Treatment of Kawasaki Disease

Patients with acute Kawasaki disease should be treated with intravenous immunoglobulin (IVIG) and high-dose aspirin as soon as possible after diagnosis and, ideally, within 10 days of disease onset.

The mechanism of action of IVIG in Kawasaki disease is unknown, but treatment should result in rapid defervescence and resolution of clinical signs of illness in 85–90% of patients. With therapy, the CRP normalizes much more quickly than the ESR, which will often increase immediately after IVIG therapy. IVIG reduces the prevalence of coronary disease from 20–25% in children treated with aspirin alone to 2–4% in those treated with IVIG and aspirin within the 1st 10 days of illness. Consideration should even be given to treatment of patients diagnosed after the 10th illness day if fever has persisted, because the anti-inflammatory effect may be helpful, although the effect of such therapy on the risk of developing coronary aneurysms is unknown. The dose of aspirin is decreased from anti-inflammatory to antithrombotic doses (3–5 mg/kg/day as a single dose) on the 14th illness day or after the patient has been afebrile for at least 3–4 days. Aspirin is continued for its antithrombotic effect until 6–8 wk after onset, when the ESR has normalized in patients that have not developed abnormalities detected by echocardiography.

Occasional patients have refractory Kawasaki disease that does not respond to an initial IVIG infusion, or exhibits only a partial or transient response. Strong consideration should be given to retreatment of these patients with an additional infusion of IVIG (2 g/kg). Optimal therapy for patients who do not respond to two infusions of IVIG is uncertain. If there is a poor response to the second dose of IVIG, some patients have responded to IV methylprednisolone at a dose of 30 mg/kg/day for 3 days. The value of infliximab (which binds TNF-?), other immunomodulators (cyclophosphamide, methotrexate), and plasmapheresis in Kawasaki disease is yet to be determined.

Acute thrombosis may occasionally occur in an aneurysmal or stenotic coronary artery. Thrombolytic therapy may be lifesaving in this circumstance . Abciximab, a glycoprotein IIb/IIIa inhibitor, has been used in some patients with Kawasaki disease who develop giant coronary aneurysms with possible thrombosis. Few data regarding efficacy are available, but the drug may reduce thrombotic complications.

Patients with a small solitary aneurysm should continue aspirin indefinitely. Patients with larger or numerous aneurysms may require the addition of clopidogrel, warfarin, or low molecular weight heparin therapy; such decisions should be made in consultation with a pediatric cardiologist. Long-term follow-up of patients with coronary artery aneurysms should include periodic echocardiography with stress testing, and possibly angiography for those with larger aneurysms.

Catheter intervention with percutaneous transluminal coronary rotational ablation, directional coronary atherectomy, and stent implantation have all been used for the management of coronary stenosis caused by Kawasaki disease, with some patients requiring coronary artery bypass grafting.

Patients receiving long-term aspirin therapy are candidates for annual influenza vaccination to reduce the risk of Reye syndrome. Varicella vaccination should be strongly considered, since the risk of Reye syndrome in children who take salicylates and who receive varicella vaccine is likely to be lower than with wild-type varicella. Patients treated with 2 g/kg IVIG should have measles-mumps-rubella and varicella vaccinations delayed for 11 mo because the specific antiviral antibody in IVIG may interfere with the immune response to live-virus vaccines. Other vaccinations do not need to be delayed.