Abstract

Sarcoidosis is a heterogenous, multi-systemic granulomatous disease with highly variable incidence (5–40/100,000) and a disproportionate mortality burden in those presented with pulmonary fibrosis or cardiac involvement. Yet, current management strategies are symptom-targeting, not always effective and come with significant side effects. Preclinical murine models of sarcoidosis have shown that aberrant mTORC1 activation promotes macrophage-driven inflammation and disrupts autophagic clearance, sustaining granuloma formation. Sirolimus, a selective mTORC1 inhibitor, restores autophagy and macrophage function, offering a targeted therapeutic approach. Herein, we present the first comprehensive review of all known clinical cases of sirolimus use in different forms of sarcoidosis. All studies reviewed suggest that sirolimus may be an effective, yet safe, mechanism-targeting therapy for patients with sarcoidosis not responding to conventional pharmacological interventions.