ORIGINAL ARTICLE Diagnosis of familial Mediterranean fever following the initial presentation of monoarthritis Yoseph HOROVITZ, 1,2 Osama TANOUS, 1 Morad KHAYAT, 3 Munir SHAKER, 1 Stavit SHALEV 2,3, * and Ronen SPIEGEL 2,3,4, * 1 Pediatric Department A 0 , Emek Medical Center, Afula, 2 Rappaport School of Medicine, Technion, Haifa, 3 Genetic Institute, Emek Medical Center, Afula, and 4 Pediatric Department B 0 , Emek Medical Center, Israel Abstract Aims: To determine if familial Mediterranean fever (FMF) genetic testing should be advised in children with ini- tial presentation of monoarthritis and to identify clinical parameters associated with FMF-induced arthritis that warrant genetic investigation. Methods: A prospective study of 71 otherwise healthy children admitted to our pediatric department between 2010–2013 with a first episode of idiopathic monoarthritis. Demographic, clinical and laboratory data were documented and genetic assay of the five common mutations in our population of the MEFV gene that cause FMF syndrome were analyzed in the entire study population. Statistical analysis compared two groups according to FMF status (FMF arthritis and idiopathic arthritis). Results: Among the cohort seven (10%) children harbored two pathogenic mutations in the MEFV gene, thus confirming diagnosis of FMF. This FMF-induced arthritis group had a statistically significant female predomi- nance compared with the idiopathic arthritis group (six [86%] vs. 19 [30%], respectively) (P = 0.006, odds ration [OR] = 14.2). In addition, associated abdominal pain during the attack (two [28%] vs. two [3%], respec- tively) (P = 0.04, OR = 12.4) and a family history of FMF (two [29%] vs. five [8%], respectively) (P = 0.1, OR 4.7,) were more common in the FMF-induced arthritis group. Conclusions: In Mediterranean populations where FMF is relatively common we recommend for every child with a first episode of arthritis, without an identifying cause to strongly consider MEFV genetic testing of the common mutations in the relevant population. Key words: arthritis, autosomal recessive, familial Mediterranean fever, mutation. INTRODUCTION Familial Mediterranean fever (FMF) is the most com- mon Mendelian autoinflammatory syndrome resulting from mutations in the MEFV gene. 1 It is particularly fre- quent in populations residing in the Mediterranean region, with estimated carrier rates up to 1 : 4–1 : 5 in certain populations. 2,3 The disease is characterized by recurrent attacks of inflammation of serosal membranes (peritoneum, pleura, synovium, pericardium) and fever resulting in acute abdominal, chest and/or joint sterile inflammation. 1 Long-standing, untreated FMF can result in renal amyloidosis, finally leading to end stage renal disease. Musculoskeletal involvement, mostly in the form of arthritis or arthralgia is the second common manifesta- tion of FMF following periodic fever and abdominal pain. 4,5 The incidence and pattern of joint involvement is highly heterogeneous depending on the population Correspondence: Dr Ronen Spiegel, Department of Pediatrics B’ and Genetic Institute, Emek Medical Center, Afula 18101, Israel. Emails: spiegelr@zahav.net.il, spiegel_ro@clalit.org.il *Equal contribution. © 2016 Asia Pacific League of Associations for Rheumatology and John Wiley & Sons Australia, Ltd International Journal of Rheumatic Diseases 2016