Clinical meaning
Sarcoidosis is a systemic granulomatous disease of unknown etiology characterized by non-caseating granulomas in affected organs. The lungs are involved in > 90% of cases. The pathogenesis involves an exaggerated Th1 immune response to an unidentified antigen: macrophages present the antigen to CD4+ T cells, which release IFN-gamma and IL-2, driving granuloma formation. Granulomas consist of tightly clustered epithelioid macrophages and multinucleated giant cells surrounded by a rim of lymphocytes. Unlike TB granulomas, sarcoid granulomas are NON-caseating (no central necrosis). Staging is radiographic: Stage 0 (normal CXR), Stage I (bilateral hilar lymphadenopathy — BHL — alone), Stage II (BHL + pulmonary infiltrates), Stage III (pulmonary infiltrates without BHL), Stage IV (pulmonary fibrosis). Spontaneous remission occurs in 60-80% of Stage I, 50-60% of Stage II, but only 30% of Stage III, making staging important for prognosis and treatment decisions.
Diagnosis & workup
Diagnostics & workup: - CXR staging: I (BHL alone), II (BHL + infiltrates), III (infiltrates alone), IV (fibrosis/honeycombing) - CT chest: bilateral symmetric hilar and mediastinal lymphadenopathy, perilymphatic nodules, upper lobe predominant - PFTs: may be normal (early), restrictive pattern, obstructive pattern (endobronchial sarcoid), reduced DLCO - Tissue biopsy: non-caseating granulomas (essential for diagnosis — sarcoidosis is diagnosis of exclusion); transbronchial biopsy via bronchoscopy (yield 60-90%) - BAL: CD4:CD8 lymphocyte ratio > 3.5 supports diagnosis (but not pathognomonic) - Serum ACE level: elevated in 60% but non-specific; useful for monitoring disease activity rather than diagnosis - Calcium metabolism: hypercalcemia (10-17%) from granuloma-produced 1,25-dihydroxyvitamin D; 24-hour urine calcium - Screening for extrapulmonary involvement: ophthalmologic exam (uveitis 25-50%), ECG/Holter (cardiac sarcoid), LFTs, creatinine, CBC