s ep

ider

mal

nev

us v

ersu

s lin

ear

psor

iasi

s. A

cl

inic

al,

hist

olog

ical

and

imun

nohi

stoc

hem

ical

stu

dy.

Acta

Der

m V

ener

eol.

199

1;71

:343

-6.

8. P

aixa

o M

, M

acha

do C

, It

o L,

Eno

kiha

ra M

, Li

near

pus

tula

r ps

oria

sis

X IL

VEN

- C

ase

repo

rt.

An

Bras

D

erm

atol

. 20

05;8

0(6)

:607

-10.

9.

Ki

m J

J, C

hang

MW

, Sh

way

der

T. T

opic

al t

reti

noin

and

5-f

luor

oura

cil

in t

he t

reat

men

t of

lin

ear

verr

ucou

s ep

ider

mal

nev

us.

J Am

Aca

d D

erm

atol

. 20

00 J

ul;4

3(1

Pt 1

):12

9-32

. 10

. Fo

x BJ

, La

pins

NA.

Com

pari

son

of t

reat

men

t m

odal

itie

s fo

r ep

ider

mal

nev

us:

a ca

se r

epor

t an

d re

view

. J

Der

mat

ol S

urg

Onc

ol 1

983;

9:

879–

885.

11

. Pa

nagi

otop

oulo

s A,

Cha

sapi

V,

Nik

olao

u V,

Sta

vrop

oulo

s P,

Kaf

ouro

s K,

Pet

ridi

s A,

Kat

sam

bas

A.

Asse

ssm

ent

of C

ryot

hera

py f

or t

he T

reat

men

t of

Ver

ruco

us E

pide

rmal

Nae

vi.

Acta

Der

m V

ener

eol

2009

; 89

: 29

2-29

4.

12.

Baba

T,

Nar

umi H

, H

anad

a K

Has

him

oto

I. S

ucce

ssfu

l tre

atm

ent

of d

ark-

colo

red

epid

erm

al n

evus

wit

h ru

by la

ser.

J D

erm

atol

199

5; 2

2: 5

67–5

70.

13.

Kauf

man

n R,

Hib

st R

. Pu

lsed

erb

ium

: YA

G l

aser

abl

atio

n in

cut

aneo

us s

urge

ry.

Lase

rs S

urg

Med

199

6;

19:

324–

330

14.

Jean

-Loi

c M

, Cr

isti

na H

, Va

lent

in H

. Re

surf

acin

g CO

2 La

ser

Trea

tmen

t of

Lin

ear

Verr

ucou

s Ep

ider

mal

N

evus

. Eu

rope

an J

ourn

al o

f D

erm

atol

ogy

2001

; 11

(5)

: 43

6-43

9.

15.L

ee B

J, M

anci

ni A

J, R

enuc

ci J

, Pa

ller

AS,

Baue

r BS

. Fu

ll-Th

ickn

ess

Surg

ical

Exc

isio

n fo

r th

e Tr

eatm

ent

of In

flam

mat

ory

Line

ar V

erru

cous

Epi

derm

al N

evus

. An

nals

of

Plas

tic

Surg

ery

2001

; 47

(3)

: 28

5-29

2.

16.

Renn

er R

, Co

lsm

an A

, St

iche

rlin

g M

. IL

VEN

: is

it p

sori

asis

? D

ebat

e ba

sed

on s

ucce

ssfu

l tre

atm

ent

wit

h et

aner

cept

. Ac

ta D

erm

Ven

ereo

l. 2

008;

88

(6):

631

-2.

17.

Renn

er R

, Ry

tter

M,

Stic

herl

ing

M.

Acit

reti

n tr

eatm

ent

of a

sys

tem

atiz

ed in

flam

mat

ory

linea

r ve

rruc

ous

epid

erm

al n

evus

. Ac

ta D

erm

Ven

ereo

l 20

05;

85:

348–

350.

18

. O

dom

R,

Dav

idso

hn I,

Jam

es W

, H

enry

J,

Berg

er T

. Cl

inic

al d

iagn

osis

by

labo

rato

ry m

etho

ds;

Dir

k M

. El

ston

(20

06).

And

rew

s' di

seas

es o

f th

e sk

in:

clin

ical

der

mat

olog

y. S

aund

ers

Else

vier

Subj

ecti

ve:

His

tory

of

Pres

ent

Illne

ss

Six

year

old

mal

e pr

esen

ts w

ith

two

disc

rete

“bi

rthm

arks

” th

at

star

ted

to d

evel

op a

ppro

xim

atel

y fo

ur y

ears

ago

. Th

ey a

re lo

cate

d on

the

for

ehea

d an

d ri

ght

chee

k. It

is o

nly

mild

ly it

chy,

but

his

mom

no

ted

that

he

scra

tche

s it

qui

te f

requ

entl

y. T

he c

heek

pla

que

was

sm

alle

r, b

ut t

he f

oreh

ead

star

ted

the

at s

ame

size

but

gre

w m

uch

larg

er.

Both

of

the

lesi

ons

have

pre

viou

sly

been

tre

ated

wit

h a

mul

titu

de o

f m

odal

itie

s th

at h

as y

ield

ed m

inim

al im

prov

emen

t. T

his

incl

ude

a se

ries

of

topi

cal m

oist

uriz

ers

and

topi

cal c

orti

cost

eroi

ds.

His

mot

her

was

rec

entl

y in

form

ed t

hat

he w

ill n

eed

lase

r or

sur

gica

l in

terv

enti

on t

o ge

t fu

rthe

r im

prov

emen

ts.

Past

Med

ical

His

tory

- m

et a

ll ap

prop

riat

e de

velo

pmen

tal

mile

ston

es.

He

was

not

a p

rem

atur

e ba

by o

r re

quir

ed p

ost

part

um

hosp

ital

izat

ion.

No

chro

nic

cond

itio

ns.

Pa

st S

urgi

cal

His

tory

- n

o pr

evio

us s

urge

ries

Pa

st F

amil

y H

isto

ry –

no

chro

nic

derm

atol

ogic

dis

ease

s.

All

ergi

es –

no

know

n dr

ug a

llerg

ies

(NKD

A)

Med

icat

ion

– no

ne b

esid

es p

revi

ousl

y pr

escr

ibed

top

ical

s O

bjec

tive

: Ph

ysic

al E

xam

Vi

tals

– w

ithi

n no

rmal

lim

its

Gen

eral

- a

wel

l app

eari

ng,

wel

l nou

rish

ed s

ix y

ear-

old

His

pani

c bo

y w

ho a

ppea

rs h

is s

tate

d ag

e.

Neu

ro -

Cra

nial

ner

ves

(CN

I –

XII)

inta

ct,

corr

ecti

ve g

lass

es f

or

visi

on.

Sk

in –

a li

near

, ro

ugh,

and

sca

ly 7

cm

by

2.5

cm p

laqu

e on

the

fo

rehe

ad,

slig

htly

rig

ht o

f th

e m

idlin

e th

at e

xten

ded

1 cm

into

the

sc

alp

line

supe

rior

ly w

ith

no in

volv

emen

t of

the

rig

ht e

yebr

ow

infe

rior

ly.

On

the

righ

t ch

eek,

a s

egm

enta

l, li

near

, ro

ugh,

and

sca

ly

plaq

ue t

hat

is 3

.7 c

m b

y 0.

3 cm

is n

oted

. M

ild e

ryth

ema

wit

hin

both

pl

aque

s bu

t no

t su

rrou

ndin

g it

. Al

so n

o si

gn o

f ex

cori

atio

n or

se

cond

ary

infe

ctio

n. T

he r

est

of t

he s

calp

was

wit

hin

norm

al li

mit

s,

no n

ail c

hang

es o

r in

volv

emen

t of

the

ext

rem

itie

s’ e

xten

sors

or

flex

ors

surf

aces

.

Ryan

Kha

nhho

ang

Pham

, D.O

. , S

tanl

ey R

ober

t Har

la, D

.O.

Uni

vers

ity o

f Nor

th Te

xas H

ealth

Sci

ence

Cen

ter

ILVE

N a

re c

onge

nita

l les

ions

tha

t co

mm

only

pre

sent

at

birt

h or

up

to 5

yea

rs o

f ag

e. It

was

fir

st r

epor

ted

by D

r. U

nna

back

in 1

896

(1).

Th

ey c

an o

ccur

dur

ing

adul

thoo

d as

wel

l (2)

. Se

en m

ore

com

mon

ly

in f

emal

es t

han

mal

es w

ith

a ra

tio

of 4

:1 a

nd u

sual

ly o

ccur

alo

ng

Blas

chko

’s li

nes

in e

ithe

r th

e up

per

or lo

wer

ext

rem

itie

s. N

o he

redi

tary

com

pone

nt h

as y

et b

een

eluc

idat

ed,

but

ther

e ha

s be

en

a ca

se o

f a

wom

an a

nd d

augh

ter

wit

h IL

VEN

(3)

. IL

VEN

is v

ery

uniq

ue

enti

ty t

hat

shar

es c

hara

cter

isti

cs o

f bo

th li

near

pso

rias

is a

nd o

f ep

ider

mal

nev

us.

Som

e re

sear

cher

s ha

ve u

sed

imm

unoh

isto

chem

istr

y as

a w

ay t

o di

ffer

enti

ate

betw

een

linea

r ps

oria

sis

and

ILVE

N (

7).

How

ever

, re

sult

s ha

ve n

ot le

ad t

o an

y re

com

men

dati

ons

for

its

use

in d

iffe

rent

iati

on o

f th

e tw

o di

agno

ses.

Co

mm

on f

irst

line

the

rapy

incl

ude

topi

cal e

mol

lient

s an

d co

rtic

oste

roid

s. V

itam

in D

ana

logs

can

als

o be

use

d in

com

bina

tion

w

ith

emol

lient

s to

rel

ieve

the

dry

ness

. To

pica

l dap

sone

was

use

d w

ith

muc

h su

cces

s in

one

cas

e (8

). In

the

pas

t th

ere

have

bee

n tw

o re

port

ed c

ases

of

trea

ting

ILVE

N w

ith

topi

cal 5

– F

luor

oura

cil (

5-FU

) in

con

junc

tion

wit

h to

pica

l tre

tino

in 0

.1%

crea

m;

alon

g w

ith

a ca

se

of c

ombi

ning

5-F

U w

ith

podo

phyl

lin (

9, 1

0).

Intr

ales

iona

l in

ject

ions

of

cor

tico

ster

oids

can

be

cons

ider

ed in

sol

itar

y, s

mal

l to

med

ium

si

zed

lesi

ons

that

are

rec

alci

tran

t to

top

ical

s. In

Gre

ece,

cr

yoth

erap

y w

as u

sed

to t

reat

sev

eral

loc

aliz

ed le

sion

s th

at y

ield

ed

posi

tive

res

ults

(11

). N

ew p

roce

dure

s th

at c

an h

elp

wit

h IL

VEN

in

clud

e ca

rbon

dio

xide

(CO

2),

puls

e ru

by,

and

ER:Y

AG la

ser

wit

h pr

omis

ing

resu

lts

(12,

13)

. Su

rgic

al e

xcis

ion

can

be c

onsi

dere

d de

pend

ing

on s

ize

and

loca

tion

of

lesi

ons.

Th

e dr

ug c

lass

ret

inoi

ds a

re m

etab

olit

es o

f vi

tam

in A

(re

tino

l) t

hat

bind

to

reti

noic

aci

d re

cept

ors

(RAR

) an

d re

tino

id x

rec

epto

rs (

RXR)

. Ph

arm

acol

ogic

eff

ects

and

sym

ptom

s ar

e di

rect

ly r

elat

ed t

o th

e co

ncen

trat

ion

of e

ach

rece

ptor

wit

hin

the

tiss

ue a

s w

ell a

s th

e af

fini

ty o

f th

e dr

ug f

or e

ach

resp

ecti

ve r

ecep

tor.

By

doin

g so

, th

ey

effe

ct t

he g

row

th a

nd d

iffe

rent

iati

on o

f ce

lls.

Whe

n ap

plie

d to

pica

lly,

it p

rom

otes

nor

mal

des

quam

atio

n of

ker

atin

ocyt

es a

nd

prov

ides

ant

i-in

flam

mat

ory

effe

cts

(18)

. G

iven

our

pat

ient

’s a

ge

and

loca

tion

of

the

lesi

ons,

top

ical

ret

inoi

d w

as c

onsi

dere

d th

e be

st

trea

tmen

t ch

oice

aft

er w

eigh

ing

the

risk

s an

d be

nefi

ts o

f ot

her

opti

ons.

Oth

er c

linic

ians

can

con

side

r us

ing

this

reg

imen

for

the

ir

ILVE

N p

atie

nts

that

hav

e no

t im

prov

ed w

ith

othe

r tr

eatm

ent

mod

alit

ies.

Trea

tmen

t of I

nfla

mm

ator

y Li

near

Ver

ruco

us E

pide

rmal

Nev

i with

Mon

othe

rapy

To

pica

l Ret

inoi

d

272

QU

ICK

TIPS

(-

-TH

IS S

ECTI

ON

DO

ES N

OT

PRIN

T--)

This

Pow

erPo

int

tem

plat

e re

quir

es b

asic

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erPo

int

(ver

sion

200

7 or

new

er)

skill

s. B

elow

is a

list

of

com

mon

ly

aske

d qu

esti

ons

spec

ific

to

this

tem

plat

e.

If y

ou a

re u

sing

an

olde

r ve

rsio

n of

Pow

erPo

int

som

e te

mpl

ate

feat

ures

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U

sing

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tem

plat

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Veri

fyin

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alit

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aphi

cs

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to t

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men

u an

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erre

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agni

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All

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phic

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valu

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hang

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mbo

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ou c

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ed.

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ate.

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This

tem

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iffe

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lum

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Rig

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back

grou

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k on

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la

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he c

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th

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e fi

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to V

IEW

an

d th

en S

LID

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ASTE

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Impo

rtin

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xt a

nd g

raph

ics

from

ext

erna

l sou

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TE

XT:

Past

e or

typ

e yo

ur t

ext

into

a p

re-e

xist

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plac

ehol

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or d

rag

in a

new

pla

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lder

fro

m t

he le

ft

side

of

the

tem

plat

e. M

ove

it a

nyw

here

as

need

ed.

PHO

TOS:

Dra

g in

a p

ictu

re p

lace

hold

er,

size

it f

irst

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ick

in it

and

inse

rt a

pho

to f

rom

the

men

u.

TABL

ES:

You

can

copy

and

pas

te a

tab

le f

rom

an

exte

rnal

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tem

plat

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IN

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ifyi

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his

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QU

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DES

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(--T

HIS

SEC

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-)

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is P

ower

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plac

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titl

es,

subt

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s, t

ext,

and

gra

phic

s.

Use

it t

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you

r pr

esen

tati

on.

Then

sen

d it

to

Post

erPr

esen

tati

ons.

com

for

pre

miu

m q

ualit

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day

affo

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W

e pr

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e a

seri

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f on

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tuto

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at w

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roug

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proc

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Pres

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tion

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866.

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ect

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Four

th S

tree

t , U

nit C

Ber

kele

y CA

947

10

p

oste

rpre

sent

er@

gmai

l.com

St

uden

t di

scou

nts

are

avai

labl

e on

our

Fac

eboo

k pa

ge.

Go

to P

oste

rPre

sent

atio

ns.c

om a

nd c

lick

on t

he F

B ic

on.

Back

grou

nd:

Moh

s su

rger

y is

one

of

the

mos

t ef

fect

ive

trea

tmen

t op

tion

s fo

r sk

in c

ance

rs a

s it

off

ers

one

of t

he h

ighe

st c

hanc

es f

or c

ure.

Moh

s su

rger

y is

a

prec

ise

tech

niqu

e th

at r

emov

es a

laye

r at

a t

ime.

Alt

houg

h th

is m

ay b

e ad

vant

ageo

us,

this

tre

atm

ent

met

hod

is d

iffi

cult

in p

atie

nts

wit

h im

mun

obul

lous

dis

ease

s. C

urre

ntly

, th

e gu

idel

ines

for

moh

s su

rger

y do

not

di

scus

s th

e pr

eman

agem

ent

of im

mun

obul

lous

pat

ient

s ab

out

to u

nder

go m

ohs

surg

ery.

O

bjec

tive

: To

adv

ocat

e fo

r in

crea

sing

pre

dnis

one

dose

in p

atie

nts

wit

h im

mun

obul

lous

dis

ease

pri

or t

o un

derg

oing

Moh

s su

rger

y.

Case

Rep

ort:

We

pres

ent

a ca

se o

f an

exc

isio

n of

a s

quam

ous

cell

carc

inom

a (S

CC)

from

a 9

4-ye

ar-o

ld w

oman

wit

h a

hist

ory

of p

emph

igus

vul

gari

s us

ing

Moh

s m

icro

grap

hic

surg

ery

(MM

S).

Co

nclu

sion

: Cu

rren

t pr

e-op

gui

delin

es f

or M

ohs

surg

ery

do n

ot a

ddre

ss t

he

issu

e of

alt

erin

g st

eroi

d m

edic

atio

ns f

or p

atie

nts

wit

h im

mun

obul

lous

dis

ease

pr

ior

to t

he p

roce

dure

. W

e su

gges

t th

at p

atie

nts

wit

h a

hist

ory

of

imm

unob

ullo

us d

isea

se u

nder

goin

g M

MS

shou

ld h

ave

an in

crea

se in

ste

roid

do

se p

rior

to

surg

ery.

Abst

ract

Case

Rep

ort

Disc

ussi

on

We

pres

ent

the

idea

of

impl

emen

ting

gui

delin

es f

or p

atie

nts

wit

h im

mun

obul

lous

dis

ease

abo

ut t

o un

derg

o M

MS.

Cur

rent

ly,

ther

e ar

e no

gu

idel

ines

in t

erm

s of

adj

usti

ng p

redn

ison

e in

pat

ient

s w

ith

imm

unob

ullo

us

dise

ase

abou

t to

und

ergo

MM

S.

Wit

h ill

def

ined

bor

ders

com

mon

ly o

ccur

ring

wit

h SC

C le

sion

s in

pat

ient

s w

ith

bullo

us d

isea

se,

MM

S is

mor

e ad

vant

ageo

us,

sinc

e it

allo

ws

for

tiss

ue s

pari

ng

whi

ch is

impe

rati

ve i

n th

ese

pati

ents

who

hav

e im

pair

ed w

ound

hea

ling

and

are

at in

crea

sed

risk

of

infe

ctio

n (1

). T

here

are

man

y ch

alle

nges

in p

erfo

rmin

g M

MS

in a

pat

ient

wit

h an

imm

unob

ullo

us d

isea

se.

The

se in

clud

e di

ffic

ulty

in

asse

ssin

g m

argi

ns d

urin

g M

MS

(1),

tis

sue

frag

ility

(1)

, po

or w

ound

hea

ling

seco

ndar

y to

a la

ck o

f ep

ider

mis

(2)

, an

d an

incr

ease

d ri

sk o

f po

st in

fect

ion

seco

ndar

y to

a n

on in

tact

epi

derm

al b

arri

er (

3).

Tiss

ue f

ragi

lity

com

plic

ates

clo

sure

in b

ullo

us d

isea

se (

1).

Alth

ough

def

ects

ca

n be

allo

wed

to

heal

by

seco

ndar

y in

tent

ion,

re-

epit

heliz

atio

n m

ay n

ot b

e ad

equa

te a

nd c

ause

poo

r w

ound

hea

ling

(2)

whi

ch m

ay a

llow

for

a r

ecur

renc

e of

ero

sion

or

ulce

rati

on (

3).

A pa

tien

t w

ho h

as a

non

inta

ct e

pide

rmal

bar

rier

is

mor

e pr

one

to in

crea

sed

risk

of

infe

ctio

n po

st s

urge

ry.

A st

rong

er a

nd in

tact

de

rmis

pri

or t

o su

rger

y ca

n be

acc

ompl

ishe

d by

incr

easi

ng s

tero

id d

ose

prio

r to

sur

gery

.

To o

ur k

now

ledg

e, t

here

has

onl

y be

en o

ne d

ocum

ente

d ca

se o

f m

argi

ns b

eing

di

ffic

ult

to a

sses

s in

a p

atie

nt w

ith

a bu

llous

dis

ease

(1)

, al

thou

gh t

his

may

al

read

y be

a c

omm

on s

cena

rio

for

derm

atol

ogis

ts w

ho h

ave

cond

ucte

d M

MS

in

pati

ents

wit

h bu

llous

dis

ease

. S

axen

a et

al.

indi

cate

tha

t th

e su

rgeo

n an

d te

chni

cian

sho

uld

exer

cise

ext

rem

e ca

re t

o m

aint

ain

the

inte

grit

y of

the

ti

ssue

sin

ce t

he e

pide

rmis

ten

ds t

o di

ssoc

iate

fro

m t

he d

erm

is d

urin

g M

MS

in

pati

ents

wit

h ep

ider

mol

ysis

bul

losa

(1)

. Th

e au

thor

s al

so r

ecom

men

d a

fres

h sc

alpe

l bl

ade

for

each

laye

r an

d a

shar

p cr

yost

atic

kni

fe t

o m

inim

ize

epid

erm

al s

epar

atio

n on

fro

zen

sect

ions

. O

ther

sug

gest

ions

incl

ude

com

plet

e ti

ssue

fre

ezin

g, w

ith

the

addi

tion

of

cryo

gen

spra

y or

hea

t ex

trac

tion

to

help

de

crea

se s

hear

ing

forc

es a

nd a

llow

for

eas

ier

froz

en s

ecti

ons.

Fur

ther

re

com

men

dati

ons

incl

ude

para

ffin

em

bedd

ing

wit

h ho

rizo

ntal

ori

enta

tion

(“

slow

Moh

s”)

if n

eede

d. M

oreo

ver,

dur

ing

the

appl

icat

ion

of d

ress

ings

, ad

diti

onal

car

e m

ust

be t

aken

to

avoi

d ti

ssue

tra

uma.

W

e be

lieve

tha

t m

ost

of t

hese

str

inge

nt m

easu

res

can

be p

reve

nted

by

incr

easi

ng s

tero

id d

osag

e pr

ior

to s

urge

ry.

In

our

exp

erie

nce,

alt

houg

h M

MS

prov

ides

pre

cise

mar

gin

cont

rol,

it is

in

adeq

uate

sin

ce e

pide

rmis

doe

s no

t pr

esen

t du

ring

cro

ss s

ecti

on.

Spec

ial

atte

ntio

n an

d ex

tra

effo

rt t

o ti

ssue

han

dlin

g, p

roce

ssin

g, m

icro

scop

ic

eval

uati

on,

clos

ure

tech

niqu

e, a

nd p

osto

pera

tive

wou

nd c

are

can

all b

e m

inim

ized

wit

h an

incr

ease

in s

tero

ids.

Refe

renc

es

Saxe

na,

A.,

Lee,

J.

B. a

nd H

umph

reys

, T.

R.

(200

6),

Moh

s M

icro

grap

hic

Surg

ery

for

Squa

mou

s Ce

ll Ca

rcin

oma

Asso

ciat

ed w

ith

Epid

erm

olys

is B

ullo

sa.

Der

mat

olog

ic S

urge

ry,

32:

128–

134.

doi

: 10

.111

1/15

24-4

725.

2006

.320

21

Swen

sson

O,

Chri

stop

hers

E.

Gen

eral

ized

atr

ophi

c be

nign

epi

derm

olys

is b

ullo

sa i

n 2

sibl

ings

com

plic

ated

by

mul

tipl

e sq

uam

ous

cell

carc

inom

as.

Arch

Der

mat

ol 1

998;

134:

199

– 2

03.

Terr

ill P

J, M

ayou

BJ,

McK

ee P

H,

Eady

RAJ

. Th

e su

rgic

al m

anag

emen

t of

dys

trop

hic

epid

erm

olys

is b

ullo

sa (

excl

udin

g th

e ha

nd).

Br

J Pl

ast

Surg

199

2;45

:426

–34.

A 94

yea

r-ol

d Ca

ucas

ian

fem

ale

wit

h no

pri

or h

isto

ry o

f sk

in c

ance

r pr

esen

ted

for

eval

uati

on o

f a

crus

ting

pla

que

on h

er m

id b

ack

whi

ch h

ad b

een

pres

ent

for

6 m

onth

s. T

he p

atie

nt´s

pas

t m

edic

al h

isto

ry w

as s

igni

fica

nt f

or

pem

phig

us v

ulga

ris

for

the

last

20

year

s w

hich

she

was

on

pred

niso

ne 2

.5m

g da

ily.

The

pati

ent

repo

rted

no

alle

rgie

s. S

he d

enie

d sm

okin

g an

d de

nied

al

coho

l use

. Re

view

of

syst

ems

was

unr

emar

kabl

e an

d ph

ysic

al e

xam

inat

ion

reve

aled

a w

ell-

deve

lope

d, w

ell-

nour

ishe

d fe

mal

e. U

pon

com

plet

e sk

in

exam

inat

ion,

the

mid

bac

k pr

esen

ted

wit

h a

5 cm

x 4

cm

ery

them

atou

s, w

axy,

an

d cr

usty

pla

que

(Fig

ure

1).

The

surr

ound

ing

area

s of

ski

n w

ere

exam

ined

an

d no

oth

er s

uspi

ciou

s le

sion

s w

ere

note

d. T

he le

sion

was

bio

psie

d an

d a

diag

nosi

s of

squ

amou

s ce

ll ca

rcin

oma

(SCC

) w

as e

stab

lishe

d.

On

the

sche

dule

d da

y of

sur

gery

, th

e pa

tien

t di

d ha

ve a

new

ora

l ulc

er o

n he

r le

ft b

ucca

l m

ucos

a. T

he p

atie

nt d

id n

ot

exhi

bit

any

othe

r ac

tive

les

ions

. H

owev

er,

duri

ng c

uret

tage

and

the

inci

sion

, he

r sk

in

beca

me

posi

tive

for

Nik

olsk

y si

gn a

nd t

he

epid

erm

is s

loug

hed

off

imm

edia

tely

(F

igur

e 2)

. Th

e sq

uam

ous

cell

carc

inom

a w

as t

hen

exci

sed

wit

h w

ider

mar

gins

usi

ng

Moh

s m

icro

grap

hic

surg

ery

(MM

S) in

one

st

age.

In c

oncl

usio

n, t

he M

MS

perf

orm

ed o

n ou

r pa

tien

t tu

rned

out

to

be q

uite

ch

alle

ngin

g. T

hus

we

sugg

est

incr

easi

ng

pred

niso

ne p

rior

to

surg

ery

in o

rder

to

wor

k w

ith

a m

ore

inta

ct e

pide

rmis

, ev

en

in p

atie

nts

who

app

ear

to h

ave

thei

r di

seas

e un

der

cont

rol.

Thi

s w

ill p

rom

ote

grea

ter

inta

ct e

pide

rmis

, th

us a

llow

ing

mor

e ac

cura

te m

argi

n di

agno

stic

s, e

asie

r cl

osur

e, a

nd le

ss p

ossi

bilit

y of

pos

t pr

oced

ure

infe

ctio

n of

the

sit

e.

anym

ore.

A c

ompr

essi

on d

ress

ing

cons

isti

ng o

f xe

rofo

rm w

as u

sed

to a

void

the

us

e of

adh

esiv

e ta

pe o

n su

rrou

ndin

g ti

ssue

tha

t ha

d be

com

e pr

one

to

blis

teri

ng.

Our

goa

l was

to

avoi

d ad

hesi

ves

alto

geth

er,

sinc

e th

ey f

urth

er

trau

mat

ize

the

frag

ile s

kin.

The

pat

ient

ret

urne

d fo

r he

r 2

wee

k fo

llow

up

for

sutu

re r

emov

al a

nd w

as d

iagn

osed

wit

h M

RSA

infe

ctio

n. T

his

was

sub

sequ

entl

y cu

ltur

ed,

and

trea

ted

wit

h do

xycy

line.

The

pat

ient

ret

urne

d 1

wee

k th

erea

fter

for

sut

ure

rem

oval

and

hea

led

wel

l wit

h no

oth

er c

ompl

icat

ions

.

Figu

re 1

- L

eft

Upp

er B

ack

– Pr

e-op

Furt

herm

ore,

clo

sing

the

lesi

on w

as

very

dif

ficu

lt (

Figu

re 3

). T

he d

efec

t w

as r

epai

red

utili

zing

3-0

Vic

ryl a

nd

4-0

Nyl

on w

hich

wer

e pl

aced

fro

m

oppo

site

edg

es o

f th

e de

fect

spa

nnin

g th

e w

idth

of

the

open

ing

to m

inim

ize

tens

ion

at t

he w

ound

edg

es.

Dur

ing

mic

rosc

opic

exa

min

atio

n of

the

fro

zen

sect

ion,

it w

as d

iffi

cult

to

asse

ss if

the

m

argi

ns w

ere

still

pos

itiv

e fo

r ca

ncer

be

caus

e th

e ep

ider

mis

was

not

pre

sent

*Jus

tin R

ubin

, D.O

. **

Khas

ha T

oulo

ei, D

.O. *

** T

racy

Fav

reau

, D.O

. **

** M

artin

Zai

ac, M

D **

***

Shin

o Ba

y, D

.O.,

FAO

CD

*Sec

ond

Year

Der

mat

olog

y Re

side

nt, N

SUCO

M/B

GM

C, F

t. La

uder

dale

, FL*

* 1st

Yea

r, Tr

aditi

onal

Rot

atin

g In

tern

ship

, Lar

go

Med

ical

Cen

ter *

** C

hairm

an o

f Der

mat

olog

y N

SUCO

M/B

GM

C, F

t. La

uder

dale

, FL*

***

Dire

ctor

of t

he D

epar

tmen

t of

Derm

atol

ogy,

Mou

nt S

inai

Med

ical

Cen

ter

****

* Re

side

ncy

Trai

ning

Pro

gram

Dire

ctor

, NSU

COM

/BG

MC,

Ft.

Laud

erda

le, F

L

Moh

s Sur

gery

in P

atie

nts w

ith Im

mun

obul

lous

Dis

ease

s: S

houl

d Pr

edni

sone

be

Incr

ease

d Pr

ior t

o Su

rger

y?

Figu

re 2

- In

tra-

op

Figu

re 3

– P

ost

op

273

Pote

ntia

l Com

plic

atio

ns o

f Ps

oria

sis

Ther

apy:

A C

ase

Repo

rt a

nd

Revi

ew o

f Ca

tast

roph

ic A

ntip

hosp

holip

id S

yndr

ome

(CA

PS)

Nic

hola

s A

. Rud

loff

, D.O

.* an

d Sc

hiel

d M

. Wik

as, D

.O.,

DF,

FA

OCD

**O

hio

Uni

vers

ity

Colle

ge o

f O

steo

path

ic M

edic

ine

Sum

ma

Wes

tern

Res

erve

Hos

pita

l, Cu

yaho

ga F

alls

, OH

, USA

*Der

mat

olog

y Re

side

nt (P

GY-

5), S

WRH

, **D

erm

atol

ogy

Resi

denc

y Pr

ogra

m D

irec

tor,

SWRH

Cata

stro

phic

ant

ipho

spho

lipid

syn

drom

e (C

APS

) is

a ra

re c

ondi

tion

tha

t m

akes

up

a sm

all s

ubse

t of

pat

ient

s w

ith

anti

phos

phol

ipid

syn

drom

e (A

PS).

It in

volv

es a

dra

mat

ic, a

ccel

erat

ed f

orm

of

APS

whi

ch r

esul

ts in

mul

ti-o

rgan

fa

ilure

and

a h

igh

mor

talit

y ra

te. T

o da

te, n

o ca

ses

of C

APS

hav

e be

en

repo

rted

in p

atie

nts

whi

le o

n et

aner

cept

for

tre

atm

ent

of c

hron

ic p

atch

and

pl

aque

pso

rias

is v

ulga

ris.

We

desc

ribe

a 5

1-ye

ar-o

ld m

ale

who

pre

sent

ed

wit

h “fl

u-lik

e” s

ympt

oms

whi

le o

n sy

stem

ic b

iolo

gic

ther

apy,

eta

nerc

ept.

H

e de

velo

ped

rapi

d on

set

of m

ulti

ple

thro

mbo

embo

li an

d a

sequ

ence

of

life-

thre

aten

ing

even

ts; h

e w

as d

iagn

osed

wit

h CA

PS. T

his

case

rep

ort

exhi

bits

pot

enti

al r

are

com

plic

atio

ns in

the

man

agem

ent

of p

sori

asis

and

re

view

s CA

PS in

clud

ing

clin

ical

pre

sent

atio

n, m

anag

emen

t an

d di

scus

sion

.

Case

Des

crip

tion

1. V

ora

SK, A

sher

son

RA, E

rkan

D. C

atas

trop

hic

antip

hosp

holip

id s

yndr

ome.

J In

tens

ive

Care

Med

. 200

6; 2

1:14

4-15

9.2.

Ber

mas

B, e

t al.

Clin

ical

man

ifest

atio

ns o

f the

ant

ipho

spho

lipid

syn

drom

e. U

ptod

ate.

201

0; D

ate

acce

ssed

2/9

/11.

3.

Buc

ciar

elli

S, E

spin

osa

G, C

erve

ra R

. The

CAP

S Re

gist

ry: m

orbi

dity

and

mor

talit

y of

the

cata

stro

phic

ant

ipho

spho

lipid

syn

drom

e. L

upus

. 200

9;18

:905

-912

.4.

Cer

vera

R, e

t al.

Cata

stro

phic

ant

ipho

spho

lipid

syn

drom

e (C

APS)

: upd

ate

from

the

‘CAP

S Re

gist

ry.’

Lupu

s. 2

010;

19:4

12-4

18.

5. C

erve

ra R

, Esp

inos

a G,

Buc

ciar

elli

S, e

t al.

Less

ons

from

the

cata

stro

phic

ant

ipho

spho

lipid

syn

drom

e (C

APS)

reg

istr

y. A

utoi

mm

unity

Rev

iew

s 6.

200

6;81

-84.

6. A

than

azio

D, e

t al.

Chro

nic

cata

stro

phic

-lik

e an

tipho

spho

lipid

syn

drom

e: a

“sm

olde

ring”

var

iant

? Rh

eum

atol

Int.

2009

;30:

123-

125.

7. S

olte

sz P

, et a

l. Ca

tast

roph

ic a

ntip

hosp

holip

id s

yndr

ome

in c

ance

r. H

aem

atol

ogia

. 200

0;30

(4):3

03-3

11.

8. B

ayra

ktar

U, e

t al.

The

clin

ical

spe

ctru

m o

f cat

astr

ophi

c an

tipho

spho

lipid

syn

drom

e in

the

abse

nce

and

pres

ence

of l

upus

. Jou

rnal

of R

heum

atol

ogy.

200

7;34

(2):

346-

352.

9. A

sher

son

RA, e

t al.

Dis

sem

inat

ed in

trav

ascu

lar

coag

ulat

ion

in c

atas

trop

hic

antip

hosp

holip

id s

yndr

ome:

clin

ical

and

hae

mat

olog

ical

cha

ract

eris

tics

of 2

3 pa

tient

s. A

nn

Rheu

m D

is. 2

005;

64:9

43-9

46.

10.

Kim

S, e

t al.

Cata

stro

phic

ant

ipho

spho

lipid

syn

drom

e tr

igge

red

by s

epsi

s. H

SSJ.

2009

;5:6

7-72

.11

. M

agee

CC,

et a

l. Ca

se 2

-200

8: A

38-

year

-old

wom

an w

ith p

ostp

artu

m v

isua

l los

s, s

hort

ness

of b

reat

h, a

nd r

enal

failu

re. N

Eng

l J M

ed. 2

008;

358:

275-

289.

12

. As

hers

on R

A, C

erve

ra R

, de

Groo

t PG,

et a

l. Ca

tast

roph

ic a

ntip

hosp

holip

id s

yndr

ome:

inte

rnat

iona

l con

sens

us s

tate

men

t on

clas

sific

atio

n cr

iteria

and

trea

tmen

t gu

idel

ines

. Lup

us. 2

003;

12:5

30-5

34.

13.

Ashe

rson

RA,

Sho

enfe

ld Y

. The

rol

e of

infe

ctio

n in

the

path

ogen

esis

of c

atas

trop

hic

antip

hosp

holip

id s

yndr

ome-

mol

ecul

ar m

imic

ry?

Jour

nal o

f Rhe

umat

olog

y.

2000

;27(

1):2

012-

2014

.14

. Ca

npol

at N

, et a

l. A

case

of c

atas

trop

hic

antip

hosp

holip

id s

yndr

ome

in a

n ad

oles

cent

girl

with

par

vovi

rus

B19

infe

ctio

n. C

linic

al P

edia

tric

s. 2

008;

47(6

):593

-597

.15

. Id

eguc

hi H

, Ohn

o S,

Ishi

gats

ubo

Y. C

atas

trop

hic

antip

hosp

holip

id s

yndr

ome

asso

ciat

ed w

ith m

alig

nanc

ies

(cas

e re

port

and

rev

iew

of t

he li

tera

ture

). Lu

pus.

20

07;1

6:59

-64.

16.

Wes

tney

G, H

arris

NE.

Cat

astr

ophi

c an

tipho

spho

lipid

syn

drom

e in

the

inte

nsiv

e ca

re u

nit.

Crit

Care

Clin

. 200

2;18

:805

-817

.17

. As

hers

on R

. Mul

tiorg

an fa

ilure

and

ant

ipho

spho

lipid

ant

ibod

ies:

the

cata

stro

phic

ant

ipho

spho

lipid

(Ash

erso

n’s)

syn

drom

e. Im

mun

onbi

olog

y. 2

005;

210:

727-

733.

18.

Peng

o V,

et a

l. An

ti B2

-gly

copr

otei

n I a

ntib

odie

s in

a p

atie

nt w

ith c

atas

trop

hic

antip

hosp

holip

id s

yndr

ome.

Clin

ical

rhe

umat

olog

y. 1

995;

14(6

):646

-649

.19

. Er

kan

D, L

ocks

hin

MD

. New

trea

tmen

ts fo

r an

tipho

spho

lipid

syn

drom

e. R

heum

Dis

Clin

N A

m. 2

006;

32:1

29-1

48.

20.

Erka

n D

, Cer

vera

R, A

sher

son

RA. C

atas

trop

hic

antip

hosp

holip

id s

yndr

ome:

whe

re d

o w

e st

and?

Art

hriti

s an

d Rh

eum

atis

m. 2

003;

48(1

2):3

320-

3327

.21

. N

euw

elt C

M, e

t al.

Cata

stro

phic

ant

ipho

spho

lipid

syn

drom

e: r

espo

nse

to r

epea

ted

plas

map

here

sis

over

thre

e ye

ars.

Art

hriti

s an

d Rh

eum

atis

m. 1

997;

40(8

):153

4-15

39.

Refe

renc

es

Abs

trac

t

CA

PS D

iagn

ostic

Cri

teri

a:1.

Clin

ical

evi

denc

e of

mul

tiple

org

an in

volv

emen

t de

velo

ping

ove

r a v

ery

shor

t per

iod

of ti

me.

2. H

isto

path

olog

ical

evi

denc

e of

mul

tiple

smal

l ves

sel

occl

usio

ns.

3. L

abor

ator

y co

nfirm

atio

n of

the

pres

ence

of

antip

hosp

holip

id a

ntib

odie

s, us

ually

in a

hig

h tit

er.

Figu

res

Dis

cuss

ion

A 5

1-ye

ar-o

ld c

auca

sian

mal

e pr

esen

ted

to t

he o

utpa

tien

t de

rmat

olog

y cl

inic

for

rou

tine

fol

low

-up

for

chro

nic

patc

h an

d pl

aque

pso

rias

is (F

ig. 1

). U

pon

revi

ew o

f sy

stem

s, t

he p

atie

nt d

escr

ibed

“flu

-lik

e” s

ympt

oms

for

seve

ral m

onth

s in

clud

ing:

fev

er, c

hills

, nig

ht s

wea

ts, w

eakn

ess,

fat

igue

and

ar

thra

lgia

s in

his

han

ds w

ith

asso

ciat

ed s

wel

ling.

Past

med

ical

his

tory

was

sig

nific

ant

for

at le

ast

a tw

enty

-yea

r hi

stor

y of

ch

roni

c pa

tch

and

plaq

ue t

ype

psor

iasi

s vu

lgar

is.

Ther

apeu

tic

stra

tegy

co

nsis

ted

of t

opic

al t

hera

py a

nd s

yste

mic

bio

logi

c th

erap

y et

aner

cept

25m

g su

bcut

aneo

usly

tw

ice

wee

kly

for

psor

iasi

s ov

er a

ppro

xim

atel

y th

e pa

st

thre

e ye

ars.

On

init

ial p

rese

ntat

ion,

the

pat

ient

app

eare

d in

no

dist

ress

. H

e ex

hibi

ted

sign

ifica

nt b

ilate

ral a

xilla

ry ly

mph

aden

opat

hy u

pon

palp

atio

n an

d ha

d ha

nd

swel

ling

invo

lvin

g th

e m

etac

arpa

l-ph

alan

geal

join

ts a

nd p

roxi

mal

in

terp

hala

ngea

l joi

nts

of b

oth

hand

s. T

he p

atie

nt w

as o

rder

ed p

rom

pt

labo

rato

ry e

valu

atio

n an

d ch

est

radi

ogra

phy

rega

rdin

g hi

s sy

mpt

oms.

A

lso,

wit

h co

ncer

n fo

r an

und

erly

ing

mal

igna

ncy,

the

pat

ient

was

ref

erre

d to

hem

atol

ogy/

onco

logy

for

con

sult

atio

n. I

niti

al la

bs:

-Ele

vate

d rh

eum

atoi

d fa

ctor

of

443

U/m

L-E

ryth

rocy

te s

edim

enta

tion

rat

e of

22

mm

/hr.

-LFT

’s, A

NA

, ACE

, tot

al c

ompl

emen

t ac

tivi

ty (C

H50

), se

rum

cry

oglo

bulin

s an

d SP

EP w

ere

all u

nrem

arka

ble.

-P

erip

hera

l sm

ear

reve

aled

a le

ukoc

ytos

is a

nd a

thr

ombo

cyto

sis

cons

iste

nt

wit

h re

acti

ve c

hang

es.

-Che

st r

adio

grap

h sh

owed

mul

tipl

e lu

ng n

odul

es in

the

bila

tera

l upp

er

lobe

s, t

he t

wo

larg

est

mea

suri

ng 1

3.3m

m in

the

rig

ht u

pper

lobe

and

15

.2m

m in

the

left

upp

er lo

be (F

ig. 2

).

Ove

r th

e co

urse

of

the

next

day

, the

pat

ient

dev

elop

ed s

ever

e ba

ck p

ain

and

bila

tera

l leg

dis

com

fort

. He

pres

ente

d to

a lo

cal c

omm

unit

y em

erge

ncy

depa

rtm

ent

and

was

fou

nd t

o ha

ve a

bsen

t bi

late

ral l

ower

ext

rem

ity

puls

es.

Com

pute

rize

d To

mog

raph

y A

ngio

gram

(CTA

) of

the

ches

t, ab

dom

en a

nd

pelv

is w

ith

bila

tera

l low

er e

xtre

mit

y ru

n-off

s sh

owed

diff

use

arte

rial

th

rom

bi in

the

aor

ta a

nd a

sad

dle

embo

lism

at

the

aort

oilia

c bi

furc

atio

n ex

tend

ing

into

the

left

com

mon

ilia

c ar

tery

(Fig

. 3).

Add

itio

nally

, inf

arct

ions

of

the

spl

een

and

kidn

eys

wer

e no

ted

(Fig

. 4).

The

pat

ient

was

imm

edia

tely

tr

ansf

erre

d to

a t

erti

ary

care

cen

ter.

He

unde

rwen

t m

ulti

ple

proc

edur

es

incl

udin

g em

erge

nt t

hrom

boem

bole

ctom

y an

d w

as t

reat

ed f

or a

nem

ia,

leuk

ocyt

osis

, thr

ombo

cyto

peni

a, S

TEM

I, ac

ute

rena

l fai

lure

, acu

te

resp

irat

ory

failu

re w

ith

mec

hani

cal v

enti

lati

on, s

yste

mic

infla

mm

ator

y re

spon

se s

yndr

ome

(SIR

S), m

ulti

ple

arte

rial

thr

ombi

, ren

al a

nd s

plen

ic

infa

rcts

. Fu

rthe

r la

bora

tory

stu

dies

rev

eale

d an

ele

vate

d an

tica

rdio

lipin

an

tibo

dy t

iter

. H

e w

as d

iagn

osed

wit

h ca

tast

roph

ic a

ntip

hosp

holip

id

synd

rom

e (C

APS

). A

fter

a t

wen

ty d

ay h

ospi

taliz

atio

n th

e pa

tien

t w

as

disc

harg

ed h

ome

in s

tabl

e co

ndit

ion.

Cata

stro

phic

ant

ipho

spho

lipid

syn

drom

e (C

APS

) is

a ra

re, l

ife-

thre

aten

ing,

w

ides

prea

d co

agul

opat

hy c

onsi

stin

g of

rap

id o

nset

of

vasc

ular

th

rom

boem

bolis

ms

that

oft

en r

esul

ts in

dea

th.1,

2

Curr

entl

y, it

com

pris

es 1

% o

f ca

ses

of A

PS.3

Mor

talit

y ra

tes

appr

oach

50%

.3-5

Mos

t ca

ses

aris

e de

nov

o (p

rim

ary)

, wit

hout

pre

viou

s hi

stor

y of

thr

ombo

sis,

3,6

but

It c

an a

lso

be a

ssoc

iate

d w

ith

othe

r au

toim

mun

e co

ndit

ions

(s

econ

dary

), su

ch a

s sy

stem

ic lu

pus

eryt

hem

atos

us, s

yste

mic

scl

eros

is a

nd

rheu

mat

oid

arth

riti

s.6-

8

Mor

e th

an h

alf

of t

he C

APS

cas

es a

re a

ssoc

iate

d w

ith

a pr

ecip

itat

ing

even

t su

ch a

s in

fect

ions

, sur

gery

, tra

uma,

neo

plas

ms

and

othe

rs. D

iagn

osis

can

be

mad

e w

ith

crit

eria

list

ed in

Fig

ure

5.9-

17

Alm

ost

all o

rgan

sys

tem

s ca

n be

invo

lved

in t

he s

pect

rum

of

CAPS

(Fig

. 6)

The

mos

t co

mm

on la

bora

tory

tes

ting

use

d to

det

ect

anti

phos

phol

ipid

an

tibo

dies

are

the

lupu

s an

tico

agul

ant

test

, ant

icar

diol

ipin

ant

ibod

y,

enzy

me

linke

d im

mun

osor

bent

ass

ay (E

LISA

) and

ant

i-B2

-gly

copr

otei

n-I

anti

body

ELI

SA.18

,19

Trea

tmen

t re

volv

es a

roun

d ea

rly

diag

nosi

s an

d ag

gres

sive

the

rapi

es.

The

mos

t pr

oven

the

rape

utic

str

ateg

ies

incl

ude:

ant

icoa

gula

tion

, co

rtic

oste

roid

s, p

lasm

a ex

chan

ge a

nd in

trav

enou

s im

mun

oglo

bulin

.20,2

1 T

he

com

bina

tion

of

thes

e st

rate

gies

hav

e be

en a

ssoc

iate

d w

ith

reco

very

rat

es

rang

ing

from

50-

80%

.12,1

9

Our

pat

ient

sur

vive

d an

d w

as d

isch

arge

d ho

me

from

the

hos

pita

l on

day

20. A

t 6

mon

th f

ollo

w u

p th

e pa

tien

t w

as s

till

livin

g an

d hi

s lo

ng-t

erm

pr

ogno

sis

is g

ood.

Th

e ro

le o

f et

aner

cept

in c

ontr

ibut

ing

to t

he c

ompl

icat

ions

of

our

pati

ent

is

diffi

cult

to

dete

rmin

e. C

once

rn f

or a

n in

fect

ious

pro

cess

tri

gger

ing

the

casc

ade-

effec

t of

CA

PS w

as a

pos

sibi

lity.

Als

o, a

n un

derl

ying

mal

igna

ncy

was

a m

ajor

con

side

rati

on in

the

init

ial w

orku

p. E

tane

rcep

t ha

s be

en

asso

ciat

ed w

ith

both

. Ce

rtai

nly,

the

re is

an

argu

men

t fo

r a

com

plet

ely

inde

pend

ent

proc

ess

such

as

a ne

w-o

nset

rhe

umat

oid

arth

riti

s. T

he

gene

ral c

onse

nsus

am

ong

the

heal

thca

re p

rovi

ders

in t

his

spec

ific

case

was

th

at e

tane

rcep

t pl

ayed

a r

ole

in t

he d

evel

opm

ent

of C

APS

; how

ever

, no

expl

icit

evi

denc

e ex

ists

to

prov

e th

is.

Alt

houg

h th

e ex

act

prec

ipit

atin

g fa

ctor

of

CAPS

in t

his

pati

ent

is d

ifficu

lt t

o pi

npoi

nt, t

his

case

rep

ort

does

re

veal

pot

enti

al r

are

com

plic

atio

ns t

hat

may

pre

sent

in t

he m

anag

emen

t of

a

pati

ent

wit

h ps

oria

sis.

Conc

lusi

onIn

sum

mar

y, C

APS

is a

rar

e co

ndit

ion,

acc

ount

ing

for

1% o

f al

l pat

ient

s w

ith

APS

. W

e de

mon

stra

ted

a ca

se-s

tudy

invo

lvin

g a

51-y

ear-

old

mal

e w

ith

psor

iasi

s vu

lgar

is w

ho p

rese

nted

to

the

outp

atie

nt d

erm

atol

ogy

office

wit

h “fl

u-lik

e” s

ympt

oms

whi

le o

n sy

stem

ic b

iolo

gic

ther

apy,

eta

nerc

ept.

In t

he

mid

st o

f ou

r w

orku

p, t

he p

atie

nt d

evel

oped

a r

apid

ons

et o

f ex

tens

ive

thro

mbo

embo

li an

d a

sequ

ence

of

life-

thre

aten

ing

even

ts t

hat

follo

wed

. Th

e pa

tien

t w

as d

iagn

osed

wit

h CA

PS.

We

revi

ewed

thi

s ra

re v

aria

nt o

f A

PS

and

disc

usse

d th

e sc

ope

of C

APS

in r

elat

ion

to o

ur p

atie

nt’s

pre

sent

atio

n.

Figu

res

(con

t.)

Fig.

1-C

hron

ic p

atch

and

pla

que

psor

iasi

s

Fig.

2-C

hest

X-r

ay s

how

ing

mul

tipl

e lu

ng n

odul

es in

the

bi

late

ral u

pper

lobe

s

Fig.

3-C

TA im

agin

g sh

owin

g sa

ddle

em

bolu

s at

the

aor

toili

ac

bifu

rcat

ion

exte

ndin

g in

to t

he le

ft

com

mon

ilia

c ar

tery

Fig.

4-C

TA im

agin

g sh

owin

g la

rge

rena

l inf

arct

s

Fig.

5-C

APS

Dia

gnos

tic

Crit

eria

11,1

2

Fig.

6-O

rgan

sys

tem

invo

lvem

ent

in C

APS

274

A re

port

of c

utan

eous

spre

ad o

f Mul

tiple

Mye

lom

a By

: Cla

yton

Sch

iltz D

O- G

enes

ys H

ospi

tal D

erm

atol

ogy

Resid

ency

, Am

y Ba

sille

DO

- St.

Jose

ph H

ospi

tal D

erm

atol

ogy

Resid

ency

, M

aria

Rob

inso

n M

D- N

YU D

erm

atol

ogy,

Tim

othy

Cha

ng M

D- M

etro

Hea

lth C

leve

land

, Kim

ball

Silv

erto

n DO

- Gen

esys

Hos

pita

l

Pres

enta

tion:

A

62 y

ear o

ld A

fric

an A

mer

ican

wom

an w

ith a

hist

ory

of m

ultip

le m

yelo

ma,

pre

sent

ed fo

r the

eva

luat

ion

of n

ew, t

ende

r les

ions

on

her a

bdom

en w

hich

ap

pear

ed o

ver s

ever

al m

onth

s. D

urin

g th

e pr

evio

us y

ear,

she

had

unde

rgon

e m

ultip

le c

ours

es o

f che

mot

hera

py fo

r her

mye

lom

a, a

ll of

whi

ch w

ere

inte

rrup

ted

seco

ndar

y to

side

effe

cts.

With

in fi

ve m

onth

s of i

nitia

l dia

gnos

is, th

e pa

tient

dev

elop

ed a

can

cero

us tu

mor

of t

he le

ft fe

mur

. Six

mon

ths

late

r, fo

llow

ing

radi

atio

n an

d sa

lvag

e tr

eatm

ent,

she

first

repo

rted

pai

nful

“kn

ots”

on

her a

bdom

en. O

n ph

ysic

al e

xam

seve

ral t

ende

r, vi

olac

eous

no

dule

s w

ere

obse

rved

on

the

left

abdo

men

(Fig

. 1) R

adio

grap

hic

eval

uatio

n re

veal

ed n

o di

rect

ext

ensio

n or

und

erly

ing

tum

ors.

Fig.

1

Hist

opat

holo

gy:

Lesio

nal b

iops

y sh

owed

shee

ts o

f mar

kedl

y at

ypic

al p

lasm

acyt

oid

cells

(Fig

.2).

Imm

unof

lour

esce

nt te

stin

g fo

r CD1

38 a

nd K

appa

ligh

t cha

ins w

ere

posit

ive

(Fig

.3),

whi

le

lam

bda

light

cha

ins

and

antib

odie

s to

CD2

0 w

ere

nega

tive.

The

se fi

ndin

gs w

ere

cons

isten

t with

cut

aneo

us in

volv

emen

t of m

ultip

le m

yelo

ma.

Out

com

e:

Desp

ite a

ggre

ssiv

e ca

re, i

nclu

ding

mul

tiple

cou

rses

of c

hem

othe

rapy

with

thal

idom

ide-

dexa

met

haso

ne a

nd b

orte

zom

ib-

dexa

met

haso

ne, t

he p

atie

nt p

asse

d aw

ay se

vera

l mon

ths a

fter d

evel

opin

g th

e cu

tane

ous

lesio

ns.

Fig.

2

Fig.

3

Disc

ussio

n:

Mul

tiple

mye

lom

a is

a m

alig

nanc

y of

pla

sma

cells

. Sig

ns a

nd sy

mpt

oms a

re v

aria

ble,

but

com

mon

pre

sent

ing

feat

ures

incl

ude

hype

rcal

cem

ia, a

nem

ia, f

atig

ue a

nd re

nal f

ailu

re. A

ccep

ted

diag

nost

ic c

riter

ia

incl

ude

bone

mar

row

pla

smac

ytos

is (>

10%

), en

d or

gan

dam

age,

and

incr

ease

d se

rum

and

urin

e m

onoc

lona

l im

mun

oglo

bulin

s.⁴

Cuta

neou

s sp

read

is a

rare

com

plic

atio

n.¹ʾ³

Cl

inic

ally

, cut

aneo

us le

sions

com

mon

ly p

rese

nt a

s mul

tiple

ery

them

atou

s or v

iola

ceou

s no

dula

r les

ions

on

the

trun

k, a

bdom

en, f

ace

or sc

alp.

Hist

olog

ical

ly, t

he le

sions

typi

cally

sho

w a

nod

ular

or d

iffus

e in

ters

titia

l pat

tern

.¹²³ N

orm

al d

erm

al st

ruct

ures

are

freq

uent

ly d

istor

ted

or d

estr

oyed

by

the

mal

igna

nt p

lasm

a ce

lls. T

he in

vadi

ng c

ells

rese

mbl

e m

atur

e-lo

okin

g pl

asm

a ce

lls.

Mor

e of

ten,

the

feat

ures

of t

he

neop

last

ic c

ells

are

atyp

ical

, and

con

sist o

f im

mat

ure

form

s.³ S

kin

lesio

ns m

ay ra

rely

dev

elop

ear

ly, h

owev

er, c

utan

eous

invo

lvem

ent g

ener

ally

app

ears

late

in th

e co

urse

of t

he d

iseas

e w

hen

a sig

nific

ant t

umor

bu

rden

exi

sts.

¹²³ g

ivin

g a

plau

sible

reas

on fo

r the

poo

r pro

gnos

is on

ce c

utan

eous

lesio

ns d

evel

op. D

eath

gen

eral

ly o

ccur

s with

in tw

elve

mon

ths a

fter t

he a

ppea

ranc

e of

cut

aneo

us le

sions

.¹ʾ³

At a

utop

sy, m

ost

patie

nts a

lso h

ave

exte

nsiv

e pl

asm

acyt

ic in

filtr

atio

n of

mul

tiple

org

ans.

³ Hi

gh-d

ose

chem

othe

rapy

with

hem

atop

oiet

ic s

tem

-cel

l tra

nspl

anta

tion

is th

e pr

efer

red

trea

tmen

t for

pat

ient

s und

er th

e ag

e of

65.

Prio

r to

stem

-cel

l tra

nspl

anta

tion,

pat

ient

s ge

nera

lly re

ceiv

e on

e or

mor

e co

urse

s of i

nduc

tion

chem

othe

rapy

.

Refe

renc

es:

1. K

ois J

M, S

exto

n M

, Loo

king

bill

DP. C

utan

eous

man

ifest

atio

ns o

f mul

tiple

mye

lom

a. A

rch

Derm

atol

. 199

1;12

7:69

-74

2. P

atte

rson

JW, P

arso

ns JM

, Whi

te R

M, F

itzpa

tric

k JE

, Koh

out-

Dutz

E. C

utan

eous

invo

lvem

ent o

f mul

tiple

mye

lom

a an

d ex

tram

edul

lary

pla

smac

ytom

a. J

Am A

cad

Derm

atol

. 198

8 N

ov;1

9(5

Pt 1

):879

-90.

Alb

erts

DS,

Ly

nch

P. C

utan

eous

pla

smac

ytom

as in

mye

lom

a. A

rch

Derm

atol

. 197

8;11

4:17

84-1

787.

3.

Req

uena

L, K

utzn

er H

, Pal

med

o G,

Cal

onje

E, R

eque

na C

, Pér

ez G

, Pas

tor M

A, S

angu

eza

OP.

Cut

aneo

us in

volv

emen

t in

mul

tiple

mye

lom

a. A

rch

Derm

atol

200

3;13

9:47

5-86

4.

Kyl

e RA

, Raj

kum

ar S

V. M

ultip

le m

yelo

ma.

Blo

od. 2

008

Mar

15;

111

(6):2

962-

72

275

M

cCun

e-A

lbri

ght

Syn

drom

e P

ezhm

an S

hour

eshi

, DO

1 , Jo

an T

ambu

rro,

DO

2 1 D

erm

atol

ogy

Res

iden

t, U

nive

rsity

Hos

pita

ls C

ase

Med

Ctr,

Cle

vela

nd, O

H, 2

Pro

fess

or o

f Der

mat

olog

y, U

nive

rsity

Hos

pita

ls C

ase

Med

Ctr,

Cle

vela

nd, O

H

Bac

kgro

und

McC

une-

Alb

right

syn

drom

e is

def

ined

by

the

triad

of p

olyo

stot

ic fi

brou

s dy

spla

sia,

pat

chy

cuta

neou

s pi

gmen

tatio

n, a

nd v

ario

us e

ndoc

rinop

athi

es. C

afé-

au-la

it pa

tche

s ar

e se

en in

at l

east

hal

f of a

ll ca

ses

and

fibro

us d

yspl

asia

is o

bser

ved

unila

tera

lly a

nd ty

pica

lly u

nder

lyin

g th

ese

café

-au-

lait

patc

hes.

Th

e on

set

of e

ndoc

rinop

athi

es o

ccur

s on

ave

rage

by

age

5 an

d m

ost

ofte

n m

anife

sts

as p

reco

ciou

s pu

berty

in

girls

. Th

ough

McC

une-

Alb

right

is

gene

rally

con

side

red

to h

ave

a go

od p

rogn

osis

, ext

ensi

ve fi

brou

s dy

spla

sia

has

bee

n as

soci

ated

with

orth

oped

ic a

nd n

euro

logi

c co

mpl

icat

ions

as

wel

l as

an

incr

ease

d ris

k fo

r mal

igna

ncy

durin

g ad

ulth

ood.

Ref

eren

ces

1. C

hans

on P

et a

l. P

edia

tr E

ndoc

rinol

Rev

. 200

7 A

ug;4

Sup

pl 4

: 453

-62.

2.

Dum

itres

cu C

et a

l. O

rpha

net J

Rar

e D

is. 2

008

May

19;

3:12

. 3.

Han

sen

M e

t al.

Sku

ll B

ase.

200

3 M

ay;1

3(2)

:79-

83.

4. D

ogan

avsa

rgil

B e

t al.

Arc

h O

rthop

Tr S

urg.

200

9 A

pr;1

29(4

):439

-44.

5.

Hus

ton

T et

al.

Bre

ast J

. 200

4 S

ep-O

ct;1

0(5)

:440

-2.

Dis

cuss

ion

McC

une-

Alb

right

is c

ause

d by

a m

utat

ion

in th

e G

NA

S1

gene

that

lead

s to

hor

mon

e in

depe

nden

t act

ivat

ion

of s

econ

d m

esse

nger

sig

nalin

g ca

scad

es

that

mim

ic m

elan

ocyt

e st

imul

atin

g ho

rmon

e re

leas

e re

sulti

ng in

pig

men

ted

mac

ules

, mim

icke

d pa

rath

yroi

d ho

rmon

e st

imul

atio

n re

sulti

ng in

ost

eocl

ast

activ

atio

n an

d ev

entu

al fi

brou

s dy

spla

sia,

and

a w

hole

hos

t of o

ther

end

ocrin

opat

hies

. Com

plic

atio

ns fr

om fi

brou

s dy

spla

sia

mos

t com

mon

ly m

anife

st

as fr

actu

res

but c

an a

lso

incl

ude

scol

iosi

s an

d co

mpr

essi

ve n

euro

path

y, w

hich

whe

n in

volv

ing

the

skul

l ca

n re

sult

in b

lindn

ess

and

deaf

ness

. R

ecen

t stu

dies

sug

gest

an

incr

ease

d ca

ncer

inci

denc

e in

adu

lthoo

d, n

amel

y os

teos

arco

ma

and

brea

st c

ance

r. T

his

appe

ars

to b

e es

peci

ally

true

in

thos

e pa

tient

s w

ith a

ssoc

iate

d gr

owth

hor

mon

e ex

cess

. O

steo

sarc

omas

app

ear t

o ar

ise

seco

ndar

y to

prio

r rad

iatio

n fo

r a p

ituita

ry a

deno

ma

whi

ch a

re

usua

lly s

omat

otro

phic

or

whe

n th

ere

is e

xten

sive

fibr

ous

dysp

lasi

a as

is th

e ca

se w

ith o

ur p

atie

nt. T

he in

crea

sed

risk

for

brea

st c

ance

r app

ears

to b

e se

cond

ary

to e

xces

s re

spon

se to

gro

wth

hor

mon

e an

d es

troge

n pa

thw

ays1

,2,3

,4,5.

This

cas

e is

pre

sent

ed f

or c

linic

al i

nter

est

and

to h

ighl

ight

the

im

porta

nce

of m

anag

ing

patie

nts

with

McC

une-

Alb

right

usi

ng a

mul

tidis

cipl

inar

y ap

proa

ch.

Cas

e R

epor

t A

2-ye

ar-o

ld b

oy w

ith a

his

tory

of p

olyo

stot

ic fi

brou

s dy

spla

sia

and

vita

min

D d

efic

ienc

y pr

esen

ted

for e

valu

atio

n of

asy

mpt

omat

ic s

kin

lesi

ons

invo

lvin

g th

e bi

late

ral

thig

hs a

nd b

utto

cks.

Rev

iew

of

syst

ems

was

sig

nific

ant

for

arth

ralg

ias

of t

he l

egs

with

no

acco

mpa

nied

wea

knes

s. G

row

th a

nd

deve

lopm

ent w

as o

ther

wis

e no

rmal

to d

ate.

P

ast m

edic

al h

isto

ry w

as n

otab

le fo

r a

term

vag

inal

del

iver

y fo

llow

ing

an u

ncom

plic

ated

pre

gnan

cy. H

e w

as ta

king

iron

and

vita

min

D s

uppl

emen

ts a

nd h

ad n

o hi

stor

y of

med

icat

ion

alle

rgie

s. T

here

was

no

fam

ily h

isto

ry o

f sim

ilar l

esio

ns.

Exa

min

atio

n re

veal

ed a

n in

tera

ctiv

e an

d co

oper

ativ

e w

ell-d

evel

oped

boy

in n

o ap

pare

nt d

istre

ss.

Inv

olvi

ng t

he p

oste

rior

scal

p w

as a

ret

icul

ated

hy

perp

igm

ente

d pa

tch

and

invo

lvin

g th

e ba

ck,

bila

tera

l thi

ghs,

left

med

ial b

utto

ck a

nd le

ft sc

rotu

m w

ere

scat

tere

d bl

ue-g

rey

and

hype

rpig

men

ted

patc

hes.

The

re w

as a

gro

up o

f pin

k pa

pule

s on

the

right

upp

er c

hest

and

a 7

x4m

m b

row

n ve

rruco

us p

apul

e on

the

right

pre

auric

ular

che

ek. I

nvol

ving

th

e rig

ht p

oste

rior t

high

was

a 7

mm

line

ar a

rran

gem

ent o

f hyp

opig

men

ted

mac

ules

. Vel

lous

hai

rs w

ere

note

d in

the

pubi

c re

gion

. The

rem

aind

er o

f the

ex

am w

as u

nrem

arka

ble.

La

bora

tory

eva

luat

ion

reve

aled

a d

ecre

ased

vita

min

D l

evel

(17

ng/

dL),

elev

ated

alk

alin

e ph

osph

atas

e (5

33 U

/L),

decr

ease

d th

yroi

d st

imul

atin

g ho

rmon

e (0

.04

mIU

/L) a

nd n

orm

al le

vels

of f

ree

T4, t

esto

ster

one,

insu

lin g

row

th fa

ctor

, cal

cium

, and

pho

spha

te.

A C

T sc

an o

f the

hea

d re

veal

ed fo

ci

of fi

brou

s dy

spla

sia

invo

lvin

g th

e ro

of o

f the

rig

ht o

rbit

as w

ell a

s th

e et

hmoi

d, s

phen

oid,

tem

pora

l, an

d oc

cipi

tal b

ones

(Fi

gure

1).

A sk

elet

al s

urve

y fu

rther

reve

aled

fibr

ous

dysp

lasi

a in

volv

ing

the

bila

tera

l hum

eri,

fem

ur, t

ibia

e, fi

bula

e, a

nd p

roxi

mal

uln

ae (F

igur

e 2)

. In

addi

tion

ther

e w

as q

uest

iona

ble

invo

lvem

ent

of t

he r

ight

thi

rd,

four

th,

and

fifth

met

acar

pals

, th

e le

ft se

cond

, th

ird,

and

four

th m

etac

arpa

ls,

the

right

sec

ond,

thi

rd,

and

four

th

met

atar

sals

, and

the

left

first

met

atar

sal.

Figu

re 2

. Ske

leta

l sur

vey

dem

onst

ratin

g gr

ound

gla

ss a

ppea

ranc

e in

dica

tive

of fi

brou

s dy

spla

sia

Figu

re 1

. CT

scan

with

3D

reco

nstru

ctio

n w

hich

dem

onst

rate

s bo

ny e

xpan

sion

of t

he la

tera

l roo

f of t

he

right

orb

it fo

und

to b

e a

focu

s of

fibr

ous

dysp

lasi

a

276

A C

ase

of C

lass

ic K

apos

i’s S

arco

ma

Trea

ted w

ith E

lect

ron B

eam

Rad

iati

on T

her

apy

Leh

igh V

alle

y H

ealt

h N

etw

ork,

Allen

tow

n,

Pen

nsy

lvan

ia a

nd P

hilad

elphia

Col

lege

of

Ost

eopat

hic

Med

icin

e, P

hilad

elphia

, P

ennsy

lvan

iaLu

is A

. Sor

o, D

O, Ste

phen

M. Pur

cell, DO, Lu

sia

S. Yi

, DO, M

S

Ref

eren

ces:

1 H

auer

sto

ck D

, Ger

stei

n W

, Vuo

ng T

. Res

ults

of

rad

iatio

n th

erap

y fo

r tr

eatm

ent

of

clas

sic

Kap

osi

sar

com

a. J

Cut

an

Med

Sur

g 2

009;

13:1

8-21

.

2 Ja

kob

L, M

etzl

er G

, Che

n K

, Gar

be

C. N

on-

AID

S a

sso

ciat

ed K

apo

si’s

sar

com

a: c

linic

al f

eatu

res

and

tre

atm

ent

out

com

e. P

los

one

201

1;6:

e183

97.

3 C

hang

LL,

Red

dy

S, S

hid

nia

H.C

om

par

iso

n o

f ra

dia

tion

ther

apy

of

clas

sic

and

ep

idem

ic K

apo

si’s

sar

com

a. A

m J

C

lin O

nco

l 199

2;15

:200

-206

.

Pa

tie

nt:

C.L

. is

a 91

yea

r o

ld m

ale

of

Lith

uani

an/B

altic

anc

estr

y.

His

tory

of

Pre

se

nt

Illn

ess:

The

pat

ient

pre

sent

ed t

o o

ur o

ffic

e in

Ap

ril 2

011

com

pla

inin

g o

f a

one

to

tw

o y

ear

hist

ory

of

a no

n-p

ruri

tic “

rash

” o

n hi

s p

alm

s, t

runk

, rig

ht k

nee,

and

fee

t. H

e ha

d

bee

n st

arte

d o

n as

pir

in a

nd c

lop

ido

gre

l in

No

vem

ber

201

0 af

ter

a st

roke

but

den

ied

any

oth

er r

ecen

t m

edic

atio

n ch

ang

es. N

o p

revi

ous

tre

atm

ents

wer

e re

po

rted

. A r

evie

w o

f sy

stem

s w

as n

egat

ive

for

feve

r, ni

ght

sw

eats

, lym

pha

den

op

athy

, nau

sea,

ab

do

min

al p

ain,

hem

ato

chez

ia, o

r o

ther

sys

tem

ic

sym

pto

ms.

Me

dic

al H

isto

ry/S

urg

ica

l H

isto

ry:

Hyp

erte

nsio

n, C

VA, h

epat

itis

B, s

easo

nal a

llerg

ies,

ap

pen

dec

tom

y, t

ons

illec

tom

y

Me

dic

atio

ns:

Allo

pur

ino

l, o

lmes

arta

n, lo

rata

din

e, f

uro

sem

ide,

am

lod

ipin

e, a

spir

in, c

lop

ido

gre

l, p

rop

oxy

phe

ne n

apsy

late

/ace

tam

ino

phe

n

Ph

ysic

al E

xa

min

atio

n:

The

re a

re s

ever

al w

ell-

dem

arca

ted

vio

lace

ous

pla

que

s o

n th

e p

alm

s ex

tend

ing

ont

o t

he f

ing

ers

with

the

left

han

d m

ore

invo

lved

tha

n th

e ri

ght

. Sca

tter

ed v

iola

ceo

us

pap

ules

and

pat

ches

are

see

n o

n th

e b

ack,

arm

s, r

ight

kne

e, f

eet,

so

les,

pen

is a

nd s

cro

tum

(Fig

ure

1).

La

bo

rato

ry D

ata

: H

IV-1

,2 A

b (0

4/21

/11)

: No

nrea

ctiv

e; C

BC

(10/

31/1

1): W

NL

exce

pt

pla

tele

ts:

105

(150

-400

Tho

usan

d/u

L), C

MP

(10/

31/1

1): W

NL

exce

pt

tota

l bili

rub

in: 2

.6 (0

.2-1

.0 m

g/d

L); I

NR

(1

0/31

/11)

: 1.5

3 (0

.86-

1.16

); H

epat

itis

pan

el (1

2/01

/11)

: HB

sAg

: no

nrea

ctiv

e, H

BcA

b: r

eact

ive,

HB

cAb

Ig

M: n

onr

eact

ive,

HC

Ab

: no

nrea

ctiv

e

Stu

die

s:

CT

of

ches

t, a

bd

om

en, a

nd p

elvi

s w

ith c

ont

rast

(04/

26/1

1) r

evea

led

no

vis

cera

l in

volv

emen

t o

r ly

mp

had

eno

pat

hy. C

hro

nic

elev

atio

n o

f th

e ri

ght

hem

idia

phr

agm

was

no

ted

. R

epea

t C

T o

f ch

est,

ab

do

men

, and

pel

vis

with

co

ntra

st (1

1/09

/11)

was

als

o n

egat

ive

with

an

inci

den

tal

find

ing

of

a d

evel

op

ing

rig

ht p

leur

al e

ffus

ion

and

mild

asc

ites.

Bio

psy:

Ad

vanc

ed D

erm

ato

log

y A

sso

ciat

es, L

TD

. (A

D11

-035

86, 0

4/01

/201

1) L

eft

low

er b

ack:

“A

sub

tle

pro

lifer

atio

n o

f ja

gg

ed, s

lit-l

ike

vasc

ular

cha

nnel

s is

co

nfig

ured

as

a b

and

acr

oss

the

sup

erfic

ial

po

rtio

n o

f a

full-

thic

knes

s p

unch

bio

psy

. Thi

s is

vag

uely

wed

ge-

shap

ed...

som

e o

f th

ese

are

situ

ated

ar

oun

d p

re-e

xist

ing

ves

sels

(pro

mo

nto

ry s

ign)

, and

sm

all n

umb

ers

of

eryt

hro

cyte

s ar

e p

rese

nt

with

in...

imm

uno

hist

och

emic

al s

tain

s d

emo

nstr

ate

uneq

uivo

cal s

catt

ered

sin

gle

cel

l nuc

lear

po

sitiv

ity

with

HH

V8.

The

re is

als

o s

catt

ered

cyt

op

lasm

ic p

osi

tivity

fo

r al

pha

-1 a

ntitr

ypsi

n an

d s

mo

oth

mus

cle

actin

(fig

ure

3).”

Dia

gn

osis

: C

lass

ic K

apo

si’s

Sar

com

aTre

atm

en

t: A

fter

bei

ng c

lear

ed o

f vi

scer

al a

nd ly

mp

h no

de

invo

lvem

ent,

the

pat

ient

was

ref

erre

d t

o

rad

iatio

n o

nco

log

y fo

r lo

caliz

ed e

lect

ron-

bea

m t

hera

py

to h

is in

volv

ed s

ites.

270

0 cG

y in

15

frac

tions

o

ver

16 d

ays

wer

e ad

min

iste

red

to

the

han

ds

and

fee

t, 1

800

cGy

in 6

fra

ctio

ns o

ver

7 d

ays

to t

he r

ight

kn

ee, 4

800

cGy

in 1

7 fr

actio

ns o

ver

18 d

ays

to t

he r

ight

up

per

bac

k, 2

000

cGy

in 1

0 fr

actio

ns o

ver

12 d

ays

to t

he p

enis

and

scr

ota

l ski

n, a

nd 3

000

cGy

in 1

5 fr

actio

ns o

ver

14 d

ays

to t

he f

ore

arm

s an

d

cent

ral a

nd lo

wer

bac

k. In

ad

diti

on,

one

hyp

erth

erm

ia t

reat

men

t w

as a

dm

inis

tere

d t

o t

he le

ft p

alm

, ri

ght

fo

ot,

left

fo

ot,

and

rig

ht k

nee

to in

tens

ify t

he e

ffec

t o

f ra

dio

ther

apy

(Fig

ure

2).

Pro

gn

osis

: M

ino

r sk

in t

oxi

city

sec

ond

ary

to t

hera

py

in t

he f

orm

of

seve

ral b

ulla

e o

n th

e ha

nds

and

fee

t w

ere

rep

ort

ed b

ut r

eso

lved

sp

ont

aneo

usly

. Ove

rall,

the

pat

ient

saw

sig

nific

ant

imp

rove

men

t o

f hi

s K

S a

t al

l tre

ated

site

s. H

e re

mai

ns w

ith s

om

e re

sid

ual v

iola

ceo

us p

atch

es o

n hi

s le

ft p

alm

, p

ost

erio

r ar

ms,

and

rig

ht k

nee

but

the

re is

no

sig

n o

f re

curr

ence

at

this

tim

e. G

iven

the

pro

pen

sity

of

new

lesi

ons

to

ap

pea

r af

ter

loca

l fie

ld r

adia

tion

ther

apy,

he

cont

inue

s to

fo

llow

up

with

his

pri

mar

y ca

re p

hysi

cian

eve

ry 3

mo

nths

and

at

our

off

ice

ever

y 6

mo

nths

.

Cas

e P

rese

nta

tion

:D

iscu

ssio

n:

Kap

osi

’s s

arco

ma

(KS

), a

rare

neo

pla

sm o

f ab

norm

al v

ascu

lar

end

oth

elia

l cel

ls, w

as f

irst

re

po

rted

by

Mo

ritz

Kap

osi

in 1

872.

Sin

ce t

hen,

fiv

e su

bty

pes

of

the

dis

ease

, all

with

var

ying

ep

idem

iolo

gy,

dis

trib

utio

n, a

nd p

rog

nose

s ha

ve b

een

des

crib

ed: c

lass

ic K

S, A

fric

an

cuta

neo

us K

S, A

fric

an ly

mp

had

eno

pat

hic

KS

, im

mun

osu

pp

ress

ive

ther

apy

or

lym

pho

ma

asso

ciat

ed K

S, a

nd A

IDS

-ass

oci

ated

KS

(Tab

le 1

). P

atie

nts

that

are

HIV

-neg

ativ

e, n

on-

imm

uno

sup

pre

ssed

, mid

dle

ag

ed t

o e

lder

ly m

ales

of

Med

iterr

anea

n o

r E

aste

rn E

uro

pea

n o

rig

in c

an b

e ap

pro

pri

atel

y cl

assi

fied

as

clas

sic

KS

.

Lesi

ons

in c

lass

ic K

S t

ypic

ally

pre

sent

as

vio

lace

ous

mac

ules

and

pat

ches

evo

lvin

g in

to

nod

ules

and

pla

que

s an

d m

ost

fre

que

ntly

invo

lve

the

low

er e

xtre

miti

es o

r fe

et. L

ater

, the

ar

ms

and

han

ds

can

bec

om

e in

volv

ed a

nd r

arel

y, t

he t

runk

, fac

e, g

enita

lia, a

nd s

oft

pal

ate.

N

onp

ittin

g e

dem

a m

ay a

cco

mp

any

the

lesi

ons

. Vis

cera

l and

lym

ph

nod

e in

volv

emen

t is

ra

re b

ut w

hen

pre

sent

, the

sm

all i

ntes

tine

is t

he m

ost

like

ly s

ite. T

he c

our

se in

cla

ssic

KS

is

slo

wly

pro

gre

ssiv

e if

left

unt

reat

ed.

Trea

tmen

t d

epen

ds

on

the

stag

e o

f th

e d

isea

se. F

or

pat

ient

s w

ith o

nly

smal

l, so

litar

y le

sio

ns, l

oca

l exc

isio

n, c

ryo

ther

apy,

lase

r ab

latio

n, o

r in

tral

esio

nal i

nter

fero

n-al

pha

, vi

nbla

stin

e, o

r d

oxo

rub

icin

can

be

effe

ctiv

e. In

pat

ient

s w

ith la

rger

lesi

ons

no

t am

enab

le

to s

urg

ery

or

in p

atie

nts

with

man

y le

sio

ns, r

adia

tion

ther

apy

is t

he m

ost

co

mm

onl

y us

ed

and

suc

cess

ful t

reat

men

t m

od

ality

. Pre

vio

us s

tud

ies

inve

stig

atin

g b

oth

loca

l and

ext

end

ed

field

the

rap

y w

ith v

aryi

ng d

ose

fra

ctio

natio

n sc

hed

ules

tha

t ra

nged

fro

m a

sin

gle

do

se o

f 8

Gy

to 3

0 G

y o

ver

10 d

aily

fra

ctio

ns s

how

ed c

om

ple

te r

esp

ons

e (C

R) r

ates

of

31-8

9%, w

ith

a m

edia

n C

R o

f 65

%. T

his

is c

om

par

able

to

the

CR

rat

e fo

r in

tral

esio

nal i

nter

fero

n-al

pha

an

d c

hem

oth

erap

y w

hich

ran

ges

fro

m 5

0-70

%. M

ost

stu

die

s in

vest

igat

ing

rad

iatio

n th

erap

y d

emo

nstr

ate

at le

ast

a p

artia

l res

po

nse

in a

ll le

sio

ns (T

able

2).

Ski

n to

xici

ty s

eco

ndar

y to

ra

dia

tion

in t

he f

orm

of

blis

teri

ng, d

erm

atiti

s, a

nd ly

mp

hed

ema

is n

ot

unco

mm

on

and

mus

t b

e m

oni

tore

d f

or

and

tre

ated

ap

pro

pri

atel

y. F

or

pat

ient

s w

ith r

apid

ly d

evel

op

ing

lesi

ons

(>

10 in

1 m

ont

h) o

r vi

scer

al in

volv

emen

t, s

yste

mic

che

mo

ther

apy

is t

he r

eco

mm

end

ed

ther

apeu

tic o

ptio

n. P

rog

nosi

s fo

r cl

assi

c K

S p

atie

nts

is f

avo

rab

le b

ut g

iven

the

pro

pen

sity

fo

r ne

w le

sio

ns t

o a

pp

ear

at p

revi

ous

ly t

reat

ed s

ites,

pat

ient

s m

ust

be

follo

wed

by

thei

r p

rim

ary

care

phy

sici

an r

egul

arly

. Lym

pho

retic

ular

mal

igna

ncy

(i.e.

Ho

dg

kin

dis

ease

, no

n-H

od

gki

n ly

mp

hom

a, le

ukem

ia) i

s ab

out

10-

20 t

imes

gre

ater

in K

S p

atie

nts

and

is a

noth

er

reas

on

for

clo

se f

ollo

w-u

p.

Fig

ure

1: (A

-D)

Wel

l-d

emar

cate

d v

iola

ceo

us p

laq

ues

on

the

left

pal

m e

xten

din

g o

nto

the

fing

ers

alo

ng w

ith

vio

lace

ous

pat

ches

and

pla

que

s o

n th

e ri

ght

kne

e, r

ight

so

le, p

enis

and

scr

otu

m.

Fig

ure

2: (A

-D)

Lesi

ons

aft

er lo

cal fi

eld

ele

ctro

n b

eam

rad

iati

on

ther

apy.

Fig

ure

3: (A

-C)

H&

E p

unch

bio

psy

of

rig

ht lo

wer

bac

k sh

ow

s a

sub

tle

pro

lifer

atio

n o

f ja

gg

ed, s

lit-l

ike

vasc

ular

cha

nnel

s co

nfig

ured

as

a b

and

acr

oss

the

sup

erfi

cial

po

rtio

n o

f a

full-

thic

knes

s p

unch

bio

psy

. As

seen

in 2

-C, s

om

e o

f th

ese

are

situ

ated

aro

und

pre

-ex

isti

ng v

esse

ls (p

rom

ont

ory

sig

n).

Fig

ure

3: (D

) H

HV-

8 im

mun

ohi

sto

chem

ical

sta

in d

emo

nstr

ates

une

qui

voca

l sca

tter

ed s

ing

le c

ell n

ucle

ar p

osi

tivi

ty.

Table

1: Ty

pes o

f Kap

osi’s

Sarco

ma

KS Typ

eDe

mogra

phics

Clinic

al Feat

ures

Progno

sis

Clas

sic K

SM

ales

>50

year

s of a

ge.

Med

iterra

nean

or E

aste

rn

Euro

pean

orig

in

Early

lesio

ns m

ost c

omm

on

on to

es, s

oles

. Arm

s, ha

nds

invo

lved

late

r and

rare

ly fa

ce,

trunk

, gen

italia

Slow

ly pr

ogre

ssive

. Rar

e lym

ph n

ose

or vi

scer

al

invo

lvem

ent

Afric

an cu

tane

ous K

SM

iddl

e-ag

ed A

frica

n m

ales

20-

50 ye

ars o

f age

. See

n in

Sub-

Saha

ran

Afric

a

Lesio

ns m

ostly

on

extre

miti

es.

Can

be a

ccom

pani

ed b

y ede

ma

of le

gs a

nd b

one

invo

lvem

ent

Loca

lly a

ggre

ssive

. Sy

stem

ically

indo

lent

Afric

an

lym

phad

enop

athi

c KS

Youn

g pa

tient

s, us

ually

child

ren

<10

year

s of a

ge in

Sub-

Saha

ran

Afric

a

Skin

lesio

ns lm

ay o

r may

not

be

pre

sent

. Lym

ph n

odes

in

volve

d. C

an d

evel

op le

sions

on

eye

lids a

nd co

njun

ctiva

Aggr

essiv

e, o

ften

fata

l w

ithin

2 ye

ars o

f ons

et

Imm

unos

uppr

essio

n-as

socia

ted

KSIa

troge

nica

lly

imm

unos

uppr

esse

d pa

tient

s, i.e

. tra

nspl

ant p

atien

ts

Lesio

ns si

mila

r to

class

ic KS

. Sit

es a

re m

ore

varia

ble

Varia

ble.

May

reso

lve

with

disc

ontin

uatio

n of

im

mun

osup

pres

sion

AIDS

-ass

ocia

ted

KSAI

DS p

atien

ts, h

omos

exua

l men

Viol

aceo

us m

acul

es ra

pidl

y pr

ogre

ssin

g to

pap

ules

, no

dule

s, pl

aque

s. He

ad, n

eck,

tru

nk, m

ucou

s mem

bran

es

mor

e co

mm

only

affec

ted

Prog

ress

ive w

ith

noda

l and

syst

emic

invo

lvem

ent e

xpec

ted

Table

2: Su

mmary

of Tr

eatm

ent O

utcom

es

Study

No. P

atien

tsTre

atmen

tRa

diatio

n Dose

CR/PR

(%)

Lo E

t al.

60LF

/EF

2-15

Gy

46/4

6

Wes

hler

Et a

l.28

EF30

GY/

10 fr

actio

ns89

/11

Ham

ilton

Et a

l.37

LF/E

F8

Gy, s

ingl

e fra

ction

73/N

R

Tur a

nd B

renn

er11

Subc

utan

eous

IFN-

alph

aN/

A63

/18

Zida

n Et

al.

10Vi

nbla

stine

N/A

50/4

0

Kreu

ter E

t al.

12Pe

gyla

ted,

lipos

omal

, dox

orbu

cinN/

A67

/25

CR

= c

om

ple

te r

esp

ons

e; L

F =

loca

l fiel

d; E

F =

ext

end

ed fi

eld

; IFN

= in

terf

ero

n;

PR

= p

arti

al r

esp

ons

eA

do

pte

d f

rom

Hau

erst

ock

D, G

erst

ein

W, V

uong

T.

Bef

ore

1-A

1-

B

1-C

1-

D

2-A

2-B

2-

C2-

D

3-A

(4x)

3-

B (2

0x)

3-C

(40x

) 3-

D (2

0x) H

HV-

8

Aft

er

277

Broo

ke W

alls,

DO,

Larg

o Med

ical C

ente

r, La

rgo,

Flor

ida

4640

CAS

E R

EPO

RT

A 49

-year

-old

Cau

casia

n fe

mal

e pre

sent

ed w

ith a

larg

e ten

der

plaq

ue o

n her

righ

t low

er ex

trem

ity. T

he p

laqu

e en

larg

ed

prog

ress

ively

over

the c

ours

e of 2

mon

ths a

nd w

as a

ssoc

iate

d wi

th a

n in

term

itten

t “st

ingi

ng” s

ensa

tion.

She

repo

rted

a hist

ory

of si

mila

r but

smal

ler a

nd se

lf-he

alin

g le

sions

sinc

e her

dia

gnos

is of

Cro

hn’s

dise

ase (

CD) a

t the

age

of 2

2. S

he d

enie

d an

y rec

ent

flare

of h

er ga

stro

inte

stin

al sy

mpt

oms.

Her

pas

t sur

gica

l hist

ory

was s

igni

fican

t for

2 la

rge b

owel

rese

ctio

ns a

nd 1

smal

l bow

el

rese

ctio

n se

cond

ary t

o CD

. Cur

rent

med

icatio

ns in

clude

6-

mer

capt

opur

ine

120

mg d

aily.

Ex

amin

atio

n of

her

righ

t pos

terio

r cal

f rev

eale

d a

tend

er, 1

0 x

12

cm, u

lcera

tive

plaq

ue w

ith u

nder

lying

ery

them

a (F

ig 1

). A

pun

ch

biop

sy w

as co

nsist

ent w

ith cu

tane

ous m

etas

tatic

Cro

hn’s

dise

ase.

Hist

opat

holo

gic f

indi

ngs i

nclu

ded

ulce

ratio

n ac

com

pani

ed b

y rea

ctive

hyp

erpl

asia

of t

he ep

ider

mis

and

nons

uppu

rativ

e gr

anul

omat

ous d

erm

al in

flam

mat

ion

(Fig

2).

Mul

tinuc

leat

ed fo

reig

n bo

dy-ty

pe gi

ant c

ells

were

pre

sent

. Sp

ecia

l sta

ins f

or a

cid-fa

st b

acill

i and

fung

i wer

e neg

ative

.

CD is

a ch

roni

c inf

lam

mat

ory b

owel

dise

ase w

ith a

rela

psin

g co

urse

. Extr

aint

estin

al m

anife

stat

ions

of C

D ar

e com

mon

and

ca

n in

clude

cuta

neou

s, ar

thrit

ic, o

cula

r, an

d pu

lmon

ary

invo

lvem

ent.

Cuta

neou

s les

ions

can

vary

from

a re

activ

e pr

oces

s su

ch a

s pyo

derm

a ga

ngre

nosu

m, t

o m

ucoc

utan

eous

exte

nsio

ns

in th

e ora

l muc

osa

or p

eria

nal a

rea,

and

/or n

utrit

iona

l def

icien

cy

synd

rom

es se

cond

ary t

o m

alab

sorp

tion.

3 How

ever

, one

of t

he

mos

t int

rigui

ng cu

tane

ous m

anife

stat

ions

of C

D is

cuta

neou

s m

etas

tatic

Cro

hn’s

dise

ase

(CM

CD),

a ra

re m

anife

stat

ion

invo

lving

lesio

ns th

at a

re h

istol

ogica

lly id

entic

al to

thos

e fou

nd in

th

e bow

el, s

pecif

ically

non

case

atin

g gr

anul

omat

ous

infla

mm

ator

y les

ions

, at n

on-c

ontig

uous

site

s fro

m th

e al

imen

tary

trac

t.4 CM

CD o

ccur

s mos

t com

mon

ly on

the p

osta

uricu

lar r

egio

n,

flexu

ral r

egio

ns, o

r extr

emiti

es b

ut m

ay o

ccur

on

any c

utan

eous

su

rface

. Ove

r hal

f of t

he p

atie

nts a

re fe

mal

e and

mos

t pat

ient

s ar

e bet

ween

the a

ges o

f 20-

40 ye

ars.1,

6 Clin

ically

, cut

aneo

us

lesio

ns co

nsist

of s

mal

l ery

them

atou

s pap

ules

, whi

ch m

ay

enla

rge

into

nod

ules

and

ulti

mat

ely u

lcera

te. T

he te

rm

“met

asta

tic” i

s a m

isnom

er si

nce t

hese

lesio

ns co

ntai

n th

e sam

e hi

stop

atho

logy

that

char

acte

rizes

CD

and

are n

ot sp

read

ing

hem

atog

enou

sly.

Hist

olog

ically

, CM

CD co

nsist

s of n

onca

seat

ing

gran

ulom

atou

s sk

in le

sions

that

are

loca

ted

at si

tes d

istan

t fro

m th

e ga

stro

inte

stin

al tr

act.2

DIS

CUSS

ION

REF

EREN

CES

FIG

URES

1 2

The e

tiolo

gy o

f CM

CD is

unk

nown

but

pot

entia

lly re

late

d to

an

exag

gera

ted

Th1

cell m

edia

ted

resp

onse

.5 Th1

resp

onse

s pr

oduc

e IN

F-γ,

a po

tent

chem

otac

tic m

edia

tor a

nd a

ctiva

tor

for h

istio

cyte

s. S

ome h

ave h

ypot

hesiz

ed a

bac

teria

l id ty

pe o

f re

actio

n. A

noth

er th

eory

rela

tes a

utoi

mm

une

phen

omen

on,

invo

lving

cros

s rea

ctin

g an

tibod

ies b

etwe

en th

e gut

and

skin

-ba

sed

antig

ens.6 R

ecen

t res

earc

h di

scov

ered

sim

ilarit

ies i

n tro

pom

yosin

isof

orm

s of t

he gu

t, sk

in, e

ye, a

nd jo

ints

that

may

co

ntrib

ute

to a

utoi

mm

unity

.7 Tre

atm

ent o

ptio

ns co

nsist

of im

mun

osup

pres

sive a

gent

s suc

h as

pred

niso

ne, a

zath

iopr

ine,

sulfa

sala

zine,

and

met

hotre

xate

. On

e of t

he m

ost e

ffect

ive tr

eatm

ents

repo

rted

is or

al

met

roni

dazo

le, a

lone

or i

n com

bina

tion

with

Infli

ximab

.8-9

1.Ro

thfu

ss, K

atja

S, E

duar

d F S

tang

e, K

laus

R H

errli

nger

. Extr

aint

estin

al m

anife

stat

ions

and

com

plica

tions

in

infla

mm

ator

y bow

el d

iseas

es. W

orld

J Ga

stro

ente

rol 2

006;

12(3

0):4

819-

4831

2.

Lars

en S

, Ben

dtze

n K, N

elso

n OH

. Extr

aint

estin

al m

anife

stat

ions

of i

nfla

mm

ator

y bow

el d

iseas

e: e

pide

mio

logy

, di

agno

sis, a

nd m

anag

emen

t. A

nn M

ed 2

010;

42(2

):97-

114

3.Le

ster

LU, R

apin

i RP.

Der

mat

olog

ic m

anife

stat

ions

of c

olon

ic di

sord

ers.

Cur

r Opi

n Ga

ster

oent

erol

200

9;25

(1):6

6-73

4.

Park

s, AG

, BC

Mor

son,

JS P

egum

. Cro

hn’s

Dise

ase w

ith C

utan

eous

Invo

lvem

ent.

Pro

ceed

ings

of th

e Roy

al S

ocie

ty of

M

edici

ne 1

965;

58:2

41-2

42

5.Po

dolsk

y, DK

. Inf

lam

mat

ory b

owel

dise

ase.

N E

ngl J

Med

200

2;34

7(6)

:417

-429

6.

Crow

son,

A. N

eil,

MD,

Ger

ard

J Nuo

vo, M

D, M

artin

C. M

ihm

, Jr,

MD,

and

Cynt

hia

Mag

ro, M

D. C

utan

eous

Man

ifest

atio

ns

of C

rohn

’s Di

seas

e, It

s Spe

ctru

m, a

nd It

s Pat

hoge

nesis

: Int

race

llula

r Con

sens

us B

acte

rial 1

6S rR

NA Is

Ass

ocia

ted

With

th

e Gas

troin

test

inal

But

Not

the C

utan

eous

Man

ifest

atio

ns o

f Cro

hn’s

Dise

ase.

Hum

an P

atho

logy

200

3;34

:11

7.Ge

ng X,

Bia

ncon

e L, D

ai H

H, Li

n JJ,

Yosh

izaki

N, D

asgu

pta A

, Pal

lone

F, D

as K

M. T

ropo

myo

sin is

ofor

ms i

n in

test

inal

m

ucos

a: p

rodu

ctio

n of

aut

oant

ibod

es to

trop

omyo

sin is

ofor

ms i

n ul

cera

tive c

oliti

s. G

astro

ente

rolo

gy 1

998;

114

:912

-92

2 8.

Risp

o, A

., R.

Sca

rpa,

E. D

iGiro

lam

o, A

. Coz

zolin

o, G

. Lem

bo, M

. Atte

no, T

. DeF

alco

, M. L

oPre

sti,

F. C

astig

lione

. In

flixim

ab in

the t

reat

men

t of e

xtra-

inte

stin

al m

anife

stat

ions

of C

rohn

’s Di

seas

e. S

cand

inav

ian

Jour

nal o

f Rh

eum

atol

ogy

2005

;387

-391

9.

Konr

ad, A

. and

F. S

eibo

ld. R

espo

nse o

f cut

aneo

us C

rohn

’s di

seas

e to

infli

ximab

and

met

hotre

xate

. Dig

estiv

e and

Live

r Di

seas

e 20

03;3

51-3

56

278

A P

rom

inen

t E

rupt

ion

in a

Fem

ale

wit

h M

yelo

dysp

last

ic S

yndr

ome

Du

stin

Wilk

es D

O, J

enn

y C

otto

n M

D P

hD

, Stu

art G

ilden

berg

MD

St. J

osep

h M

ercy

Hos

pita

l •

Ann

Arb

or, M

ichi

gan

REM

AR

KA

BLE

MED

ICIN

E. R

EMA

RK

AB

LE C

AR

E.

Swee

t’s S

yndr

ome

At t

he in

itial

con

sult

Afte

r ste

roid

s w

ere

star

ted

Prio

r to

expi

ratio

n

Exa

min

atio

nC

linic

al e

xam

inat

ion

reve

aled

a l

arge

, te

nder

, ind

urat

ed, e

ryth

emat

ous a

nd v

io-

lace

ous p

laqu

e w

ith

a th

ick

whi

te/y

ello

w

scal

e/cr

ust i

nvol

ving

the

righ

t sid

e of

her

fa

ce in

clud

ing

the

enti

re c

heek

, tem

ple,

up

per

and

low

er e

yelid

s, na

sal

ala,

and

ch

in.

The

re w

ere

sim

ilar

lesi

ons

pres

-en

t ove

r the

left

scap

ula

and

righ

t dor

sal

hand

. T

he p

atie

nt w

as n

oted

to

have

a

low

-gra

de fe

ver o

f 37.

94 °

C.

Lab

orat

ory

Labo

rato

ry r

esul

ts o

n ad

mis

sion

con

-si

sted

of

a no

rmoc

ytic

ane

mia

, th

rom

-bo

cyto

peni

a, a

nd t

race

blo

od i

n th

e ur

ine.

T

he w

hite

blo

od c

ell

coun

t w

as

wit

hin

norm

al li

mit

s. B

lood

and

tis

sue

cult

ures

wer

e ne

gati

ve.

His

topa

thol

ogy

Bio

psy

from

the

pat

ient

’s ri

ght

chin

rev

eale

d an

ex

uber

ant

scal

e ov

erly

ing

a de

nse

neut

roph

ilic

infla

mm

ator

y in

filtr

ate

wit

h le

ukoc

ytoc

lasi

s an

d pa

pilla

ry d

erm

al e

dem

a.

Fibr

inoi

d ne

cros

is a

nd

intr

avas

cula

r thr

ombi

wer

e no

t obs

erve

d.

Cou

rse

and

The

rapy

The

pat

ient

was

sta

rted

on

IV m

ethy

lpre

dnis

o-lo

ne.

Her

faci

al, b

ack,

and

han

d le

sion

s im

prov

ed

sign

ifica

ntly

ove

r th

e ne

xt f

ew d

ays.

Alt

houg

h he

r fa

cial

les

ions

sho

wed

dra

mat

ic i

mpr

ovem

ent,

the

pati

ent’s

co

ndit

ion

dete

rior

ated

an

d sh

e su

bseq

uent

ly

expi

red

from

co

mpl

icat

ions

of

m

yelo

dysp

last

ic sy

ndro

me

and

pneu

mon

ia.

His

tory

A 7

7 ye

ar-o

ld fe

mal

e, w

ith

a pa

st m

edic

al h

isto

ry si

gnifi

cant

for d

iabe

tes m

ellit

us, r

efra

ctor

y an

emia

, an

d a

rece

nt d

iagn

osis

of m

yelo

dysp

last

ic sy

ndro

me,

was

adm

itte

d to

the

hosp

ital

wit

h a

14 d

ay h

is-

tory

of

slig

htly

pai

nful

, vio

lace

ous

plaq

ues

on h

er f

ace,

tru

nk, a

nd e

xtre

mit

ies.

Her

ini

tial

les

ions

st

arte

d te

n da

ys a

fter

the

diag

nosi

s of m

yelo

dysp

last

ic sy

ndro

me.

At t

hat t

ime

she

deve

lope

d a

smal

l vi

olac

eous

pla

que

on h

er r

ight

nas

al a

la, f

ollo

wed

by

a ra

pidl

y en

larg

ing

plaq

ue o

n th

e ri

ght

side

of

her f

ace.

Tw

o da

ys la

ter s

he n

otic

ed a

vio

lace

ous p

laqu

e ne

ar h

er le

ft sc

apul

a re

gion

and

on

her r

ight

tr

icep

are

a. D

ue to

the

prog

ress

ion

of h

er sk

in d

isea

se a

nd in

volv

emen

t of h

er ri

ght e

ye sh

e w

as a

d-m

itte

d to

the

hosp

ital

for f

urth

er in

vest

igat

ion

and

trea

tmen

t.

Dis

cuss

ion

Swee

t’s S

yndr

ome

is c

hara

cter

ized

by

a co

n-st

ella

tion

of

cl

inic

al

sym

ptom

s, ph

ysic

al

feat

ures

, an

d pa

thol

ogic

fin

ding

s, w

hich

in

clud

e fe

ver,

neut

roph

ilia,

tend

er e

ryth

ema-

tous

ski

n le

sion

s, an

d a

diffu

se in

filtr

ate

con-

sist

ing

pred

omin

antl

y of

mat

ure

neut

roph

ils

that

are

typi

cally

loca

ted

in th

e up

per d

erm

is.

3 Ty

pes

Cla

ssic

(Id

iopa

thic

) Sw

eet’s

Syn

drom

e•

Mor

e co

mm

on in

wom

en

• M

ajor

ity

have

an

an

tece

dent

up

per

resp

irat

ory

infe

ctio

n (s

trep

toco

ccus

)•

Oth

er c

ause

s: ga

stro

inte

stin

al i

nfec

tion

, re

cent

vac

cina

tion

, pre

gnan

cy, a

nd in

flam

-m

ator

y di

seas

es,

espe

cial

ly i

nflam

mat

ory

bow

el d

isea

se

Mal

igna

ncy-

asso

ciat

ed S

wee

t’s S

yndr

ome

• H

emat

olog

ic

mal

igna

ncie

s ac

coun

t fo

r m

ore

than

85%

of t

he c

ases

• M

ost c

omm

on: a

cute

mye

loid

leuk

emia

• T

he m

ost

com

mon

sol

id t

umor

s ar

e ca

rci-

nom

as o

f th

e ge

nito

urin

ary

trac

t, br

east

, an

d ga

stro

inte

stin

al tr

act

Dru

g-in

duce

d Sw

eet’s

Syn

drom

e•

Mos

t com

mon

: gra

nulo

cyte

-col

ony

st

imul

atin

g fa

ctor

• O

ther

cau

ses:

min

ocyc

line,

trim

thop

rim

-su

lfam

etho

xazo

le, c

arba

maz

epin

e, a

bcav

ir,

hydr

alaz

ine,

imat

inib

, clo

zapi

ne, d

iaze

pam

, pr

opyl

thio

urac

il, l

evon

orge

stre

l,

furo

sem

ide,

cel

ecox

ib, d

iclo

fena

c,

all-

tran

s ret

inoi

c ac

id, a

nd 1

3-ci

s-re

tino

ic

acid

• O

nce

the

caus

ativ

e ag

ent

has

been

di

scon

tinu

ed,

the

dise

ase

man

ifest

atio

ns

freq

uent

ly im

prov

e

Ref

eren

ces

1. C

ohen

PR

. Sw

eet’s

synd

rom

e--a

com

preh

ensi

ve re

view

of a

n ac

ute

febr

ile n

eutr

ophi

lic d

erm

atos

is. O

rpha

net J

Rar

e D

is.

2007

Jul 2

6; 2

:34.

2. F

azili

T, D

unca

n D

, Wan

i L. A

m J

Med

. Sw

eet’s

synd

rom

e. 2

010

Aug

; 123

(8):

694-

6.3.

Roc

hael

MC

, Pan

tale

ão L

, Vila

r EA

, Zac

aron

LH

, Spa

da E

Q, X

avie

r MH

, Rod

rigu

es K

S. S

wee

t’s sy

ndro

me:

stud

y of

73

case

s, em

phas

izin

g hi

stop

atho

logi

cal fi

ndin

gs. A

n B

ras D

erm

atol

. 201

1 A

ug; 8

6(4)

:702

-7.

4. B

uck

T, G

onzá

les L

M, L

ambe

rt W

C, S

chw

artz

RA

. Sw

eet’s

synd

rom

e w

ith

hem

atol

ogic

dis

orde

rs: a

revi

ew a

nd re

ppra

is-

al. I

nt J

Der

mat

ol. 2

008;

47:7

75-8

2.5.

Nis

chal

KC

, Kho

pkar

U. A

n ap

roac

h to

the

diag

nosi

s of n

eutr

ophi

lic d

erm

atos

es: A

his

topa

thol

ogic

al p

ersp

ecti

ve. I

n-di

an J

Der

mat

ol V

ener

ol L

epro

l. 20

07:1

3:22

2-30

.6.

Bon

amig

o R

R, R

azer

a F,

Olm

GS.

Neu

trop

hilic

der

mat

oses

: par

t I. A

n B

ras D

erm

atol

. 201

1 Fe

b; 8

6(1)

:11-

25; q

uiz 2

6-7.

7. C

ohen

PR

, Kur

zroc

k R

. Sw

eet’s

synd

rom

e re

visi

ted:

a re

view

of d

isea

se c

once

pts.

Int J

Der

mat

ol. 2

003;

42:7

61-7

8.8.

Par

sapo

ur K

, Ree

p M

D, G

ohar

K, S

hah

V, C

hurc

h A

, Shw

ayde

r TA

. Fam

ilial

Sw

eet’s

synd

rom

e in

2 b

roth

ers,

both

seen

in

the

first

2 w

eeks

of l

ife. J

Am

Aca

d D

erm

atol

. 200

3;49

:132

-8.

His

topa

thol

ogy

• D

ense

an

d di

ffuse

de

rmal

ne

utro

phili

c in

filtr

ate;

lym

phoc

ytes

, his

tioc

ytes

, and

a fe

w

eosi

noph

ils m

ay b

e pr

esen

t•

No

true

vas

culit

is (

no v

esse

l wal

l nec

rosi

s)•

Pap

illar

y de

rmal

ede

ma

is c

omm

on

• E

pide

rmal

spon

gios

is a

nd su

bepi

derm

al

vesi

cles

may

be

pres

ent

Dia

gnos

tic

Cri

teri

aN

eed

2 m

ajor

cri

teri

a an

d 2

min

or c

rite

ria

to

esta

blis

h di

agno

sis

Maj

or C

rite

ria

• A

brup

t ons

et o

f pai

nful

ery

them

atou

s no

dule

s or p

laqu

es•

His

topa

thol

ogic

al fi

ndin

gs o

f den

se

neut

roph

ilic

infil

trat

e w

itho

ut e

vide

nce

of

leuk

ocyt

ocla

stic

vas

culit

isM

inor

Cri

teri

a•

Fev

er>

38

°C•

Ass

ocia

tion

wit

h he

mat

olog

ic o

r vi

scer

al

mal

igna

ncy,

infl

amm

ator

y di

seas

e or

pre

g-na

ncy,

or

pr

eced

ed

by

uppe

r re

spir

ator

y tr

act

infe

ctio

n, g

astr

oint

esti

nal

infe

ctio

n or

va

ccin

atio

n•

Exc

elle

nt

resp

onse

to

tr

eatm

ent

wit

h sy

stem

ic c

orti

cost

eroi

ds o

r pot

assi

um io

dide

• A

bnor

mal

itie

s in

la

bora

tory

te

sts

(thr

ee

of f

our)

: er

ythr

ocyt

e se

dim

enta

tion

rat

e >

20

mm

/Hr,

high

C-r

eact

ive

prot

ein,

leu

ko-

cyte

s > 8

,000

wit

h >

70%

neu

trop

hils

.

Tre

atm

ent

Firs

t-lin

e•

Sys

tem

ic C

orti

cost

eroi

ds•

In

loca

lized

lesi

ons,

high

-pot

ency

topi

cal

cort

icos

tero

ids o

r int

rale

sion

al c

orti

co-

ster

oids

may

be

used

• A

ltern

ativ

es: p

otas

sium

iodi

de a

nd c

olch

icin

e Se

cond

-lin

e•

Ind

omet

haci

n, c

lofa

zim

ine,

dap

sone

, cy

clos

pori

ne

279

Hav

ing

an in

crea

sed

num

ber o

f mas

t cel

ls in

one

or m

ore

orga

ns

cons

titut

es th

e di

agno

sis o

f mas

tocy

tosi

s.1 M

asto

cyto

sis

repr

esen

ts a

spec

trum

of d

isor

ders

that

are

clin

ical

ly

hete

roge

neou

s. T

he o

rgan

mos

t com

mon

ly in

volv

ed is

the

skin

. Th

e sp

ectru

m o

f cut

aneo

us m

asto

cyto

sis (

CM

) inc

lude

s; so

litar

y m

asto

cyto

ma,

diff

use

CM

, urti

caria

pig

men

tosa

(UP)

, and

te

lang

iect

asia

mac

ular

is e

rupt

iva

pers

tans

(TM

EP).2

TM

EP is

a

rare

form

of C

M. I

t occ

urs i

n ab

out 1

per

cent

of a

ll ca

ses o

f CM

.

Adu

lts re

pres

ent t

he m

ajor

ity o

f pat

ient

s affe

cted

. Th

e co

urse

if

ofte

n de

scrib

ed a

s ind

olen

t in

natu

re, u

nlik

e ot

her f

orm

s of C

M

(i.e.

, UP)

that

ofte

n re

solv

es b

y ad

oles

cenc

e.3,

4

Alth

ough

the

exac

t etio

logy

of C

M is

unk

now

n, in

CM

the

inte

ract

ion

betw

een

mas

t cel

l gro

wth

fact

or a

nd th

e pr

otei

n pr

oduc

t of t

he c

-KIT

pro

to-o

ncog

ene

appe

ars t

o be

ess

entia

l for

no

rmal

dev

elop

men

t and

diff

eren

tiatio

n. T

he c

-KIT

pro

to-

onco

gene

enc

odes

KIT

(CD

117)

, a ty

rosi

ne k

inas

e th

at is

the

rece

ptor

for m

ast c

ell g

row

th fa

ctor

. In

CM

, stu

dies

sugg

est a

n al

tera

tion

in b

oth

the

dist

ribut

ion

and

met

abol

ism

of m

ast c

ell

grow

th fa

ctor

. Th

is is

thou

ght t

o re

sult

in a

reac

tive

hype

rpla

sia

vers

us n

eopl

asia

. In

syst

emic

mas

tocy

tosi

s and

spor

adic

cas

es o

f ad

ult m

asto

cyto

sis,

a so

mat

ic m

utat

ion

(pos

tzyg

otic

) in

the

c-K

IT

prot

o-on

coge

ne le

ads t

o co

nstit

utiv

e ac

tivat

ion

of K

IT.

This

re

sults

in m

ast c

ell p

rolif

erat

ion,

and

pre

vent

ion

of a

popt

osis

.5,6

The

diag

nosi

s of T

MEP

is o

ften

base

d on

the

clin

ical

and

hi

stop

atho

logi

cal f

indi

ngs.

The

clin

ical

feat

ures

of T

MEP

con

sist

of

ill-d

efin

ed, t

an to

pin

k, te

lang

iect

atic

mac

ules

/pat

ches

that

ra

nge

in si

ze fr

om 2

– 6

mm

.7 T

hese

are

ofte

n sy

mm

etric

ally

ar

rang

ed o

n th

e tru

nk a

nd e

xtre

miti

es, u

sual

ly sp

arin

g th

e fa

ce,

palm

s, an

d so

les.1,

2,4,

8 D

arie

r’s si

gn is

typi

cally

neg

ativ

e or

m

ildly

pos

itive

.3,4,

9

The

diag

nost

ic e

valu

atio

n in

pat

ient

s with

pur

e cu

tane

ous d

isea

se

will

ofte

n de

mon

stra

te n

orm

al tr

ypta

se le

vels

. In

the

setti

ng o

f ra

re sy

stem

ic in

volv

emen

t, au

thor

s hav

e fo

und

that

mos

t pat

ient

s re

veal

tryp

tase

leve

ls g

reat

er th

an 2

0 ng

/ml.10

,11

One

stud

y sh

owed

that

a tr

ypta

se le

vel o

f 75

ng/m

l rep

rese

nted

a th

resh

old

for 1

00 p

erce

nt p

ositi

vity

, whe

reas

tryp

tase

leve

ls 2

0-75

ng/m

l de

mon

stra

ted

50-p

erce

nt p

ositi

vity

.12

Cas

e R

epor

t

Ref

eren

ces

Mas

tocy

tosi

s rep

rese

nts a

wid

e sp

ectru

m o

f dis

orde

rs th

at re

sult

in th

e ac

cum

ulat

ion

of m

ast c

ells

in o

ne o

r mor

e or

gan

syst

ems.

Th

e or

gan

mos

t com

mon

ly in

volv

ed is

the

skin

. Te

lang

iect

asia

m

acul

aris

eru

ptiv

a pe

rsta

ns (T

MEP

) is a

rare

form

of c

utan

eous

m

asto

cyto

sis t

hat o

ften

pres

ents

in a

dulth

ood

and

carr

ies a

n in

dole

nt c

ours

e. T

reat

men

t is o

ften

focu

sed

on sy

mpt

omat

ic

relie

f and

avo

idan

ce o

f exa

cerb

atin

g tri

gger

s. W

e de

scrib

e a

case

of a

20-

year

-old

Cau

casi

an fe

mal

e th

at p

rese

nted

with

m

ultip

le a

sym

ptom

atic

tan

to p

ink

tela

ngie

ctat

ic m

acul

es.

The

cuta

neou

s H&

E bi

opsy

was

con

sist

ent w

ith T

MEP

. C

linic

al a

nd

labo

rato

ry fi

ndin

gs fa

iled

to d

emon

stra

te sy

stem

ic in

volv

emen

t.

Ab

stra

ct

.

Te

lang

iect

asia

Mac

ular

is E

rupt

iva

Pers

tans

: A C

ase

Rep

ort

Sa

mue

l M. W

ilson

, DO

, R. S

cott

Tho

mas

, DO

, Alli

son

K. D

iver

s, M

D, D

anie

l S. H

urd,

DO

, FA

OC

D

His

tory

A

20-

year

-old

Cau

casi

an fe

mal

e pr

esen

ted

to th

e de

rmat

olog

y cl

inic

for a

one

-yea

r his

tory

of m

ultip

le a

sym

ptom

atic

, per

sist

ent,

“red

sp

ots”

on

her b

reas

ts, a

bdom

en a

nd u

pper

thig

hs.

Rev

iew

of s

yste

ms f

aile

d to

reve

al a

ny a

bnor

mal

ities

. Pas

t med

ical

his

tory

incl

uded

; lin

ear s

cler

oder

ma

requ

iring

trea

tmen

t with

met

hotre

xate

at t

he a

ge o

f eig

ht, g

ener

aliz

ed a

nxie

ty, a

nd o

ccas

iona

l hea

dach

es.

Phys

ical

Exa

m

Phys

ical

exa

m re

veal

ed a

wel

l-dev

elop

ed, 2

0-ye

ar-o

ld fe

mal

e w

ith m

ultip

le 2

-3m

m ta

n to

pin

k, b

lanc

habl

e, te

lang

iect

atic

mac

ules

sc

atte

red

over

the

brea

sts,

low

er a

bdom

en a

nd u

pper

thig

hs (F

igur

e 1)

. Th

e or

al, g

enita

l, oc

ular

muc

osa

and

face

wer

e un

invo

lved

. D

arie

r’s si

gn w

as m

ildly

pos

itive

. Sh

e ha

d no

pal

pabl

e ly

mph

aden

opat

hy.

Labo

rato

ry D

ata

and

His

topa

thol

ogy

A 4

mm

pun

ch b

iops

y of

the

skin

, dem

onst

rate

d a

spar

se p

auci

cellu

lar i

nfilt

rate

con

sist

ing

pred

omin

antly

of m

ast c

ells

aro

und

dila

ted

vess

els o

f the

supe

rfic

ial v

ascu

lar p

lexu

s (Fi

gure

2).

The

imm

unoh

isto

chem

ical

stai

n fo

r mas

t cel

l try

ptas

e co

nfirm

ed th

e pr

esen

ce o

f m

ast c

ells

. Th

e su

gges

tive

clin

ical

and

his

topa

thol

ogic

find

ings

con

firm

ed th

e di

agno

sis o

f (TM

EP).

A se

rum

tryp

tase

leve

l was

en

terta

ined

as p

art o

f the

pat

ient

’s d

iagn

ostic

eva

luat

ion.

Giv

en th

e pa

tient

’s a

sym

ptom

atic

pre

sent

atio

n th

e in

itial

wor

k-up

incl

uded

onl

y a

CB

C w

ith d

iffer

entia

l whi

ch w

as n

orm

al.

Trea

tmen

t and

Out

com

e

The

diag

nosi

s and

dis

ease

cou

rse

was

dis

cuss

ed in

det

ail.

The

pat

ient

was

edu

cate

d on

the

pote

ntia

l trig

gers

and

act

ivat

ors

of h

er d

isea

se.

She

was

pre

scrib

ed a

n ep

inep

hrin

e in

ject

or fo

r pre

caut

iona

ry m

easu

res.

Reg

ular

follo

w-u

p by

the

derm

atol

ogis

t and

prim

ary

care

pro

vide

r w

as a

dvis

ed a

s was

a y

early

CB

C.

Dis

cuss

ion

Dis

cuss

ion

(co

nti

nu

ed)

1. N

guye

n N

Q.

Tela

ngie

ctas

ia m

acul

aris

eru

ptiv

e pe

rsta

ns.

Der

mat

olog

y O

nlin

e Jo

urna

l, 20

04; 1

0(3)

: 1

2. S

oter

NA

. Th

e sk

in in

mas

tocy

tosi

s. J

Inve

st D

erm

atol

, 199

1; 9

6(3

supp

l):32

S-38

S 3.

Oliv

eira

CR

, Alb

uque

rque

GC

, Sim

on E

F, Q

uine

te S

S, C

arva

lho

CR

S. C

aso

para

dia

gnos

tic.

Tela

ngie

ctas

ia m

acul

aris

eru

ptiv

e pe

rsta

ns.

An B

ras D

erm

atol

. 20

09; 8

4(1)

:87-

89

4. C

hang

A, T

ung

RC

, Sch

lesi

nger

T, B

ergf

eld

WF,

Dijk

stra

J, K

ahn

TA.

Fam

ilial

cut

aneo

us m

asto

cyto

sis.

Ped

iatr

Der

mat

ol, 2

001;

18

(4):

271-

276

5. L

ongl

ey B

J, M

orga

nrot

h G

S, T

yrre

ll L,

Din

g TG

, And

erso

n D

M, W

illia

ms

DE,

Hal

aban

R.

Alte

red

met

abol

ism

of m

ast-c

ell g

row

th

fact

or (c

-kit

ligan

d) in

cut

aneo

us m

asto

cyto

sis.

N E

ngl J

Med

, 199

3; 3

28(1

8):1

302-

7 6.

Lon

gley

BJ,

Met

calfe

DD

, Tha

rp M

, Wan

g X

, Tyr

rell

L, L

u SZ

, Hei

tjan

D, M

a Y.

Act

ivat

ing

and

dom

inan

t ina

ctiv

atin

g c-

KIT

ca

taly

tic d

omai

n m

utat

ions

in d

istin

ct c

linic

al fo

rms o

f hum

an m

asto

cyto

sis.

Pro

c N

atl A

cad

Sci,

1999

; 96(

4): 1

609-

1614

7.

Tur

chin

I, B

aran

kin

B, S

chlo

ss E

. U

nusu

al c

utan

eous

find

ings

of u

rtica

ria p

igm

ento

sa a

nd te

lang

iect

asia

mac

ular

is e

rupt

iva

pers

tans

as

soci

ated

with

mar

ked

mye

lofib

rosi

s. In

tern

atio

nal J

ourn

al o

f Der

mat

olog

y, 20

06; 4

5:12

15-1

217.

8.

Chu

ng-L

eddo

n J.

Tel

angi

ecta

sia

mac

ular

is e

rupt

ive

pers

tans

. D

erm

atol

ogy

Onl

ine

Jour

nal,

2000

; 6(1

): 6

9. W

atki

ns C

E, B

okor

WB

, Lei

cht S

, You

ngbe

rg G

, Kris

hnas

wam

y G

. Te

lang

ieca

sia

mac

ular

is e

rupt

ive

pers

tans

: mor

e th

an sk

in d

eep.

D

erm

atol

ogy

Repo

rts,

2011

; 3(1

) 10

. Hor

ny H

P, S

otla

r K, V

alen

t P. M

asto

cyto

sis:

sta

te o

f the

art.

Pat

hobi

olog

y, 2

007;

74:1

21-3

217.

Gol

kar L

, Ber

nhar

d JD

. M

asto

cyto

sis.

The

Lan

cet,

1997

; 349

(906

2):1

379-

1385

. 11

. Hei

de R

, Van

DK

, Mul

der P

G, v

an T

oore

nenb

erge

n AW

, Bei

shui

zen

A, d

e G

root

H, T

ank

B, O

ranj

e AP.

Ser

um tr

ypta

se a

nd

SCO

RM

A (S

CO

Rin

g M

Ast

ocyt

osis

) Ind

ex a

s dis

ease

seve

rity

para

met

ers i

n ch

ildho

od a

nd a

dult

cuta

neou

s mas

tocy

tosi

s. C

lin E

xp

Der

mat

ol, 2

009;

34:4

62-8

12

. Sch

war

tz L

B, I

rani

AM

. Se

rum

tryp

tase

and

the

labo

rato

ry d

iagn

osis

of s

yste

mic

mas

tocy

tosi

s. H

emat

ol O

ncol

Nor

th A

m, 2

000;

14

:641

13

. Chu

ng-L

eddo

n J.

Tel

angi

ecta

sia

mac

ular

is e

rupt

ive

pers

tans

. D

erm

atol

ogy

Onl

ine

Jour

nal,

2000

; 6(1

): 6

14. L

iu A

Y, L

owe

RC

, Lev

y B

D, K

atz

JT, L

osca

lzo

J. C

linic

al p

robl

em-s

olvi

ng. A

rash

hyp

othe

sis.

N E

ngl J

Med

, 201

0;36

3:72

-8

15. B

olog

nia

JL, J

oriz

zo JL

, Rap

ini R

P, e

dito

rs.

Der

mat

olog

y. E

dinb

urgh

: M

osby

, Inc

; 200

8; p

g 18

51-5

2 16

. Bet

ti R

, Ver

gani

R, T

olom

io E

, Mar

tino

P, C

rost

i C.

Tela

ngie

ctas

ia m

acul

aris

eru

ptiv

e pe

rsta

ns in

volv

ing

the

uppe

r arm

s in

an

adul

t m

ale.

Eur

opea

n Jo

urna

l of D

erm

atol

ogy,

200

0; 1

0(7)

:563

-564

17

. Cen

gizl

ier R

, Huc

umen

oglu

S, O

zen

A, T

ulin

Say

li R

. Tr

eatm

ent o

f tel

angi

ecta

sia

mac

ular

is e

rupt

iva

pers

tans

with

mon

telu

kast

. Al

lerg

ol Im

mun

opat

hol,

2009

; 37(

6): 3

34-3

36

18. A

ltine

r A, T

zu J,

Pat

el R

, Mee

han

S, S

anch

ez M

. Te

lang

iect

asia

mac

ular

is e

rupt

iva

pers

tans

. D

erm

atol

ogy

Onl

ine

Jour

nal,

2011

; 17

(10)

:7

19. E

llis D

L. T

reat

men

t of t

elan

giec

tasi

a m

acul

aris

eru

ptiv

e pe

rsta

ns w

ith th

e 58

5-nm

flas

hlam

p-pu

mpe

d dy

e la

ser.

Der

mat

ol S

urg,

19

96; 2

2:33

-37

20. A

dapt

ed f

rom

Wat

kins

CE,

Bok

or W

B, L

eich

t S, Y

oung

berg

G, K

rishn

asw

amy

G.

Tela

ngie

casi

a m

acul

aris

eru

ptiv

e pe

rsta

ns: m

ore

than

skin

dee

p. D

erm

atol

ogy

Repo

rts,

2011

; 3(1

) 21

. Im

age

from

http

://w

ww.

vgrd

.org

/cur

rent

/cur

rent

.htm

l, C

ase

pres

enta

tion

give

n by

Hai

mis

h D

unw

oodi

e M

D, S

kidg

ate,

Que

en

Cha

rlotte

Isla

nd, B

.C.,

Can

ada

on N

ovem

ber 1

0, 2

011

Con

clu

sion

TMEP

is ra

re fo

rm o

f cut

aneo

us m

asto

cyto

sis.

The

cou

rse

is o

ften

indo

lent

in n

atur

e. T

he p

atho

gene

sis i

s not

fully

und

erst

ood

and

requ

ires f

urth

er c

linic

al st

udie

s. Tr

eatm

ent i

s ofte

n ce

nter

ed o

n co

ntro

lling

sym

ptom

s and

trig

ger a

void

ance

. A

lthou

gh ra

re, c

ase

repo

rts o

f sys

tem

ic in

volv

emen

t hav

e be

en a

ssoc

iate

d w

ith T

MEP

, th

us a

thor

ough

his

tory

and

phy

sica

l exa

m is

ess

entia

l. In

the

afor

emen

tione

d ca

se, t

he p

atie

nt p

rese

nted

with

out a

ny c

once

rnin

g sy

mpt

oms o

r lab

orat

ory

findi

ngs t

o su

gges

t und

erly

ing

syst

emic

in

volv

emen

t. G

iven

the

beni

gn p

rese

ntat

ion,

the

patie

nt w

as

advi

sed

on fr

eque

nt e

xam

inat

ions

by

her p

rimar

y ca

re p

rovi

der

and

derm

atol

ogis

t alo

ng w

ith a

yea

rly C

BC

.

Figu

re 1

. Tan

to p

ink,

bl

anch

able

, tel

angi

ecta

tic

mac

ules

on

the

late

ral b

reas

t.

Figu

re 2

. Spa

rse

pauc

icel

lula

r inf

iltra

te c

onsi

stin

g pr

edom

inan

tly o

f mas

t cel

ls a

roun

d di

late

d ve

ssel

s of

the

supe

rfic

ial p

lexu

s.21

Sym

ptom

atic

trea

tmen

t with

em

phas

is o

n th

e av

oida

nce

of

trigg

ers i

s the

prim

ary

treat

men

t goa

l. Sy

mpt

omat

ic re

lief m

ay

be a

ccom

plis

hed

with

ant

ihis

tam

ines

, dis

odiu

m c

rom

ogly

cate

, le

ukot

riene

ant

agon

ists

, top

ical

ster

oids

, pso

rale

n pl

us U

VA

light

, 585

-nm

flas

hlam

p-pu

mpe

d pu

lse

dye

lase

r.9 Pa

tient

s sh

ould

be

educ

ated

on

avoi

danc

e of

the

com

mon

trig

gers

as w

ell

as th

e ris

k of

ana

phyl

axis

with

con

trast

dye

s and

ane

sthe

sia

(Tab

le 1

).3,9,

17 P

rovi

ding

an

epin

ephr

ine

inje

ctor

for e

mer

genc

y us

e is

reco

mm

ende

d al

ong

with

a m

edic

al a

lert

brac

elet

.9,18

Fr

eque

nt e

xam

inat

ions

and

yea

rly m

onito

ring

of C

BC

, ser

um

trypt

ase

and

24-h

our u

rinar

y hi

stam

ine

has b

een

advi

sed.

9

Syst

emic

ther

apy

for a

ggre

ssiv

e/se

vere

syst

emic

mas

tocy

tosi

s m

ay in

clud

e in

terf

eron

--2

b, ra

diat

ion

and

chem

othe

rape

utic

ag

ents

.8,15

,19

Dis

cuss

ion

(co

nti

nu

ed)

Sym

ptom

s sug

gest

ive

of sy

stem

ic d

isea

se in

clud

e; fe

ver,

head

ache

s, flu

shin

g, p

alpi

tatio

ns, p

rurit

us, g

astro

inte

stin

al (G

I) c

ompl

aint

s, dy

spne

a, b

one

pain

, ana

phyl

axis

, and

hep

atos

plen

omeg

aly.

13 I

n th

e se

tting

of

sugg

estiv

e sy

stem

ic d

isea

se, a

dditi

onal

test

ing

may

in

clud

e; 2

4-ho

ur u

rine

N-m

ethy

lhis

tam

ine,

bon

e m

arro

w b

iops

y, b

one

scan

, GI e

ndos

copy

, and

CT

of th

e ch

est,

abdo

men

and

pel

vis.

9,14

,15

His

topa

thol

ogic

exa

min

atio

n of

skin

bio

psie

s is e

ssen

tial i

n or

der t

o es

tabl

ish

a de

finiti

ve d

iagn

osis

and

to d

iffer

entia

te a

mon

g th

e va

rious

ty

pes.

TMEP

usu

ally

pos

sess

es le

ss a

ppar

ent h

isto

path

olog

ic fi

ndin

gs.

Ther

e us

ually

exi

sts a

mild

incr

ease

in m

ast c

ells

, par

ticul

arly

in

the

inte

rstit

ial c

olla

gen

and

arou

nd th

e su

perf

icia

l ple

xus b

lood

ves

sels

of t

he to

p th

ird o

f the

der

mis

.4,16

With

TM

EP, a

utho

rs h

ave

foun

d th

e va

lue

of m

ast c

ells

per

hig

h po

wer

fiel

d to

be

arou

nd 1

5 - 2

0, th

ough

a si

mpl

e co

ntra

stin

g di

ffere

nce

of m

ast c

ells

whe

n co

mpa

ring

norm

al a

nd a

ffect

ed sk

in c

an su

ffice

for d

iagn

osis

.4,9,

17 S

tain

s use

d to

vis

ualiz

e m

ast c

ells

and

thei

r cyt

opla

smic

gra

nule

s inc

lude

Gie

msa

, to

luid

ine

blue

, and

chl

oroa

ceta

te e

ster

ase

(i.e.

, Led

er st

ain)

.13 M

onoc

lona

l ant

ibod

ies t

hat r

ecog

nize

KIT

(CD

117)

and

/or t

rypt

ase

are

mor

e se

nsiti

ve a

nd u

sefu

l in

conf

irmin

g th

e di

agno

sis o

f mas

tocy

tosi

s.9,

15

Etha

nol

Psyc

holo

gica

l/Em

otio

nal s

tress

Ph

ysic

al e

xerc

ise

Bac

teria

l tox

ins

Food

alle

rgen

s (e.

g., s

hellf

ish,

pe

anut

s)

Imm

unol

ogic

stim

uli (

e.g.

, IgE

) So

lar r

adia

tion

Hot

/col

d te

mpe

ratu

re e

xtre

mes

Ve

nom

s (e.

g., h

ymen

opte

ra)

Oth

er in

sect

bite

s Ph

arm

aceu

tical

age

nts:

•

Ace

tyls

alic

ylic

aci

d •

Am

phot

eric

in B

•

d-Tu

bocu

rarin

e •

Dex

trom

etho

rpha

n •

Gal

lium

•

Iodi

ne-b

ased

con

trast

dye

s •

Nar

cotic

s (e.

g., m

orph

ine,

m

eper

idin

e, c

odei

ne)

•N

onst

eroi

dal a

nti-

infla

mm

ator

y dr

ugs

•Po

lym

yxin

B

•Po

lym

eric

eye

dro

ps

•Q

uini

ne

•R

eser

pine

•

Scop

olom

ine

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e 1.

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reca

lcitr

ant h

eada

ches

se

cond

ary

to su

prao

rbita

l/sup

ratro

chle

ar n

erve

(s) t

raum

a du

e to

faci

al fi

ller i

njec

tions

. Pa

ram

ount

to m

inim

izin

g ad

vers

e ev

ents

, eve

ry in

ject

or sh

ould

hav

e a

firm

und

erst

andi

ng o

f th

e pr

oper

ties a

nd th

e pr

oper

inje

ctio

n te

chni

ques

ass

ocia

ted

with

of e

ach

of th

e fil

lers

and

of

the

rele

vant

ana

tom

ical

stru

ctur

es/d

ange

r zon

es o

n th

e fa

ce.

ABSTRA

CT

A 7

1-ye

ar-o

ld C

auca

sian

wom

an p

rese

nted

to th

e of

fice

for f

acia

l rej

uven

atio

n th

erap

y w

ith in

ject

able

pol

y-L-

lact

ic a

cid

(PLL

A; S

culp

tra A

esth

etic

, San

ofi-A

vent

is).

The

pat

ient

w

as tr

eate

d w

ith tw

o vi

als o

f PLL

A w

ithou

t inc

iden

t. T

wo

days

afte

r the

pro

cedu

re, t

he

patie

nt w

oke

up w

ith a

sudd

en p

ain

on h

er ri

ght n

asal

side

wal

l and

righ

t eye

that

radi

ated

to

her r

ight

fore

head

and

righ

t fro

ntal

scal

p. T

here

was

no

late

ral s

prea

d of

the

pain

to th

e le

ft si

de o

f the

face

or h

ead.

The

pat

ient

des

crib

ed th

e pa

in a

s a c

onst

ant,

5/10

, pre

ssur

e-lik

e pa

in.

Whe

n fu

rther

que

stio

ned

rega

rdin

g sy

mpt

oms a

ssoc

iate

d w

ith a

nd p

rior t

o th

e he

adac

he, s

he d

enie

d na

usea

, vom

iting

, pho

toph

obia

, lac

rimat

ion,

dip

lopi

a, b

lurr

ed v

isio

n,

scot

oma,

dys

geus

ia, d

ysno

smia

, ano

rexi

a, ti

nnitu

s, w

eakn

ess,

fatig

ue, a

nd p

ares

thes

ias.

A

revi

ew o

f sys

tem

s rev

eale

d no

per

tinen

t pos

itive

s. T

he p

atie

nt to

ok ib

upro

fen

with

no

relie

f.

The

re is

no

fam

ily h

isto

ry o

f mig

rain

e he

adac

hes,

HTN

, DM

or c

ance

r. S

he h

as n

o kn

own

drug

alle

rgie

s and

den

ies t

akin

g an

y m

edic

atio

ns, h

erba

l sup

plem

ents

or v

itam

ins.

The

pa

tient

has

not

had

any

rece

nt d

enta

l pro

cedu

res p

erfo

rmed

. Th

e pa

tient

’s p

ast m

edic

al

hist

ory

is p

ositi

ve o

nly

for s

easo

nal a

llerg

ies w

ith re

sulta

nt si

nus h

eada

ches

.

Thi

nkin

g he

r sym

ptom

s may

be

due

to a

sinu

s hea

dach

e, th

e pa

tient

wen

t to

her E

NT

for

eval

uatio

n. A

ccor

ding

to th

e EN

T, h

er si

nuse

s wer

e cl

ear a

nd a

re n

ot th

e ca

use

of h

er

cons

tant

hea

dach

es.

The

pain

pro

gres

sive

ly w

orse

ned

and

2 w

eeks

afte

r the

pro

cedu

re, s

he

retu

rned

to th

e of

fice

com

plai

ning

of a

con

stan

t, rig

ht-s

ided

, 10/

10, p

ress

ure-

like

pain

. Th

e pa

tient

was

giv

en g

abap

entin

100

mg

thre

e tim

es p

er d

ay (o

ne p

ill in

the

mor

ning

, one

pill

in

the

afte

rnoo

n an

d tw

o pi

lls in

the

even

ing

befo

re b

ed).

Als

o, tw

elve

uni

ts o

f on

abot

ulin

umto

xinA

wer

e in

ject

ed in

to h

er g

labe

llar c

ompl

ex in

ord

er to

pos

sibl

y re

leas

e th

e te

nsio

n pl

aced

on

the

supr

aorb

ital/s

upra

troch

lear

ner

ve(s

) by

the

corr

ugat

or su

perc

illi.

T

wo

wee

ks la

ter,

even

afte

r med

icat

ion

ther

apy

and

onab

otul

inum

toxi

nA in

ject

ions

, the

pa

tient

con

tinue

d to

suffe

r fro

m c

onst

ant,

right

-sid

ed, 5

/10

pres

sure

-like

pai

n. A

t thi

s poi

nt,

she

wen

t to

be e

valu

ated

by

an a

cupu

nctu

rist.

The

acu

punc

turis

t the

n tre

ated

her

onc

e w

eekl

y fo

r eig

ht w

eeks

. A

fter h

er 5

th tr

eatm

ent,

the

patie

nt h

ad d

isco

ntin

ued

use

of

gaba

pent

in b

ecau

se h

er p

ain

was

slow

ly b

eing

alle

viat

ed.

Afte

r the

eig

hth

sess

ion,

her

pai

n ha

d de

crea

sed

in in

tens

ity to

a 2

/10.

How

ever

, on

her n

inth

vis

it, h

er a

cupu

nctu

rist h

ad

stud

ents

pra

ctic

e th

eir t

echn

ique

s on

her a

fter w

hich

, her

exc

ruci

atin

g, 1

0/10

hea

dach

es

retu

rned

. Th

e pa

tient

rest

arte

d he

r gab

apen

tin a

nd is

now

abl

e to

kee

p th

e pa

in se

verit

y to

a

5/10

. To

rule

out

org

anic

cau

ses o

f her

hea

dach

es, M

RI s

tudi

es w

ere

cond

ucte

d an

d w

ere

nega

tive.

CASE REPORT

In

faci

al re

juve

natio

n th

erap

y, th

e tra

ditio

nal f

ocus

was

on

a tw

o-di

men

sion

al p

lane

; ho

wev

er, t

his f

ocus

faile

d to

app

reci

ate

and

addr

ess t

he th

ree-

dim

ensi

onal

asp

ects

of t

he

face

, mai

nly

the

volu

me

loss

and

skel

etal

rem

odel

ing

asso

ciat

ed w

ith a

ging

. C

onse

quen

tly,

ther

e ha

s bee

n a

para

digm

shift

in fa

cial

reju

vena

tion

ther

apy;

trea

tmen

t is n

o lo

nger

focu

sed

on c

hasi

ng li

nes b

ut in

stea

d st

rives

to a

chie

ve th

e ap

pear

ance

of y

outh

fuln

ess b

y vo

lum

e au

gmen

tatio

n, so

ft-tis

sue

enve

lope

repo

sitio

ning

, and

resh

apin

g, re

-con

tour

ing

and

re-

text

uriz

ing

the

aged

face

(Sha

w2 ,C

arru

ther

s5 ).

For s

ucce

ssfu

l fac

ial r

ejuv

enat

ion

ther

apy,

the

volu

me

of th

e so

ft tis

sue

in th

e de

flate

d m

alar

and

zyg

omat

ic re

gion

s, br

ow a

nd in

frao

rbita

l ho

llow

s mus

t be

repl

aced

or a

ugm

ente

d (C

arru

ther

s5 ).

A v

arie

ty o

f inj

ecta

ble

fille

rs a

nd

bios

timul

ator

s can

be

used

to a

ccom

plis

h th

is g

oal b

y oc

cupy

ing

phys

ical

vol

ume

and

by

indu

cing

pro

duct

ion

of ty

pe I

colla

gen

(Fitz

gera

ld3 )

.

To

augm

ent/r

epla

ce v

olum

e in

cer

tain

ana

tom

ic lo

catio

ns su

ch a

s the

tem

ples

, tea

r tro

ughs

, zyg

oma,

max

illa,

man

dibl

e, b

row

and

chi

n, su

prap

erio

stea

l inj

ectio

ns a

re u

sual

ly

empl

oyed

. W

hen

inje

ctin

g an

y fil

ler o

r bio

stim

ulat

or o

nto

the

perio

steu

m, i

t wou

ld b

e pr

uden

t to

first

ack

now

ledg

e th

e lo

catio

n an

d pr

oxim

ity o

f the

seve

n da

nger

zon

es o

n th

e fa

ce w

here

the

mot

or o

r sen

sory

ner

ves t

rave

l mor

e su

perf

icia

lly o

r ner

ve ro

ots e

mer

ge fr

om

the

skul

l for

amin

a. K

ey st

ruct

ures

to a

void

incl

ude:

1) t

he su

prao

rbita

l and

supr

atro

chle

ar

bran

ches

of t

he o

phth

alm

ic b

ranc

h of

the

trige

min

al n

erve

and

acc

ompa

nyin

g bl

ood

vess

el;

2) th

e in

frao

rbita

l bra

nche

s of t

he m

axill

ary

bran

ch o

f the

trig

emin

al n

erve

and

the

infr

aorb

ital v

esse

ls; 3

) the

men

tal b

ranc

h of

the

man

dibu

lar b

ranc

h of

the

trige

min

al n

erve

; 4)

the

tem

pora

l (fr

onta

l) br

anch

of t

he fa

cial

ner

ve; 5

) the

mar

gina

l man

dibu

lar b

ranc

h of

the

faci

al n

erve

; 6) t

he b

ucca

l and

zyg

omat

ic b

ranc

hes o

f the

faci

al n

erve

and

the

paro

tid

Sten

sen’

s duc

t; an

d 7)

the

paro

tid g

land

(Sec

kel6 )

[Fig

1, T

able

1].

The

impo

rtanc

e of

ack

now

ledg

ing

and

avoi

ding

the

faci

al d

ange

r zon

es c

an b

e se

en in

m

ultip

le p

ublis

hed

repo

rts.

As L

azze

ri et

al (

Lazz

eri7 )

repo

rted,

blin

dnes

s has

occ

urre

d fo

llow

ing

cosm

etic

inje

ctio

ns o

f the

face

. Li

kew

ise,

in th

e ca

se d

escr

ibed

abo

ve, e

ither

car

e w

as n

ot ta

ken

to p

alpa

te fo

r and

avo

id th

e su

prao

rbita

l for

amen

and

its a

ssoc

iate

d ne

rves

and

ve

ssel

s, or

the

fille

r’s fl

ow ra

te a

nd/o

r inj

ectio

n sp

eed

was

too

fast

. W

hate

ver t

he c

ause

, the

re

sult

was

the

sam

e: r

ecal

citra

nt h

eada

ches

seco

ndar

y to

trau

ma

of th

e su

prao

rbita

l and

/or

supr

atro

chle

ar n

erve

(s).

Thi

s is t

he fi

rst c

ase

repo

rted

in th

e lit

erat

ure

in w

hich

reca

lcitr

ant

head

ache

s occ

urre

d po

st fi

ller i

njec

tions

, how

ever

, it w

ill n

ot b

e th

e la

st.

Due

to th

e sh

ift in

fo

cus o

f fac

ial r

ejuv

enat

ion

ther

apy

with

mor

e em

phas

is o

n vo

lum

e lo

ss d

ue to

bon

e re

sorp

tion,

mor

e ph

ysic

ians

will

util

ize

supr

aper

iost

eal f

iller

inje

ctio

ns, a

nd u

nles

s car

e is

ta

ken

to a

void

the

dang

er z

ones

of t

he fa

ce, m

ore

and

poss

ibly

nov

el a

dver

se e

ffect

s may

oc

cur.

DISCUSSION

Table 1: Facial D

anger Z

ones and Underlying Nerves

REFERENCES

1. A

mer

ican

Soc

iety

of P

last

ic S

urge

ons.

201

1 C

osm

etic

Pla

stic

Sur

gery

Sta

tistic

s.

Arli

ngto

n H

eigh

ts, I

L.

2. S

haw

RB

Jr, K

ahn

DM

: Agi

ng o

f the

mid

face

bon

y el

emen

ts: a

thre

e-di

men

sion

al

com

pute

d to

mog

raph

ic st

udy.

Pla

st R

econ

str S

urg

2007

, 119

:675

-681

. 3.

Fitz

gera

ld R

, Vle

ggaa

r D.

Faci

al v

olum

e re

stor

atio

n of

the

agin

g fa

ce w

ith p

oly-

l-la

ctic

aci

d. D

erm

atol

The

r. 20

11 Ja

n-Fe

b;24

(1):2

-27.

4.

Hof

fman

n K

; Juv

éder

m V

olum

a St

udy

Inve

stig

ator

s Gro

up.

Volu

miz

ing

effe

cts o

f a

smoo

th, h

ighl

y co

hesi

ve, v

isco

us 2

0-m

g/m

L hy

alur

onic

aci

d vo

lum

izin

g fil

ler:

pros

pect

ive

Euro

pean

stud

y. B

MC

Der

mat

ol. 2

009

Aug

27;

9:9.

5.

Car

ruth

ers J

, Car

ruth

ers A

, Tez

el A

, Kra

emer

J, C

raik

L.

Volu

miz

ing

with

a 2

0-m

g/m

L sm

ooth

, hig

hly

cohe

sive

, vis

cous

hya

luro

nic

acid

fille

r and

its r

ole

in fa

cial

re

juve

natio

n th

erap

y. D

erm

atol

Sur

g. 2

010

Nov

;36

Supp

l 3:1

886-

92.

6. S

ecke

l, B

R.

Faci

al D

ange

r Zon

es:

Avoi

ding

Ner

ve In

jury

in fa

cial

pla

stic

surg

ery.

St

. Lou

is:

Qua

lity

Med

ical

Pub

lishi

ng, 1

994.

7.

Laz

zeri

D, A

gost

ini T

, Fig

us M

, Nar

di M

, Pan

talo

ni M

, Laz

zeri

S. B

lindn

ess

follo

win

g co

smet

ic in

ject

ions

of t

he fa

ce.

Plas

t Rec

onst

r Sur

g. 2

012

Apr

;129

(4):

995-

1012

.

CONTA

CT

Mat

thew

Zar

raga

, DO

W

ellin

gton

Reg

iona

l Med

ical

Cen

ter

1010

1 Fo

rest

Hill

Blv

d W

ellin

gton

, FL

3341

4 dr

mbz

arra

ga@

gmai

l.com

From

Sec

kel B

R. F

acia

l Dan

ger Z

ones

: Avo

idin

g N

erve

Inju

ry in

Fac

ial P

last

ic S

urge

ry, 2

nd E

ditio

n. S

t. Lo

uis:

Q

ualit

y M

edic

al P

ublis

hing

, 201

0.

Ada

pted

from

Sec

kel B

R. F

acia

l Dan

ger Z

ones

: Avo

idin

g N

erve

Inju

ry in

Fac

ial P

last

ic S

urge

ry, 2

nd E

ditio

n. S

t. Lo

uis:

Qua

lity

Med

ical

Pub

lishi

ng, 2

010.

I

t is n

ow re

cogn

ized

that

vol

ume

loss

, rep

ositi

onin

g of

faci

al fa

t, an

d sk

elet

al re

mod

elin

g ar

e fu

ndam

enta

l com

pone

nts c

ontri

butin

g to

the

faci

al a

ging

pro

cess

(Sha

w2 )

. Fa

cial

yo

uthf

ulne

ss is

cha

ract

eriz

ed b

y th

e sy

mm

etry

and

bal

ance

seen

in th

e cl

assi

c he

art s

hape

or

inve

rted

trian

gle;

the

bony

com

pone

nts o

f the

face

con

tribu

te to

its a

ppea

ranc

e by

pro

vidi

ng a

th

ree-

dim

ensi

onal

con

tour

and

susp

ensi

on o

f the

soft

tissu

es.

Furth

erm

ore,

the

yout

hful

face

ha

s an

ampl

e am

ount

of v

olum

e an

d is

cha

ract

eriz

ed b

y a

smoo

th tr

ansi

tion

betw

een

subc

utan

eous

fat c

ompa

rtmen

ts (F

itzge

rald

3 ).

As a

ging

pro

gres

ses,

ther

e is

an

infe

rior

mig

ratio

n of

the

fat c

ompa

rtmen

ts a

nd a

n in

ferio

r vol

ume

shift

with

in th

e co

mpa

rtmen

ts

alte

ring

faci

al p

ropo

rtion

s and

dis

torti

ng th

e sm

ooth

tran

sitio

ns.

Exac

erba

ting

this

cha

nge,

gr

avity

alte

rs th

e po

sitio

ning

of t

he fa

cial

stru

ctur

es a

s tis

sue

lose

s its

ela

stic

ity a

nd b

ecom

es

less

resi

lient

(Hof

fman

4 ).

Con

sequ

ent o

f int

rinsi

c ag

ing,

faci

al b

one

rem

odel

ing

and

shrin

kage

oc

curs

resu

lting

in a

dec

reas

e in

the

max

illar

y an

gle

with

mar

ked

outb

owin

g at

the

med

ial h

alf

of th

e m

axill

ary

arch

, a d

ecre

ase

in th

e gl

abel

lar a

ngle

, and

an

incr

ease

in th

e py

rifor

m

aper

atur

e ar

ea (S

haw

2 ).

It is

this

com

bina

tion

of fa

cial

fat l

oss a

nd m

igra

tion

and

skel

etal

re

mod

elin

g th

at le

ads t

o vi

sibl

e si

gns o

f agi

ng. *Dermatology Resident, PGY-‐3, Wellington Regional Medical Center, Wellington, FL **Medical Director, Shino Bay Cosme.c Dermatology Plas.c Surgery and Laser Ins.tute, Fort Lauderdale, FL;

Program Director, Broward General Medical Center Dermatology Residency Program, Fort Lauderdale, FL

MaG

hew B. Zarraga, D

O*, Shino

Bay Aguilera, D

O, FAO

CD**

Recalcitrant H

eadaches Secon

dary to

Facial Filler InjecOon

s

Facial Danger

Zone

LocaOo

n Nerve

LocaOo

n of Zon

al

Injury

1 6.5cm below external

auditory canal

Great auricular

Inferior 2/3s of ear

and adjacent cheek

and neck

2 Below a line drawn from

0.5cm below tragus to 2cm

above lateral eyebrow and

above zygoma

Temporal branch of

facial

Forehead

3 Midmandible 2cm

posterior to oral

commissure

Marginal mandibular

branch of facial

Lower lip

4

Triangle formed by

connec.ng dots on malar

eminence, posterior border

of mandibular angle, and

oral commissure

Zygoma.c and buccal

branches of facial

Upper lip and cheek

5 Superior orbital rim above

midpupil

Supraorbital and

supratrochlear

Forehead, upper

eyelid, nasal dorsum,

scalp

6 1cm below inferior orbital

rim below midpupil

Infraorbital

Side of upper nose,

cheek, upper lip,

lower eyelid

7 Midmandible below

second premolar

Mental

Half of lower lip and

chin

Figure 1: SchemaO

c of Facial D

anger Zon

es and

Und

erlying Nerves

281

2012 AnnuAl Meeting SponSorS

Fallene

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topMD Skin Care

tru-Skin Dermatology

2012 AnnuAl MeetinggrAntS

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Stiefel, a gSK Company

Valeant Dermatology

Warner Chilcott

2012 CorporAte MeMberS

DiAMonD leVelgaldermaMedicis

golD leVelbiopelle

SilVer leVelranbaxy laboratories, inc.Stiefel, a gSK Company

Valeant Dermatology

bronZe leVelAbbott pharmaceuticals

Dermatopathology laboratories of Central States

Ferndale HealthcareSanofi-Aventis

triax pharmaceuticals

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