误诊为幼年型特发性关节炎的儿童家族性地中海热三例

Three cases with familial Mediterranean fever misdiagnosed as juvenile idiopathic arthritis

目的 探讨家族性地中海热患儿的诊断治疗要点.方法 回顾性分析北京协和医院儿科2014年1月-2016年6月收治的3例误诊为幼年型特发性关节炎（JIA）的家族性地中海热患儿的病历资料,探讨其临床表现、基因突变特点、治疗及预后情况.结果 3例中男2例,女1例.平均发病月龄17月龄（3 ～36月龄）,平均确诊年龄为6岁8月龄（24月龄～11岁）.临床表现周期性弛张热、分布于全身的红色斑疹及关节炎3例,贫血2例,淋巴结肿大2例,肝脾肿大1例.3例患儿曾经在常规抗感染无效、除外了感染性疾病及肿瘤性疾病后被诊断为JIA,但接受糖皮质激素及多种免疫抑制剂治疗效果不佳.经基因检测3例均存在MEFV基因突变,且均为复合杂合突变.发现的4种突变：R202Q、E148Q、L110P、P369S均为已报道的致病突变.3例患儿目前均接受口服秋水仙碱（按照起始剂量推荐5岁以下儿童为≤0.5 mg/d、5 ～10岁儿童为0.5～1.0 mg/d、10岁以上儿童和成人为1.0～1.5 mg/d）治疗,症状较治疗前明显改善.结论 家族性地中海热可以表现为反复弛张高热、全身红色斑疹、关节炎,在临床表现上容易与JIA相混淆,仅依靠临床表现鉴别有难度.3例均为MEFV基因复合杂合突变.予秋水仙碱口服后随访半年以上,症状均有明显缓解.

Objective To explore the key points of diagnosis and treatment of familial Mediterranean fever （FMF）.Method The clinical data of 3 cases with FMF misdiagnosed as Juvenile idiopathic arthritis（JIA）seen from January 2014 to June 2016 in Peking Union Medical College Hospital were retrospectively collected.The clinical manifestations,gene mutation characteristics,treatment and prognosis were also evaluated.Result Two cases were male and 1 was female.The mean age of onset was 17 months （3 months to 36 months）,while the average age of diagnosis was 6 years and 8 months （24 months to 11 years）.All the 3 cases presented with periodic fever,red rash and arthritis.Two of them suffered from anemia,2 of them showed lymphadenopathy,and 1 of them presented with hepatosplenomegaly.All of the 3 cases were diagnosed as JIA by excluding infectious diseases and neoplastic diseases and respondiug poorly to anti-infection treatment,but they benefitted little from glucocorticoids and a variety of immunosuppressive therapy.The nutations of MEFV gene were found in 3 cases by gene detection,and all of them were complex heterozygous mutations.Four reported pathogenic mutations were found：R202Q,E148Q,L110P,P369S.All the 3 cases are currently receiving oral colchicine （in accordance with the initial dose of children under the age of 5 recommended ≤ 0.5 mg/d,5 to 10 years old children 0.5-1.0 mg/d,10 years old children and older children 1.0-1.5 mg/d）,and the symptoms were significantly improved.Conclusion The familial Mediterranean fever can be characterized by repeated remittent fever,red rash,arthritis,and is easy to be confused with JIA in clinical manifestation.In this paper,3 cases were diagnosed as complex heterozygous MEFV gene mutation by gene analysis.During the 6 months follow-up,all of the 3 patients responded well to colchicine.