Angelo Ravelli1, Francesca Minoia2, Sergio Davì2, AnnaCarin Horne3, Francesca Bovis2, Angela Pistorio2, Maurizio Aricò4, Tadej Avcin5, Edward M Behrens6, Fabrizio De Benedetti7, Lisa Filipovic8, Alexei A Grom8, Jan-Inge Henter3, Norman T Ilowite9, Michael B Jordan8, Raju Khubchandani10, Toshiyuki Kitoh11, Kai Lehmberg12, Daniel J Lovell8, Paivi Miettunen13, Kim E Nichols14, Seza Ozen15, Jana Pachlopnik Schmid16, Athimalaipet V Ramanan17, Ricardo Russo18, Rayfel Schneider19, Gary Sterba20, Yosef Uziel21, Carol Wallace22, Carine Wouters23, Nico Wulffraat24, Erkan Demirkaya25, Hermine I Brunner8, Alberto Martini1, Nicolino Ruperto2, Randy Q Cron26. 1. Università degli Studi di Genova and Istituto Giannina Gaslini, Genoa, Italy. 2. Istituto Giannina Gaslini, Genoa, Italy. 3. Karolinska Institute and Karolinska University Hospital Solna, Stockholm, Sweden. 4. Azienda Sanitaria Provinciale 7, Ragusa, Italy. 5. University Children's Hospital, Ljubljana, Slovenia. 6. The Children's Hospital of Philadelphia, Philadelphia, Pennsylvania. 7. Ospedale Pediatrico Bambino Gesù, Rome, Italy. 8. Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio. 9. Albert Einstein College of Medicine and Children's Hospital at Montefiore, Bronx, New York. 10. Jaslok Hospital and Research Centre, Mumbai, India. 11. Aichi Medical University, Nagakute, Japan. 12. University Medical Center, Hamburg, Germany. 13. University of Calgary, Calgary, Alberta, Canada. 14. St. Jude Children's Research Hospital, Memphis, Tennessee. 15. Hacettepe University, Ankara, Turkey. 16. University Children's Hospital, Zurich, Switzerland. 17. Bristol Royal Hospital for Children, Bristol, UK. 18. Hospital de Pediatria Juan P. Garrahan, Buenos Aires, Argentina. 19. University of Toronto and Hospital for Sick Children, Toronto, Ontario, Canada. 20. Mount Sinai Medical Center, Miami Beach, Florida. 21. Meir Medical Centre, Kfar Saba, Israel. 22. Seattle Children's Hospital and University of Washington, Seattle. 23. University Hospital Leuven, Leuven, Belgium. 24. Wilhelmina Children's Hospital and University Medical Center Utrecht, Uthrecht, The Netherlands. 25. Gulhane Military Medical Faculty, Ankara, Turkey. 26. University of Alabama at Birmingham.
Abstract
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 (κ = 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.
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 (κ = 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.
Authors: Grant S Schulert; Shima Yasin; Brenna Carey; Claudia Chalk; Thuy Do; Andrew H Schapiro; Ammar Husami; Allen Watts; Hermine I Brunner; Jennifer Huggins; Elizabeth D Mellins; Esi M Morgan; Tracy Ting; Bruce C Trapnell; Kathryn A Wikenheiser-Brokamp; Christopher Towe; Alexei A Grom Journal: Arthritis Rheumatol Date: 2019-10-01 Impact factor: 10.995
Authors: Grant S Schulert; Mingce Zhang; Ndate Fall; Ammar Husami; Diane Kissell; Andrew Hanosh; Kejian Zhang; Kristina Davis; Jeffrey M Jentzen; Lena Napolitano; Javed Siddiqui; Lauren B Smith; Paul W Harms; Alexei A Grom; Randy Q Cron Journal: J Infect Dis Date: 2015-11-23 Impact factor: 5.226