Genetic, and clinical features in Italian and lebanese subjects with familial mediterranean fever (FMF).

Abstract

Familial Mediterranean Fever (FMF) is a hereditary autoinflammatory disease with variable manifestations across Mediterranean regions. This study compares FMF cohorts from Italy (Apulia) and Lebanon. We analyzed a cohort of 443 FMF patients, 165 Italians (females: males = 90:75) and 278 Lebanese (females: males = 173:105). Clinical records/interviews provided data on demographics, MEFV genetic testing, and treatments. A 55-item questionnaire in 54 Italians and 42 Lebanese patients assessed disease knowledge, management, misdiagnoses, attack frequency (yearly), duration (days), body temperature, symptoms prevalence and frequency, and severity score before/after treatment. Italians were significantly older at disease onset, diagnosis, and had longer diagnostic delay than Lebanese patients (p < 0.00001). The most common MEFV variants were E148Q and R202Q in Italians, and M694V and E148Q in Lebanese, with fewer pathogenic and homozygous cases in Italians. Italian patients had lower prevalence of FMF symptoms (10-92% vs. 30-99%; p < 0.00001) and fewer attacks. All Italians received treatment compared to 88.5% of Lebanese. Colchicine was first-line treatment, while biological drug use was higher in Italians. In the subgroups study, Italians reported lower disease knowledge and were followed up mainly by internists, while Lebanese were followed up by gastroenterologists or pediatricians. Italians were misdiagnosed with appendicitis, whereas Lebanese were misdiagnosed with gastrointestinal diseases. Italians exhibited lower symptom frequency, lower severity scores, and a better response compared to Lebanese patients. In conclusion, FMF presentation differed by country, with Italians showing milder symptoms and better treatment response, while Lebanese showed severe symptoms linked to pathogenic MEFV variants. Gene-environment interactions require further studies.