Predicting Macrophage Activation Syndrome in Childhood-onset Systemic Lupus Erythematosus Patients at Diagnosis

Abstract

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.

Macrophage Activation Syndrome in Pediatric Systemic Lupus Erythematosus: A Systematic Review of the Diagnostic Aspects

“…The final output of this systematic literature search consisted of 28 papers, including case reports/series (n = 24) and clinical studies (n = 4). The former type of articles provided individual clinical and laboratory data of patients affected with the pSLErelated MAS , whereas the clinical studies provided these data in aggregated form (11,(37)(38)(39). One article provided both types of data: individual information for pSLE-related MAS patients and aggregated values (which were compared to a control group of pSLE patients without MAS) (33).…”

“…In addition to case reports and series, we also analyzed the four [actually five, including the paper by Sato et al (34)] clinical studies providing aggregated data on clinical and laboratory characteristics of MAS occurring in pSLE patients (11,33,(37)(38)(39). Those articles providing aggregated data for both adult and pediatric patients (without any chance to assess them separately) were excluded.…”

“…This systematic review also included those few clinical studies (n = 5) providing aggregated data specific for pediatric patients with pSLE and MAS (11,33,(37)(38)(39).…”

“…(33) : the ferritin values resulted 7,579 ± 16,647 and 2,796 ± 2,164 ng/ml, respectively. Based on this experience, they suggested a ferritin cut-off of 669 ng/ml as reliable to diagnose MAS in their two cohorts (39).…”

Hyperferritinemia Wins Again: Defining Macrophage Activation Syndrome in Pediatric Systemic Lupus Erythematosus

“…Guidelines to diagnose MAS in children with SLE have been previously proposed though not further validated 4 . In the current issue of The Journal of Rheumatology, Gerstein and colleagues present novel criteria to discriminate MAS from active disease in patients with newly diagnosed cSLE, especially in those who are hospitalized, and compare the performance of their developed criteria to existing criteria 5 .…”