Exosomes in brain diseases: Mechanisms, advances, and perspectives.

Sarcoidosis is a complex multisystem granulomatous disease of unknown etiology, characterized by the formation of non-necrotising granulomas in affected organs. Although pulmonary involvement is the predominant manifestation, sarcoidosis can involve almost any organ system, resulting in a highly variable clinical presentation and disease course. Approximately 50–70% of patients undergo spontaneous resolution, whereas 10–30% develop persistent or progressive disease, irreversible organ dysfunction, and life-threatening cardiac and neurological involvement, which are associated with significant morbidity and mortality (–). While sarcoidosis affects individuals of all ages, it occurs most frequently in young and middle-aged adults. A bimodal age distribution has been described, with a second peak in older adults, particularly among women (, ). The incidence of sarcoidosis varies widely by race, ethnicity and geographic region (, ). Recent population-based data from England demonstrated an increase in incidence from 6.65 to 7.73 per 100,000 person-years between 2003 and 2023, accompanied by a corresponding rise in mortality (). Despite being first described in the late 19th century based on its cutaneous manifestations, sarcoidosis remains a complex disease with ongoing challenges in diagnosis and management (, ). Current guidelines recommend corticosteroids as first-line therapy for patients requiring treatment (–). However, increasing recognition of corticosteroid-related toxicity, prolonged treatment requirements, frequent relapse during tapering or withdrawal, and limited evidence regarding long-term disease modification have contributed to growing interest in steroid-sparing approaches and evolving treatment paradigms in sarcoidosis management (, , ). Recent clinical trial data evaluating methotrexate as an earlier treatment option in pulmonary sarcoidosis, together with growing evidence supporting biologic and targeted therapies, reflect evolving therapeutic strategies in sarcoidosis management (, ). Given this evolving therapeutic landscape and the increasing complexity of treatment decision-making, there remains a need for an updated review of current evidence to guide sarcoidosis management. This review examines contemporary treatment approaches, and emerging targeted therapies, while also addressing current challenges in disease monitoring and future directions.