Interstitial Lung Disease in Anti-MDA5 Positive Dermatomyositis

• Published in: Clinical reviews in allergy & immunology 2021-04, Vol.60 (2), p.293-304
• Main Authors: Wu, Wanlong, Guo, Li, Fu, Yakai, Wang, Kaiwen, Zhang, Danting, Xu, Wenwen, Chen, Zhiwei, Ye, Shuang
• Format: Article
• Language: English
• Subjects: Allergology; Autoimmune diseases; CD4 antigen; Clinical trials; Computed tomography; CXCR4 protein; Cyclophosphamide; Dermatomyositis; Development and progression; Etiology; Exanthema; Ferritin; Glucocorticoids; Health aspects; Immunology; Internal Medicine; Intravenous administration; Lung diseases; Lymphocytes T; Medical prognosis; Medicine; Medicine & Public Health; Melanoma; Mortality; Prognosis; Tacrolimus; Terminology
• ISSN: 1080-0549; 1559-0267
• DOI: 10.1007/s12016-020-08822-5

Anti-melanoma differentiation-associated gene 5–positive dermatomyositis (MDA5 + DM) is a rare autoimmune disease predominantly reported in East Asia. MDA5 + DM is an intractable disease with impressively high mortality due to rapid-progressive interstitial lung disease (RPILD). Other typical clinical manifestations comprise DM-specific rash (Gottron’s papules, heliotrope rash) and amyopathic/hypomyopathic muscle involvement. Multiple prognostic factors have been identified. Baseline forced vital capacity (FVC) %-based staging could serve as a simplified risk stratification system. Serum biomarkers including MDA5 Ab titers, ferritin, KL-6 levels, and CD4 + CXCR4 + T cell percentage could provide additional surrogate value of ILD severity and treatment response, as well as potential predictive value for survival. Spontaneous pneumomediastinum (PNM), ground-glass opacity (GGO), and consolidation were demonstrated to be the most significant features in pulmonary high-resolution computed tomography (HRCT) findings of MDA5 + DM-ILD. The semi-quantitative assessment of lesions in HRCT has also been demonstrated relevant to the outcome. The current treatment of this disease is still largely empirical. Immunosuppressive treatments, i.e., “triple therapy” (combination of high-dose glucocorticoids, tacrolimus, and intravenous cyclophosphamide) and JAK inhibitor-based therapy, are the mainstream regimens for MDA5 + DM-ILD, supported by the recently published trials. However, more efficacious regimen with favorable safety profile and high-level evidence is still urgently demanded for patients with MDA5 + DM-ILD, especially those at advanced-stage. We will summarize the terminology, etiology and pathogenesis, clinical features and outcome, prognostic factors, and treatment of MDA5 + DM-ILD in this review.