Management during the acute phase is directed at decreasing inflammation of the myocardium and coronary artery wall and providing supportive care. Therapy should be initiated when the diagnosis is established or strongly suspected, optimally within the first 10 days of illness. Once the acute phase has passed, therapy is directed at prevention of coronary artery thrombosis. Specific recommendations for therapy include the following measures.

Immune Globulin Intravenous

Therapy with high-dose IGIV and aspirin initiated within 10 days of the onset of fever substantially decreases progression to coronary artery dilation and aneurysms, compared with Treatment with aspirin alone, and results in more rapid resolution of fever and other clinical and laboratory indicators of acute inflammation. Therapy with IGIV should be initiated as soon as possible; its efficacy when initiated later than the 10th day of illness or after detection of aneurysms has been evaluated in only one controlled trial. However, therapy with IGIV and aspirin should be provided for patients diagnosed after day 10 who have manifestations of continuing inflammation (eg, fever or elevated ESR or CRP concentration) or of evolving coronary artery disease. Despite prompt Treatment with IGIV and aspirin, 2% to 4% of patients develop coronary artery abnormalities.

Dose

A dose of 2 g/kg as a single dose, given over 10 to 12 hours, has been proven to reduce the risk of coronary artery aneurysm from 17% to 4%. Few complications occur from this regimen.

ReTreatment

Up to 20% of patients who receive IGIV and aspirin therapy have persistent fever after IGIV or recurrence of fever after an initial period of being afebrile. In these situations, reTreatment with IGIV (2 g/kg) within 24 to 48 hours of persistent or recrudescent fever and continued aspirin therapy generally is given. Persistent or recrudescent fever is associated with high concentrations of proinflammatory cytokines and an increased risk of coronary artery abnormalities. The benefit and possible detriment of use of systemic corticosteroids in Treatment of Kawasaki disease are controversial. Corticosteroids are not beneficial for primary therapy. For the limited number of patients who are refractory to at least 2 doses of IGIV, rescue therapy of intravenous methylprednisolone (usually 30 mg/kg/day for 1 to 3 days) or infliximab (5 mg/kg as one infusion) may be administered in attempt to reduce inflammation and improve coronary artery outcomes. Lack of data on use of these modalities precludes definitive recommendations.

Aspirin

Aspirin is used for anti-inflammatory and antithrombotic actions, although aspirin alone does not decrease risk of coronary artery abnormalities. The optimal dose or duration of aspirin Treatment is unknown. Aspirin is administered in doses of 80 to 100 mg/kg per day in 4 divided doses once the diagnosis is made. Children with acute Kawasaki disease have decreased aspirin absorption and increased clearance and rarely achieve therapeutic serum concentrations. In most children, it is not necessary to monitor aspirin concentrations. After fever is controlled for 48 hours (usually around the 14th day of illness), the aspirin dose is decreased to 3 to 5 mg/kg per day for antithrombotic activity. Aspirin is discontinued if no coronary artery abnormalities have been detected by 6 to 8 weeks after onset of illness. Low-dose aspirin therapy should be continued indefinitely for people in whom coronary artery abnormalities are present. Because of the theoretical risk of Reye syndrome in patients with influenza or varicella receiving salicylates, parents of children receiving aspirin should be instructed to contact their child's physician promptly if the child develops symptoms of or is exposed to either disease. In general, ibuprofen should be avoided in children with coronary aneurysms taking aspirin for its antiplatelet effects, because ibuprofen antagonizes the platelet inhibition that is induced by aspirin. The child and household contacts should be given influenza vaccine at diagnosis of Kawasaki disease according to seasonal recommendations.

Cardiac Care

An echocardiogram should be obtained at the time of diagnosis and then 1 to 2 and 6 to 8 weeks after onset. Children at higher risk-for example, those with persistent or recrudescent fever after initial IGIV or baseline coronary abnormalities-should have more frequent echocardiograms to guide the need for additional therapies. Children also should be assessed during this time for arrhythmias, congestive heart failure, and valvular regurgitation. The care of patients with significant cardiac abnormalities should involve a pediatric cardiologist experienced in management of patients with Kawasaki disease and in assessing echocardiographic studies of coronary arteries in children. Long-term management of Kawasaki disease should be based on the extent of coronary artery involvement. In patients with persistent moderately large coronary artery abnormalities that are not large enough to require anticoagulation, prolonged low-dose aspirin and clopidogrel (1 mg/kg/day) are recommended in combination. Development of giant coronary artery aneurysms (diameter 8 mm or larger) usually requires addition of anticoagulant therapy, such as warfarin or low-molecular weight heparin, to prevent thrombosis. Anticoagulation also sometimes is used in young infants with coronary artery aneurysms measuring less than 8 mm in diameter but for whom the size is equivalent to giant aneurysms when body surface area is considered. For example, a 3-month-old infant with coronary arteries 6 or 7 mm in diameter often would be a candidate for anticoagulation.

Subsequent Immunization

Measles and varicella-containing vaccines should be deferred for 11 months after high-dose IGIV for Treatment of Kawasaki disease. If the child's risk of exposure to measles or varicella is high, the child should be immunized and then reimmunized at least 11 months after administration of IGIV (see Measles). The schedule for administration of inactivated childhood vaccines should not be interrupted.