Familial Mediterranean fever is no longer a rare disease in Japan.
Familial Mediterranean fever is no longer a rare disease in Japan.
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DOI：
10.1186/s13075-016-1071-5
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发表时间：
2016-07-30
影响因子：
4.9
通讯作者：
Kawakami A
中科院分区：
文献类型：
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作者：
Migita K;Izumi Y;Jiuchi Y;Iwanaga N;Kawahara C;Agematsu K;Yachie A;Masumoto J;Fujikawa K;Yamasaki S;Nakamura T;Ubara Y;Koga T;Nakashima Y;Shimizu T;Umeda M;Nonaka F;Yasunami M;Eguchi K;Yoshiura K;Kawakami A
本研究的目的是评估家族性地中海热(FMF)在具有不明原因发热和风湿症状的日本患者中的临床表现和患病率。我们在2009年至2015年期间在日本各地招募了601名原因不明发热或疑似FMF的患者。根据tel Hashmer标准，患者被分为三组：确定的FMF、可能的FMF和非FMF患者，包括明确的风湿性疾病。用直接测序法检测FMF基因MEFV外显子1、2、3、10的突变。共有192例患者(31.9%)根据FMF诊断标准诊断为FMF。这些病例可分为确诊型(56.3%，n = 108)和疑似型(43.7%，n = 84)。发热、腹部症状和胸部症状在FMF患者中明显比非FMF患者更常见。在FMF患者中，26例(13.5%)伴有风湿性疾病。大多数FMF患者(94.3%，181/192)携带至少一个MEFV突变。FMF患者M694I(13.5%vs0%)和E148Q(39.1%vs24.8%)突变的等位基因频率显著高于正常对照组。FMF患者常见MEFV基因突变的等位基因频率依次为M694I(13.5%)、P369S(8.6%)、R408Q(8.1%)、G304R(2.9%)、R202Q(4.4%)、E148Q(39.1%)、L110P(11.7%)和E84K(3.1%)。MEFV外显子10突变频率(M694I)和外显子3突变频率(P369S、R408Q)明显高于可能FMF表型患者。本研究证实了日本不明原因发热患者中FMF的高患病率。在不明原因发热或非特异性风湿症状的病例中应怀疑FMF，MEFV突变分析可能有助于预测日本FMF的临床表型。
The 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. We 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. A 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. The 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.