Predictors of AA amyloidosis in familial Mediterranean fever

Abstract

The aim of the study was to evaluate the clinical and genetic predictors of AA amyloidosis in patients with familial Mediterranean fever (FMF). We retrospectively studied 170 Armenian patients who were admitted to the two tertiary centers in 2003-2014. The diagnosis of amyloidosis that was suspected clinically (new proteinuria or nephrotic syndrome) was confirmed histologically. Screening for MEFV gene mutations was performed in 70 patients. The most common genotype was M694V/M694V (in 36 % of patients). Biopsy-proven AA amyloidosis was found in 102 (60 %) of 170 patients. AA amyloidosis was diagnosed in 17 (68 %) of 25 patients with homozygous M694V mutation, 17 (53 %) of 32 patients with heterozygous M694V allele and 4 (31 %) of 13 patients with other MEFV gene mutations. The M694V homozygosity and heterozygosity were associated with increased risk of AA amyloidosis, but this association did not reach statistical significance (odds ratio 2.43; 95 % CI 0.87-6.76, and 3.33; 0.91-12.1, respectively). Male gender, early onset of disease, severity of FMF, frequent attacks, peritonitis, pleuritis and erysipelas-like erythema also did not predict AA amyloidosis development. Recurrent arthritis was the only clinical finding that was significantly associated with AA amyloidosis (odds ratio 2.28; 95 % CI 1.17-4.42). Involvement of the joint synovial membrane, that is capable of active serum amyloid A production, is the main predictor of renal amyloidosis in FMF.

Familial Mediterranean fever

“…This has been reported in a child as young as 5 years of age [24]. This has been reported in a child as young as 5 years of age [24].…”

Lack of clear and univocal genotype‐phenotype correlation in familial Mediterranean fever patients: A systematic review

“…75 Particularly, the M694I/M694I genotype, identified in 52% patients, was significantly associated with the development of amyloidosis in Algerians and Arabs. 68 Authors also described a relationship between the M694I mutation and a higher prevalence of serositis and familial aggregation in Japanese patients with FMF. 76 M680I has been associated with a more severe disease activity, including development of renal amyloidosis.…”

“…65 Particularly, unexpectedly though, despite the fact that it has been observed only in the patients with amyloidosis, studies did not link the M694V/M694V genotype to the renal complication. [66][67][68] Moreover, other authors noted that, in southeast Turkey population, the M694V mutation frequency was lower, and disease severity was relatively mild in FMF patients. 16 In addition, any significant association with M694V mutations and pro-inflammatory cytokine as well as markers of oxidative stress was detected in patients with FMF.…”

Renal Amyloidosis in Deficiency of Adenosine Deaminase 2: Successful Experience With Canakinumab

“…20 Another study from Armenia revealed similar results in adults with typical FMF symptoms, and only 9% of patients with amyloidosis were found to be heterozygous for the Met694Val mutation in MEFV. 22 Renal amyloidosis can also be an initial presentation in ∼7% to 25% of patients with FMF, without typical symptoms. This condition is named phenotype II, which is extremely rare in childhood.…”