Different phenotypes in dermatomyositis associated with anti-MDA5 antibody
Yves Allenbach, Y. Uzunhan, S. Toquet, Gaëlle Leroux, Laure Gallay, Alicia Marquet, Alain Meyer, Constance Guillaud, Nicolas Limal, Frédéric Gagnadoux, B. Hervier, Raphaël Borie, C. Deligny, Benjamin Terrier, A. Bérezné, Sylvain Audia, Nicolas Champtiaux, H. Devilliers, Nicol C. Voermans, Elizabeth Diot, Amélie Servettaz, Thierry Marhadour, Vincent Castelain, S. Humbert, Claire Blanchard‐Delaunay, N. Tieulié, Pierre Charles, M. Gérin, A. Mékinian, Pascaline Priou, Jean Claude Meurice, Abdellatif Tazi, Vincent Cottin, Makoto Miyara, Benjamin Grange, Dominique Israël-Biet, S. Phin-Huynh, Camille Bron, Luc de Saint Martin, Nicole Fabien, K. Mariampillai, Hilario Nunès, Olivier Benvéniste, the French Myositis Network
Abstract
<h3>Objectives</h3> The predominance of extramuscular manifestations (e.g., skin rash, arthralgia, interstitial lung disease [ILD]) as well as the low frequency of muscle signs in anti–melanoma differentiation-associated gene 5 antibody–positive (anti-MDA5+) dermatomyositis caused us to question the term myositis-specific antibody for the anti-MDA5 antibody, as well as the homogeneity of the disease. <h3>Methods</h3> To characterize the anti-MDA5+ phenotype, an unsupervised analysis was performed on anti-MDA5+ patients (n = 83/121) and compared to a group of patients with myositis without anti-MDA5 antibody (anti-MDA5−; n = 190/201) based on selected variables, collected retrospectively, without any missing data. <h3>Results</h3> Within anti-MDA5+ patients (n = 83), 3 subgroups were identified. One group (18.1%) corresponded to patients with a rapidly progressive ILD (93.3%; <i>p</i> < 0.0001 across all) and a very high mortality rate. The second subgroup (55.4%) corresponded to patients with pure dermato-rheumatologic symptoms (arthralgia; 82.6%; <i>p</i> < 0.01) and a good prognosis. The third corresponded to patients, mainly male (72.7%; <i>p</i> < 0.0001), with severe skin vasculopathy, frequent signs of myositis (proximal weakness: 68.2%; <i>p</i> < 0.0001), and an intermediate prognosis. Raynaud phenomenon, arthralgia/arthritis, and sex permit the cluster appurtenance (83.3% correct estimation). Nevertheless, an unsupervised analysis confirmed that anti-MDA5 antibody delineates an independent group of patients (e.g., dermatomyositis skin rash, skin ulcers, calcinosis, mechanic9s hands, ILD, arthralgia/arthritis, and high mortality rate) distinct from anti-MDA5− patients with myositis. <h3>Conclusion</h3> Anti-MDA5+ patients have a systemic syndrome distinct from other patients with myositis. Three subgroups with different prognosis exist.