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
- 1Department of Rheumatology, Allergy and Immunology, Tan Tock Seng Hospital, Singapore, Singapore
- 2Department of Epidemiology and Preventive Medicine, Tan Tock Seng Hospital, Singapore, Singapore
- 3Department of Respiratory and Critical Care Medicine, Tan Tock Seng Hospital, Singapore, Singapore
Abstract
Objective: This 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.
Methods: Chart 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.
Results: Among 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).
Conclusion: In 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.
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BibTeX
@article{chua2026comparison,
title = {{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}},
author = {Choon-Guan Chua and Zhaoxiang Fan and Hwee-Pin Phua and Wei-Yen Lim and Gin Tsen Chai and Mona Manghani},
journal = {Frontiers in Medicine},
year = {2026},
month = oct,
doi = {10.3389/fmed.2026.1969582},
url = {https://doi.org/10.3389/fmed.2026.1969582},
note = {CC BY 4.0},
}
RIS
TY - JOUR
TI - 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
AU - Choon-Guan Chua
AU - Zhaoxiang Fan
AU - Hwee-Pin Phua
AU - Wei-Yen Lim
AU - Gin Tsen Chai
AU - Mona Manghani
PY - 2026
DA - 2026/10/12
JO - Frontiers in Medicine
DO - 10.3389/fmed.2026.1969582
UR - https://doi.org/10.3389/fmed.2026.1969582
AB - Objective: This 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. Methods: Chart 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. Results: Among 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). Conclusion: In 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.
SN - 2296-858X
ER -