Sarcoidosis is a multisystem granulomatous disease characterized by noncaseating granulomas. Cutaneous sarcoidosis occurs in up to one-third of patients and may be the initial or sole manifestation. Skin lesions are polymorphic, including papules/plaques, lupus pernio, scar or tattoo infiltration, subcutaneous nodules, and erythema nodosum (a reactive, non-specific lesion). Cutaneous disease can correlate with systemic involvement and chronicity. Diagnosis requires clinicopathologic correlation and exclusion of infections and foreign-body granulomatous reactions. Management ranges from topical/intralesional corticosteroids to systemic immunomodulators for extensive, disfiguring, or refractory disease.
Epidemiology
- Variable incidence; higher in people of African or Northern European ancestry; female predominance in some cohorts.
- Onset typically young to middle adulthood.
- Cutaneous phenotypes may predict systemic course: lupus pernio associated with chronic upper airway/pulmonary disease.
Pathophysiology
- Dysregulated cell-mediated immunity with Th1/Th17 skewing; macrophage epithelioid granuloma formation.
- Genetic susceptibility (e.g., BTNL2, HLA alleles); environmental/occupational exposures implicated.
- Triggering by cutaneous injury: scar/tattoo sarcoidosis.
Clinical Features
- Specific sarcoidosis lesions (granulomas on biopsy):
- Papular sarcoidosis: small red-brown papules, often periorificial or on face.
- Plaque sarcoidosis: infiltrated plaques; annular or serpiginous variants.
- Lupus pernio: violaceous indurated plaques on nose, cheeks, ears; chronic and disfiguring.
- Scar/tattoo sarcoidosis: granulomatous infiltration of prior scars/ink.
- Subcutaneous sarcoidosis (Darier–Roussy): firm nodules on extremities/trunk.
- Nonspecific lesions:
- Erythema nodosum: tender septal panniculitis, typically on shins; part of Löfgren syndrome (EN, bilateral hilar adenopathy, arthritis) with good prognosis.
- Other clues: apple-jelly translucency on diascopy; anhidrosis, alopecia in involved areas.
Differential Diagnosis
- Granulomatous infections: cutaneous TB, atypical mycobacteria, deep fungal infections (histoplasmosis, blastomycosis).
- Granuloma annulare, necrobiosis lipoidica, foreign body reactions, lupus vulgaris, leprosy, rosacea (for facial lesions).
Diagnostic Workup
- Skin biopsy: noncaseating epithelioid granulomas with sparse lymphocytic infiltrate; special stains and cultures to exclude infections (AFB, PAS/GMS).
- Assess systemic involvement:
- Chest imaging (CXR or HRCT) for hilar/mediastinal adenopathy or parenchymal disease.
- Serum ACE (nonspecific), calcium (hypercalcemia/hypercalciuria), CBC/CMP.
- Organ-directed assessments as indicated: ophthalmology (uveitis), PFTs, ECG; consider PET-CT for extent in refractory/systemic disease.
- Review occupational/environmental exposures; check for foreign material in lesions (polarization).
Management
- Localized cutaneous disease
- High-potency topical corticosteroids; intralesional triamcinolone for plaques, lupus pernio, and scar lesions.
- Topical calcineurin inhibitors as adjuncts in sensitive areas.
- Extensive/disfiguring or refractory cutaneous disease, or significant systemic involvement
- Systemic corticosteroids are first-line for rapid control.
- Steroid-sparing agents: methotrexate (most evidence), hydroxychloroquine or chloroquine (especially for cutaneous disease and hypercalcemia), leflunomide, azathioprine, mycophenolate.
- Biologics for refractory cases: TNF-α inhibitors (infliximab, adalimumab) have supportive data in cutaneous and systemic sarcoidosis, including lupus pernio.
- Emerging/adjunctive: JAK inhibitors reported in refractory sarcoidosis; tetracyclines (anti-granulomatous), minocycline/doxycycline; thalidomide for stubborn cutaneous lesions.
- Erythema nodosum (nonspecific)
- Treat underlying sarcoidosis; symptomatic therapy with NSAIDs, rest, compression; short steroid course for severe pain.
Prognosis and Monitoring
- Many patients experience chronic or relapsing disease; lupus pernio indicates persistent course and may require aggressive therapy.
- Monitor for systemic organ involvement over time; ophthalmologic exams are important.
- Track steroid-sparing strategy to minimize long-term corticosteroid toxicity.
References (recent guidelines and key reviews)
- ERS/ATS/WASOG statements on sarcoidosis diagnosis and management, 2021–2024 updates.
- Dermatology-focused reviews of cutaneous sarcoidosis and treatment algorithms, 2022–2024.
- Evidence for TNF inhibitors and methotrexate in sarcoidosis (systematic reviews, 2021–2024).
- Case series and reports on JAK inhibitors in refractory sarcoidosis, 2022–2024.