Predictors of rapidly progressive- interstitial lung disease and mortality in patients with autoantibodies against melanoma differentiation-associated protein 5 dermatomyositis

Anti-melanoma differentiation-associated protein 5 (MDA5) positive dermatomyositis (DM) is associated with rapidly progressive interstitial lung disease (RP-ILD) and high mortality. This multicentre retrospective study aimed to identify predictors for mortality and RP-ILD. Anti-MDA5 positive DM patients were identified from the Hong Kong Myositis Registry and the Clinical Data Analysis and Reporting System. Clinical characteristics were reviewed. Risk factors for mortality and RP-ILD were identified. Among the 116 recruited patients, 100 (86.2%) had ILD, 47 (40.5%) had RP-ILD and 44 (37.9%) patients died. Cox regression analysis revealed that RP-ILD (HR 9.735, 95%CI 3.905-24.272), age >52 (HR 4.750, 95%CI 1.692-13.333), ferritin level >2800pmol/l (HR 3.042, 95%CI 1.323-6.997) and lactate dehydrogenase (LDH) >400 IU/l (HR 2.290, 95% CI 1.009-5.198) were independent predictors of mortality. With regard to RP-ILD, analyses showed that potential predictors at baseline included age >50 years old (HR 2.640, 95%CI 1.277-5.455), LDH >300IU/l (HR3.189, 95%CI 1.469-6.918), fever (HR 1.903, 95% CI: 0.956-3.790) and neutrophil to lymphocyte ratio (NLR) >7.0 (HR 1.967, 95%CI 0.942-4.107). We proposed a prediction model, based on Fever, LDH, Age and White cell count ("FLAW"), to stratify risk of development of RP-ILD. The probability of RP-ILD in a patient with a score of 4 was 100%. A small internal validation cohort showed the odds of RP-ILD with FLAW scores of 0, 1, 2 and 3 were 0%, 0%, 42.9% and 75% respectively. Anti-MDA5-associated RP-ILD is significantly associated with poor survival rates. The "FLAW" model maybe useful to predict the development of RP-ILD.