Differentiating macrophage activation syndrome in systemic juvenile idiopathic arthritis from other forms of hemophagocytic lymphohistiocytosis

J Pediatr. 2013 Jun;162(6):1245-51. doi: 10.1016/j.jpeds.2012.11.081. Epub 2013 Jan 17.


Objectives: To identify measures distinguishing macrophage activation syndrome (MAS) in systemic juvenile idiopathic arthritis (sJIA) from familial hemophagocytic lymphohistiocytosis (FHL) and virus-associated hemophagocytic lymphohistiocytosis (VA-HLH) and to define appropriate cutoff values. To evaluate suggested dynamic measures differentiating MAS in patients with sJIA from sJIA flares.

Study design: In a cohort of patients referred for evaluation of hemophagocytic lymphohistiocytosis, we identified 27 patients with sJIA and MAS (MAS/sJIA) fulfilling the criteria of the proposed preliminary diagnostic guideline for the diagnosis of MAS in sJIA. Ten measures at diagnosis were compared between the MAS/sJIA group and 90 patients with FHL and 42 patients with VA-HLH, and cutoff values were determined. In addition, 5 measures were analyzed for significant change from before MAS until MAS diagnosis.

Results: Neutrophil count and C-reactive protein were significantly higher in patients with MAS/sJIA compared with patients with FHL and patients with VA-HLH, with 1.8×10(9)/L neutrophils (sensitivity 85%, specificity 83%) and 90 mg/L C-reactive protein (74%, 89%) as cutoff values. Soluble CD25<7900 U/L (79%, 76%) indicated MAS/sJIA rather than FHL/VA-HLH. Platelet (-59%) and white blood cell count (-46%) displayed a significant decrease, and neutrophil count (-35%) and fibrinogen (-28%) showed a trend during the development of MAS. However, a substantial portion of patients had values at diagnosis of MAS within or above the normal range for white blood cells (84%), neutrophils (77%), platelets (26%), and fibrinogen (71%).

Conclusion: Readily available measures can rapidly differentiate between MAS/sJIA and FHL/VA-HLH. The findings substantiate that a decline of measures may facilitate the distinction of MAS from flares of sJIA.

MeSH terms

  • Arthritis, Juvenile / diagnosis*
  • Arthritis, Juvenile / immunology
  • Biomarkers / analysis
  • Child
  • Diagnosis, Differential
  • Female
  • Humans
  • Lymphohistiocytosis, Hemophagocytic / diagnosis*
  • Lymphohistiocytosis, Hemophagocytic / immunology
  • Macrophage Activation Syndrome / diagnosis*
  • Macrophage Activation Syndrome / immunology
  • Male


  • Biomarkers