Clinical and Genetic Spectrum of Familial Mediterranean Fever in Adult Patients: Insights from a Canadian Autoinflammatory Clinic

Objectives We aim to describe the clinical and genetic characteristics of adult patients with Familial Mediterranean Fever (FMF) and explore potential challenges in the diagnosis and treatment in this population. Methods Patients over age 18 years meeting the Tel HaShomer diagnostic criteria for FMF were recruited from an Autoinflammatory Clinic in Toronto. Clinical records and data were analyzed. Gene panel testing was performed with Next Generation Sequencing at the Hospital for Sick Children. Variants were classified as per the American College of Medical Geneticists criteria. All patients provided written consent to be included in a case series. Results A total of 37 patients were included (38% male). The cohort was composed of a variety of ethnicities, predominantly including Middle Eastern (35%), Caucasian (27%) and West Asian (10%). The median age at enrollment was 43 years, symptom onset was 15 years, and diagnosis was 35 years. Thirteen patients had first symptom onset after age 18. The median diagnostic delay was 7 years. Specific triggers for flares were reported in 51% of patients; the most common being stress (42%). The most common symptoms were abdominal pain (97%), fever (83%), and arthritis (73%). CRP was elevated during flares in 80% of patients. Of 36 patients with genetic data; 17 (47%) were homozygous/compound heterozygous, 13 (36%) were heterozygous, and 6 (17%) had no detectable variants in MEFV. The most common variants were V726A (9/36), E148Q and M694V (both in 8/36), and M680I (4/36). All were classified as variants of uncertain significance, or likely/pathogenic. Six patients did not carry any MEFV variants. A positive response to colchicine was observed in 88%, though 33% reported intolerances. IL-1 inhibitors were requested for 11 patients; all applications were denied under public funding, but compassionate access resulted in universal clinical improvement. Conclusion FMF remains under-recognized in adults, with significant diagnostic delay (maximum 60 years in our cohort). Colchicine intolerance limits therapy for some, and restricted IL-1 access remains a major barrier. This study adds to the limited Canadian data on adult FMF and highlights the need for greater awareness and advocacy for equitable access to evidence-based biologic therapy. Further studies are needed also to investigate the potential causes of mutation negative FMF.