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Background  Interstitial lung disease (ILD) is frequently observed in anti-melanoma differentiation-associated protein 5 (MDA5) antibody positive dermatomyositis (DM) and anti-synthetase syndrome (ASS), where they often develop a rapidly progressive ILD (RP-ILD) leading to poor prognosis.    Objective  The aim of this study was to construct multivariable prediction risk factors for rapid progressive ILD (RP-ILD) in anti-MDA5 positive DM (MDA5 + DM) and ASS.    Methods  333 idiopathic inflammatory myopathy (IIM) associated ILD patients were studied retrospectively. Risk factors for RP-ILD in MDA5 + DM and ASS patients were identified by univariate and multivariable logistic regression analysis. The mortality was assessed using Kaplan-Meier analysis.    Results  RP-ILD was more prevalent in MDA5 + DM patients than ASS patients. MDA5 + DM patients with RP-ILD had significantly lower survival rates than those in ASS patients. The independent risk factors for RP-ILD in MDA5 + DM patients were fever (OR 3.67, 95% CI:1.79-7.52), lymphopenia (OR 2.14, 95% CI:1.01-4.53), especially decreased levels of CD3 + T cells (OR 2.56, 95% CI:1.17-5.61), decreased levels of CD3 + CD4 +  T cells (OR 2.80, 95% CI:1.37-5.73), CD3 + CD8 + T cells (OR 2.18, 95% CI:1.05-4.50), elevated CD5 - CD19 +  B cells (OR 3.17, 95% CI:1.41-7.13), elevated ALT (OR 2.36, 95% CI:1.15-4.81), high lactate dehydrogenase (LDH) (OR 3.08, 95% CI:1.52-6.27), hyper-ferritin (OR 4.97, 95% CI:1.97-12.50), elevated CEA (OR 2.28, 95% CI:1.13-4.59), and elevated CA153 (OR 3.31, 95% CI:1.50-7.27). While the independent risk factors for RP-ILD in ASS patients were elevated CEA (OR 5.25, 95% CI: 1.73-15.93), CA125 (OR 2.79, 95% CI: 1.10-7.11) and NSE (OR 4.86, 95% CI: 1.44-16.37). Importantly, serum ferritin&amp;gt;2200ng/ml predicted patient’s death within half a year in MDA5 + DM patients with RP-ILD, but not in ASS patients.    Conclusions  There were significant different mortality and multivariable risk factors for RP-ILD in MDA5 + DM patients and ASS patients. Potential clinical benefits of using these different risk factors deserve assessment of severity and prognosis in IIM patients.

frontiers in immunology

Different Multivariable Risk Factors for Rapid Progressive Interstitial Lung Disease in Anti-MDA5 Positive Dermatomyositis and Anti-Synthetase Syndrome