Introduction: Macrophage activation syndrome (MAS) is a life threatening disease that is increasingly recognized in children with inflammatory conditions including Kawasaki disease (KD). We describe the prevalence, clinical features and outcomes of patients with MAS secondary to KD.
Methods: All patients diagnosed and treated for KD at The Hospital for Sick Children between 2001 and 2013 were included and reviewed for features of MAS. A diagnosis of MAS required 4 out of the following clinical findings: fever, hepatosplenomegaly, cytopenia in at least 2 cell lines, hyperferritinemia, hypofibrinogenemia and/or hypertriglyceridemia, and presence of biopsy-proven hemophagocytosis.
Results: Of 1,020 patients included in this study, 21 met MAS diagnostic criteria for an incidence of 2.1% (95% CI: 1.4-3.1%). All patients had fever, 9 (43%) hepatosplenomegaly, 10 (47%) hypofibrinogenemia and/or hypertriglyceridemia, 19 (90%) hyperferritinemia, 19 (90%) cytopenia, and 7 (33%) biopsy-confirmed hemophagocytosis. MAS was associated with: older age at KD diagnosis (median 5.7 vs. 3.0 years, p=0.06), longer fever duration prior to diagnosis (median 10 vs. 6 days, p=0.01), and higher incidence of incomplete KD (57% vs. 32%, p=0.04) and confirmed infection during acute phase (48% vs. 19%, p=0.02). Treatment included multiple IVIGs for 12 patients (57%), methylprednisolone for 15 (71%), oral prednisone for 13 (62%) and cyclosporine for 2 (10%). Median total duration of fever was 13 days (vs. 7 days, p=0.001), duration of fever after first IVIG treatment was 4 days, and median duration of hospital stay was 6 days (vs. 3 days, p=0.01). 5 patients received pRBC transfusions, 3 required ICU care, 1 had severe CNS involvement, and 1 developed multisystem organ failure dying 28 days after admission. Mild transient coronary dilatation was seen in 3 patients
Conclusions: The clinical presentation of KD and MAS are quite similar. Both entities are syndrome complexes defined by massive immune activation and share pro-inflammatory cytokine signatures. MAS is a rare but important complication with KD. Further research is needed to optimize diagnosis and management.