Yves Allenbach1, Yurdagul Uzunhan2, Ségolène Toquet2, Gaëlle Leroux2, Laure Gallay2, Alicia Marquet2, Alain Meyer2, Constance Guillaud2, Nicolas Limal2, Frédéric Gagnadoux2, Baptiste Hervier2, Raphaël Borie2, Christophe Deligny2, Benjamin Terrier2, Alice Berezne2, Sylvain Audia2, Nicolas Champtiaux2, Hervé Devilliers2, Nicol Voermans2, Elizabeth Diot2, Amélie Servettaz2, Thierry Marhadour2, Vincent Castelain2, Sébastien Humbert2, Claire Blanchard-Delaunay2, Nathalie Tieulie2, Pierre Charles2, Magdalena Gerin2, Arsène Mekinian2, Pascaline Priou2, Jean Claude Meurice2, Abdellatif Tazi2, Vincent Cottin2, Makoto Miyara2, Benjamin Grange2, Dominique Israël-Biet2, Sophie Phin-Huynh2, Camille Bron2, Luc De Saint Martin2, Nicole Fabien2, Kubéraka Mariampillai2, Hilario Nunes2, Olivier Benveniste2. 1. From the Departments of Clinical Immunology and Internal Medicine (Y.A., S.T., G.L., B.H., N.C., K.M., O.B.), Immunobiology (M.M.), and Biostatistics, Public Health, and Medical Information (B.G.), Pitié-Salpêtrière Hospital, APHP, Sorbonne Universities; Myology Research Centre (Y.A., O.B.), INSERM, UMRS 974, Paris; Department of Pneumology (Y.U., H.N.), APHP, Avicenne Hospital, INSERM U1272, Université Sorbonne Paris Nord, Bobigny; Department of Internal Medicine (L.G., A. Marquet), Lyon Sud Hospital, Lyon Sud University, Paris; Reference Centre for Rare Autoimmune Diseases (A. Meyer) and Medical Intensive Care Unit, Hautepierre Hospital (V. Castelain), Hôpitaux Universitaires de Strasbourg, Strasbourg University; Division of Pneumology (R.B.), Bichat Hospital, AP-HP, Paris-Diderot University, Paris; Department of Pneumology (F.G., P.P.), Centre Hospitalier Universitaire, Angers University; Department of Internal Medicine Infectieuses (C.D.), CHU de Martinique, Fort de France; Departments of Internal Medicine and Clinical Immunology (S.A.) and Internal Medicine and Systemic Diseases (H.D.), François-Mitterrand University Hospital, University of Bourgogne-Franche-Comté, Dijon; Internal Medicine Department (B.T., A.B.), Cochin Hospital, AP-HP, René Descartes University, Paris; Department of Internal Medicine (C.G., N.L.), Henri Mondor Hospital, Paris Est Créteil University, Créteil, France; Department of Neurology (N.V.), Donders Institute for Brain, Cognition, and Behaviour, Radboud University Medical Centre, Nijmegen, the Netherlands; Department of Internal Medicine (E.D.), Hôpital Bretonneau Tours, Tours University; Internal Medicine Department (A.S.), Hôpital Robert-Debré, Reims University; Departments of Rheumatology (T.M.) and Internal Medicine (L.D.S.M.), Bretagne Occidentale University, Centre Hospitalo-Universitaire de Brest; Department of Internal Medicine (S.H.), CHU de Besançon; Department of Internal Medicine (C.B.-D.), Centre Hospitalier Général de Niort; Department of Internal Medicine (N.T.), Nice University, CHU Nice; Department of Internal Medicine (P.C.), Institut Mutualiste Montsouris, Paris; Department of Internal Medicine (M.G.), Jean Verdier Hospital, Paris Seine-Saint-Denis University, Bondy; Department of Internal Medicine (A. Mekinian), Saint Antoine Hospital, APHP, Sorbonne Universities, Paris; Department of Pneumology CHU (J.C.M.), Poitiers University; Department of Pneumology (A.T.), Hôpital Saint-Louis, APHP, Sorbonne Paris Cité, University Paris-Diderot, Paris; Department of Respiratory Medicine (V. Cottin), National Reference Center for Rare Pulmonary Diseases, Hospices Civils de Lyon, Claude Bernard University Lyon 1, Lyon University; Department of Pneumology (D.I.-B.), European George Pompidou Hospital, APHP, Paris V University; Department of Pneumology (S.P.-H.), Sainte-Camille Hospital, Bry-sur-Marne; Department of Pneumology (C.B.), Foch Hospital, Saint Quentin en Yveline University, Suresnes; and Department of Immunology (N.F.), Lyon-Sud Hospital, Hospices Civils-de-Lyon, Pierre-Bénite, France. yves.allenbach@aphp.fr. 2. From the Departments of Clinical Immunology and Internal Medicine (Y.A., S.T., G.L., B.H., N.C., K.M., O.B.), Immunobiology (M.M.), and Biostatistics, Public Health, and Medical Information (B.G.), Pitié-Salpêtrière Hospital, APHP, Sorbonne Universities; Myology Research Centre (Y.A., O.B.), INSERM, UMRS 974, Paris; Department of Pneumology (Y.U., H.N.), APHP, Avicenne Hospital, INSERM U1272, Université Sorbonne Paris Nord, Bobigny; Department of Internal Medicine (L.G., A. Marquet), Lyon Sud Hospital, Lyon Sud University, Paris; Reference Centre for Rare Autoimmune Diseases (A. Meyer) and Medical Intensive Care Unit, Hautepierre Hospital (V. Castelain), Hôpitaux Universitaires de Strasbourg, Strasbourg University; Division of Pneumology (R.B.), Bichat Hospital, AP-HP, Paris-Diderot University, Paris; Department of Pneumology (F.G., P.P.), Centre Hospitalier Universitaire, Angers University; Department of Internal Medicine Infectieuses (C.D.), CHU de Martinique, Fort de France; Departments of Internal Medicine and Clinical Immunology (S.A.) and Internal Medicine and Systemic Diseases (H.D.), François-Mitterrand University Hospital, University of Bourgogne-Franche-Comté, Dijon; Internal Medicine Department (B.T., A.B.), Cochin Hospital, AP-HP, René Descartes University, Paris; Department of Internal Medicine (C.G., N.L.), Henri Mondor Hospital, Paris Est Créteil University, Créteil, France; Department of Neurology (N.V.), Donders Institute for Brain, Cognition, and Behaviour, Radboud University Medical Centre, Nijmegen, the Netherlands; Department of Internal Medicine (E.D.), Hôpital Bretonneau Tours, Tours University; Internal Medicine Department (A.S.), Hôpital Robert-Debré, Reims University; Departments of Rheumatology (T.M.) and Internal Medicine (L.D.S.M.), Bretagne Occidentale University, Centre Hospitalo-Universitaire de Brest; Department of Internal Medicine (S.H.), CHU de Besançon; Department of Internal Medicine (C.B.-D.), Centre Hospitalier Général de Niort; Department of Internal Medicine (N.T.), Nice University, CHU Nice; Department of Internal Medicine (P.C.), Institut Mutualiste Montsouris, Paris; Department of Internal Medicine (M.G.), Jean Verdier Hospital, Paris Seine-Saint-Denis University, Bondy; Department of Internal Medicine (A. Mekinian), Saint Antoine Hospital, APHP, Sorbonne Universities, Paris; Department of Pneumology CHU (J.C.M.), Poitiers University; Department of Pneumology (A.T.), Hôpital Saint-Louis, APHP, Sorbonne Paris Cité, University Paris-Diderot, Paris; Department of Respiratory Medicine (V. Cottin), National Reference Center for Rare Pulmonary Diseases, Hospices Civils de Lyon, Claude Bernard University Lyon 1, Lyon University; Department of Pneumology (D.I.-B.), European George Pompidou Hospital, APHP, Paris V University; Department of Pneumology (S.P.-H.), Sainte-Camille Hospital, Bry-sur-Marne; Department of Pneumology (C.B.), Foch Hospital, Saint Quentin en Yveline University, Suresnes; and Department of Immunology (N.F.), Lyon-Sud Hospital, Hospices Civils-de-Lyon, Pierre-Bénite, France.
Abstract
OBJECTIVES: 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. METHODS: 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. RESULTS: Within anti-MDA5+ patients (n = 83), 3 subgroups were identified. One group (18.1%) corresponded to patients with a rapidly progressive ILD (93.3%; p < 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%; p < 0.01) and a good prognosis. The third corresponded to patients, mainly male (72.7%; p < 0.0001), with severe skin vasculopathy, frequent signs of myositis (proximal weakness: 68.2%; p < 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, mechanic's hands, ILD, arthralgia/arthritis, and high mortality rate) distinct from anti-MDA5- patients with myositis. CONCLUSION: Anti-MDA5+ patients have a systemic syndrome distinct from other patients with myositis. Three subgroups with different prognosis exist.
OBJECTIVES: 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. METHODS: 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. RESULTS: Within anti-MDA5+ patients (n = 83), 3 subgroups were identified. One group (18.1%) corresponded to patients with a rapidly progressive ILD (93.3%; p < 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%; p < 0.01) and a good prognosis. The third corresponded to patients, mainly male (72.7%; p < 0.0001), with severe skin vasculopathy, frequent signs of myositis (proximal weakness: 68.2%; p < 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, mechanic's hands, ILD, arthralgia/arthritis, and high mortality rate) distinct from anti-MDA5- patients with myositis. CONCLUSION: Anti-MDA5+ patients have a systemic syndrome distinct from other patients with myositis. Three subgroups with different prognosis exist.
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