Sarcoidosis: a state-of-the-art review

Sarcoidosis is a complex systemic granulomatous disease that can affect multiple organs, with pulmonary involvement being the most common. Its pathogenesis involves genetic predisposition and chronic immune dysregulation, which increase susceptibility to environmental or endogenous triggers, leading to an aberrant immune response. Imaging plays a central role in diagnosis and has evolved from traditional chest radiography Scadding staging to a computed tomography-based classification and radiomics that improves disease phenotyping. Due to its variable presentation, diagnosing sarcoidosis and attributing symptoms to the disease can be challenging; therefore, awareness and consideration of alternative diagnoses remain essential. The clinical course of sarcoidosis is unpredictable; many patients do not require therapy. Treatment decisions must be individualised, balancing disease severity, risk of organ damage, quality of life and potential toxicity of medication. However, the lack of both reliable prognostic tools and clear criteria for high-risk cases contributes to substantial heterogeneity in disease management. While the guidelines still recommend corticosteroids as first-line treatment, recent data show that methotrexate and prednisone have comparable effects on pulmonary function, although differ in side-effect profiles and time to efficacy. For refractory cases, second-line therapy involves combining or switching drugs, with anti-tumour necrosis factor agents representing third-line options, ideally in expert hands. Novel therapies targeting pathways involved in disease pathogenesis are under investigation. There is growing consensus on the need to revise current treatment algorithms to minimise corticosteroid use and adopt more evidence-based approaches. Future priorities include identifying prognostic biomarkers, refining trial design and establishing meaningful end-points to improve individualised care for the heterogeneous population of patients with sarcoidosis.