Abstract
Familial Mediterranean Fever (FMF) is rare autosomal recessive autoinflammatory disorder characterized by periodic bouts of fever, serositis, synovitis, and/or cutaneous inflammation. Painful febrile attacks last 1 to 3 days and can vary in severity. FMF is almost exclusively affecting subjects with Mediterranean origin, especially Armenian, Arab, Jewish, Turkish, North Africans and Arabic descents. Cases have been reported in Italian population with a cluster of Italians patients living in Apulia and Basilicata. FMF results from the mutations in the MEFV (Mediterranean Fever) gene, consisting of 10 exons located on chromosome 16p13.3. MEFV encodes a 781 amino acid (86kDa) protein (pyrin or marenostrin) expressed in granulocytes, monocytes, serosal and synovial fibroblasts. In FMF, pyrin function is dysregulated with abnormal transcription of intranuclear peptides involved in inflammation. During acute attacks, a marked acute-phase response leads in leukocytosis, and elevated erythrocyte sedimentation rate, fibrinogen, C reactive protein, Serum Amyloid A protein. A worrisome manifestation of FMF is the evolution towards the secondary AA glomerular amyloidosis which puts a subgroup of patients at risk of end-stage kidney disease. Treatment of symptomatic FMF patients is aimed to prevent the acute attacks, and the development and progression of amyloidosis. Colchicine treatment given lifelong is the safe and effective in FMF patients at any age. In the few colchicine-resistant/ intolerant FMF patients, experimental off-label treatments include IL-1β inhibitors (anakinra, rilonacept, canakinumab), and anti-TNF-α agents (etanercept). This review describes pathophysiologic, diagnostic, and therapeutic aspects of FMF.
Highlights
Familial Mediterranean Fever (FMF, MIM249100) is a rare autosomal recessive an systemic autoinflammatory disorder characterized by recurrent bouts of fever, serositis, synovitis, and/or cutaneous inflammation [1,2,3]
FMF consists of recurrent and self-limited attacks of fever and symptoms accompanied by a marked acute-phase response
FMF cases have been reported in Italian population [14] and we recently identified cluster of 60 Italian subjects with MEFV gene mutations (70% symptomatic FMF patients) living in Apulia and Basilicata Regions with likely Jewish-Armenian-Greek historical roots [15,16]
Summary
Familial Mediterranean Fever (FMF, MIM249100) is a rare autosomal recessive an systemic autoinflammatory disorder characterized by recurrent bouts of fever, serositis, synovitis, and/or cutaneous inflammation [1,2,3]. Mutation of different components of the multi protein inflammasome complex [32,33] accounts for AIDs in the group of Cryopyrin-Associated Periodic Syndromes (CAPS), where fever is usually an ancillary feature [2]. In 90% of FMF patients, the first attack occurs before 20 years of age [51] and comprises recurrent sudden episodes of febrile severe pain (due to serositis at one or more sites with peritonitis, pleuritis, and synovitis), lasting 1-3 days and resolving spontaneously (Table 1). Decreased albumin levels and a significant increase of fibrinogen, C-reactive protein, the β2 and α2 globulin, haptoglobin and lipoproteins were detected during the different phases of FMF These laboratory findings occurred especially during and immediately after the attacks, and even more markedly in the progression of amyloidosis [56]. Recurrent febrile episodes Erysipelas-like erythema FMF in first-degree relative
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