Familial Mediterranean fever (FMF) is an autosomal recessive disorder characterized by recurrent attacks of fever and inflammation in the peritoneum, synovium, or pleura, accompanied by pain.
Amyloidosis with renal failure is a complication and may develop without overt crises.
The cardinal feature of FMF is recurrent attacks of fever with associated serosal inflammation. The latter most often takes the form of sterile peritonitis but pleuritis, arthritis and rarely, pericarditis may be part of the clinical picture. In addition, a few FMF patients develop an erysipelas-like rash over their lower legs.
The inflammatory episodes usually last one to three days, and they subside spontaneously. The patient returns to full, robust health during interim periods.
The attacks may occur anywhere from once every ten days to as infrequently as once or twice a year. The most dreaded complication of untreated FMF is amyloidosis, which eventuates in renal failure in as many as 20% of patients in some populations.
Etiology
familial mediterranean fever (FMF) (MIM.249100) is caused by mutation in the pyrin gene (MEFV) (MIM.608107).
The gene for FMF, MEFV, was cloned in 1997. It encodes a 781 amino acid protein known as pyrin.
Pyrin is believed to have both intranuclear and cytoplasmic actions. Within the nucleus it acts via NF-β to either down regulate pro-inflammatory cytokines or conversely, up regulate anti-inflammatory cytokines. Within the cytoplasm, pyrin most likely modulates the cytoskeletal events in neutrophils. It also attenuates the production of IL-1β by inflammasomes.
Differential diagnosis
autosomal dominant FMF (MIM.134610), which is caused by heterozygous mutation in the MEFV gene.
Synopsis
idiopathic recurrent acute pericarditis (IRAP) (16218464)
Treatment
The advent of daily colchicine therapy, introduced in the early 1970’s, has provided complete protection against the development of amyloidosis, as well as the known effect of this hoary drug in abolishing or markedly attenuating the inflammatory episodes.
The recommended dosage is 1.2 mg/day; it may be doubled in patients who do not achieve satisfactory remission on this regimen. Colchicine is generally very well tolerated. Some patients may experience mild diarrhea that is easily controlled by over-the-counter preparations.
The drug’s effect is probably mediated by its property of disaggregating the microtubular elements of neutrophils, thus impairing their participation in the inflammatory cycle.