Pathogenesis and management of Kawasaki disease

Abstract

Kawasaki disease (KD) is an acute systemic inflammatory illness of young children that can result in coronary artery aneurysms, myocardial infarction and sudden death in previously healthy children. Clinical and epidemiologic features support an infectious cause, but the etiology remains unknown four decades after KD was first identified by Tomisaku Kawasaki. Finding the cause of KD is a pediatric research priority. We review the unique immunopathology of KD and describe the current treatment. New research has led to identification of viral-like cytoplasmic inclusion bodies in acute KD tissues; this finding could lead to identification of the elusive etiologic agent and result in significant advances in KD diagnosis and treatment. Current management of acute KD is based upon prospective, multicenter treatment trials of intravenous immunoglobulin (IVIG) with high-dose aspirin. Optimal therapy is 2 g/kg IVIG with high-dose aspirin as soon as possible after diagnosis during the acute febrile phase of illness, followed by low-dose aspirin until follow-up echocardiograms indicate a lack of coronary abnormalities. The addition of one dose of intravenous pulse steroid has not been shown to be beneficial. For the 10–15% of patients with refractory KD, few controlled data are available. Options include repeat IVIG (our preference), a 3-day course of intravenous pulse methylprednisolone, or infliximab (Remicade^®). Patients with mild-to-moderate coronary abnormalities should receive an antiplatelet agent such as low-dose aspirin (3–5 mg/kg/day) or clopidogrel (1 mg/kg/day up to 75 mg), and those with giant (∼8 mm diameter) or multiple coronary aneurysms should receive an antiplatelet agent with an anticoagulant such as warfarin or low-molecular-weight heparin. Acute coronary obstruction requires acute thrombolytic therapy with a surgical or percutaneous interventional procedure.

Keywords::

• coronary artery aneurysms
• cytoplasmic inclusion bodies
• IgA immune response
• IgA plasma cells
• inclusion bodies
• intravenous immunoglobulin
• Kawasaki disease
• synthetic antibodies
• vasculitis

Financial & competing interests disclosure

Anne H Rowley is supported by National Institutes of Health grant HL63771 and the Kawasaki Disease Fund of the Children’s Memorial Hospital. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

No writing assistance was utilized in the production of this manuscript.