Immunosuppressive Therapies in Pulmonary Sarcoidosis: A Practical, Evidence-Based Review

Sarcoidosis is a chronic inflammatory disease of unknown etiology that can involve virtually any organ, with pulmonary involvement seen in over 90% of cases. Although many patients experience spontaneous remission, approximately 10-30% develop progressive pulmonary disease, which may lead to fibrocystic changes, respiratory failure, and death. Oral glucocorticoids remain the cornerstone of treatment for symptomatic patients with pulmonary infiltrates and abnormal pulmonary function tests, with typical starting doses ranging from 20 to 40 mg/day followed by a slow taper over 6-18 months based on clinical and radiographic response. However, prolonged glucocorticoid therapy is associated with significant toxicity, and many patients require additional immunosuppressive agents for disease control or steroid-sparing purposes. Antimetabolites such as methotrexate, azathioprine, mycophenolate mofetil, and leflunomide are commonly used second-line therapies. For refractory disease, particularly in those with metabolically active lesions on FDG-PET, anti-tumor necrosis factor (TNF) agents like infliximab may be effective but carry risks of serious adverse effects. In select cases, newer strategies-including RCI, rituximab, JAKi or investigational regimens-are being explored. Management must also account for non-inflammatory complications such as sarcoidosis-associated pulmonary hypertension and bronchiectasis, which can mimic disease progression and require distinct therapeutic approaches. Given the heterogeneity of sarcoidosis and lack of robust clinical trial data, a stepwise and individualized approach to immunosuppression remains essential in optimizing outcomes while minimizing treatment-related harm.