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2016 Classification Criteria for Macrophage Activation Syndrome Complicating Systemic Juvenile Idiopathic Arthritis
  1. Angelo Ravelli1,
  2. Francesca Minoia2,
  3. Sergio Davì2,
  4. AnnaCarin Horne3,
  5. Francesca Bovis2,
  6. Angela Pistorio2,
  7. Maurizio Aricò4,
  8. Tadej Avcin5,
  9. Edward M Behrens6,
  10. Fabrizio De Benedetti7,
  11. Lisa Filipovic8,
  12. Alexei A Grom8,
  13. Jan-Inge Henter3,
  14. Norman T Ilowite9,
  15. Michael B Jordan8,
  16. Raju Khubchandani10,
  17. Toshiyuki Kitoh11,
  18. Kai Lehmberg12,
  19. Daniel J Lovell8,
  20. Paivi Miettunen13,
  21. Kim E Nichols14,
  22. Seza Ozen15,
  23. Jana Pachlopnik Schmid16,
  24. Athimalaipet V Ramanan17,
  25. Ricardo Russo18,
  26. Rayfel Schneider19,
  27. Gary Sterba20,
  28. Yosef Uziel21,
  29. Carol Wallace22,
  30. Carine Wouters23,
  31. Nico Wulffraat24,
  32. Erkan Demirkaya25,
  33. Hermine I Brunner8,
  34. Alberto Martini1,
  35. Nicolino Ruperto2,
  36. Randy Q Cron26
  37. on behalf of the Paediatric Rheumatology International Trials Organisation, the Childhood Arthritis and Rheumatology Research Alliance, the Pediatric Rheumatology Collaborative Study Group, and the Histiocyte Society
  1. 1Università degli Studi di Genova and Istituto Giannina Gaslini, Genoa, Italy
  2. 2Istituto Giannina Gaslini, Genoa, Italy
  3. 3Karolinska Institute and Karolinska University Hospital Solna, Stockholm, Sweden
  4. 4Azienda Sanitaria Provinciale 7, Ragusa, Italy
  5. 5University Children's Hospital, Ljubljana, Slovenia
  6. 6The Children's Hospital of Philadelphia, Philadelphia, Pennsylvania, USA
  7. 7Ospedale Pediatrico Bambino Gesù, Rome, Italy
  8. 8Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio, USA
  9. 9Albert Einstein College of Medicine and Children's Hospital at Montefiore, Bronx, New York, USA
  10. 10Jaslok Hospital and Research Centre, Mumbai, India
  11. 11Aichi Medical University, Nagakute, Japan
  12. 12University Medical Center, Hamburg, Germany
  13. 13University of Calgary, Calgary, Alberta, Canada
  14. 14St Jude Children's Research Hospital, Memphis, Tennessee, USA
  15. 15Hacettepe University, Ankara, Turkey
  16. 16University Children's Hospital, Zurich, Switzerland
  17. 17Bristol Royal Hospital for Children, Bristol, UK
  18. 18Hospital de Pediatria Juan P. Garrahan, Buenos Aires, Argentina
  19. 19University of Toronto and Hospital for Sick Children, Toronto, Ontario, Canada
  20. 20Mount Sinai Medical Center, Miami Beach, Florida, USA
  21. 21Meir Medical Centre, Kfar Saba, Israel
  22. 22Seattle Children's Hospital and University of Washington, Seattle, USA
  23. 23University Hospital Leuven, Leuven, Belgium
  24. 24Wilhelmina Children's Hospital and University Medical Center Utrecht, Uthrecht, The Netherlands
  25. 25Gulhane Military Medical Faculty, Ankara, Turkey
  26. 26University of Alabama at Birmingham, Birmingham, UK
  1. Correspondence to Professor Angelo Ravelli, Pediatria II, Istituto G. Gaslini, Largo G. Gaslini 5, Genoa 16147, Italy; angeloravelli{at}

A European League Against Rheumatism/American College of Rheumatology/Paediatric Rheumatology International Trials Organisation Collaborative Initiative


To develop criteria for the classification of macrophage activation syndrome (MAS) in patients with systemic juvenile idiopathic arthritis (JIA). 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. 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 (κ=0.76). 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.

  • Adult Onset Still's Disease
  • Amyloidosis
  • Analgesics
  • Ankylosing Spondylitis
  • Ant-CCP

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