Familial Mediterranean fever —basic research and clinical management—

Abstract

  Autoinflammatory disease is defined by recurrent episodes of generalized inflammation and fever in the absence of infections or autoimmune causes. Autoinflammatory disease is an innate immune-mediated inflammatory disorder in contrast to an autoimmune disease, which is defined as a disease caused by the abnormalities in adoptive immunity; however, autoimmune disease and autoinflammatory disease have a number of similar clinical characteristics. 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. A nationwide survey conducted in Japan 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 mutations in exon 10 are associated with the more typical FMF phenotype. Conversely, Japanese FMF patients with mutations in exons 2 or 3 of the MEFV gene 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.