Hair loss and plaquelike skin lesions

A healthy 35-year-old African American woman presented for evaluation of hair loss (Figure 1). Examination of her scalp revealed areas of alopecia with absent hair follicles, erythematous papules, and a few pustules, consistent with a scarring (cicatricial) form of alopecia. Additionally, there were hypopigmented lesions on her arms (Figure 2) and targetoid plaquelike lesions on her legs (Figure 3).

Figure 1.

Posterior scalp with areas of scarring alopecia and erythematous papules and plaques

Figure 2.

Hypopigmented macules on the arm.

Figure 3.

Lower legs with targetoid plaques.

What is your diagnosis?

DIAGNOSIS: Sarcoidosis.

DISCUSSION

Sarcoidosis is a multisystem granulomatous disease of unknown etiology that involves the lungs in >90% of patients, eyes in 25% to 50%, lymph nodes in 75%, and skin in 25% to 30% (1–4). Pure cutaneous involvement is seen in approximately 25% of patients (5). The mucocutaneous lesions of sarcoidosis are diverse (Table) and can be divided into those that are specific and those that are nonspecific. Specific lesions demonstrate histological evidence of noncaseating granulomas in the dermis and are associated with chronic disease. A recent review of cutaneous sarcoidosis found that 73% of the patients had specific lesions at the beginning of their disease, with 70% of those patients having systemic manifestations concomitantly. The remaining 30% developed systemic disease between 6 months and 3 years later (17, 28). Clinically, specific lesions include a wide variety of papules, plaques, lupus pernio (red-purple papules and plaques on the face and fingers), pits/spicules, and alopecia. Other specific lesions may be verrucous, angiolupoid (having a prominent vascular or telangiectatic component), ulcerative, mutilating, pustular, or erythrodermic. Nonspecific lesions do not reveal granulomatous inflammation in the dermis but are associated with systemic involvement of sarcoidosis. Examples of nonspecific lesions include erythema nodosum (17%), clubbing, calcinosis cutis, and erythema multiforme. Usually, nonspecific lesions such as erythema nodosum are associated with acute disease and portend a more favorable prognosis.

Table.

Mucocutaneous manifestations of sarcoidosis

Manifestation	Description/comments
Alopecia (6, 7)	Can present as cicatricial (scarring) and noncicatricial (nonscarring) hair loss.
Calcinosis cutis* (2, 3)	May or may not be associated with hypercalcemia.
Eczematous dermatitis (8)	Sarcoidosis in children under 6 years of age is rare; however, these children typically present with a triad of skin, eye (keratitis and uveitis), and progressive joint involvement. Cutaneous lesions usually take the form of asymptomatic eczematous dermatitis, which leaves pitted scars when it resolves, or infiltrated plaques and papules.
Erythema (9)	Faint erythema on the trunk of 10 years, duration reported in a 44-year-old man.
Erythema multiforme–like lesions* (10)	Targetoid lesions seen most commonly on the lower extremities.
Erythema nodosum* (11)	Tender erythematous dermal and subcutaneous nodules present on the pretibial region of the lower extremities. The lesions are considered a hallmark of acute benign systemic disease. The most common cutaneous lesion seen in sarcoidosis.
Erythrodermic lesions (12)	Multiple erythematous to yellow-brown macules that coalesce to produce large areas of exfoliative dermatitis. The lesions are usually localized; less often they are diffuse and confluent.
Follicular lesions (7)	May have widespread distribution of reddish brown lesions.
Hypopigmentation (13)	Lesions may be dermal nodules with surrounding hypopigmentation or macular hypopigmented patches; usually on the legs.
Ichthyosiform lesions (14)	Most commonly presenting as ichthyosiform plaques on the extremities.
Keratotic spines and pits (15)	Lesions appeared on the dorsa of the hands and fingers and on the posterior neck of a 6-year-old boy who also had generalized erythroderma. Keratotic spines resembled those of pityriasis rubra pilaris.
Lichenoid eruptions (16)	Lesions are small pinkish brown papules, which coalesce and give the skin a cobblestone-surface appearance.
Lupus pernio (17)	Red-purple indurated lesions on ears, nose, cheeks, and fingers. Commonly associated with chronic fibrotic lung disease, bone cysts, and lymph node involvement.
Maculopapular lesions (18)	Symmetric red-brown lesions that commonly appear on the face, trunk, dorsum of extremities, and nuchal area. While usually asymptomatic, the lesions are pruritic in some patients. May be transient and at times may herald the onset of systemic disease.
Morpheaform lesions	Indurated sclerotic plaques, which may be linear.
Mutilating lesions (19)	Associated with cyst formation and destruction of bones and cartilage clinically mimicking Hansens disease (lepromatous leprosy) or cutaneous tuberculosis (lupus vulgaris).
Nail dystrophy* (20, 21)	Nail changes include clubbing, increased fragility, longitudinal ridges, pterygium formation, and thickening. X-ray of hands may show a lacelike reticulated trabecular pattern and punched-out cystlike lesions involving the phalanges.
Ocular involvement (22)	25% of patients will have ocular manifestations including conjunctival nodules (small pale yellow nodules), lacrimal gland enlargement, uveitis (anterior, posterior, and panuveitis), and xerophthalmia.
Oral involvement (22)	Small mucosal papules may be confused with Fordyce spots.
Photodistributed eruption (23)	Presents as a lupus erythematosus-like lesion (butterfly rash). Appears as individual or confluent papules. Antinuclear antibody titers and other lupus serologies are negative.
Plaques (24)	Morphology is variable; lesions may appear annular, ulcerated, hypopigmented, telangiectatic, diffuse, and psoriasiform. Scarring may be present. Plaques are located on the back, buttocks, face, extremities, and scalp. Skin lesions are typically associated with a chronic course. Sometimes referred to as Hutchinsons plaques.
Subcutaneous nodules (25)	Firm, mobile, and may be tender. Usually a late finding associated with systemic involvement. Darier-Roussy sarcoid.
Trauma/scar infiltration (22)	Papules, nodules, and plaques that appear within sites of tattoo, venipuncture, surgery, and acne scars.
Ulcerative lesions (26)	The legs are the most common site.
Verrucous lesions (27)	May be associated with automanipulation. Clinically mimics a deep fungal infection or possibly warts.

*Nonspecific skin lesions.

Several medically important entities are associated with sarcoidosis. Lofgren's syndrome is characterized by bilateral hilar lymphadenopathy, fever, arthralgias, erythema nodosum, and uveitis. Typically, 80% of these cases resolve within 2 years. Uveoparotid fever (Heerfordt's syndrome) consists of parotid and lacrimal gland involvement, facial nerve palsy, uveitis, and fever; in addition, central nervous system involvement is frequently present. Cutaneous lesions on the nose are commonly associated with sarcoidosis of the upper respiratory tract.

Histology

On histologic examination, specific lesions have well-defined epithelioid granulomas with minimal, if any, necrosis or inflammation (i.e., naked granulomas). Giant cells may be present. Three types of inclusion bodies have been seen but may not be specific for sarcoidosis: 1) Schaumann's bodies (calcium carbonate, phosphate, and iron), 2) asteroid bodies (lipoprotein), and 3) residual bodies (lipomucoprotein granules) (29).

Laboratory evaluation

Increased calcium has been found in blood and urine of patients with sarcoidosis. Additionally, increased angiotensin-converting enzyme levels have been reported; however, this can also be seen in patients with diabetes, alcoholic liver disease, various infections like leprosy, and Gaucher's disease. The Kveim- Siltzbach test, an intradermal injection of heat-sterilized sarcoid tissue followed by a biopsy at the injection site 6 weeks later, shows granulomas in 80% of patients with active disease (2).

Differential diagnosis

Sarcoidosis, like syphilis, has a great variety of cutaneous manifestations. The most common mimics include the following:

1. Infections (leprosy, lupus vulgaris [cutaneous tuberculosis], leishmaniasis, syphilis)

2. Inflammatory skin diseases (lichen planus, granuloma annulare, necrobiosis lipoidica diabeticorum, lupus erythematosus, rosacea)

3. Neoplasms (cutaneous lymphomas and leukemias)

Treatment

There is no cure for sarcoidosis. Treatment is dictated by the extent of involvement. Cutaneous sarcoidosis has been treated successfully with systemic, intralesional, and topical steroids. Other agents employed include antimalarials (30), retinoids, and immunosuppressives such as methotrexate (31). For more disfiguring cutaneous lesions, even in the absence of systemic disease, systemic therapy is frequently indicated.