The myths we believed in familial Mediterranean fever: what have we learned in the past years?

Abstract

Familial Mediterranean fever is the most common monogenic periodic fever syndrome over the world especially in the eastern Mediterranean. It presents with recurrent and self-limited inflammatory attacks of fever and polyserositis along with high acute-phase reactants. The disease is associated with mutations in the MEFV gene that encodes pyrin, a component of inflammasome, which leads to exaggerated inflammatory response through uncontrolled production of interleukin 1. With the identification of the gene associated with the disease, we believed that everything was solved and that this was an ordinary monogenic disease with autosomal recessive inheritance. However, through the breathtaking progress in the basic research field as well as the clinical care of these patients, we have understood that the picture for this monogenic disorder was more complicated than we had anticipated. In this review, we have discussed the myths we believed in familial Mediterranean fever and how they have evolved during the past years.

Familial Mediterranean Fever: Recent Developments in Pathogenesis and New Recommendations for Management

“…E148Q, the most frequent sequence alteration in the MEFV gene (27), is the result of the substitution of glutamine for glutamic acid at codon 148 in exon 2 (28, 29). E148Q is a common variant in the general population; however, the pathogenic role of E148Q is still uncertain (30). …”

“…We give colchicine treatment to patients who express the typical FMF phenotype. However, some heterozygotes can sometimes “outgrow” the phenotype (30). Ben-Zvi et al previously demonstrated that their patients (not using colchicine) experienced years of symptom-free interval where 22 out of these 33 were heterozygotes (136).…”

Familial Mediterranean fever patients homozygous for E148Q variant may have milder disease

“…Familial Mediterranean fever (FMF) is the most common monogenic auto-inflammatory disease (AID) characterized by recurrent, self-limited fever attacks associated with polyserositis. 1 The prevalence of FMF is very high among certain ethnic groups such as Jewish, Turkish, Armenian and Arabs, reaching figures as high as 1/500; 2,3 however, it can be seen all around the world. 4 FMF results from mutations in the MEFV gene on chromosome 16p.…”

Case report: recurrent abdominal symptoms in a child with panhypopituitarism – there is always a differential

“…It is thought to be gene-associated as an autosomal recessive trait. Lately, doubts have been raised as cases of patients suffering from FMF with heterozygous status have been reported [ 8 ]. While the etiology is still uncertain, it is seen primarily in certain ethnic groups, such as Sephardic Jewish, Armenian, Turkish and Arab populations [ 5 ], although there have been reports of large cohorts in different populations, e.g.…”