• Kiyoshi Migita, Yasumori Izumi, Yuka Jiuchi, Nozomi Iwanaga, Chieko Kawahara, Kazunaga Agematsu, Akihiro Yachie, Junya Masumoto, Keita Fujikawa, Satoshi Yamasaki, Tadashi Nakamura, Yoshifumi Ubara, Tomohiro Koga, Yoshikazu Nakashima, Toshimasa Shimizu, Masataka Umeda, Fumiaki Nonaka, Michio Yasunami, Katsumi Eguchi, Koh-Ichiro Yoshiura, and Atsushi Kawakami.
• Department of Rheumatology, Fukushima Medical University School of Medicine, Hikarigaoka 1, Fukushima, Fukushima, 960-1295, Japan. migitakiyoshi@gmail.com.
• Arthritis Res. Ther. 2016 Jul 30; 18: 175.

BackgroundThe aim of this study was to evaluate the clinical manifestations and prevalence of familial Mediterranean fever (FMF) in Japanese patients with unexplained fever and rheumatic manifestations.MethodsWe enrolled 601 patients with unexplained fever or suspected FMF throughout Japan between 2009 and 2015. Patients were divided into three groups according to Tel Hashomer criteria: sure FMF, probable FMF, and non-FMF patients, including definitive rheumatic diseases. Mutation detection in exons 1, 2, 3, and 10 of the FMF gene MEFV was performed by direct sequencing.ResultsA total of 192 patients (31.9 %) were diagnosed with FMF according to FMF diagnostic criteria. These could be divided into sure FMF (56.3 %, n = 108) and probable FMF (43.7 %, n = 84) patients. Fever, abdominal symptoms, and thoracic symptoms were significantly more common in FMF than non-FMF patients. Among FMF patients, 26 (13.5 %) had concomitant rheumatic diseases. Most FMF patients (94.3 %, 181/192) carried at least one MEFV mutation. Allele frequencies of M694I (13.5 % vs 0 %) and E148Q (39.1 % vs 24.8 %) mutations were significantly higher in FMF compared with healthy subjects. Allele frequencies of common MEFV mutations in FMF patients were M694I (13.5 %), P369S (8.6 %), R408Q (8.1 %), G304R (2.9 %), R202Q (4.4 %), E148Q (39.1 %), L110P (11.7 %), and E84K (3.1 %). Patients with a sure FMF phenotype had a higher frequency of MEFV exon 10 mutation (M694I) and a lower frequency of MEFV exon 3 mutations (P369S, R408Q) compared with those with a probable FMF phenotype.ConclusionThe high prevalence of FMF in Japanese patients with unexplained fever was confirmed in the present study. FMF should be suspected in cases of unexplained fever or non-specific rheumatic manifestations, and mutational analysis of MEFV could be useful to predict the clinical phenotypes of FMF in Japan.

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