1.4.1 Sarcoidosis

Rare disease. Skin involvement in 20-35% of cases; in 11% skin as first manifestation.

The estimated prevalence in Europe is around 10/100,000 inhabitants, and is significantly higher in northern countries. A bimodal age distribution between the ages of 25 and 35 years and between 45 and 65 years was reported.

Still unclear, found worldwide, female > male. It occurs most commonly in young and middle-aged individuals of both genders and all races with Afro-Caribbeans and African-Americans more commonly involved. It is a primary Th1 cell driven disease, however, multiple other T-cell types including Th17, Th17.1 cells, and T regulatory cells are involved. In building up granulomas, maintaining or resolving those a pattern of different cytokines, i.e., transforming growth factor-ß (TGF-ß), IL-13 and IL-10 are involved. Several drugs as trigger factor in particular during or after oncologic immunotherapy with CTLA-4 and PD-1/PD-L1 inhibitors25 and during tumor necrosis factor (TNF) inhibition as well as with recombinant type 1 interferon (α and β) therapy have been reported.

Two standardized outcome instruments exist—the Sarcoidosis Activity and Severity Index (SASI) and the Cutaneous Sarcoidosis Activity and Morphology Instrument (CSAMI).

Special forms:

• Löfgren’s syndrome (acute onset of fever, bilateral hilar lymphadenopathy and erythema nodosum, 5%).

• Lupus pernio (centrofacial skin involvement).

• Scar and tattoo sarcoidosis.

• Rare forms, e.g. Heerfordt’s syndrome (uveitis, parotid gland swelling, chronic fever, occasionally palsy of the facial nerve, 1%).

• Angiotensin converting enzyme (ACE; indicating cumulative involvement) and interleukin 2 receptor (IL2R (CD25); indicating disease activity) in serum sometimes elevated

• Hypercalcaemia

• Lymphopaenia

• ESR elevated

• Impaired delayed (type IV) hypersensitivity

• Tuberculin skin test (negative) / Quantiferon test

• Chest x-ray (may show bilateral hilar lymphadenopathy or interstitial changes)

Tuberculosis, leprosy, granuloma annulare, necrobiosis lipoidica, lymphoma and pseudolymphoma, leishmaniasis, syphilis, rosacea (lupus pernio).

Prevention of occupational and individual chronic small particle inhalation

• Skin involvement: Corticosteroids (topical, intralesional, systemic; first line), methotrexate (second line), chloroquine/hydroxychloroquine, (isotretinoin, allopurinol, thalidomide), PUVA

• Systemic involvement: Corticosteroids (systemic; first line), methotrexate (second line), azathioprine, (leflunomide, mycophenolate mofetil, cyclophosphamide), TNF antangonists. JAK inhibitors are one of the most important potential therapeutic agents for sarcoidosis currently under investigation. Some biologics may induce sarcoidosis.