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Development and initial validation of the MS score for diagnosis of macrophage activation syndrome in systemic juvenile idiopathic arthritis
  1. Francesca Minoia1,2,
  2. Francesca Bovis3,
  3. Sergio Davì2,
  4. AnnaCarin Horne4,
  5. Michel Fischbach5,
  6. Michael Frosch6,
  7. Adam Huber7,
  8. Marija Jelusic8,
  9. Sujata Sawhney9,
  10. Deborah K McCurdy10,
  11. Clóvis A Silva11,
  12. Donato Rigante12,13,
  13. Erbil Unsal14,
  14. Nicolino Ruperto2,
  15. Alberto Martini2,3,
  16. Randy Q Cron15,
  17. Angelo Ravelli2,3,16
  18. on behalf of the Pediatric Rheumatology International Trials Organization, the Childhood Arthritis & Rheumatology Research Alliance, the Pediatric Rheumatology Collaborative Study Group and the Histiocyte Society
  1. 1 Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Milano, Italy
  2. 2 Istituto Giannina Gaslini, Genova, Italy
  3. 3 Università degli Studi di Genova, Genova, Italy
  4. 4 Karolinska University Hospital Solna, Stockholm, Sweden
  5. 5 Hopital Universitaire Hautepierre, Strasbourg, France
  6. 6 School of Medicine Witten/Herdecke, Datteln, Germany
  7. 7 IWK Health Centre, Halifax, Nova Scotia, Canada
  8. 8 University of Zagreb School of Medicine, Zagreb, Croatia
  9. 9 Sir Ganga Ram Hospital, New Delhi, India
  10. 10 Mattel Children’s Health Center UCLA, Los Angeles, California, USA
  11. 11 Childrens’ Institute, Hospital das Clinicas HCFMUSP, Faculdade de Medicina, Universidade de Sao Paulo, Sao Paulo, Brazil
  12. 12 Fondazione Policlinico Universitario A Gemelli IRCCS, Roma, Italy
  13. 13 Università Cattolica del Sacro Cuore, Roma, Italy
  14. 14 Dokuz Eylu ̈l University Medical School, Izmir, Turkey
  15. 15 University of Alabama at Birmingham, Birmingham, Alabama, USA
  16. 16 Sechenov First Moscow State Medical University, Moscow, Russian Federation
  1. Correspondence to Francesca Minoia, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Milano 20122, Italy; francesca.minoia{at}


Objective To develop and validate a diagnostic score that aids in identifying macrophage activation syndrome (MAS) in patients with systemic juvenile idiopathic arthritis (sJIA).

Methods The clinical and laboratory features of 362 patients with sJIA-associated MAS and 404 patients with active sJIA without evidence of MAS were collected in a multinational collaborative project. Eighty percent of the study population was used to develop the score and the remaining 20% constituted the validation sample. A Bayesian Model Averaging approach was used to assess the role of each clinical and laboratory variables in the diagnosis of MAS and to obtain the coefficients of selected variables. The final score, named MAS/sJIA (MS) score, resulted from the linear combination of these coefficients multiplied by the values of each variable. The cut-off that best discriminated MAS from active sJIA was calculated by means of receiver operating characteristic (ROC) curve analysis. Score performance was evaluated in both developmental and validation samples.

Results The MS score ranges from −8.4 to 41.8 and comprises seven variables: central nervous system dysfunction, haemorrhagic manifestations, active arthritis, platelet count, fibrinogen, lactate dehydrogenase and ferritin. A cut-off value ≥−2.1 revealed the best performance in discriminating MAS from active sJIA, with a sensitivity of 0.85, a specificity of 0.95 and a kappa value of 0.80. The good performance of the MS score was confirmed in the validation sample.

Conclusion The MS score is a powerful and feasible tool that may assist practitioners in making a timely diagnosis of MAS in patients with sJIA.

  • macrophage activation syndrome
  • systemic juvenile idiopathic arthritis
  • hemophagocytic syndrome
  • diagnostic score
  • still’s disease

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  • Handling editor Josef S Smolen

  • Contributors We confirm that all authors have contributed to the generation of the manuscript.

  • Funding The authors have not declared a specific grant for this research from any funding agency in the public, commercial or not-for-profit sectors.

  • Competing interests None declared.

  • Patient consent for publication Not required.

  • Provenance and peer review Not commissioned; externally peer reviewed.

  • Data availability statement All data relevant to the study are included in the article or uploaded as supplementary information.