Moving from Dermatomyositis Associated with Anti-Melanoma Differentiation-Associated Gene 5 Antibody to Anti-Melanoma Differentiation-Associated Gene 5 Syndrome

Yves Allenbach¹, Yurdagul Uzunhan², Ségolène Toquet³, Gaëlle Leroux⁴, Laure Gallay⁵, Aude Rigolet⁶, Baptiste Hervier⁶, Nicolas Champtiaux⁶, Mathieu Vautier⁶, Perrine Guillaume⁶, Nicolas Limal⁷, Alain Meyer⁸, Christophe Deligny⁹, Bernard Bonnotte¹⁰, Hervé Devilliers¹¹, Sylvain Audia¹², Maxime Samson¹³, Amélie Servettaz¹⁴, Nathalie Costedoat¹⁵, David Saadoun¹⁶, elisabeth diot¹⁷, Alice Berezne¹⁸, Arsène Mékinian¹⁹, Kuberaka Mariampillai²⁰, Hilario Nunes² and Olivier Benveniste⁶, ¹Internal Medicine and Clinical Immunology, Sorbonne University - Assistance Public - Hopitaux de Paris, Pitié-Salpêtrière University Hospital, Paris, France, ²Pulmonary diseases department, Avicenne Hospital (AP-HP), Bobigny, France, ³Sorbonne Universités, UPMC Univ Paris 06, INSERM UMRS_974, CNRS FRE 3617, Center of Research in Myology., Paris, France, ⁴Internal Medicine, Pitié-Salpêtrière University Hospital, Paris, France, ⁵Internal Medicine, Université de Lyon - CHU Lyon, Lyon, France, ⁶Department of Internal Medicine and Clinical Immunology and Inflammation-Immunopathology-Biotherapy Department (I2B), Pitié-Salpêtrière University Hospital, Assistance Publique-Hôpitaux de Paris, East Paris Neuromuscular Diseases Reference Center, Paris, France, ⁷Internal Medicine, APHP - Henri Mondor Hospital, Paris, France, ⁸15Département de Rhumatologie, Centre de Référence des Maladies Auto-immunes Rares, Hôpitaux Universitaires de Strasbourg, Strasbourg, France, ⁹Zobda Quitman Hospital, Rheumatology and Internal Medicine, Fort de France, Martinique, ¹⁰Dijon, Dijon, France, ¹¹Service de Médecine Interne et Maladies Systémiques, CHU de Dijon, Dijon, France, ¹²Department of Internal Medicine and Clinical Immunology, Hôpital François Mitterrand, CHU de Dijon; INSERM, UMR1098, University of Bourgogne Franche-Comté, FHU INCREASE, Dijon, France, ¹³Dijon University Hospital, Dijon, France, ¹⁴Internal Medicine, CHU - Reims University, Reims, France, ¹⁵Internal Medicine, Paris Descartes Université - APHP, paris, France, ¹⁶Sorbonne Universités, UPMC Univ Paris 06, UMR 7211, and Inflammation-Immunopathology-Biotherapy Department (DHU i2B), F-75005, Paris, France; INSERM, UMR_S 959, F-75013, Paris, France; CNRS, FRE3632, F-75005, Paris, France; AP-HP, Groupe Hospitalier, Paris, France, ¹⁷Internal Medicine, Université Tours - CHU, Tours, France, ¹⁸Internal Medicine, CH Annecy, Annecy, France, ¹⁹Service de médecine interne. Hôpital Saint-Antoine., Paris, France, ²⁰Département de Médecine Interne et Immunologie Clinique, Centre de Référence des Maladies Neuro-Musculaires Paris Est, Assistance Publique – Hôpitaux de Paris (AP-HP), Hôpital Universitaire Pitié-Salpêtrière, Paris, France

Meeting: 2018 ACR/ARHP Annual Meeting

Keywords: autoantibodies, dermatomyositis, interstitial lung disease, myopathy and myositis

Session Information

Date: Monday, October 22, 2018

Title: Muscle Biology, Myositis and Myopathies Poster II: Basic and Translational Science

Session Type: ACR Poster Session B

Session Time: 9:00AM-11:00AM

Background/Purpose: Dermatomyositis (DM) is a heterogenous group of diseases ranging from skin limited disorders to non-specific auto-immune diseases with patients suffering from additional extra-cutaneous manifestations. The myositis specific antibody (Ab) anti-melanoma differentiation-associated gene 5 antibody (MDA5+) delineates a group of patients with a DM skin rash, arthralgia and an interstitial lung disease (ILD), sometimes severe because rapidly progressive (RP-ILD), whereas clinical signs of myositis are absent.

The variety and the predominance of the extra-muscle manifestations question the term of ‘myositis specific Ab’ and the homogeneity of the related disease. Precising the clinical phenotype, as well as the prognosis of MDA5+ patients is necessary to improve the management of this severe disease.

Methods: MDA5+ patients were defined as patients with a DM skin rash and/or arthralgia and/or ILD without other aetiology in presence of anti-MDA5 Ab. Clinical, laboratory and imaging data were collected (multicentric study). As control, a cohort of anti-MDA5- myositis patients was used. Unsupervised analyses were performed either on both groups (anti-MDA5+ and control) or on anti-MDA5+ patients only.

Results: Anti-MDA5+ patients’ (n=121) characteristics were in line with the previous reports. Patients were mainly female, 49 years old [34-58], with a DM skin rash (87.5%) and signs of vasculopathy (Raynaud phenomenon, skin ulcers, calcinosis and/or digital necrosis), with ILD (77%; RP-ILD, 32.7%) and with arthralgia (69%). Death occurred in 25.4% of cases.

MDA5+ patients’ phenotype was clearly distinct from controls (n=323). Unsupervised analysis (without including data of the serological status) showed clearly two clusters. One was characterized by more frequent DM skin rash, skin ulcers, calcinosis, mechanics hands, ILD, arthralgia/arthritis and patients with a higher mortality rate. In this cluster 87% of patients were MDA5+.

Within MDA5+ group, analysis showed three clusters. As previously reported, one corresponds to patients with RP-ILD (ILD 100% and RP-ILD 95%; p<0.0001), but mechanics’ hands were frequent (65%; p<0.0001). Two new subgroups were identified. One is an ‘athro-cutaneo-form’ (arthralgia/arthritis, 85%; p<0.0001; RP-ILD, 9.5%; p<0.0001) and another is a ‘vasculo-cutaneo-muscular-form’ corresponding to male patients (71.4%; p<0.0001) with a severe skin vasculopathy (frequent Raynaud phenomenon, skin ulcers, digital necrosis and calcinosis) and with frequent sign of myositis (weakness 71.3%; p<0.0001).

The outcome depends on the form of the disease. A very high mortality rate is observed in the ‘RP-ILD form’ (65%), in contrast to the good outcome in the ‘athrocutaneo-form’ (0% of mortality) and intermediate one in the ‘vasculo-dermatomyo-form’ (19% of mortality).

Conclusion: MDA5+ patients are a distinct group from myositis patients, characterised by a systemic syndrome composed by three different entities with different outcomes.

Disclosure: Y. Allenbach, None; Y. Uzunhan, None; S. Toquet, None; G. Leroux, None; L. Gallay, None; A. Rigolet, None; B. Hervier, None; N. Champtiaux, None; M. Vautier, None; P. Guillaume, None; N. Limal, None; A. Meyer, None; C. Deligny, None; B. Bonnotte, None; H. Devilliers, None; S. Audia, None; M. Samson, None; A. Servettaz, None; N. Costedoat, None; D. Saadoun, Medimmune, Abbvie, Bristol Meyer Squibb, Roche, Servier, Gilead, AstraZeneca and Glaxo Smith Kline, 5; E. diot, None; A. Berezne, None; A. Mékinian, None; K. Mariampillai, None; H. Nunes, None; O. Benveniste, None.

To cite this abstract in AMA style:

Allenbach Y, Uzunhan Y, Toquet S, Leroux G, Gallay L, Rigolet A, Hervier B, Champtiaux N, Vautier M, Guillaume P, Limal N, Meyer A, Deligny C, Bonnotte B, Devilliers H, Audia S, Samson M, Servettaz A, Costedoat N, Saadoun D, diot E, Berezne A, Mékinian A, Mariampillai K, Nunes H, Benveniste O. Moving from Dermatomyositis Associated with Anti-Melanoma Differentiation-Associated Gene 5 Antibody to Anti-Melanoma Differentiation-Associated Gene 5 Syndrome [abstract]. Arthritis Rheumatol. 2018; 70 (suppl 9). https://acrabstracts.org/abstract/moving-from-dermatomyositis-associated-with-anti-melanoma-differentiation-associated-gene-5-antibody-to-anti-melanoma-differentiation-associated-gene-5-syndrome/. Accessed .

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