Are the 2016 EULAR/ACR/PRINTO classification criteria for macrophage activation syndrome applicable to patients with adult-onset Still’s disease?
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The objectives of this study are to determine whether the 2016 European League Against Rheumatism/American College of Rheumatology/Paediatric Rheumatology International Trials Organization classification criteria for macrophage activation syndrome (MAS) complicating systemic juvenile idiopathic arthritis (SJIA) can be used to identify MAS in patients with adult-onset Still’s disease (AOSD). Using laboratory data from 76 AOSD patients with and without MAS, we analyzed the ability of the collective and individual constitutive elements of the 2016 MAS in SJIA criteria and additional laboratory measures to discriminate between AOSD patients with (n = 16) and without (n = 60) MAS. Cutoff values to determine the sensitivity, specificity, and predictive values were calculated from receiver operating characteristic curves, and modified classification criteria for MAS in AOSD were evaluated. The 2016 MAS in SJIA classification criteria had an overall sensitivity of 100%, specificity of 70.0%, positive predictive value of 47.1%, and negative predictive value of 100% to discriminate between AOSD patients with and without MAS based on laboratory data. Among the individual criteria, the sensitivity of triglycerides (46.7%) and the specificity of ferritin (15.0%) for MAS in AOSD were particularly low. The sensitivity and specificity for classifying MAS in AOSD patients were increased to 100 and 93%, respectively, by excluding triglycerides and changing the cutoff values for other criteria in the 2016 MAS in SJIA classification. The 2016 classification criteria for MAS in SJIA had higher sensitivity but lower specificity to identify MAS in AOSD patients compared with SJIA patients.
KeywordsAdult-onset Still’s disease Macrophage activation syndrome Classification criteria Ferritin Fibrinogen Platelet
The authors thank Ms. Eguchi and Ms. Ibe for secretarial assistance and Atsushi Kawaguchi for statistical analysis. We thank Edanz Group (http://www.edanzediting.com/ac) for editing a draft of this manuscript.
YT was responsible for the design of the study, acquisition, analysis and evaluation of the data, and manuscript preparation. SI, NO, and SK were responsible for acquisition and evaluation of the data, and discussion; AM, RS, MS, YS, and YM were responsible for the acquisition and interpretation of the data. All the authors have read, revised, and approved the content of the manuscript. All the authors agreed to be accountable for the accuracy or integrity of the work.
Compliance with ethical standards
Conflict of interest
Author Tada Y has received research grants and personal fees from Mitsubishi-Tanabe, Chugai, Astellas, Takeda, Teijin, and Eisai, personal fees from Novartis, Sanofi, Actelion, Daiichi Sankyo, Ayumi, Abbvie, Bristol-Myers Squibb, Janssen, Asahikasei, Nippon Kayaku, and Pfizer, outside the submitted work. Author Maruyama A has received a speaker honorarium from Janssen, Mitsubishi-Tanabe, Chugai, Astellas, and Bristol-Myers Squibb, outside the submitted work. Author Ono N has received personal fees from Mitsubishi-Tanabe, Chugai, Astellas, Takeda, Teijin, Abbvie, and Bristol-Myers Squibb, outside the submitted work. Author Arinobu Y has received personal fees from Mitsubishi-Tanabe, Chugai, Astellas, Takeda, Eisai, Actelion, Abbvie, Bristol-Myers Squibb, Daiichi-Sankyo, Ayumi, Asahikasei, and Nihon Shinyaku, outside the submitted work. Author Koarada S has received personal fees from Mitsubishi-Tanabe, Chugai, Astellas, Takeda, Eisai, Novartis, Abbvie, Bristol-Myers Squibb, Sanofi, Janssen, Pfizer, and Asahikasei, outside the submitted work. The authors Inokuchi S, Suematsu R, Sakai M, and Sadanaga Y declare that they have no conflict of interest.
All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki Declaration and its later amendments or comparable ethical standards. For this type of study formal consent is not required. This study was approved by the Saga University Hospital Ethics Committee (#2017-07-R-01) and the Kyushu University Hospital Ethics Committee (#29–521).
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