2016 Classification Criteria for Macrophage Activation Syndrome Complicating Systemic Juvenile Idiopathic Arthritis: A European League Against Rheumatism/American College of Rheumatology/Paediatric Rheumatology International Trials Organisation Collaborative Initiative

Ravelli, Angelo; Minoia, Francesca; Davì, Sergio; Horne, Annacarin; Bovis, Francesca; Pistorio, Angela; Aricò, Maurizio; Avcin, Tadej; Behrens, Edward M.; De Benedetti, Fabrizio; Filipovic, Lisa; Grom, Alexei A.; Henter, Jan Inge; Ilowite, Norman T.; Jordan, Michael B.; Khubchandani, Raju; Kitoh, Toshiyuki; Lehmberg, Kai; Lovell, Daniel J.; Miettunen, Paivi; Nichols, Kim E.; Ozen, Seza; Pachlopnik Schmid, Jana; Ramanan, Athimalaipet V.; Russo, Ricardo; Schneider, Rayfel; Sterba, Gary; Uziel, Yosef; Wallace, Carol; Wouters, Carine; Wulffraat, Nico; Demirkaya, Erkan; Brunner, Hermine I.; Martini, Alberto; Ruperto, Nicolino; Cron; Randy Q. APPENDIX A. PARTICIPATING PHYSICIANS The following physicians contributed patient data for use in the study: Mario Abinun; MD; Amita Aggarwal, MD; Jonathan Akikusa, MD; Sulaiman M. Al Mayouf, MD; Maria Alessio, MD; Jordi Anton, MD; Maria Teresa Apaz, MD; Itziar Astigarraga, MD; Nuray A. Ayaz, MD; Patrizia Barone, MD; Blanca Bica, MD; Isabel Bolt, MD; Luciana Breda, MD; Vyacheslav Chasnyk, MD; Rolando Cimaz, MD; Fabrizia Corona, MD; Ruben Cuttica, MD; Gianfranco D’Angelo, MD; Zane Davidsone, MD; Carmen De Cunto, MD; Jaime De Inocencio, MD; Eli Eisenstein, MD; Sandra Enciso, MD; Graciela Espada, MD; Michel Fischbach, MD; Michael Frosch, MD; GALLIZZI, Romina; Maria Luz Gamir, MD; Yi Jin Gao, MD; Thomas Griffin, MD; Soad Hashad, MD; Teresa Hennon, MD; Gerd Horneff, MD; Zeng Huasong, MD; Adam Huber, MD; Norman Ilowite, MD; Antonella Insalaco, MD; Maka Ioseliani, MD; Marijia Jelusic Drazic, MD; Michael Jeng, MD; Agneza Kapovic, MD; Ozgur Kasapcopur, MD; Toshiyuki Kitoh, MD; Isabelle Kone Paut, MD; Sheila Knupp Feitosa de Oliveira, MD; Bianca Lattanzi, MD; Loredana Lepore, MD; Caifeng Li, MD; Jeffrey M. Lipton, MD; Silvia Magni Manzoni, MD; Despoina Maritsi, MD; Deborah McCurdy, MD; Rosa Merino, MD; Velma Mulaosmanovic, MD; Susan Nielsen, MD; Priyankar Pal, MD; Sampath Prahalad, MD; Donato Rigante, MD; Ingrida Rumba Rozenfelde, MD; Claudia Saad Magalhaes, MD; Helga Sanner, MD; Sujata Sawhney, MD; Wafaa M. Sewairi, MD; Bita Shakoory, MD; Susan Shenoi, MD; Artur Silva Clovis, MD; Valda Stanevicha, MD; Kimo C. Stine, MD; Gordana Susic, MD; Flavio Sztajnbok, MD; Syuji Takei, MD; Hasan Tezer, MD; Ralf Trauzeddel, MD; Elena Tsitsami, MD; Erbil Unsal, MD; Olga Vougiouka, MD; Lehn K. Weaver, MD; Jennifer Weiss, MD; Sheila Weitzman, MD; Mabruka Zletni, M.D.

doi:10.1002/art.39332

Objective To develop criteria for the classification of macrophage activation syndrome (MAS) in patients with systemic juvenile idiopathic arthritis (JIA). Methods A multistep process, based on a combination of expert consensus and analysis of real patient data, was conducted. A panel of 28 experts was first asked to classify 428 patient profiles as having or not having MAS, based on clinical and laboratory features at the time of disease onset. The 428 profiles comprised 161 patients with systemic JIA-associated MAS and 267 patients with a condition that could potentially be confused with MAS (active systemic JIA without evidence of MAS, or systemic infection). Next, the ability of candidate criteria to classify individual patients as having MAS or not having MAS was assessed by evaluating the agreement between the classification yielded using the criteria and the consensus classification of the experts. The final criteria were selected in a consensus conference. Results Experts achieved consensus on the classification of 391 of the 428 patient profiles (91.4%). A total of 982 candidate criteria were tested statistically. The 37 best-performing criteria and 8 criteria obtained from the literature were evaluated at the consensus conference. During the conference, 82% consensus among experts was reached on the final MAS classification criteria. In validation analyses, these criteria had a sensitivity of 0.73 and a specificity of 0.99. Agreement between the classification (MAS or not MAS) obtained using the criteria and the original diagnosis made by the treating physician was high (kappa=0.76). Conclusion We have developed a set of classification criteria for MAS complicating systemic JIA and provided preliminary evidence of its validity. Use of these criteria will potentially improve understanding of MAS in systemic JIA and enhance efforts to discover effective therapies, by ensuring appropriate patient enrollment in studies