Familial Mediterranean Fever

Abstract

Familial Mediterranean fever (FMF) is the most common hereditary recurrent fever syndrome that may cause serositis, synovitis, and/or cutaneous inflammation. FMF belongs to the group of autoinflammatory diseases with mutations in MEFV gene that encodes pyrin, which usually affects people from Mediterranean origin like Sephardic Jews, Turks, Arabs, and Armenians. The clinical picture of FMF consists of attacks with rapid development of high-grade fever and constitutional symptoms accompanied by acute-phase response. Duration of attacks is generally short (6–96 h) with irregular occurrences. The main clinical features during attacks are peritonitis (95 %), arthritis (>50 %) (mono-oligoarticular), pleuritis (40 %), and less frequently pericarditis, scrotal swelling, myalgia, and erysipeloid skin rash. The first attack appears before the age of 20 in more than 85 % of the patients. The most important chronic manifestation of FMF is secondary AA amyloidosis which generally presents with proteinuria and may cause chronic renal insufficiency. Erysipeloid erythema (ELE) is the typical skin rash of FMF. The reported frequency of ELE is variable (3–46 %) and it is prevalent in childhood-onset patients. ELE may be an early sign and sometimes precedes systemic symptoms. Bullous lesions, erythema, urticaria, and pyoderma have been reported as additional skin manifestations in patients with FMF. Other diseases with skin manifestations may accompany FMF (or patients with MEVF mutations) like polyarteritis nodosa, Henoch-Schonlein purpura, Behçet’s disease, and relapsing polychondritis. Differential diagnosis is needed as erythematous patches resembling FMF lesions may be caused by other dermatoses like erysipelas, cellulitis, and Sweet’s syndrome. Other hereditary recurrent fever syndromes, for example, HIDS (hyperimmunoglobulinemia D syndrome) and TRAPS, with various skin manifestations are included in the differential diagnosis of FMF. It should be noted that the histopathological features of ELE and nonspecific skin lesions are not diagnostic for FMF.