Familial Mediterranean fever: overview of pathogenesis, clinical features and management.

Familial Mediterranean fever (FMF) is the most common monogenic autoinflammatory disease, and is characterized by recurrent attacks of fever and polyserositis. It is associated with mutations in the MEFV gene encoding pyrin, which result in inflammasome activation and the uncontrolled production of IL-1β. FMF mainly affects individuals originating from the Mediterranean basin; however, a Japanese nationwide survey demonstrated that FMF is not uncommon in Japan. The survey also indicated that Japanese FMF patients are clinically or genetically distinct from Mediterranean FMF patients, suggesting a genotype-phenotype correlation. In Japanese patients with FMF, MEFV exon 10 mutations are associated with the more typical FMF phenotype. Conversely, Japanese FMF patients with mutations in MEFV exons 2 or 3 present with an atypical FMF phenotype. Colchicine is the mainstay of FMF treatment, and its regular use prevents febrile attacks and decreases the long-term risk of AA amyloidosis. However, a minority of FMF patients are colchicine-resistant, and anti-IL-1 treatment has proven beneficial in suppressing inflammation in these patients. Although Japanese FMF patients may develop less severe disease compared with Mediterranean FMF patients, they should nevertheless be treated early to prevent recurrent attacks and the subsequent development of AA amyloidosis.