Although macrophage activation syndrome (MAS) has been reported in association with almost all rheumatic diseases, it is by far most common in systemic juvenile idiopathic arthritis (sJIA). Reported mortality rates in MAS reach 10-20%. Standardized treatment guidelines for MAS are currently lacking, but management commonly includes high-dose corticosteroids combined with another immunosuppressive agent. Etoposide is a well established therapy in primary hemophagocytic lymphohistiocytosis. A recent systematic literature review on treatments of MAS in sJIA identified only a few patients who were given etoposide. We aimed to investigate etoposide usage among pediatric patients with MAS complicating sJIA and to identify predictors of etoposide administration.

Methods:  Retrospective collected data from 362 patients included in the multinational study of the 2016 classification criteria for MAS in sJIA were examined to identify patients treated with etoposide and record potential predictors of etoposide administration. Variables significantly associated with etoposide usage in univariate analysis were entered in a multivariate regression model. Continuous variables were dichotomized according to the cut-off value obtained through ROC curve analysis.

Results:

Forty of the 362 patients (11 %) were treated with etoposide and 17 of those had information on all variables studied. Factors significantly associated with etoposide administration in multivariate analysis included multiorgan failure (OR 7.9, 95% CI 2.2-28.5), platelet count ≤ 132 x 109/liter (OR 5.8, 95% CI 1.8-18.2), triglycerides > 270.8 mg/dl (OR 3.7, 95% CI 1.3-10.4), aspartate aminotransferase > 389 units/liter (OR 3.7, 95% CI 1.3-10.3), and fibrinogen ≤ 1.53 gm/liter (OR 2.9, 95% CI 1.1-7.5). The AUC of the model was 0.86. In univariate analysis, there was no significant difference in mortality rate between patients given or not given etoposide.

Conclusion:  Patients treated with etoposide were sicker than patients who did not receive this medication. However, mortality rate did not differ between the two treatment groups, suggesting that etoposide may be part of aggressive therapeutic interventions for severely ill children with MAS.