Molecular profiling and gene expression analysis in cutaneous sarcoidosis: the role of interleukin-12, interleukin-23, and the T-helper 17 pathway.

BACKGROUND: Cutaneous sarcoidosis (CS) skin provides relatively noninvasive access to granulomatous sarcoidosis tissue. OBJECTIVE: We sought to explore the role of the T-helper (Th)1 and Th17 pathways in sarcoidosis. METHODS: We used molecular profiling and gene expression analysis to analyze the Th1 and Th17 pathways and other immune-mediated pathways in CS. Molecular profiles were obtained from sarcoidosis skin lesions (lesional skin [LS]), unaffected skin from patients with CS (non-LS), and the skin of healthy control subjects. Whole blood was collected to compare the molecular profile of sarcoidosis skin lesions and whole blood. RESULTS: Twenty participants were enrolled: 15 with active CS and 5 healthy volunteers. Microarray analyses comparing non-LS and healthy volunteer skin with LS showed several thousand genes differentially expressed (≥2-fold change false discovery rate, P < .01). Targeted selections of genes associated with Th1 and Th17 phenotypes showed a strong Th1 profile of sarcoidosis and expression of interleukin (IL)-23 and IL-23R with limited expression of other Th17 pathway genes. IL-21 and signal transducer and activator of transcription 3 (STAT3) were also dysregulated in skin and whole blood, providing additional evidence for involvement of the IL-12 pathway and potential activation of the Th17 pathway. LIMITATIONS: Measurements were made at a single point in time and may not identify mechanisms that may be identified in patients followed up longitudinally. CONCLUSION: These findings provide novel insight into the dysregulated pathways that may be involved in the pathogenesis of sarcoidosis.

Cutaneous sarcoidosis.

Sarcoidosis is a systemic disease with skin manifestations. Skin manifestations are classified as nonspecific if they are not characterized by granulomatous inflammation and specific if the lesions have granulomas histologically. Erythema nodosum is the most common nonspecific skin manifestation, and it portends a good prognosis. Specific skin lesions have a varied clinical appearance, although often they can be distinguished by their yellow translucent character. Despite the potential variable appearance, there are common clinical presentations. Lupus pernio lesions are nodular violaceous specific skin lesions found predominantly on the face associated with scarring and a poor prognosis. Treatment of cutaneous sarcoidosis is primarily done to avoid scarring and cosmetic disfigurement. Local and systemic corticosteroids are the mainstay of treatment for the disease. Corticosteroid-sparing agents used to manage the disease include antimalarials, methotrexate, and tetracycline antibiotics. Tumor necrosis factor-alpha (TNF-alpha) antagonists such as infliximab may have a role in cutaneous sarcoidosis, especially in refractory cases that are resistant to the standard regimens.

Chronic cutaneous lesions of sarcoidosis.

Sarcoidosis involvement of the skin is common. The skin lesions of sarcoidosis may be nonspecific, showing a nondiagnostic inflammatory reaction pattern on histologic evaluation. Nonspecific skin lesions are often associated with an acute presentation of sarcoidosis and, in general, portend a good prognosis. Specific sarcoidosis skin lesions reveal typical sarcoid granulomas on histologic examination. These lesions tend to be chronic and require therapy for resolution. This article will review the epidemiology, diagnostic evaluation, and description of the various chronic skin lesions of sarcoidosis. Various images of these skin lesions will be demonstrated.