Comparison of Clinical Features Between Early-onset (≤2 Years) and Later-onset Familial Mediterranean Fever

The objective of this study was to investigate differences between familial Mediterranean fever (FMF) patients with symptom onset at aged 2 years or younger and those with later onset, with a focus on clinical presentation, disease course, and treatment outcomes.

The medical records of FMF patients aged 0 to 18 years who were followed in the Pediatric Rheumatology Department between 2013 and 2024 were reviewed. Patients with symptom onset at aged 2 years or younger were classified as having early-onset, and patients with missing data or <6 months of follow-up were excluded.

A total of 1255 patients with FMF were divided into 2 groups according to the age at symptom onset: ≤2 years (early-onset FMF, n = 346) and >2 years (later-onset FMF, n = 909). Early-onset FMF patients exhibited longer diagnostic delays, higher attack frequency, and more frequent fever attacks compared with later-onset patients ( p < 0.05). Disease severity and the prevalence of colchicine-resistant FMF were higher in the early-onset group ( p = 0.021 and p = 0.002). M694V homozygosity was more common among early-onset FMF patients (29.9% vs. 22.1%, p = 0.005). In multivariate analysis, a family history of colchicine-resistant FMF (OR = 2.64, 95% CI: 1.48-4.71) and fever (OR = 3.05, 95% CI: 2.12-4.40) were identified as independent predictors of early disease onset FMF.

Early-onset FMF is associated with a more severe clinical presentation, including higher disease severity, increased colchicine resistance, and a greater frequency of M694V homozygosity. A family history of colchicine-resistant FMF is an independent predictor of early onset, highlighting the importance of detailed family history assessment in clinical practice.