Exploring Kawasaki Disease

Up to 85% of children with KD have full resolution of fever with a single dose of IVIG and do not require further therapy. Those children who develop fevers of 38°C or higher between 36 hours and seven days after completing the first IVIG treatment are said to have IVIG resistance and are at higher risk for CAA.

There are two approaches to treating high-risk children: 1) intensification of primary therapy with cortico­steroids or such agents as TNF inhibitors, or 2) providing rescue therapy for those children with persistent or recrudescent fever after initial treatment.

Intensification of primary therapy by the addition of corticosteroids has been tested in the U.S. and in Japan. A randomized trial performed by the Pediatric Heart Network revealed no difference in echo­cardiographic outcomes in children with KD who received a single pulsed dose of methylprednisolone (30 mg/kg) prior to standard therapy when compared with those who received standard therapy.¹⁴ However, a beneficial role for corticosteroids in KD has recently been supported by a well-designed study from Japan called the RAISE study (Randomized Controlled Trial to Assess Immunoglobulin Plus Steroid Efficacy for Kawasaki Disease).¹⁵ High-risk children, as defined by a Kobayashi risk score of 5 or higher, were randomized to IVIG or IVIG+ prednisolone arms, with the pred­nisolone given intravenously for five days at 2 mg/kg/day, followed by an oral taper. The incidence of coronary artery abnormalities was significantly lower in the prednisolone treated group. Additionally, the prednisolone-treated group had fewer days of fever and were less likely to need additional treatments. The differences in outcomes between these two studies may be in part due to the ability of the Kobayashi score to correctly identify children at high risk for CAA and perhaps to the longer duration of corticosteroids.

This swollen, granular appearance of the tongue is characteristic of Kawasaki disease.

Intensification of primary therapy with TNF inhibitors has recently been evaluated in a randomized double-blind placebo controlled trial, using a single dose of infliximab (5 mg/kg) + IVIG vs. placebo + IVIG. The results were presented at this year’s ACR/ARHP Annual Meeting by Jane Burns, MD, professor of pediatric infectious diseases at the University of Washington in Seattle. The primary endpoint of differences in rates of IVIG resistance between the two arms was not met. However, there were no differences in adverse events between the two groups. Finally, the group treated with infliximab had more rapid improvement of their inflammatory markers and less fever, but did not have significant differences in their coronary artery outcomes.