Familial Mediterranean fever in children from central-southern Italy: a multicentric retrospective cohort study

Introduction: Although familial Mediterranean fever (FMF) is a relevant disease in countries surrounding the Mediterranean Sea, there are still few reports from Italy. Methods: We retrospectively evaluated patients with FMF diagnosed according to the EuroFever/PRINTO classification criteria in three pediatric rheumatology referral centers in central-southern Italy. Logistic regression analysis assessed the associations between age at disease onset and symptoms. Results: Overall, 48 patients were enrolled (28 females, 20 males), with a median age at onset of 3.3 [3.1] years, and a median follow-up period of 5.1 [10.8] years. The most common MEFV genotype was M694V/- (11 patients, 22.9%), followed by M694V/M694V (6 patients, 12.5%). At onset, recurrent fever was observed in 47 patients (97.9%), with a median time between attacks of 18 [11] days. Overall, recurrent fever was observed in all patients, abdominal pain in 44 (91.7%), and chest pain in 18 (37.5%). At the last follow-up visit, 24 patients were on colchicine (50%), 2 on biologic (4.2%), and 6 on both (12.5%). Canakinumab was the most used biologic drug, in 6 (12.5%) patients. MEFV genotype was associated with disease severity (p = 0.007) and the use of a biological drug (p = 0.01). FMF prevalence in the Abruzzo region was found highly than expected (at least 1:45,000). Differently, we found a relevant gap among FMF patients expected and observed in the Apulia and Sicily regions. Conclusions: FMF is a relevant issue in central-southern Italy. A large epidemiologic study should be performed to better define its prevalence in the country. Key Points • Italian children with familial Mediterranean fever tend to have an early age of onset, primarily manifesting with recurrent fever and characteristic associated symptoms. • Many MEFV gene variants are present in Italian children with familial Mediterranean fever, and these patients are most often heterozygous, exhibiting a mild to moderate phenotype. • The prevalence of familial Mediterranean fever in Italy is still unknown but recently estimated to be around 1:60,000, probably higher in central and southern Italy. • According to our cohort, the prevalence of FMF in the Abruzzo region is at least 1:45,000, higher than expected. Differently, we found lower prevalence rates of the disease in Apulia and Sicily.