Adult Patients with Familial Mediterranean Fever - A Single-Center Case Series

Objectives Describe the clinical characteristics of adult patients with FMF (Familial Mediterranean Fever) and identify 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 reviewed and analyzed. Gene panel testing was performed at the Division of Genome Diagnostics, Hospital for Sick Children. All patients provided written consent to be included in a case series. Results A total of 22 patients were included (59% male). The cohort was composed of a variety of ethnicities including Middle Eastern (45%), Caucasian (18%), Southeast Asian and African (both 14%). The median ages at enrollment were 45 years, symptom onset (12.5 years), and diagnosis (35.5 years). Seven patients had first symptom onset after age 18. The median diagnostic delay was 7.5 years. A family history of FMF was present in 63% of patients. The most common trigger for flares was stress (41%). The most common symptoms were abdominal pain (95%), followed by fever (91%) and arthritis (72%). CRP was elevated during flares in 89% of patients. Notable comorbidities included spondyloarthropathy in 2 patients. Genetic testing was available in 20 patients. 14 were homozygous and 6 were heterozygous for variants in MEFV. The most common variants were V726A (7/20), M694V/M680I/E148Q (each in 4/20), and M694I (2/20). All were variants of uncertain significance, or likely/pathogenic by American College of Medical Geneticists classification. One patient carried 3 variants in MEFV (homozygous E148Q, and p369S), while 2 patients carried additional NOD2 variants (R791W, R702W). 86% of patients responded to colchicine, but 55% reported side effects. As such, IL-1 inhibitors such as anakinra or canakinumab were applied for to the provincial Exceptional Access Program in 8 patients. Funding for this medication was denied in 7 of them. Compassionate medication release was provided to 5 patients, for which 4 exhibited marked benefit. Conclusion FMF remains an underrecognized entity as demonstrated by the significant diagnostic delay (maximum 42 years) in our cohort. Moreover, it can present for the first time in adulthood (32% of our cohort). IL-1 blockade has been shown to be highly effective, but limited access to public funding remains a significant barrier. It will be important to continue to raise awareness for FMF and advocate for improved access to genetic testing as well as effective, evidence-based therapy.[1,2] [1.] Ozen S. Ann Rheum Dis 2015:1-8. [2.] Gattorno M. Int J Mol Sci 2023:1-24.