Country as the primary risk factor for renal amyloidosis in familial mediterranean fever

Abstract

Objective. Familial Mediterranean fever (FMF), the prototype of autoinflammatory disorders, is caused by recessive mutations in the MEFV gene. Some FMF patients develop renal amyloidosis, a potentially fatal condition. This complication has mainly been associated with the M694V mutation, although the different study designs, small numbers of patients, and/or evaluation of few or no covariables calls this association into question. The aim of this study was to examine the controversial issue of amyloidosis susceptibility in FMF by determining the relative contributions of MEFV and numerous epidemiologic factors to the risk of renal amyloidosis.Methods. Online questionnaires were completed at the MetaFMF database by patients at 35 centers in 14 countries. Using a standardized mode of data collection, we retrieved crude initial data from over half of the genetically confirmed FMF patients referred worldwide until May 2003 (2,482 cases, including 260 patients who developed renal amyloidosis).Results. Amyloid nephropathy was present in 11.4% of the cases. In the total study population, country of recruitment was the leading risk factor for this manifestation (odds ratio 3.2 [95% confidence interval 1.8-5.9]), followed by M694V homozygosity, proband status, and disease duration. Differing results were found when countries were stratified.Conclusion. Country of recruitment, rather than MEFV genotype, is the key risk factor for renal amyloidosis in FMF. This risk, which parallels infant mortality rates, indicates a possible environmental origin of amyloidosis susceptibility. The patient's country should be considered in addition to MEFV genotype as an indication for prophylactic colchicine, a treatment suggested for asymptomatic individuals who are incidentally discovered to be M694V homozygous.Familial Mediterranean fever (FMF) is the most frequent and the best understood hereditary periodic fever (1). When complete, the clinical picture reveals short episodes of fever, abdominal, thoracic, and joint pain, and erysipelas-like erythema.

Role of genetics in pediatric rheumatology

“…Previous studies have shown that the risk of developing severe disease phenotype is higher in patients who are homozygous for M694V (10). It was observed that the homozygous state for M694V was a high risk factor for amiloidosis in Armenians, Israelis, and Arabs (11). In a meta-analysis that included 3505 Turkish patients, it was shown that 189 of 400 patients who developed amilosidosis were M694V homozygous (12).…”

Periodic fever and apoptosis of accumulated neutrophils in familial mediterranean fever: Comment on the article by Touitou et al

“…FMF is an autoinflammatory disorder that occurs in the absence of autoantibodies or antigen-specific T cells. It is characterized by recurrent self-limited episodes of periodic fever and painful polyserositis, affecting mainly the peritoneum, pleura, and synovium (1,2). Why the attacks cease in the disease is as intriguing as why they start, and why amyloidosis develops in some patients is another intriguing question.…”

“…The drug should be used continuously (1), not intermittently as in the treatment of gout attacks. Colchicine inhibits neutrophil motility (chemotaxis; infiltration into the tissue) continuously, and prevents cellular accumulation and weakens serum amyloid formation in the inflamed regions.…”

Systemic AA amyloidosis as a unique manifestation of a combined mutation of TNFRSF1A and MEFV genes

“…FMF is an autosomal-recessive inherited inflammatory disease caused by mutations in the MEFV gene encoding a protein called pyrin (also known as marenostrin). A multicenter study published by Touitou et al [1] found an overall prevalence of AA amyloidosis in FMF patients of 11.4%. The incidence varied depending on the country of residence and M694V homozygosity.…”