Identification of Children with Kawasaki Disease at High Risk for Immunoglobulin Unresponsiveness

Background: Kawasaki disease (KD) is the most common cause of acquired heart disease in the pediatric population due to inflammation resulting in damage to coronary arteries. Treatment with intravenous immunoglobulin (IVIG) has been shown to decrease inflammation and impact coronary artery damage. Despite treatment with IVIG, some children require additional therapy. Here we report the requirement for additional therapy in patients who meet high-risk criteria at the outset of treatment and are given methylprednisolone.

Methods: A retrospective chart review was undertaken of children under 18 years old who were admitted to Loma Linda University Children’s Hospital for KD before and after introduction of a risk protocol. The protocol involved addition of methylprednisolone to IVIG for high-risk children. The high-risk criteria included age ≤ 12 months or ≥ 8 years, coronary artery size Z score ≥ 3.5 in the left anterior descending or right coronary arteries on initial echocardiography, or CRP ≥ 15 mg/dL with at least one additional finding of the following: WBC ≥ 20,000, platelet count ≤ 150,000, sodium ≤ 133, albumin ≤ 2.8, hemoglobin ≤ 8, and/or ALT ≥ 100. A patient was considered unresponsive to IVIG if additional therapy was given such as IVIG, steroids, infliximab or another agent. We compared the rate of unresponsiveness to IVIG therapy among the children who met high-risk before and after the implementation of the protocol.

Results: There was a total of 143 patients and 59 were female (41%). The number of patients who met high risk KD criteria was 63, 32 were female (51%), and 40 (63%) met criteria by age alone. Prior to the implementation of the protocol 49 (40%) patients met high-risk criteria and 14 (67%) after. Of the 49 children who would have met high-risk criteria in the pre-implementation period, 16 (32%) required additional therapy whereas only 2 (14%) of the 14 high-risk children required additional therapy in the post-implementation period. One of those 2 children did not receive methylprednisolone but was given a second dose of IVIG and the other child received methylprednisolone, a second dose of IVIG and infliximab. In 71 patients who did not meet high-risk criteria in the pre-implementation period, 10 (14%) required additional therapy and in the post-implementation period 1 (14%) out of 7 required additional therapy.

Conclusion: After the implementation of the high-risk KD protocol, there was a significant improvement in the responsiveness to IVIG. During the two different time periods, there was no change in unresponsiveness to IVIG in children who did not meet high-risk criteria. We believe that early steroid administration in these high-risk patients can prevent the need for additional therapy.