Purpose: This work aimed at investigating demographic, clinical, and genetic characteristics of individuals experiencing their first familial Mediterranean fever (FMF) attack at age ≥40 years in a very large cohort of Armenian FMF patients.
Methods: In total, 10,370 Armenian patients diagnosed with FMF based on the Tel Hashomer criteria and carrying at least one MEFV mutant allele were included in this study.
Results: A total of 354 (3.40%) patients had late-onset FMF. Of these, 194 (54.80%) were female and 160 (45.20%) were male. The following genotypes were significantly associated with the late-onset variant: M680I/E148Q (P = 0.004), M694V/E148Q (P < 0.001), and V726A/V726A (P< 0.001). Of note, 12/354 (3.40%) patients were found to be homozygous for the M694V mutation. Individuals with late-onset FMF had a milder disease phenotype presenting significantly less frequent fever, skin manifestation, and chest pain compared to individuals with a disease onset before 40 years of age. Abdominal pain was found more often in the late-onset FMF group, whereas arthritis, proteinuria, and amyloidosis did not differ significantly between the two groups.
Conclusion: Our data suggest that late-onset FMF is more prevalent in women and is of greater clinical as well as genetic heterogeneity than previously reported.
Keywords: MEFV mutation; disease phenotype; familial Mediterranean fever; late onset.