Clinical Vignettes - Florida Osteopathic Medical Association · who are fair and burn or tan easily versus individuals ... Industrial exposure ... Pathophysiology is multifactorial

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

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

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

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

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)

Ionizing radiation

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

Basex syndrome

Rasmussen syndrome

Rombo syndrome

Other syndromes associated with the development

of BCC include:

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%

Types of Basal Cell Carcinoma

Superficial

Nodular

Morpheaform

Infiltrative

Fibroepithelial

Infundibulocystic

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

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

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

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

Morpheaform BCC

This type of BCC is indurated and ivory in color

Atrophic with telangiectasias

May resemble scar or morphea

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

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

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

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%

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

Blister formation occurs due to:

Complement activation

Mast cells

Eosinophils

Neutrophils

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

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

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

Other variants of BP

Vesicular pemphigoid

Pemphigod nodularis

Pemphigoid vegetans

Erythrodermic pemphigoid

Non-bullous variant

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

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

Course

BP runs its course over 5-6 years

Relapses can be seen in 15% of patients

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 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

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

Forehead

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

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:

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

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

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

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

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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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

Systemic Manifestations

Weight loss

Arthralgia

Dysphonia

Dysphagia

Gastroesophageal

reflux

Dyspnea

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

Imaging studies

CT scanning of chest, abdomen, and pelvis

Transvaginal ultrasound and mammography

Barium swallow

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

Management

Occult malignancy is seen in up to one-third of the patients

Breast

Pancreatic

Ovarian

Lymphoma

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.

Thank you

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