Eur J Intern Med. 2025 Nov 1:106576. doi: 10.1016/j.ejim.2025.106576. Online ahead of print.
ABSTRACT
Sarcoidosis exemplifies the complexity of modern internal medicine, requiring comprehensive, system-based management. The disease is characterized by non-caseating granulomas and can affect virtually any organ, with pulmonary involvement in over 90 % of patients and extrapulmonary manifestations in up to 70 %. Its heterogeneous spectrum, variable course, and risk of organ damage make early recognition and multidisciplinary collaboration essential. This narrative review outlines the clinical manifestations of sarcoidosis, emphasizing organ-specific and systemic non-organ specific symptoms such as fatigue and small fiber neuropathy, which substantially impair quality of life (QoL). Advances in imaging, including cardiac MRI and 18F-FDG PET/CT, together with biomarkers such as soluble IL-2 receptor, have improved diagnostic accuracy, risk stratification, and monitoring. Yet, histological confirmation is almost invariably needed. Therapeutic strategies continue to evolve from the classical glucocorticoid-centered step-up approach toward more personalized regimens. Steroid-sparing agents such as methotrexate, azathioprine, and leflunomide are widely used, while biologics, particularly anti-TNF agents, and emerging small-molecule inhibitors (e.g., JAK and mTOR inhibitors) offer additional options in refractory disease. New investigational therapies, including efzofitimod, are under evaluation. Beyond pharmacology, sarcoidosis management increasingly relies on multidisciplinary teams, integration of primary and tertiary care, and attention to comorbidities and QoL. Digital health tools, telemedicine, and mindfulness-based interventions show promise in supporting patient-centered care. Artificial intelligence and multi-omics approaches may further enhance diagnostic accuracy, phenotyping, and precision medicine in the near future. In conclusion, sarcoidosis stands as a paradigm of complexity in internal medicine, underscoring the need for holistic care, innovation, and collaboration to improve long-term outcomes.
PMID:41176424 | DOI:10.1016/j.ejim.2025.106576