Myalgia in Familial Mediterranean Fever: From Clinical Phenotypes to Management

Familial Mediterranean fever (FMF)-associated myalgia represents a heterogeneous spectrum of musculoskeletal manifestations that extends beyond simple attack-related muscle pain and contributes substantially to disability and impaired quality of life. Growing evidence indicates that exercise-induced leg pain (ELP), spontaneous myalgia, and protracted febrile myalgia syndrome (PFMS) are distinct clinical phenotypes with different triggers, tissue involvement, and therapeutic responses. Recent advances have highlighted heterogeneous tissue-specific mechanisms, including tendon and entheseal involvement in ELP and prominent fascial and myofascial involvement in PFMS. Recognition of these phenotypes is essential because PFMS may mimic inflammatory myopathies, systemic vasculitis, and infectious myositis despite persistently normal creatine kinase levels. Magnetic resonance imaging, histopathology, and genotype–phenotype studies have further refined current understanding, while accumulating evidence supports the central role of interleukin-1–mediated inflammation and the therapeutic efficacy of IL-1 blockade in selected refractory cases. This review summarizes current evidence regarding the epidemiology, clinical spectrum, pathophysiology, diagnosis, genetic determinants, and management of FMF-associated myalgia, proposes a practical clinicopathological framework for its evaluation, and highlights remaining gaps requiring future multicenter prospective studies.