[Three cases report of juvenile dermatomyositis with positive anti-melanoma differentiation associated gene 5 (MDA5) antibody and severe interstitial lung disease and literature review].

Objective: To report the clinical features of anti-MDA5 antibody positive juvenile dermatomyositis (JDM) complicated with severe interstitial lung disease (ILD). Methods: The clinical data of three patients, who was admitted to the Department of Rheumatology and Immunology, Children's Hospital of the Capital Institute of Pediatrics from September 2016 to July 2017, with anti-melanoma differentiation associated gene 5 (MDA5) antibody positive JDM complicated with ILD were retrospectively extracted and analyzed. Meanwhile, PubMed database, CNKI, Wanfang database and China Biology Medicine disc (from their establishment to February 2019) with the key words "juvenile dermatomyositis" "interstitial lung disease" , and "anti-MAD5 antibody" both in English and Chinese were searched. Results: There were 2 females and 1 male (P1-P3), aged from 10 years 3 months to13 years 4 months, the time from onset to diagnosis were 2 months, 4 months and 10 months. All presented with rash. One of them had decreased muscle strength, and two had decreased activity tolerance. Creatine kinase was 588, 915 and 74 U/L, and serum ferritin were 1 792, >2 000 and 195.4 μg/L. All three patients had positive anti-MDA5 antibodies. At the time of diagnosis, all of them had ILD, pneumothorax and mediastinal emphysema, but had no respiratory symptoms. All three patients received oral methylprednisolone and cyclophosphamide pulse therapy, while human immunoglobulin was given only to P1 and P2. P1 developed rapid progressive pulmonary interstitial disease (RPILD) and died of respiratory failure after 2 months. While P2 and P3 were followed up for 1 to 2 years, who had complete remission, as anti-MDA5 antibody turned to negative and ILD improved significantly. Ten related reports in literature were retrieved, without reported Chinese cases, and most cases initiated with rash and very likely complicated with arthritis. Some of them were more likely to have ILD rather than muscle weakness. It also showed that Japanese JDM children had higher rate of positive anti-MDA5 antibody than patients from the U.S. and U.K., and are more susceptible to ILD and RPILD. The mortality rate of patients with RPILD is extremely high. Conclusions: The cases of JDM with positive anti-MDA5 antibody mainly presented with rash and mild muscle weakness, and could be complicated with ILD, pneumothorax and mediastinal emphysema without respiratory symptoms at early stage. Anti-MDA5 antibody titer is related to disease activity and can turn to negative after treatment.目的： 报道儿童抗黑色素瘤分化相关基因5（MDA5）抗体阳性幼年皮肌炎（JDM）合并严重肺间质病变（ILD）的临床特点。 方法： 对首都儿科研究所附属儿童医院风湿免疫科2016年9月至2017年7月收治的3例抗MDA5抗体阳性JDM合并严重ILD患儿的临床资料进行回顾性分析，以"juvenile dermatomyositis" "interstitial lung disease" "anti-MAD5 antibody"和"幼年型皮肌炎" "肺间质病变" "抗MDA5抗体"作为关键词，对PubMed数据库、中国知网、万方数据库、中国生物医学文献数据库（建库至2019年2月）进行文献检索。 结果： 3例患儿女2例、男1例，年龄10岁3月龄~13岁4月龄；起病到确诊时间分别为2、4、10个月；3例均以皮疹起病，1例肌力下降，2例活动耐量下降；肌酸激酶分别为588、915及74 U/L，血清铁蛋白分别为1 792、>2 000及195.4 μg/L，抗MDA5抗体均阳性；确诊时3例均有ILD，3例均合并气胸及纵隔气肿，临床无呼吸道症状。治疗均给予甲泼尼龙及环磷酰胺冲击，例1和例2同时给予静脉免疫球蛋白。例1发展为快速进展性肺间质疾病（RPILD），2个月后死于呼吸衰竭，例2、例3随访1~2年，病情完全缓解，抗MDA5抗体转阴，ILD明显好转。检索相关文献10篇，未见中国儿童病例报道。此类患儿多以皮疹为首发症状，易合并关节炎，部分患儿肌力改变不明显，易合并ILD，文献显示日本JDM患儿抗MDA5抗体检出率高于英美国家，且更易合并ILD及RPILD，合并RPILD者病死率极高。 结论： 中国儿童JDM存在抗MDA5抗体阳性病例；患儿多以皮疹首发，肌力下降不明显，可合并ILD、气胸及纵隔气肿，早期无呼吸道症状；亚洲儿童JDM更易发生ILD及RPILD，且病情更重；抗MDA5抗体滴度与病情活动相关，治疗后可以阴转。.