Clinical presentation and disease severity in adolescent-onset familial Mediterranean fever

Familial Mediterranean fever (FMF) shows marked phenotypic variability depending upon age at symptom onset. This study compared clinical characteristics, genetic variants, and disease severity of paediatric FMF patients according to age at symptom onset.

This study included 1203 paediatric FMF patients followed 2015 through 2025. Patients were classified into two groups based on age at symptom onset: <10 or ≥10 years. Demographic, clinical, genetic, and treatment-related variables were compared between groups. Multivariate logistic regression analysis identified factors independently associated with age at symptom onset ≥10 years.

Symptoms began at <10 years in 1043 patients (86.7%) and at ≥10 years in 160 patients (13.3%). Patients with later onset had shorter diagnostic delay (P < 0.05). Fever and abdominal pain were more common in patients with onset <10 years (P < 0.001), whereas chest pain (29.3% vs. 21.5%, P = 0.029) and arthritis (25.6% vs. 14.5%, P < 0.001) were more frequent in those with onset ≥10 years. M694V homozygosity was significantly less frequent in the ≥10 group (13.1% vs. 26.9%, P = 0.004). In multivariate analysis, age at symptom onset ≥10 years was independently associated with lower fever frequency (odds ratio [OR] 0.32, 95% confidence interval [CI] 0.22 to 0.46) and higher chest pain frequency (OR 1.63, 95% CI 1.07 to 2.49).

Age at symptom onset is closely related to clinical phenotype in paediatric FMF. Adolescent-onset FMF is more frequently characterized by chest pain. These findings highlight the importance of considering FMF in adolescents with recurrent chest pain, even without typical febrile attacks.