AbstractObjectiveThe objective of this study is to investigate clinical features and prognostic factors of antimelanoma differentiation‐associated gene 5 (anti‐MDA5)‐positive dermatomyositis with rapidly progressive interstitial lung disease (RP‐ILD) in Chinese patients.MethodsClinical features and prognostic factors of patients with newly diagnosed or recurrent dermatomyositis patients were retrospectively analyzed. All patients were divided into the anti‐MDA5‐positive or negative dermatomyositis, and with or without RP‐ILD groups. Clinical features and prognostic factors were statistically compared among different groups.ResultsThe serum ferritin (SF) levels (1500.0 [658.80, 1844.0]) and γ‐glutamyl transpeptidase (γ‐GT) (125.5 [61.0, 232.0] vs. 28 [16.0, 41.0],Z= 5.528;p< .001) were markedly higher, and phosphocreatine myoenzyme (CK) (73.0 [42.0, 201.0] vs. 1333.0 [79.0, 8000.0],Z= −2.739,p= .006), serum albumin level (32.51 ± 5.23 vs. 35.81 ± 5.88,t= −2.542,p= .013), and lymphocyte count (0.80 ± 0.36 vs. 1.45 ± 0.77,t= −4.717,p< .001) were lower than those in anti‐MDA5‐negative counterparts. Among patients with anti‐MDA5 antibody (Ab) with RP‐ILD, the SF level (1531.0 [1163.8, 2016.5] vs. 584.9 [564.8, 1042.5],Z= 2.664,p= .008), γ‐GT (134.0 [81.0, 204.5] vs. 123.0 [76.0, 189.0],Z= 3.136,p= .002) and positive rate of anti‐RO‐52 Ab (90.9% vs. 50.0%,χ2= 7.222,p= .013) were higher and lymphocyte count (0.79 ± 0.38 vs. 1.32 ± 0.74,t= −3.025,p= .029) was lower than those in their counterparts without RP‐ILD. The SF level of anti‐MDA5 nonsurvivors (1544 [1447.32, 2089.0] vs. 584.9 [515.7, 1500.0],Z= 2.096,p= .030), anti‐RO‐52 Ab‐positive rate ([16/18, 88.9%] vs. [9/16, 56.2%],χ2= 4.636,p= .031) were higher than those in survivors. Lymphocytopenia was a risk factor for RP‐ILD and death of patients with anti‐MDA5‐positive dermatomyositis. The area under receiver operating characteristic curve was 0.888 (95% confidence interval: 0.756, 1.000;p< .001), the sensitivity was 85.7%, the specificity was 93.8%, and Youden's index was 0.795.ConclusionsAnti‐MDA5‐positive dermatomyositis patients are prone to developing RP‐ILD. Declined lymphocyte count is a critical risk factor for RP‐ILD, probably acting as a simple and effective predictor for Chinese patients with anti‐MDA5‐positive dermatomyositis.