OBJECTIVES: To compare clinical characteristics, including the frequency of cutaneous, extramuscular manifestations and malignancy, between adults with anti-synthetase syndrome (ASyS) and DM. METHODS: Using data regarding adults from the MYONET registry, a cohort of DM patients with anti-Mi2/-TIF1γ/-NXP2/-SAE/-MDA5 autoantibodies, and a cohort of ASyS patients with anti-tRNA synthetase autoantibodies (anti-Jo1/-PL7/-PL12/-OJ/-EJ/-Zo/-KS) were identified. Patients with DM sine dermatitis or with discordant dual autoantibody specificities were excluded. Sub-cohorts of patients with ASyS with or without skin involvement were defined based on presence of DM-type rashes (heliotrope rash, Gottron's papules/sign, violaceous rash, shawl sign, V-sign, erythroderma, and/or periorbital rash). RESULTS: In total 1054 patients were included (DM, n = 405; ASyS, n = 649). In the ASyS cohort, 31% (n = 203) had DM-type skin involvement (ASyS-DMskin). A higher frequency of extramuscular manifestations, including Mechanic's hands, Raynaud's phenomenon, arthritis, interstitial lung disease and cardiac involvement differentiated ASyS-DMskin from DM (all P < 0.001), whereas higher frequency of any of four DM-type rashes-heliotrope rash (n = 248, 61% vs n = 90, 44%), violaceous rash (n = 166, 41% vs n = 57, 9%), V-sign (n = 124, 31% vs n = 28, 4%), and shawl sign (n = 133, 33% vs n = 18, 3%)-differentiated DM from ASyS-DMskin (all P < 0.005). Cancer-associated myositis (CAM) was more frequent in DM (n = 67, 17%) compared with ASyS (n = 21, 3%) and ASyS-DMskin (n = 7, 3%) cohorts (both P < 0.001). CONCLUSION: DM-type rashes are frequent in patients with ASyS; however, distinct clinical manifestations differentiate these patients from classical DM. Skin involvement in ASyS does not necessitate increased malignancy surveillance. These findings will inform future ASyS classification criteria and patient management.

Center for Rheumatology and Spine Diseases Copenhagen University Hospital Copenhagen Denmark

Centre for Musculoskeletal Research Division of Musculoskeletal and Dermatological Sciences The University of Manchester Faculty of Biology Medicine and Health Manchester UK

Clinica Medica Dipartimento di Scienze Cliniche e Molecolari Universita Politecnica delle Marche Ancona Italy

Clinical Immunology and Rheumatology St John's National Academy of Health Sciences Bangalore Karnataka India

Department of Gastroenterology Dermatology and Rheumatology Karolinska University Hospital Stockholm Sweden

Department of Immunology University of Debrecen Debrecen Hajdú Bihar Hungary

Department of Neurology and Pain Treatment Neuromuscular Center Center for Translational Medicine Immanuel Klinik Rüdersdorf University Hospital of the Brandenburg Medical School Theodor Fontane Rüdersdorf bei Berlin Germany

Department of Neurology Universitair Ziekenhuis Gent Ghent Belgium

Department of Neurology University Medical Center Göttingen Göttingen Germany

Department of Pharmacy and Pharmacology University of Bath Bath UK

Department of Rheumatology Alder Hey Children's NHS Foundation Trust Liverpool UK

Department of Rheumatology and Immunology Inselspital University Hospital Bern Bern Switzerland

Department of Rheumatology Arcispedale Santa Maria Nuova di Reggio Emilia Reggio Emilia Emilia Romagna Italy

Department of Rheumatology China Japan Friendship Hospital Beijing China

Department of Rheumatology Mayo Clinic Rochester MN USA

Department of Rheumatology Oslo University Hospital Oslo Norway

Department of Rheumatology Royal National Hospital for Rheumatic Diseases Bath UK

Division de Medicina Interna Servicio de Reumatologia Hospital Civil Dr Juan 1 Menchaca Universidad de Guadalajara Guadalajara Jalisco Mexico

Division of Population Health Health Services Research and Primary Care The University of Manchester Faculty of Biology Medicine and Health Epidemiology and Public Health Group Manchester UK

Division of Rheumatology Department of Medicine Karolinska Institutet Stockholm Sweden

Faculty of Health Sciences Brandenburg Brandenburg Medical School Theodor Fontane Rüdersdorf bei Berlin Germany

Faculty of Science and Engineering Manchester Metropolitan University Manchester UK

Great Ormond Street Hospital for Children NHS Foundation Trust Infection Immunity and Inflammation London UK

Institute of Rheumatology and Department of Rheumatology Charles University Praha Czech Republic

Internal Medicine Department Hanoi Medical University Hanoi Vietnam

MRC ARUK Institute of Ageing and Chronic Disease University of Liverpool Liverpool UK

Myositis UK Southampton UK

Northern Care Alliance NHS Foundation Trust Department of Rheumatology Salford Royal Hospital Salford UK

Northern Care Alliance NHS Foundation Trust Manchester Centre for Clinical Neuroscience Salford Royal Hospital Salford UK

The University of Manchester National Institute for Health Research Manchester Biomedical Research Centre Manchester UK

Zitelab Aps Copenhagen Denmark

Rheumatology (Oxford). 2024 Aug 1;63(8):2316. doi: 10.1093/rheumatology/keae186. PubMed

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