Comparison of clinical features between patients with anti-synthetase syndrome and dermatomyositis: Results from the MYONET registry

Ryan Malcolm Hum; James B Lilleker; Janine A Lamb; Alexander G S Oldroyd; Guochun Wang; Lucy R Wedderburn; Louise P Diederichsen; Jens Schmidt; Maria Giovanna Danieli; Paula Oakley; Zoltan Griger; Thuy Nguyen Thi Phuong; Chanakya Kodishala; Monica Vazquez-Del Mercado; Helena Andersson; Boel De Paepe; Jan L De Bleecker; Britta Maurer; Liza McCann; Nicolo Pipitone; Neil McHugh; Robert Paul New; William E Ollier; Niels Steen Krogh; Jiri Vencovsky; Ingrid E Lundberg; MYONET registry; Hector Chinoy

doi:10.1093/rheumatology/kead481

Comparison of clinical features between patients with anti-synthetase syndrome and dermatomyositis: Results from the MYONET registry

Rheumatology (Oxford). 2023 Sep 12:kead481. doi: 10.1093/rheumatology/kead481. Online ahead of print.

Authors

Ryan Malcolm Hum^{1

2}, James B Lilleker^{1

3}, Janine A Lamb⁴, Alexander G S Oldroyd^{1

2}, Guochun Wang⁵, Lucy R Wedderburn⁶, Louise P Diederichsen⁷, Jens Schmidt⁸, Maria Giovanna Danieli⁹, Paula Oakley¹⁰, Zoltan Griger¹¹, Thuy Nguyen Thi Phuong¹², Chanakya Kodishala^{13

14}, Monica Vazquez-Del Mercado¹⁵, Helena Andersson¹⁶, Boel De Paepe¹⁷, Jan L De Bleecker¹⁷, Britta Maurer¹⁸, Liza McCann¹⁹, Nicolo Pipitone²⁰, Neil McHugh^{21

22}, Robert Paul New²³, William E Ollier²⁴, Niels Steen Krogh²⁵, Jiri Vencovsky²⁶, Ingrid E Lundberg^{27

28}; MYONET registry; Hector Chinoy^{1

29}

Collaborators

MYONET registry:
Sophie D'Hose, Xin Lu, Xiaolan Tian, Heřman Mann, Olga Kryštůfková, Lenka Pleštilová, Martin Klein, Tereza Barochová, Kateřina Kubínová, Chiara Gelardi, Alberto Paladini, Mario Andrea Piga, Luis J Jara, Miguel A Saavedra, Claudia V Cruz-Reyes, Olga Vera-Lastra, Lilia Andrade-Ortega, Gabriel Medrano-Ramírez, Minoru Satoh, Mario Salazar-Páramo, Efrain Chavarría-Ávila, Andrea Aguilar-Vazquez, Jesus-Aureliano Robles-de Anda, Marcelo H Petri, Øyvind Molberg, Maryam Dastmalchi, Antonella Notarnicola, Karina Gheorghe, Johan Rönnelid, Maria Liden, Balsam Hanna, Awat Jalal, Helena Hellström, Jehns Christian Martineus, Nguyen Thi Ngoc Lan, Leonid Padyukov, Paul New, Hazel Platt, Simon Rothwell, Yasmeen Ahmed, Raymond Armstrong, Robert Bernstein, Carol Black, Simon Bowman, Ian Bruce, Robin Butler, John Carty, Chandra Chattopadhyay, Easwaradhas Chelliah, Fiona Clarke, Peter Dawes, Christopher Denton, Joseph Devlin, Christopher Edwards, Paul Emery, John Fordham, Alexander Fraser, Hill Gaston, Patrick Gordon, Bridget Griffiths, Harsha Gunawardena, Frances Hall, Michael Hanna, Beverley Harrison, Elaine Hay, David Hilton-Jones, Lesley Horden, John Isaacs, David Isenberg, Adrian Jones, Sanjeet Kamath, Thomas Kennedy, George Kitas, Peter Klimiuk, Sally Knights, John Lambert, Peter Lanyon, Ramasharan Laxminarayan, Bryan Lecky, Raashid Luqmani, Pedro Machado, Jeffrey Marks, Michael Martin, Dennis McGonagle, Neil McHugh, Francis McKenna, John McLaren, Michael McMahon, Euan McRorie, Peter Merry, Sarah Miles, James Miller, Anne Nicholls, Jennifer Nixon, Voon Ong, Katherine Over, John Packham, Nicolo Pipitone, Michael Plant, Gillian Pountain, Thomas Pullar, Mark Roberts, Paul Sanders, David Scott, David Scott, Michael Shadforth, Thomas Sheeran, Arul Srinivasan, David Swinson, Lee-Suan Teh, Michael Webley, Brian Williams, Jonathan Winer

Affiliations

¹ Centre for Musculoskeletal Research, Division of Musculoskeletal & Dermatological Sciences, The University of Manchester Faculty of Biology Medicine and Health, Manchester, Manchester, UK.
² The University of Manchester, National Institute for Health Research Manchester Biomedical Research Centre, Manchester, Manchester, UK.
³ Northern Care Alliance NHS Foundation Trust, Manchester Centre for Clinical Neuroscience, Salford Royal Hospital, Salford, Manchester, UK.
⁴ The University of Manchester Faculty of Biology Medicine and Health, Epidemiology and Public Health Group, Manchester, Manchester, UK.
⁵ Department of Rheumatology, China-Japan Friendship Hospital, Beijing, Beijing, CN.
⁶ Great Ormond Street Hospital for Children NHS Foundation Trust, Infection, Immunity and Inflammation, London, London, UK.
⁷ Center for Rheumatology and Spine Diseases, Copenhagen University Hospital, Kobenhavn, DK.
⁸ Department of Neurology, University Medical Center Göttingen, Gottingen, Niedersachsen, DE.
⁹ Clinica Medica, Dipartimento di Scienze Cliniche e Molecolari, Universita Politecnica delle Marche, Ancona, IT.
¹⁰ Myositis UK, Myositis UK, Southampton, UK.
¹¹ Department of Immunology, University of Debrecen, Debrecen, Hajdú-Bihar, HU.
¹² Hanoi Medical University, Internal Medicine Department, Hanoi, Dong Da, VN.
¹³ Clinical Immunology and Rheumatology, St John's National Academy of Health Sciences, Bangalore, Karnataka, IN.
¹⁴ Department of Rheumatology, Mayo Clinic, Rochester, MN, USA.
¹⁵ Division de Medicina Interna, Servicio de Reumatologia, Hospital Civil Dr. Juan I. Menchaca, Universidad de Guadalajara, Guadalajara, Jalisco, MX.
¹⁶ Department of Rheumatology, Oslo University Hospital, Oslo, NO.
¹⁷ Department of Neurology, Universitair Ziekenhuis Gent, Ghent, BE.
¹⁸ Department of Rheumatology and Immunology, Inselspital University Hospital Bern, Bern, Bern, CH.
¹⁹ Department of Rheumatology, Alder Hey Children's NHS Foundation Trust, Liverpool, Merseyside, UK.
²⁰ Department of Rheumatology, Arcispedale Santa Maria Nuova di Reggio Emilia, Reggio Emilia, IT, Emilia-Romagna.
²¹ Department of Rheumatology, Royal National Hospital for Rheumatic Diseases, Bath, UK.
²² Department of Pharmacy and Pharmacology, University of Bath, Bath, UK.
²³ MRC/ARUK Institute of Ageing and Chronic Disease, University of Liverpool, Liverpool, UK.
²⁴ Faculty of Science and Engineering, Manchester Metropolitan University, Manchester, Manchester, UK.
²⁵ Zitelab Aps, Zitelab Aps, Copenhagen, DK.
²⁶ Institute of Rheumatology and Department of Rheumatology, Charles University, Praha, Praha, CZ.
²⁷ Division of Rheumatology, Department of Medicine, Karolinska Institutet, Stockholm, SE.
²⁸ Department of Gastroenterology, Dermatology, and Rheumatology, Karolinska University Hospital, Stockholm, SE.
²⁹ Northern Care Alliance NHS Foundation Trust, Department of Rheumatology, Salford Royal Hospital, Salford, Manchester, UK.

PMID: 37698987
DOI: 10.1093/rheumatology/kead481

Abstract

Objectives: To compare clinical characteristics, including the frequency of cutaneous, extramuscular manifestations, and malignancy, between adults with anti-synthetase syndrome (ASyS) and dermatomyositis (DM).

Methods: Using data regarding adults from the MYONET registry, a cohort of DM patients with anti-Mi2/-TIF1ɣ/-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 1,054 patients were included (DM, n = 405; ASyS, n = 649). In 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.

Keywords: Antisynthetase syndrome; MYONET; Raynaud’s phenomenon; cutaneous; dermatomyositis; epidemiology; extramuscular; malignancy; rashes; skin.