Clinical expression of symptomatic Familiar Mediterranean Fever (FMF) in Lebanese patients: a real-life survey study

ABSTRACT

Background: Familial Mediterranean fever (FMF) is an autosomal recessive autoinflammatory disease characterized by recurrent fever and serositis attacks. We aimed to explore clinical aspects of FMF including knowledge, diagnosis, symptoms, and medication in a Lebanese cohort enrolled by ad-hoc questionnaire. Methods: During November 2021-March 2022 we conducted an online survey by a google form questionnaire (33 items) advertised across Lebanese communities, hospitals, internists, and specialists. Patients and children's parents voluntarily provided information about FMF knowledge, diagnosis, presence, and severity of symptoms before and after medication. Since COVID-19 and FMF may share some common symptoms due to activation of the inflammasome pathway, we further investigated this aspect in the FMF cohort with symptomatic COVID-19. Results: A total of 123 FMF patients participated in this survey (75 females, age range 1-67 years;10 subjects from Armenia, Persia, and Turkey). The most frequent MEFV variants were M694V, M694I, E148Q, V726A, R202Q, and A744S. Before the diagnosis 70% of the subjects had no knowledge about FMF. The diagnosis was late in 40% of subjects (at age ≥20 years). A misdiagnosis occurred in 21% of subjects and was associated with unnecessary procedures such as heavy antibiotic prescription, appendectomy, and abdominal surgery. Prior to the diagnosis and targeted FMF therapy, subjects described typical febrile periodical attacks of systemic serositis with a frequency of more than attack once per month (48%) with intensity ranging from moderate to severe (95%). Following therapy with colchicine, 65% of the subjects reported mild symptoms. In addition, 60% of subjects had COVID-19 infection which was symptomatic in 80% of the cases. Concerning COVID-19, 63% of symptomatic COVID-19 subjects reported that FMF symptoms were higher compared to COVID-19, 23% reported that COVID-19 symptoms were higher than FMF symptoms, and 14% reported no difference between the two diseases. Additionally, 12% reported consequences of FMF-COVID- 19 combined symptoms, mainly joint pain due to persisting arthralgias. Conclusion: In Lebanon, an endemic region for FMF with a mixture of the ethnic communities from the Mediterranean area, FMF diagnosis can be missed, delayed, or initially erroneously classified. Nevertheless, the diagnostic ability is improving over time. This is the first study in Lebanon to clarify aspects of FMF knowledge, diagnosis, and symptoms as well as evaluation of COVID-19 and FMF interplay. The complex interaction and consequences between COVID-19 infection and the genetic autoinflammatory FMF is being further investigated.