Pos1221 clinical features of patients with anti-synthetase syndrome and dermatomyositis-associated skin manifestations: results from the myonet registry

Background Up to 28% of patients with anti-synthetase syndrome (AsyS) have dermatomyositis (DM)-type rashes. However, it is not clear whether ASyS patients with DM-type rashes should be treated similarly to patients with DM or classified as DM in a clinical trial setting. Furthermore, it is not known if presence of DM-type rashes confers an increased risk of DM-specific extramuscular manifestations, such as malignancy. Objectives To compare clinical characteristics, including the frequency of cutaneous, extramuscular features, and malignancy, between adults with ASyS and DM. Methods Using data from the MYONET registry, an adult cohort of DM patients with anti-Mi2/TIF1ɣ/NXP2/SAE/MDA5 autoantibodies, and an ASyS cohort of patients with anti-tRNA synthetase autoantibodies (anti-Jo1/PL7/PL12/OJ/EJ/KS), were identified. Patients with DM sine dermatitis and with dual autoantibody specificities were excluded. Sub-cohorts of ASyS patients with or without skin involvement were defined based on presence of DM-type rashes (heliotrope rash, Gottron’s papules, violaceous rash, shawl sign, V sign, erythroderma, and/or periorbital rash). Results In total, 737 patients were included (DM, n=251; ASyS, n=486). Within the ASyS cohort, 34% (n=163) had DM-type skin involvement (ASyS-skin). A higher frequency of Raynaud’s phenomenon differentiated ASyS-skin from DM (n=72, 44% vs n=34, 14%, p<0.01), whereas higher frequency of any of four DM-type rashes: heliotrope rash (n=155, 62% vs n=73, 45%), V sign (n=69, 28% vs n=22, 14%), periorbital rash (n=53, 21% vs n=27, 17%), and shawl sign (n=89, 36% vs n=15, 9%) differentiated DM from ASyS-skin (all p<0.01). Cancer-associated myositis (CAM) was more frequent in DM (17%) compared to ASyS (3%) and ASyS-skin (3%) cohorts (both p<0.01) (Table 1). Conclusion DM-type rashes are frequent in patients defined as having ASyS; however, certain clinical features differentiate these patients from classical DM. Skin involvement in ASyS does not necessitate increased malignancy surveillance or investigation. These findings will help to inform future ASyS-based classification criteria. References [1]Hervier, Baptiste et al. “Hierarchical cluster and survival analyses of antisynthetase syndrome: phenotype and outcome are correlated with anti-tRNA synthetase antibody specificity.” Autoimmunity reviews vol. 12,2 (2012): 210-7. [2]Lilleker, James B et al. “The EuroMyositis registry: an international collaborative tool to facilitate myositis research.” Annals of the rheumatic diseases vol. 77,1 (2018): 30-39. Table 1 Clinical manifestations of disease DM (n=251) ASyS (n=486) ASyS-skin (n=163) ASyS-without-skin (n=323) DM vs ASyS Adjusted p-value DM vs ASyS-skin Adjusted p-value ASyS-skin vs ASyS-without-skin Adjusted p-value DM-type rashes n (% )Heliotrope Rash 155 (62) 73 (15) 73 (45) 0 (0) <0.01 <0.01 <0.01 Gottron’s Papules or Sign 145 (58) 110 (23) 110 (68) 0 (0) <0.01 0.66 <0.01 Violaceous Rash 94 (38) 51 (11) 51 (31) 0 (0) <0.01 0.23 <0.01 Erythroderma 22 (9) 9 (2) 9 (6) 0 (0) <0.01 0.11 <0.01 Periorbital Rash 53 (21) 27 (6) 27 (17) 0 (0) <0.01 0.04 <0.01 V Sign Rash 69 (28) 22 (5) 22 (14) 0 (0) <0.01 <0.01 <0.01 Shawl Sign 89 (36) 15 (3) 15 (9) 0 (0) <0.01 <0.01 <0.01 Extramuscular manifestations n (% )Periungual Erythema 72 (29) 75 (15) 43 (26) 32 (10) <0.01 0.045 <0.01 Calcinosis 7 (3) 9 (2) 6 (4) 3 (1) 0.62 0.81 0.15 Ulceration 11 (4) 5 (1) 3 (2) 2 (1) 0.04 0.65 0.72 Vasculitis 4 (2) 1 (0.2) 0 (0) 1 (0.3) 0.045 0.61 1 Mechanic’s Hands 11 (4) 142 (29) 62 (38) 80 (25) <0.01 <0.01 <0.01 Raynaud’s Phenomenon 34 (14) 178 (37) 72 (44) 106 (33) <0.01 <0.01 <0.01 Arthritis 29 (12) 221 (46) 77 (47) 144 (45) <0.01 <0.01 1 Dysphagia 72 (29) 88 (18) 35 (22) 53 (16) <0.01 0.25 0.22 Alopecia 24 (10) 26 (5) 12 (7) 14 (4) 0.17 1 0.21 Interstitial Lung Disease 28 (11) 320 (66) 100 (61) 220 (68) <0.01 <0.01 0.11 Cardiac Involvement 4 (2) 30 (6) 14 (9) 16 (5) 0.03 <0.01 0.20 CAM n (% ) 42 (17) 16 (3) 5 (3) 11 (3) <0.01 <0.01 0.90 Acknowledgements This publication was supported by researchers at the National Institute for Health Research (NIHR) Manchester Biomedical Research Centre (BRC). The views expressed are those of the authors and not necessarily those of the United Kingdom (UK) National Health Service (NHS), the NIHR or the UK Department of Health. Disclosure of Interests Ryan Malcolm Hum: None declared, James B. Lilleker: None declared, Janine Lamb: None declared, Alexander Oldroyd: None declared, William Ollier: None declared, Guochun Wang: None declared, Chanakya Kodishala: None declared, Lucy Wedderburn: None declared, Louise Diederichsen Consultant of: Data safety monitoring board for Corbus Pharmaceuticals, Grant/research support from: Boehringer Ingelheim, Jens Schmidt: None declared, Maria Giovanna Danieli: None declared, Katalin Dankó: None declared, THI PHUONG THUY NGUYEN: None declared, Mónica Vázquez-Del Mercado Espinosa: None declared, Helena Andersson: None declared, Boel De Paepe: None declared, Jan De Bleecker: None declared, Britta Maurer Speakers bureau: Boehringer-Ingelheim, GSK, Novartis, Consultant of: Novartis, Boehringer Ingelheim, Janssen-Cilag, GSK, Grant/research support from: AbbVie, Protagen, Novartis, Medtalk, Pfizer, Roche, Actelion, Mepha, MSD, Liza McCann: None declared, Nicolo Pipitone: None declared, Robert Paul New: None declared, Niels Steen Krogh: None declared, Neil McHugh: None declared, Jiří Vencovský: None declared, Ingrid E. Lundberg Shareholder of: Roche, Novartis, Consultant of: Corbus Pharmaceuticals Inc, Advisory board for Corbus Pharmaceutical, EMD Serono, Argenx, Octapharma, Kezaar, Orphazyme, Pfizer, and Janssen., Grant/research support from: Astra Zeneca, Hector Chinoy: None declared.