Familial Mediterranean Fever

Familial Mediterranean fever (FMF) is an autosomal recessive disease characterized by recurrent self-limited febrile episodes. The hallmarks of a typical attack are fever, peritonitis, pleuritis, arthritis and/or erysipelas-like erythema that resolve within hours or days. The disease primarily affects Sephardic Jews, Armenians, Turks and North African Arabs. The frequency of the attacks can vary and the inciting factors are not always clear. Almost half of all patients with FMF have arthritis of the ankle, knee or hip, and there are increasing reports of vasculitic features. The first episode of FMF typically occurs during childhood or adolescence, but the disease may be evident even in infancy. By age 20, approximately 90% of patients have had their first attack. FMF is caused by a defect in the gene that encodes pyrin, a protein that affects the actions of neutrophils and monocytes during the inflammatory response. This "MEFV gene" is located on the short arm of chromosome 16, and 89 MEFV variants have been described to date. The most common MEFV mutations are M694V, M680I, V726A and M694I (all located in exon 10) and E148Q (located in exon 2). Genotype-phenotype correlations in FMF are not yet clear. The most important complication of this illness is development of secondary amyloid A-type amyloidosis. Amyloid fibrils are deposited in the patient's kidneys, gastrointestinal tract, liver, adrenal glands and spleen. Proteinuria is usually the first laboratory finding that indicates renal involvement and, in most cases, this progresses to end-stage renal failure. The incidence rates of FMF-related amyloidosis in different ethnic groups vary widely. Several risk factors for more severe FMF or development of FMF-related amyloidosis have been identified: homozygosity for the M694V mutation and for the complex V726A-E148Q allele of MEFV, male gender, family history of FMF, and the a/a genotype for the serum amyloid A1 gene. However, results in the literature are conflicting with respect to possible relationships between the M694V mutation and the severity of FMF or development of FMF-related amyloidosis. Colchicine effectively reduces the frequency and duration of attacks in most FMF patients, and is the mainstay of treatment for this condition. This agent also helps prevent or arrest the development of amyloidosis in FMF patients.