Time from symptom onset to treatment in familial mediterranean fever: determinants and clinical implications

To determine the time from symptom onset to diagnosis in Familial Mediterranean Fever (FMF) patients, identify the clinical characteristics associated with diagnostic delay, and evaluate the effect of age at symptom onset on the time to diagnosis.

Medical records of FMF patients aged 0 to 18 years followed at a tertiary pediatric rheumatology center between 2013 and 2024 were retrospectively analyzed. Patients fulfilling the 2019 Eurofever/PRINTO criteria were included. Clinical, genetic, treatment data and disease severity assessed by the International Severity Scoring System for FMF (ISSF) were evaluated.

A total of 1259 FMF patients were included. The median time from symptom onset to diagnosis was 17 (IQR 10 to 36) months. Patients were categorized into 2 groups based on the elapsed time from symptom onset to diagnosis (≤12 months, n = 469 and >12 months, n = 790). Those with a longer diagnostic delay had a younger age at symptom onset but higher ages at referral and diagnosis (P < 0.001). Fever (P = 0.007), abdominal pain (P = 0.006), and erysipelas-like erythema (P = 0.017) were more frequent in the delayed group, whereas a positive family history was linked to shorter diagnostic intervals (P = 0.012 for parents, P < 0.001 for siblings). No significant differences were found in MEFV variant distribution (P = 0.972) or ISSF scores (P = 0.151). Age at symptom onset was negatively correlated with time to diagnosis (ρ = -0.210, P < 0.001).

Diagnostic delay remains common in pediatric FMF, especially among young children with early and nonspecific symptoms. Increasing awareness among primary and secondary care physicians may help shorten diagnostic intervals and improve outcomes.