Clinical spectrum time course in non-Asian patients positive for anti-MDA5 antibodies.

Lorenzo Cavagna, Federica Meloni, Alain Meyer, Gianluca Sambataro, Mirko Belliato, Ellen De Langhe, Ilaria Cavazzana, Nicolò Pipitone, Konstantinos Triantafyllias, Marta Mosca, Simone Barsotti, Giuseppe Zampogna, Alessandro Biglia, Giacomo Emmi, Marianne De Visser, Anneke Van Der Kooi, Paola Parronchi, Sandrine Hirschi, Jose Antonio Pereira da Silva, Carlo Alberto Scirè, Federica Furini, Margherita Giannini, Olga Martinez Gonzalez, Laura Damian, Yves Piette, Vanessa Smith, Antonio Mera-Valera, Javier Bachiller-Corral, Ivan Cabezas Rodriguez, Anahy M Brandy-Garcia, François Maurier, Julie Perrin, Juan Gonzalez-Moreno, Ulrich Drott, Christiane Delbruck, Andreas Schwarting, Eugenio Arrigoni, Gian Domenico Sebastiani, Annamaria Iuliano, Carlotta Nannini, Luca Quartuccio, Ana B Rodriguez Cambron, Maria Á Blázquez Cañamero, Ignacio Villa Blanco, Giovanni Cagnotto, Alberto Pesci, Fabrizio Luppi, Giulia Dei, Fredeswinda Isabel Romero Bueno, Franco Franceschini, Ilaria Chiapparoli, Giovanni Zanframundo, Sara Lettieri, Ludovico De Stefano, Maurizio Cutolo, Alessandro Mathieu, Matteo Piga, Sergio Prieto-González, Maria Francisca Moraes-Fontes, Joao Eurico Fonseca, Vega Jovani, Valeria Riccieri, Alessandro Santaniello, Stephen Montfort, David Bilocca, Gian Luca Erre, Elena Bartoloni, Roberto Gerli, M Cristina Monti, Hanns M Lorenz, Domenico Sambataro, Silvia Bellando Randone, Udo Schneider, Claudia Valenzuela, Raquel Lopez-Mejias, Jose Cifrian, Mayra Mejia, Monserrat-Ixchel Gonzalez Perez, Sarah Wendel, Marco Fornaro, Giacomo De Luca, Giovanni Orsolini, Maurizio Rossini, Philippe Dieude, Johannes Knitza, Santos Castañeda, Reinhard E Voll, Jorge Rojas-Serrano, Adele Valentini, Carlo Vancheri, Marco Matucci-Cerinic, Eugen Feist, Veronica Codullo, Florenzo Iannone, Jorg H Distler, Carlomaurizio Montecucco, Miguel A Gonzalez-Gay

To define the clinical spectrum time-course and prognosis of non-Asian patients positive for anti-MDA5 antibodies. We conducted a multicentre, international, retrospective cohort study. 149 anti-MDA5 positive patients (median onset age 53 years, median disease duration 18 months), mainly females (100, 67%), were included. Dermatomyositis (64, 43%) and amyopathic dermatomyositis (47, 31%), were the main diagnosis; 15 patients (10%) were classified as interstitial pneumonia with autoimmune features (IPAF) and 7 (5%) as rheumatoid arthritis. The main clinical findings observed were myositis (84, 56%), interstitial lung disease (ILD) (108, 78%), skin lesions (111, 74%), and arthritis (76, 51%). The onset of these manifestations was not concomitant in 74 cases (50%). Of note, 32 (21.5%) patients were admitted to the intensive care unit for rapidly progressive-ILD, which occurred in median 2 months from lung involvement detection, in the majority of cases (28, 19%) despite previous immunosuppressive treatment. One-third of patients (47, 32% each) was ANA and anti-ENA antibodies negative and a similar percentage was anti-Ro52 kDa antibodies positive. Non-specific interstitial pneumonia (65, 60%), organising pneumonia (23, 21%), and usual interstitial pneumonia-like pattern (14, 13%) were the main ILD patterns observed. Twenty-six patients died (17%), 19 (13%) had a rapidly progressive-ILD. The clinical spectrum of the anti-MDA5 antibodies-related disease is heterogeneous. Rapidly-progressive ILD deeply impacts the prognosis also in non-Asian patients, occurring early during the disease course. Anti-MDA5 antibody positivity should be considered even when baseline autoimmune screening is negative, anti-Ro52 kDa antibodies are positive, and radiology findings show a NSIP pattern.