Clinical Vignettes in Dermatology ASFA AKHTAR D.O., FAOCD, FAAD DEPARTMENT OF DERMATOLOGY CLEVELAND CLINIC FLORIDA
Clinical Vignettes
in DermatologyASFA AKHTAR D.O., FAOCD, FAAD
DEPARTMENT OF DERMATOLOGY
CLEVELAND CLINIC FLORIDA
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Basal Cell Carcinoma
Basal Cell Carcinoma (BCC)
BCC is the most common skin cancer in humans
Arises from the basal layer cells of the epidermis
30% of all malignancies
Accounts for 70-80% of all cutaneous
malignancies
Basal Cell Carcinoma (BCC)
In 2006, the incidence was 2.6 million
Continues to rise at an average rate of 4% to 8%
Incidence of BCC is rising in the younger
papulation
Poses a significant health problem in terms of
incidence and health care costs
Basal Cell Carcinoma (BCC)
Ultraviolet radiation (UVR) is the most common
factor in the pathogenesis of BCC
The risk of developing BCC is higher in individuals
who are fair and burn or tan easily versus individuals
that those who are darkly pigmented
Blistering sunburns in childhood increase the risk
UV induced epidermal DNA damage is the primary
carcinogenic insult leading to BCC formation
Eg. Xeroderma Pigmentosum
Basal Cell Carcinoma (BCC)
Xeroderma pigmentosum (XP)
Hallmarks are photosensitivity, photophobia, and
conjunctivitis
Patients lack the ability to repair UV induced DNA
damage (defective DNA thymidine excision
repair)
Multiple basal cell carcinomas, squamous cell
carcinomas and melanoma develop in
childhood
Basal Cell Carcinoma (BCC)
The patched gene 1 (PTCH1) is a tumor suppressor
gene mutated in patients with Basal cell nevus
syndrome (Gorlin syndrome)
Multiple BCCs, odontogenic cysts of the jaw, frontal
bossing, pitting on the hands and feet, and ocular
hypertelorism
The usual age of development of BCC is 17-35 years
The central face is mostly affected (eyelids,
forehead, nose, upper lip and cheeks)
Basal Cell Carcinoma (BCC)
Ionizing radiation
Acne
Tinea capitis
Arsenic exposure
Well water
Fowler’s solution
Other risk factors for the development of BCC
include:
Industrial exposure (mining, smelting)
Pesticides
Topical Nitrogen mustard
Scars
Burns
Basal Cell Carcinoma (BCC)
Basex syndrome
Rasmussen syndrome
Rombo syndrome
Other syndromes associated with the development
of BCC include:
Basal Cell Carcinoma (BCC)
Most basal cell carcinomas occur in sun-
exposed areas
20% occur in sun-protected areas
Men have a higher incidence than women
Metastasis of BCC is very rare and ranges from
0.0028% to 0.1%
Basal Cell Carcinoma (BCC)
Types of Basal Cell Carcinoma
Superficial
Nodular
Morpheaform
Infiltrative
Fibroepithelial
Infundibulocystic
Basal Cell Carcinoma (BCC)
Superficial BCC
AKA superficial multicentric BCC
Dry, scaly lesion
Comprises at least 50% of BCCs
Favors the trunk and distal extremities but can
occur on the head and neck
Basal Cell Carcinoma (BCC)
Superficial BCC
Multiple lesions may be present
Can vary in size from a few millimeters to
several centimeters in diameter
Misdiagnosed as eczema or psoriasis
Most common pattern seen in HIV infection
Basal Cell Carcinoma (BCC)
Nodular BCC
Classic BCC comprising 50-80% of all BCCs
Waxy or skin-colored papules that may crust,
ulcerate, or bleed
A rolled border is present on larger lesions
(rodent ulcer)
The lesion gradually enlarges over months to
years
Basal Cell Carcinoma (BCC)
Nodular BCC
Can reach a large size and extend deeply
Most frequently found on the face (>80% on
the head and neck)
Melanin pigment may be present, making it
easily confused with a melanocytic lesion
Basal Cell Carcinoma (BCC)
Morpheaform BCC
This type of BCC is indurated and ivory in color
Atrophic with telangiectasias
May resemble scar or morphea
Basal Cell Carcinoma (BCC)
Infiltrative BCC
Aggressive type of BCC characterized by deep
infiltration into the dermis, subclinical spread, and
high recurrence rate
30% of all primary BCCs fall into this category
Ill-defined clinical margins
Basal Cell Carcinoma (BCC)
Treatment
Depends on the type and aggressiveness of the
tumor, patient age, patient sex, and site of the
lesion
A biopsy should be performed in all cases to
determine the histologic subtype
Aim of treatment is total removal or destruction
with best cosmetic results
Basal Cell Carcinoma (BCC)
Excision
Mohs micrographic surgery
Curettage and electrodessication
Radiation treatment
Cryosurgery
Treatment Options
Lasers
Photodynamic therapy
Immune response modifiers
Topical chemotherapy
Systemic hedgehog inhibitors
References
Rigel, D. S., Friedman, R. J., & Dzubow, L. M. (2005). Chapter 9, Basal
Cell Carcinoma. In Cancer of the Skin (pp. 101-132). New York, NY:
Elsevier.
James, W. D., Berger, T. G., & Elston, D. M. (2006). Chapter 29,
Dermal and Subcutaneous Tumors. In Andrews' Diseases of the Skin
Clinical Dermatology (10th ed., pp. 646-652). Philadelphia, PA:
Saunders Elsevier.
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Bullous Pemphigoid
Bullous Pemphigoid (BP)
Bullous Pemphigoid (BP) is a chronic
autoimmune bullous disorder most commonly
seen in the elderly population. It can occur in
young children as well
Originally described by Lever in 1953
Most common autoimmune bullous disease in
the Western Hemisphere
6-7 cases/million population per year
Bullous Pemphigoid (BP)
BP is characterized by large, tense bullae in a
generalized distribution with a predilection for
flexural areas.
Once the bullae rupture, large denuded patches
are seen
In the early course of the disease, pruritic patches
and plaques may be seen with no bullous lesions
Urticarial lesions and targetoid lesions can be seen
Incidence of oral involvement is about 20%
Bullous Pemphigoid (BP)
Blister formation results from antibodies directed
against the hemidesmosomal antigens
BP Ag1 230 (230 kD)
BP Ag2 180 (180 kD)
The antibody to BP Ag2 is the primary
pathogenic factor
Bullous Pemphigoid (BP)
Blister formation occurs due to:
Complement activation
Mast cells
Eosinophils
Neutrophils
Bullous Pemphigoid (BP)
Histology reveals a subepidermal blister with a mixed inflammatory infiltrate mostly comprised of eosinophils
Direct immunofluorescence (DIF) demonstrates linear deposition of IgG and complement (C3) along the basement membrane zone (BMZ)
Indirect immunofluorescence (IIF) on salt-split skin is also helpful
DIF is more sensitive than IIF
Eosinophil-rich subepidermal blister with a smooth epidermal undersurface consistent with bullous
pemphigoid
Direct immunofluorescence: linear deposition of IgG and C3 along the basement membrane zone
Indirect immunofluorescence: circulating IgG anti-basement membrane antibodies binding only to epidermal side of salt split skin with a titer of 1:80
Bullous Pemphigoid (BP)
Must differentiate between BP and epidermolysis
bullosa acquisita (EBA)
Type IV collagen mapping localizes to the roof
of the blister in EBA but to the base of the blister
in BP
Bullous Pemphigoid (BP)
BP has several subtypes which have been classified into primary cutaneous and mucosal variants and into generalized and localized forms.
Localized BP is a rare variant of bullous pemphigoid which is classified into two types:
1. Brunsting and Perry type
Characterized by scarring lesions of the head and neck
2. Localized cutaneous non-scarring bullous pemphigoid (Eberhartinger and Niebauer type)
Characterized by non-scarring, bullous lesions of the extremities, especially the pretibial region.
This variant may also be present at other sites including forearms, chest, buttocks, and umbilicus
Bullous Pemphigoid (BP)
Other variants of BP
Vesicular pemphigoid
Pemphigod nodularis
Pemphigoid vegetans
Erythrodermic pemphigoid
Non-bullous variant
Bullous Pemphigoid (BP)
Treatment
Few controlled trials on BP
Treatment depends on extent of disease on time of diagnosis and progression of disease
High-potency glucocorticoids are the mainstay of treatment for localized disease
Systemic glucocorticoids are most beneficial for generalized disease with the addition of a steroid sparing agent
Bullous Pemphigoid (BP)
Treatment
Steroid sparing agents are added to avoid
long-term corticosteroid use
Mycophenolate mofetil, tetracycline and
niacinamide, dapsone, erythromycin,
methotrexate, cyclosporine,
cyclophosphamide, chlorambucil and IVIG
have been used
Bullous Pemphigoid (BP)
Course
BP runs its course over 5-6 years
Relapses can be seen in 15% of patients
Bullous Pemphigoid (BP)
Course
BP runs its course over 5-6 years
Relapses can be seen in 15% of patients
References
1. Chan L. Bullous Pemphigoid. eMedicine. 2007 http://www.emedicine.com/derm/topic64.htm.
2. Salomon, R. G. , Briggaman, R.A., Wernikoff, S.Y. et.al. Localized bullous pemphigoid. Arch Dermatol 1987; 123: 389-392.
3. Kaplan, R. P. Cutaneous involvement in localized forms of bullous pemphigoid. Clin Dermatol, 1987; 5: 43-51.
4. Seishima M, Izumi T, Kitajima Y. Antibody to bullous pemphigoid antigen 1 binds the antigen at perilesional but not uninvolved skin, in localized bullous pemphigoid. Eur J Dermatol 1999; 9: 39-42.
5. Cecchi R, Paoli S, Giomi A. Peristomal bullous pemphigoid. J Eur Acad Dermatol Venereol 2004; 18(4): 515-516.
6. Jappe U, Bonnekoh B, Gollnick H. Initially localized bullous pemphigoid at the irradiation site of breast carcinoma. Eur J Dermatol 1999; 9: 139-41.
7. Balachandran C, Rai VM. Localised bullous pemphigoid in the breast. Indian J Dermatol VenerolLeprol 2006; 72: 158-9.
8. Nousari HC, Anhalt GJ. Pemphigus and bullous pemphigoid. Lancet 1999; 354(9179): 667-72.
9. Surjushe A, Saple DG. Mycophenolate mofetil. Indian J Dermatol Venerol Leprol 2008; 74: 180-4.
Derm101.com
Rosacea
Rosacea
Rosacea is a common inflammatory skin disease that
affects the central facial skin
Chronic inflammatory skin disorder that includes transient
and permanent erythema, inflammatory papules and
pustules, phymatous changes, and ocular symptoms
Pathophysiology is multifactorial and an altered innate
immune response is thought to be involved in this disease
Complex disease with involvement of the neural,
immune, and vascular pathways
Rosacea
Clinical features of rosacea include:
Papules and or/pustules
Flushing
Skin sensitivity
Burning or stinging
Erythematous plaques
Facial dryness
Scaling
Edema
Rosacea
Four subtypes recognized by the National
Rosacea Society
1. Erythematotelangiectatic
2. Papulo-pustular
3. Phymatous
4. Ocular
Rosacea
The National Rosacea Society Expert Committee
(NRSEC) designated that patients may present
with features that encompass more than one
single rosacea subtype
Rosacea
Flushing and persistent central facial erythema
Telangiectases
Highly sensitive cosmetically intolerant skin
Must be distinguished from other inflammatory
conditions such as chronic actinic damage and
connective tissue disease
Subtype 1: Erythematotelangiectatic rosacea
Rosacea
Persistent central facial erythema
Transient papules and pustules
Absence of comedones and truncal lesions
Older age group
Must be distinguished from acne vulgaris,
seborrheic dermatitis, perioral dermatitis,
folliculitis and demodicidosis
Subtype 2: Papulopustular rosacea
Rosacea
Thickened skin
Nodules
Localized enlargement
Firm induration of the skin secondary to fibrosis
Rare variants such as granulomatous rosacea
must be distinguished from other conditions such
as sarcoidosis
Subtype 3: Phymatous rosacea
Rosacea
Subtype 4: Ocular rosacea
Bloodshot appearance
Foreign body sensation
Burning
Stinging
Light sensitivity
Blepharitis
Conjunctivitis
Chalazions, hordeolum,
and corneal
complications
Rosacea
Hallmark of rosacea is persistent central facial
erythema mostly affecting the convex surfaces
Cheeks
Chin
Forehead
Nose
Sparing of the periocular and perioral areas
Rosacea
In patients with darker skin type, the diagnosis of
rosacea can be missed or delayed
Features in darker skin type may include
Burning/stinging
Dryness
Edema
Sensitive skin
Sensation of flushing
Rosacea
Ranges from 1%-20%
Rosacea affects an estimated 16 million Americans
Distribution of rosacea is reported as equal or female
predominant.
Risk factors include:
Age
Phototype
Gender
Alcohol consumption
Genetic makeup
UV exposure
Rosacea
Infectious Organisms Associated with Rosacea
Demodex
Staphylococus epidermidis
H. pylori
http://www.animaldermatologysolutions.com.au
Rosacea
Pathophysiology
Complex
Genetic component
Interplay of adaptive and innate immune system
AMP
Antimicrobial peptides secreted by the keratinocytes
in response to a microbial challenge
Eccrine glands, mast cells, and sebocytes are
capable of producing AMP as well
Rosacea
Defensins and Cathelicidins are AMPs in human skin
α and β defensins are gene encoded
Cathelicidin AMP (CAMP) is a cathelicidin gene
identified in humans
Increased levels of cathelicidins and protease activity
are seen in patients with rosacea
Mechanism is not fully understood
Different signaling pathways including retinoid, Vitamin
D, and cytokine-activated cascades are involved
Rosacea
Therapy
Rosacea negatively impacts the quality of life
of affected individuals
Patients with rosacea can experience
embarrassment, stress, social phobia, lack of
confidence, and depression
Moustafa, Farah et al. The psychological impact of rosacea and the influence of current management options. Journal of the American
Academy of Dermatology , Volume 71 , Issue 5 , 973 - 980
Rosacea
Therapy
Subantimicrobial-dose cyclines
The anti-inflammatory effects of tetracyclines led to
the development of subantimicrobial dose
doxycycline (SDD)
Thought to act by various mechanisms
↓ activity of kallikrein 5 enzyme which in turn
↓ Cathelicidins
Rosacea
Therapy
β-blockers
Oral ivermectin
Rosacea
New topical therapy
Brimonidine tartrate gel 0.33%
α-2 adrenergic agonist that causes peripheral
vasoconstriction of smooth muscle receptors
First drug approved to treat facial erythema of rosacea
Ivermectin
Anti-inflammatory and acaricidal properties against
Demodex
Oxymetazoline
Rosacea
Ivermectin 1% cream
Two 40-week extension studies were
conducted to assess the long term safety of
ivermectin 1% cream vs azelaic acid 15% gel
Lower incidence of adverse events in the
ivermectin group compared to azelaic acid
group
Safe and effective for up to 52 weeksLong-Term Safety of Ivermectin 1% Gel in Treating Inflammatory
Results of Two 40-Week Controlled, Stein Gold et al, Journal of Drugs
in Dermatology, Nov. 2014, Vol 13, issue 11
Rosacea
IGA= 4; Lesion count = 63
Baseline
IGA= 1; Lesion count = 2
Week 12
Data on file. Fort Worth, TX; Galderma Laboratories, L.P.
Stein Gold L, et al. J Drugs Dermatol. 2014;13:316-323.
Rosacea
Therapy
Vascular Lasers
Pulse dye laser (PDL, 585-595nm)
Potassium-titanyl-phosphate laser (KTP, 532nm)
Diode-pumped frequency doubled laser (532nm)
Neodymium-doped yttrium aluminium garnet laser
(Nd:YAG, 1064nm)
Images Courtesy of Tom Rohrer, MD
RosaceaCourtsey: Syneron Candela Corp.
Rosacea
Chronic condition with no cure
Exact cause is unknown
Dysregulation of the immune system as well as neurovascular system
Adversely affects the quality of life
Identification of trigger factors
Cosmetic intolerance and increased sensitivity of skin are common features
Use of gentle, broad spectrum sunscreens, avoidance of extended sun exposure and use of non irritating cosmetics is recommended
Therapy should be tailored to the predominant clinical subtype to optimize therapy
Summary
References1. Steinhoff, Martin et al. New insights into rosacea pathophysiology: A review of recent findings. Journal of the American Academy of Dermatology , Volume 69 ,
Issue 6 , S15 - S26
2. Augustin, M., Herberger, K., Hintzen, S., Heigel, H., Franzke, N., and Schafer, I. Prevalence of skin lesions and need for treatment in a cohort of 90,880 workers. Br J Dermatol. 2011; 165: 865–873
3. Spoendlin, J., Voegel, J.J., Jick, S.S., and Meier, C.R. A study on the epidemiology of rosacea in the UK. Br J Dermatol. 2012; 167: 598–605
4. McAleer, M.A., Fitzpatrick, P., and Powell, F.C. Papulopustular rosacea: prevalence and relationship to photodamage. J Am Acad Dermatol. 2010; 63: 33–39
5. Bakar, O., Demircay, Z., Yuksel, M., Haklar, G., and Sanisoglu, Y. The effect of azithromycin on reactive oxygen species in rosacea. Clin Exp Dermatol. 2007; 32: 197–200
6. Gerber, P.A., Buhren, B.A., Steinhoff, M., and Homey, B. Rosacea: the cytokine and chemokine network. J Investig Dermatol Symp Proc. 2011; 15: 40–47
7. Cribier, B. Pathophysiology of rosacea: redness, telangiectasia, and rosacea. Ann Dermatol Venereol. 2011; 138: S184–S191
8. Lazaridou, E., Fotiadou, C., Ziakas, N.G., Giannopoulou, C., Apalla, Z., and Ioannides, D. Clinical and laboratory study of ocular rosacea in northern Greece. J EurAcad Dermatol Venereol. 2011; 25: 1428–1431
9. Lacey, N., Delaney, S., Kavanagh, K., and Powell, F.C. Mite-related bacterial antigens stimulate inflammatory cells in rosacea. Br J Dermatol. 2007; 157: 474–481
10. Whitfeld, M., Gunasingam, N., Leow, L.J., Shirato, K., and Preda, V. Staphylococcus epidermidis: a possible role in the pustules of rosacea. J Am Acad Dermatol. 2011; 64: 49–52
11. Cowland, J.B., Johnsen, A.H., and Borregaard, N. hCAP-18, a cathelin/pro-bactenecin-like protein of human neutrophil specific granules. FEBS Lett. 1995; 368: 173–176
12. Larrick, J.W., Hirata, M., Zhong, J., and Wright, S.C. Anti-microbial activity of human CAP18 peptides. Immunotechnology. 1995; 1: 65–72
13. Del Rosso, J.Q., Webster, G.F., Jackson, M., Rendon, M., Rich, P., Torok, H. et al. Two randomized phase III clinical trials evaluating anti-inflammatory dose doxycycline (40-mg doxycycline, USP capsules) administered once daily for treatment of rosacea. J Am Acad Dermatol. 2007; 56: 791–802
14. Hsu, C.C. and Lee, J.Y. Pronounced facial flushing and persistent erythema of rosacea effectively treated by carvedilol, a nonselective beta-adrenergic blocker. J Am Acad Dermatol. 2012; 67: 491–493
15. Hsu, C.C. and Lee, J.Y. Carvedilol for the treatment of refractory facial flushing and persistent erythema of rosacea. Arch Dermatol. 2011; 147: 1258–1260
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Dermatomyositis
Dermatomyositis (DM)
Dermatomyositis (DM) is a condition that is
characterized by an inflammatory myopathy
with characteristic cutaneous findings
It is a systemic disorder that most commonly
affects the skin and muscles but can also affect
the joints, muscles, esophagus, and occasionally
the heart
DM with subclinical or absent myopathy is called
amyopathic dermatomyositis
Dermatomyositis (DM)
Cutaneous Manifestations of Dermatomyositis
The disease begins with erythema and edema of the
face including the eyelids
Gottron’s papules
Flat topped, polygonal violaceous papules over the
knuckles
Heliotrope eruption
Violaceous erythema over the eyelids
Psoriasiform dermatitis of the scalp
Heliotrope
Dermatomyositis (DM)
Cutaneous Manifestations of Dermatomyositis Gottron’s sign
Erythematous, atrophic, scaly patches on the MCPs, elbows, and knees
Shawl sign
Erythema with or without poikiloderma on the shoulders and upper back
V-neck-sign
Erythematous patches on the chest in a V-shaped distribution
Flagellate erythema
Prominent telangiectatic vessels of the proximal nail fold with cuticular hypertrophy
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Dermatomyositis (DM)
Muscle disease may occur simultaneously,
precede or follow the skin symptoms
Symmetric proximal muscles weakness mostly
involving the shoulder girdle and occasionally
the pelvis region
Muscle weakness can be noted on climbing
stairs, combing hair, or rising from a chair
Dermatomyositis (DM)
Systemic Manifestations
Weight loss
Fever
Arthralgia
Dysphonia
Dysphagia
Gastroesophageal
reflux
Dyspnea
Dermatomyositis (DM)
Laboratory Evaluation
Muscle enzymes
Creatine kinase (CK)
Aldolase
Aspartate aminotransferase (AST)
Lactic dehydrogenase (LD)
Antinuclear antibodies
Myositis-specific antibodies
Electrocardiography
Esophageal manometry
Colonoscopy
Papanicolaou smear
CA-125 and CA-19-9
Pulmonary function tests
Dermatomyositis (DM)
Imaging studies
MRI
CT scanning of chest, abdomen, and pelvis
Transvaginal ultrasound and mammography
Barium swallow
Dermatomyositis (DM)
Histopathology
Histology reveals thinning of the epidermis, subtle
interface vacuolar infiltrate, not significant increased
basement membrane thinning or dyskeratosis and
significantly increased dermal mucin
Direct Immunofluorescence: Cutaneous DIF is positive
in at least 90% of patients
Cytoid bodies, continuous granular staining with C5b-
9, stronger than C3, and focal granular IgG and IgM
along the basement membrane
Dermatomyositis (DM)
Management
Occult malignancy is seen in up to one-third of the patients
Colon
Breast
Pancreatic
Ovarian
Lymphoma
Dermatomyositis (DM)
Corticosteroids
Prednisone is first-line
therapy
Immune globulins
Antimalarial agents
Hydroxychloroquine
Chloroquine
Corticosteroid sparing immunosuppressants
Methotrexate
Azathioprine
Mycophenolate mofetil
Sirolimus
Cyclosporine
Tacrolimus
Treatment
References
James, W. D., Berger, T. G., & Elston, D. M. (2006). Chapter 8,
Connective Tissue Diseases. In Andrews' Diseases of the Skin Clinical
Dermatology (10th ed., pp. 166-171). Philadelphia, PA: Saunders
Elsevier.
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