Cutaneous sarcoidosis: differential diagnosis

doi:10.1016/j.clindermatol.2007.03.004

Clinics in Dermatology

Volume 25, Issue 3, May–June 2007, Pages 276-287

https://doi.org/10.1016/j.clindermatol.2007.03.004 Get rights and content

Abstract

Sarcoidosis is a multisystem disease with cutaneous lesions present in 20%-35% of patients. Given the wide variability of clinical manifestations, it is one of the “great imitators,” making it necessary to consider clinical, epidemiological, radiographic, laboratory, and histopathological criteria to make the diagnosis.

Cutaneous lesions have been classified as specific and nonspecific, depending on the presence of noncaseating granulomas on histologic studies. Specific lesions include maculopapules, plaques, nodules, lupus pernio, scar infiltration, alopecia, ulcerative lesions, and hypopigmentation among others. Nail, mucosal, and childhood sarcoidosis represent a distinct subset of the disease process. The most common nonspecific lesion is erythema nodosum. Others include calcifications, prurigo, erythema multiforme, nail clubbing, and Sweet syndrome.

The importance of considering cutaneous sarcoidosis in the clinical differential diagnosis of a given skin lesion relies on the association with systemic involvement and the convenience of the skin as a tissue source for histologic analysis.

Introduction

The manifestations of sarcoidosis in the skin can represent a diagnostic challenge for physicians. Cutaneous sarcoidosis is known as the great imitator because of its widely variable morphologies.1, 2 A high index of clinical suspicion is needed to consider sarcoidosis.

Skin manifestations in sarcoidosis occur in about 20%-35% of patients and are usually present at the onset of the disease.3, 4, 5, 6, 7 Some studies have reported an increased female-male ratio in sarcoidosis patients with skin involvement, compared with those patients with no skin disease.5, 6, 7, 8

The importance of considering sarcoidosis in the differential diagnosis of a given clinical presentation relies on the following reasons:

1.
Cutaneous sarcoidosis is usually an early manifestation of the disease, prompting the necessity to evaluate for systemic involvement, regardless of the percentage of skin surface affected.⁹ The skin is a convenient source for tissue and histologic diagnosis. The diagnosis of sarcoidosis is more rapid in patients with cutaneous sarcoidosis than other forms of the disease.10, 11
2.
Different forms of cutaneous sarcoidosis may represent a prognostic factor during the course of systemic disease, especially erythema nodosum.9, 12 The presence of a specific type of lesion may be beneficial regarding the treatment plan and the prognosis.
3.
Sarcoidosis can be associated with different malignancies, most commonly those of hematologic origin.13, 14

Classically, skin lesions of sarcoidosis have been classified as specific and nonspecific.4, 15, 16 Specific lesions reveal noncaseating granulomas on histologic examination. The most typical specific lesions include maculopapules, nodules, plaques, infiltrative scars, and lupus pernio.7, 17 Nonspecific lesions represent a reactive process and do not contain the classic granulomas.¹⁷ Erythema nodosum is the most common nonspecific lesion.

Clinical information that may aid the physician in considering this disease as part of the differential diagnosis includes:

1.
Epidemiologically, sarcoidosis has a bimodal age distribution (25-35 and 45-55 years of age), most common in women and in patients of Scandinavian or African American descent.18, 19, 20
2.
A common feature of the disease is multiorgan involvement.²¹ The presence of systemic findings, that is, ocular or respiratory symptoms, in a patient with suspicious skin lesions should raise the possibility of sarcoidosis.
3.
Diascopy, in which a microscopic slide is compressed against a cutaneous lesion, reveals a yellowish-brown or apple-jelly color in sarcoidal skin lesions. This method is thought to press out the vascular and inflammatory erythema of sarcoidosis, revealing the epithelioid granulomas.²² This finding on physical examination is better appreciated on sarcoid plaques and papules, in patients with lighter skin color. It is not pathognomonic for sarcoidosis; it can be present in other granulomatous entities such as granulomatous rosacea, lupus miliaris disseminatus facei, and granulomatous periorificial dermatitis.²³ Despite the nonspecificity, it is a simple, noninvasive procedure that may provide an additional clinical clue to differentiate among the long list of diseases considered in the differential diagnosis of sarcoidosis. Furthermore, Veien et al⁹ proposed the use of diascopy to monitor treatment results, considering the reappearance of positive diascopy as insufficient dosage.
4.
Sarcoidosis lesions are usually multiple, hyperpigmented or violaceous in color, and commonly asymptomatic, although pruritus is present in 10%-15% of patients.²⁴

The clinical and histopathological differential diagnosis of this disease process includes a vast number of pathologic entities. A practical approach is to consider the individual types of clinical manifestations separately.

Section snippets

Papules and maculopapules

Maculopapules are the most common type of specific lesions.7, 15 They are asymptomatic red-brown to purple papules, less than 1 cm in diameter, often affecting the eyelids, periorbital area, and nasolabial folds. They can appear, however, anywhere in the body including mucous membranes (Fig. 1, Fig. 2).4, 7, 15 Maculopapular eruptions seem to herald the onset of systemic disease.⁶ These lesions may be transient or may enlarge and coalesce to form plaques or annular lesions.7, 15 Spontaneous

Other forms

Clinically atypical and infrequently reported sarcoidal skin lesions include rhinophyma-like66, 67; lipodermatosclerosis-like⁶⁸; morpheaform,69, 70 leonine facies71, 72, 73; erythema multiforme-like²⁴; nodular fingertip lesions⁷⁴; erythroderma75, 76, 77; ichthyosiform erythroderma⁷⁸; faint erythema⁷⁹; verrucous⁸⁰; erythema annulare centrifugum⁸¹; nodular lesions on palms and soles82, 83; erythroderma, keratotic spines, and palmar pits⁸⁴; lichenoid eruptions⁸⁵; pustular folliculitis; umbilicated

Histologic differential diagnosis

The characteristic histologic picture of sarcoidosis is that of noncaseating epithelioid granulomas, with minimal or absent associated lymphocytes or plasma cells (naked granuloma).18, 29 Within the giant cells, Schaumann bodies and asteroid bodies may be found but are not specific for sarcoidosis. Schaumann bodies are rounded, laminated basophilic inclusions that represent degenerating lysosomes, whereas asteroid bodies represent engulfed collagen seen as eosinophilic stellate inclusions.18,

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