Macrophage activation syndrome in Kawasaki disease: more common than we thought?

Objectives: To analyze the clinical characteristics, treatment, and outcomes of Kawasaki Disease (KD) patients associated with macrophage activation syndrome (MAS) and to compare two diagnostic standards (the HLH 2009 and Ravelli׳s criteria).

Methods: All of the studied patients with Kawasaki Disease (KD) were treated at The Children׳s Hospital, Zhejiang University School of Medicine, during 2007-2010. Clinical and laboratory findings were analyzed.

Results: In 719 KD patients, eight patients (1.11%, 81.3 ± 49.4 months, all male) were diagnosed by Ravelli׳s criteria, but only three (0.42%) patients were diagnosed by the HLH 2009 criteria. Aspartate aminotransferase increased significantly in all cases. Alanine aminotransferase, lactate dehydrogenase, and serum ferritin increased significantly in seven cases. Cytopenia and hypertriglyceridemia (>1.5mmol/L) were found in six and five cases, respectively. Hypofibrinogenemia (<1.5g/L) was found in two cases. Three cases showed evidence of hemophagocytosis, but only one case met the HLH 2009 criteria. Ectasia of the coronary arteries occurred in two cases. Seven patients were non-responsive to IVIG. One case died after the combined application of DXM, VP16, and CSA.

Conclusions: MAS may be a frequently under-recognized complication of KD, because the understanding of complications and diagnostic criteria are still in progress. The HLH 2009 criteria have low sensitivity and specificity for the diagnosis of MAS complicating KD. When hepatosplenomegaly is present in KD patients with abnormal laboratory findings, such as cytopenia, liver dysfunction, hyperferritinemia, elevated serum LDH, hypofibrinogenemia, and hypertriglyceridemia, the presence of MAS should be considered.