中国循证儿科杂志 ›› 2021, Vol. 16 ›› Issue (2): 93-98.DOI: 10.3969/j.issn.1673-5501.2021.02.003

• 论著 • 上一篇    下一篇

幼年型皮肌炎常见肌炎抗体与临床表型的关联分析

管皖珍, 李国民, 李一帆, 张涛, 姚文, 龚一女, 刘海梅, 史雨, 周利军, 徐虹, 孙利   

  1. 复旦大学附属儿科医院风湿科 上海,201102
  • 收稿日期:2020-06-30 修回日期:2021-01-21 出版日期:2021-04-25 发布日期:2021-06-04
  • 通讯作者: 孙利,email:lillysun@263.net

The analysis of clinical phenotypes and the common myositis specific antibodies in juvenile dermatomyositis

GUAN Wanzhen, LI Guomin, LI Yifan, ZHANG Tao, YAO Wen, GONG Yinv, LIU Haimei, SHI Yu, ZHOU Lijun, XU Hong, SUN Li   

  1. Department of Rheumatology, Children's Hospital of Fudan University, Shanghai 201102, China
  • Received:2020-06-30 Revised:2021-01-21 Online:2021-04-25 Published:2021-06-04
  • Contact: SUN Li, email: lillysun@263.net

摘要: 背景 目前成人和儿童皮肌炎的肌炎抗体谱与临床表型谱的分析受单纯与复合抗体、是否已治疗等混杂因素影响。目的 探讨幼年型皮肌炎(JDM)肌炎特异性抗体(MSA)与临床表型的相关性。设计 病例系列报告。方法 JDM诊断参照Bohan/Peter标准或2017年EULAR/ACR标准。纳入复旦大学附属儿科医院(我院)风湿科2011年开始建立的JDM随访系统中2017年3月至2020年4月行欧蒙免疫印迹法检测16种肌炎抗体的连续病例。从我院HIS系统中和风湿科JDM随访系统中采集来我院就诊时的临床数据:发病年龄,诊断时病程,随访病程,体温,皮肤、骨和关节、肺、肝、肾表现,实验室检查,MAS,重叠SLE,儿童肌力(CMAS)评分。主要结局指标 单纯和复合抗-MDA5抗体患儿临床表型特点。结果 符合本文纳入标准的103例JDM进入分析,男54例(52.4%),诊断JDM后未经治疗前行特异性抗体谱检测60例。初诊时CMAS评分中位数为33(23.0,44.7)。主要临床表现:发热、皮肤溃疡、皮肤钙化、关节痛或关节炎、间质性肺炎、合并重症肺炎、吞咽困难、血尿和IgA肾病、合并巨噬细胞活化综合征。103例JDM患儿中,肌炎抗体阳性68例(66.0%),其中MSA阳性64例,肌炎相关性抗体(MAA)阳性24例,MSA+MAA阳性20例。抗-MDA5抗体组、抗-NXP2抗体组、抗-TIF-1γ抗体组及抗体全阴性组4组间发病年龄和初诊时病程比较差异有统计学意义。抗-TIF-1γ抗体组发病年龄更小,初诊时病程更长。抗-MDA5抗体组更易发生皮肤溃疡、关节炎/关节痛,更多合并间质性肺炎和发热。4组间CMAS评分、ALT、AST、LDH、α-羟丁酸脱氢酶(HBDH)、CK、Fer差异有统计学意义,抗-NXP2抗体组CMAS评分最低,CK、LDH和HBDH最高,抗-MDA5抗体组ALT、AST最高、CK最低,Fer最高;抗-TIF-1γ抗体组ALT、AST、LDH、Fer最低;抗体全阴性组ALT、AST、CK、LDH、HBDH未显示有意义的特点。初治单纯抗-MDA5组(n=9)HBDH、Fer基本正常,初治复合抗-MDA5组(n=10)HBDH、Fer显著增高。结论 抗-MDA5、抗-NXP2和抗-TIF-1γ抗体阳性JDM患儿呈现了足以鉴别的临床表型和实验室检查结果,未治疗情况下单纯与复合抗-MDA5抗体阳性JDM患儿HBDH和Fer有明显的鉴别意义,抗体全阴性患儿临床表型和实验室结果无明显特征。

关键词: 幼年性皮肌炎, 肌炎特异性抗体, 肌炎相关性抗体, 抗-MDA5抗体

Abstract: Background At present, the analysis of myositis specific antibody (MSA) and clinical phenotype in dermatomyositis or juvenile dermatomyositis (JDM) is affected by some confounding factors, including simple or complex antibodies and treatment.Objective To observe the relationship between MSA and clinical phenotype in JDM.DesignCase series report.Methods The diagnosis of JDM was based on Bohan/Peter criteria or 2017 EULAR/ACR criteria. We enrolled JDM patients who were listed in the JDM follow-up system of the rheumatology departments of Children's Hospital of Fudan University since 2011 and were detected by MSAs and MAAs with Euroline Autoimmune Inflammatory Myopathies 16Ag kit from March 2017 to April 2020. Clinical characteristics including clinical data, onset age, course of disease at diagnosis, follow-up course, body temperature, skin, bone and joint system, lung, liver, kidney, laboratory examination, macrophage activation syndrome(MAS), overlapping SLE and CMAS scores were collected from the HIS system and JDM follow-up system.Main outcome measures Clinical phenotypic characteristics of children with simple and combined anti-MDA5 antibody.Results A total of 103 patients with JDM who met the inclusion criteria of this study were included in the analysis with 54 males(52.4%). Sixty patients were detected with specific antibody spectrum before treatment after the diagnosis of JDM. The median CMAS score was 33 (23.0,44.7). The main clinical manifestations were fever, skin ulcer, skin calcification, arthralgia or arthritis, interstitial pneumonia, severe pneumonia, dysphagia, hematuria and IgA nephropathy, and MAS. Among 103 cases of JDM, 68 cases (66.0%) were myositis antibody positive, 64 cases were MSA positive, 24 cases were MAA positive and 20 cases were MSA and MAA positive. There were significant differences in age of onset and course of disease at first diagnosis among anti-MDA5 antibody positive group, anti-NXP2 antibody positive group, anti-TIF-1γ antibody positive group and all antibody negative antibody group. Younger onset age and longer course of disease at first diagnosis were seen in anti-TIF-1γ antibody positive group. Skin ulcer, arthritis / arthralgia, ILD and fever were more likely to occur in patients with anti-MDA5 antibody. The CMAS score, ALT, AST, LDH, HBDH, CK and Fer were significantly different among the four groups. Anti-NXP2 antibody positive patients have the lowest CMAS score and the highest CK, LDH and HBDH level. Anti-MDA5 antibody positive patients have the highest ALT, AST, Fer, but the lowest CK. Especially, Anti-TIF-1γ antibody positive patients have the lowest ALT, AST, LDH and Fer. Antibody negative group did not show significant characteristics in ALT, AST, CK, LDH or HBDH. Furthermore,HBDH and Fer were normal in initial group of anti-MAD5 alone group (n=9) while increasing significantly in initial group of combined anti-MDA5 group (n=10).Conclusion Anti-MDA5、 anti-NXP2 and anti-TIF-1γ antibody positive JDM present identifiable clinical phenotypes and laboratory test results.The untreated patients only with anti-MDA5 positive and with other positive antibodies are of differential significance. MSAs and MAAs negative JDM have no obvious clinical phenotypes and laboratory test results.

Key words: Juvenile dermatomyositis, Myositis specific antibody, Myositis related antibody, Anti-MDA5 antibody