Macrophage Activation Syndrome in the Acute Phase of Kawasaki Disease

Abstract

Rare cases of macrophage activation syndrome (MAS) occurring during the acute phase of Kawasaki disease (KD) have been reported. We sought to characterize, review treatment, and outcomes of KD patients with clinical features of MAS. Medical histories of patients treated for KD and MAS between January 2001 and March 2008 were reviewed. Of 638 KD patients seen, 12 (1.9%) had additional clinical findings usually associated with MAS; 7 of them were males older than 5 years (6.1%; odds ratio: 6.8, P=0.002). Clinically, 9 patients had at least 4 of 5 KD clinical signs, and all patients had prolonged fever beyond initial intravenous immunoglobulin treatment. Hepatosplenomegaly, cytopenia in two or more cell lines, hypertriglyceridemia and/or hypofibrinogenemia, and increased D-dimers were seen in 11 patients. Hyperferritinemia and elevated hepatic enzymes were seen in all patients. Four patients had biopsy-proven evidence of hemophagocytosis. All but 2 patients met at least 5 of 8 criteria necessary for MAS diagnosis. Treatment beyond the standard KD protocol (aspirin + intravenous immunoglobulin) was necessary in all but 1 patient. All patients eventually recovered with no long-term sequelae. A high index of suspicion for clinical features associated with MAS is warranted for KD patients to provide appropriate and timely treatment.

Macrophage Activation Syndrome: A Potentially Fatal Complication of Kawasaki Disease

“…[7][8][9] There have been few reported cases of MAS in KD. Latino et al 10 reported that 1.9% of KD patients had additional clinical findings of MAS, and 10 out of 12 patients with KD in their series met at least five of the eight criteria necessary for diagnosis of MAS. Treatment beyond the standard KD protocol (aspirin + IVIg) was necessary in all but one patient.…”

Hemophagocytosis in the Acute Phase of Fatal Kawasaki Disease in a 4 Month-Old Girl

“…The mechanism by which HLH develops in these patients is unknown. Hypercytokinemia, as a result of abnormal immune-regulation, has been proposed to contribute to the pathogenesis of both diseases (2,4).…”

“…Hemophagocytic lymphohistiocytosis (HLH), is a systemic inflammatory disorder characterized by uncontrolled histiocytic proliferation, hemophagocytosis, macrophage activation, and up-regulation of inflammatory cytokines, which can complicate the course of KD (2)(3)(4). In most of the reported cases, HLH develop long after treatment or during the recurrent course of the disease (3)(4)(5)(6). Herein we report a case with secondary HLH occurring during the acute phase of fatal KD in a 4 month-old girl.…”

Kawasaki Disease; A Review Article

“…Acute phase reactants [erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP)] are almost always increased. Increased leukocytosis (neutrophil dominant) is frequent (24,25). Thrombocytosis as a characteristic feature of KD usually occurs during the 2 weeks of the illness.…”

“…Thrombocytosis as a characteristic feature of KD usually occurs during the 2 weeks of the illness. Increased serum transaminase levels, hypoalbuminemia and sterile pyuria are common (24,25).…”