Characterizing Protracted Febrile Myalgia: Fasciitis and Vasculitis of the Fascia and Muscle as Novel Histopathological Features.

Background: Protracted febrile myalgia (PFM) is a rare but severe form of myalgia mainly occurring in pediatric patients with familial Mediterranean fever (FMF). PFM imaging and histopathological data remain scarce. Objectives: A comprehensive clinical, imaging, and histopathological characterization of PFM was performed by retrospectively analyzing a reference center cohort of adult patients with FMF and myalgia, and by a PubMed search of well-described cases with PFM. Results: Among 56 adults with FMF from our center, 32 (57.1%) experienced myalgia, which was generalized in 21 (37.5%) and affected lower limbs in 11 (19.6%) subjects. One (1.8%) patient suffered PFM, mainly affecting calves and Achilles tendons. From our patient's detailed information and the data from 123 PFM cases reported in the literature, PFM was characterized as usually presenting with fever and severe generalized myalgia, with occasional involvement of lower legs and calves. It is mainly associated (in >90% of cases) with the pathogenic mutation M694V in the MEFV gene. Raised acute phase reactants and normal creatine kinase levels are constant. High glucocorticoid doses are useful in most patients, and sustained colchicine treatment protects from PFM recurrences. MRI may identify a variable degree of muscle inflammatory changes, especially subfascial and myofascial lesions with extension to tendinous structures. PFM histopathology is characterized by T-cell rich inflammatory infiltrates and vasculitis mainly involving the fasciae and myofascial areas, with a lower muscle extent. Conclusions: PFM can occur in children and adults and appears to be clinically manifested as fasciitis/tendinitis caused by a vasculitis of the fasciae rather than a major muscle vasculitis.