A comparison of clinical phenotype and outcomes in anti- melanoma differentiation-associated protein 5 dermatomyositis and anti-synthetase syndrome in a multiethnic cohort in Singapore

ObjectiveThis study aimed to compare the clinical characteristics and outcomes of anti-MDA5 dermatomyositis (MDA5-DM) and anti-synthetase syndrome (ASyS) in a multi-ethnic Southeast Asian cohort, and identify features that facilitate phenotypic differentiation and prognostic stratification.MethodsChart review was performed on consecutive idiopathic inflammatory myopathies (IIM) patients managed at our centre from January 2015 to June 2021. Patients were classified using the 2017 EULAR/ACR IIM criteria, 2017 European Neuromuscular Centre criteria for immune-mediated necrotising myopathy (IMNM), and Connor's criteria for ASyS. Overlap myositis (OM) was defined as IIM in association with an underlying connective tissue disease or in the presence of a myositis-associated autoantibody. Rapidly progressive interstitial lung disease (RP-ILD) was defined as dyspnoea and/or hypoxaemia with worsening radiologic interstitial lung changes within 3 months of respiratory symptoms onset.ResultsAmong 119 IIM patients, dermatomyositis was the predominant subtype (57.1%), followed by ASyS (23.5%), OM (15.1%), and IMNM (4.2%). Anti-MDA5 antibodies were detected in 35.3% of dermatomyositis. MDA5-DM and ASyS exhibited comparable demographic characteristics. Anti-Jo1 (n = 14) was the commonest anti-tRNA synthetase antibody detected amongst ASyS patients. Compared with ASyS, MDA5-DM demonstrated significantly more prominent cutaneous manifestations—cutaneous ulcers, palmar papules, violaceous rash, Gottron's sign, inverse Gottron's sign, periungual erythema, and heliotrope rash (all p < 0.017); musculoskeletal features were similar between groups. Median peak creatine kinase levels were significantly higher in ASyS than MDA5-DM patients (median [IQR] 1317 [269−2713] vs. 227 [100−518] U/L; Hodges–Lehmann estimate = 773.5 U/L, 95% CI 150−1,788 U/L). ILD occurred in 42.0% of all IIM-subtypes; 78.9% of dermatomyositis-ILD cases were anti-MDA5 positive. RP-ILD was identified in 14 patients, of which 8 cases were anti- MDA5-DM and 4 ASyS. MDA5-DM/ASyS patients with RP-ILD had higher median peak AST levels (median [IQR] 103.5 [88−343] vs. 59 [44−119] U/L; Hodges–Lehmann estimate = 51 U/L, 95% CI 8−191 U/L) and markedly increased mortality compared with those without RP-ILD (75.0% vs. 12.5%; absolute risk difference 62.5%, 95% CI 35.7%–89.3%). The 1-year survival rates were 18.8% (95% CI 1.1%–53.5%) among MDA5-DM patients with RP-ILD, 75.0% (95% CI 12.8%–96.1%) among ASyS patients with RP-ILD and 97.4% (95% CI 83.2%–99.6%) among MDA5-DM or ASyS patients without RP-ILD. Survival differed significantly across these 3 groups (log rank p < 0.001).ConclusionIn our cohort, MDA5-DM and ASyS shared high burden of ILD but differed in cutaneous manifestations, risk of RP-ILD and survival, highlighting important diagnostic and prognostic distinctions warranting further investigation and informing clinical management.