The Prototype of Hereditary Periodic Fevers: Familial Mediterranean Fever

Abstract

Autoinflammatory disorders are multisystem periodic fever syndromes, and characterized with recurrent unprovoked inflammation of the serosal membranes. Unlike autoimmune disorders, autoinflammatory disorders lack the production of high-titer autoantibodies or antigen-specific T cells. These diseases primarily include hereditary syndromes (Table 1); Familial Mediterrenean fever (FMF), TNF receptor-associated periodic fever syndrome (TRAPS), hyperimmunoglobulinaemia D and periodic fever syndrome (HIDS), and the cryopyrin-associated periodic syndrome (CAPS) which involves familial cold autoinflammatory syndrome (FCAS), Muckle–Wells syndrome (MWS) and neonatal onset multi-system inflammatory disease (NOMID)/chronic infantile neurological cutaneous and articular syndrome (CINCA). Familial mediterrenean fever has been considered as the most prevalent of innate immune system disorders involving systemic autoinflammatory reaction effecting joints, skin, bones and the kidney. Systemic amyloidosis is the most severe manifestation of the disease, commonly effecting the kidneys (11% of cases), and sometimes the adrenals, intestine, spleen, lung, and testis (1). As an innate immune system disorder, FMF is characterized by recurrent episodes of unseemingly unprovoked inflammation and fever with lasting 1to 3-day attacks accompanied by sterile peritonitis, pleurisy, rash, arthritis, and in some cases amyloidosis leading to renal failure. this (Sohar et al., 1967). Apart from the typical implications of the disease, there is increasing evidence about the expanding clinical spectrum of FMF that embraces unusual clinical characters (2-4). These are the rare presentations of the disease and therefore undescores the role of molecular analysis in particular for the suspicious and probable cases.