MAS was most likely to develop concomitantly with childhood-onset SLE diagnosis. The majority of the MAS patients were successfully treated with corticosteroids with no MAS relapses. Although the numbers were small, there was a higher risk of death associated with MAS compared to SLE without MAS.

Objective Macrophage activation syndrome (MAS), a life-threatening inflammatory complication, is increasingly recognized in childhood-onset SLE (cSLE). It can be a challenge to differentiate active cSLE from MAS. We generated decision rules for discriminating MAS from active cSLE in newly diagnosed patients. Methods We conducted a retrospective cohort study of consecutive, newly diagnosed, active cSLE patients with fever, requiring hospital admission to SickKids from January 2003 - December 2007 (cohort 1), and January 2008 - December 2013 (Cohort 2). All patients met ≥4 ACR or SLICC criteria, were steroid naïve and infection free. MAS was diagnosed based on expert opinion. Recursive partitioning was applied to each cohort to derive a decision rule based on clinical and laboratory features, distinguishing MAS from non-MAS cSLE. Each decision rule was applied to the alternate, independent cohort. Sensitivity and specificity of these decision rules were compared to existing criteria. Results Cohort 1 (n=34) and cohort 2 (n=41) each had 10 MAS patients. Recursive partitioning in cohort 1 identified ferritin ≥699 μg/L, as the sole best discriminator between MAS and non- MAS patients (R2=0.48) and in cohort 2 ferritin ≥1107 μg/L, followed by lymphocytes < 0.72 x103/mm3 were the best discriminators for MAS (R2=0.52). Cross-validation of our decision rules maintained 90-100% sensitivity and 65-85% specificity. Conclusion Our decision rule demonstrated improved performance compared to preliminary guidelines for MAS in cSLE from the Lupus Working Group of the Paediatric Rheumatology European Society, and familial Hemophagocytic Lymphohistiocytosis diagnostic criteria. Validation in independent cohorts is required.

A better understanding of pathophysiology may elucidate novel molecules as therapeutic targets in cSLE. Advances in the field of biomarkers may enable a more accurate prediction of clinical outcome, optimizing early interventions and therefore improving disease prognostics.