抗MDA5抗体阳性幼年皮肌炎临床特点及治疗转归分析

Analysis on clinical features and treatment outcomes of anti-MDA5 antibody-positive juvenile dermatomyositis

目的分析抗黑色素瘤分化相关基因5(MDA5)抗体阳性幼年皮肌炎(JDM)的临床特点及治疗转归。方法收集首都医科大学附属北京儿童医院风湿科2015年6月至2022年2月收治的487例JDM患儿的临床资料,其中41例(8.42%)为抗MDA5抗体阳性者。对其临床特点、疾病评估、治疗药物及疾病转归进行总结分析。结果41例抗MDA5抗体阳性JDM患儿中,最常见的临床表现是皮肤和黏膜异常,其次为肌无力,发热和关节炎也较为常见,部分患儿出现呼吸系统症状和皮肤溃疡。皮肤评估工具(CAT)评分以3~5分占大多数。儿童肌炎评估量表(CMAS)评分为(33.88±9.57)分。间质性肺疾病(ILD)的发病率为87.80%,12.20%的患儿发展为快速进展型ILD(RP-ILD)。5例(12.20%)在病程中出现皮下钙化。90.24%的抗MDA5抗体阳性JDM患儿有高危病征。静脉注射甲基泼尼松龙(IVMP)(63.41%)、静脉注射免疫球蛋白(IVIG)(68.29%)和口服环孢素A(65.85%)是治疗的主要方法。9例(21.95%)患儿口服托法替布。75.61%的患儿表现为单一病程,19.51%的患儿为复发性病程,4.88%的患儿为持续的活动性病程。1年、2年、3年和4年的完全临床应答率分别为65.79%(25/38)、65.38%(17/26)、63.64%(14/22)和70.59%(12/17)。5年完全临床缓解率为14.29%(2/14),2年疾病复发率为19.23%(5/26)。在2年的随访中,95.00%(19/20)的患儿肺部病变完全吸收。随访3个月、6个月、9个月和12个月时,泼尼松的中位剂量分别为1.40 mg/kg、1.00 mg/kg、0.71 mg/kg和0.60 mg/kg,糖皮质激素停用的中位时间为69个月。截至2022年2月,41例患儿中有15例(36.59%)停用糖皮质激素,9例(21.95%)停用所有药物。结论抗MDA5抗体阳性JDM是一种特殊类型的JDM,主要表现为特征性皮疹、肌无力、发热和关节炎,ILD是主要危害。该病完全临床缓解率仍然较低,复发率相对较高。

Objective To analyze the clinical features and treatment outcomes of anti-melanoma differentiation-associated gene 5(MDA5)antibody-positive juvenile dermatomyositis(JDM).Methods The clinical data of 487 pediatric patients with JDM who were admitted to the Department of Rheumatology of Beijing Children′s Hospital,Capital Medical University from June 2015 to February 2022 were collected,and among the pediatric patients,41 cases(8.42%)were positive for anti-MDA5 antibody.The clinical characteristics,disease evaluation,therapeutic drugs and disease outcome of the pediatric patients were summarized and analyzed.Results In the 41 cases of JDM with positive anti-MDA5 antibody,the most common clinical manifestation was abnormal skin and mucous membrane,followed by muscle weakness,and fever and arthritis were also common,and some pediatric patients had respiratory symptoms and skin ulcers.The majority of Cutaneous Assessment Tool(CAT)scores were 3 to 5 points.The scores of Childhood Myositis Assessment Scale(CMAS)were(33.88±9.57)points.The incidence rate of interstitial lung disease(ILD)was 87.80%,and 12.20%of the pediatric patients developed rapid progressive ILD(RP-ILD).Subcutaneous calcification occurred in 5 cases(12.20%)during the course of the disease.There were 90.24%of the anti-MDA5 antibody-positive JDM patients had high-risk physical signs.Intravenous methylprednisolone(IVMP)(63.41%),intravenous immunogloblin(IVIG)(68.29%)and oral cyclosporine A(65.85%)were the main treatment methods.Nine pediatric patients(21.95%)were orally administered tofacitinib.There were 75.61%of the pediatric patients presenting with a single course of the disease,and 19.51%with recurrent courses,and 4.88%with persistent active courses.The complete clinical response rates at 1,2,3 and 4 years were 65.79%(25/38),65.38%(17/26),63.64%(14/22)and 70.59%(12/17),respectively.The five-year clinical complete remission rate was 14.29%(2/14),and the two-year disease recurrence rate was 19.23%(5/26).During the 2-year follow-up,95.00%(19/20)of the pediatric patients′lung lesions were completely absorbed.At 3,6,9 and 12 months of follow-up,the median dose of prednisone was 1.40 mg/kg,1.00 mg/kg,0.71 mg/kg and 0.60 mg/kg,respectively,and the median duration of glucocorticoid discontinuation was 69 months.Until February 2022,glucocorticoids were discontinued in 15 of 41 cases(36.59%)and all drugs were discontinued in 9 cases(21.95%).Conclusion Anti-MDA5 antibody-positive JDM is a special type of JDM,which mainly presents with characteristic rash,muscle weakness,fever and arthritis,and ILD is the main hazard.The complete clinical remission rate of the disease is still low,and the recurrence rate is relatively high.