Abstract
Timely initiation of intravenous immunoglobulin plus aspirin is necessary for decreasing the risk of recrudescent fever and coronary artery abnormalities in children with Kawasaki disease (KD). The optimal dose of aspirin, however, remains unclear. To evaluate whether initial treatment with low-dose compared with high-dose aspirin in children with KD is associated with an increase in fever recrudescence. A retrospective cohort study of 260 children with KD at Riley Hospital for Children, Indianapolis, Indiana, between January 1, 2007, and December 31, 2018, was conducted. Children aged 0 to 18 years with a first episode of KD, identified by International Classification of Diseases, Ninth Revision and International Statistical Classification of Diseases and Related Health Problems, Tenth Revision diagnosis codes treated within 10 days of symptom onset with high-dose intravenous immunoglobulin plus aspirin were eligible. Patients who received an alternative diagnosis, experienced a second episode of KD, did not receive intravenous immunoglobulin plus aspirin for initial treatment, were not treated within 10 days of symptoms, or had incomplete records were excluded. High-dose (≥10 mg/kg/d) or low-dose (<10 mg/kg/d) aspirin therapy. The primary outcome was recrudescent fever necessitating retreatment of KD. The secondary outcomes were coronary artery abnormalities and hospital length of stay. Among the 260 patients included, the median (interquartile range) age was 2.5 (1.6-4.3) years, 103 (39.6%) were girls, 166 (63.8%) were non-Hispanic white, 57 (21.9%) were African American, 22 (8.5%) were Asian, 11 (4.2%) were Hispanic, and 4 (1.5%) were of unknown race/ethnicity. One hundred-forty-two patients (54.6%) were treated with low-dose aspirin. There was no association between recrudescent fever and aspirin dose, with 39 children (27.5%) having recrudescent fever in the low-dose group compared with 26 children (22.0%) in the high-dose group (odds ratio [OR], 1.34; 95% CI, 0.76-2.37; P = .31), with similar results after adjusting for potential confounding variables (OR, 1.63; 95% CI, 0.89-2.97; P = .11). In a subset analysis of 167 children with complete KD, however, there was nearly a 2-fold difference in the odds of recrudescent fever with low-dose aspirin (OR, 1.87; 95% CI, 0.82-4.23; P = .14), although this difference did not reach statistical significance. In addition, no association was identified between treatment group and coronary artery abnormalities (low-dose, 7.4% vs high-dose, 9.4%; OR, 0.86; 95% CI, 0.48-1.55; P = .62) or median (interquartile range) length of stay (3 [3-5] days for both groups; P = .27). In this study, low-dose aspirin for the initial treatment of children with KD was not associated with fever recrudescence or coronary artery abnormalities. Given the potential benefits, further study of low-dose aspirin to detect potentially clinically relevant outcome differences is warranted to inform treatment decisions and guideline development.
Highlights
Kawasaki disease (KD) is an acute systemic vasculitis of unknown cause with the potential for serious sequelae, including coronary artery abnormalities, in 15% to 25% of untreated patients.[1,2] With timely initiation of treatment, the risk of coronary artery abnormalities is greatly reduced
There was no association between recrudescent fever and aspirin dose, with 39 children (27.5%) having recrudescent fever in the low-dose group compared with 26 children (22.0%) in the high-dose group, with similar results after adjusting for potential confounding variables (OR, 1.63; 95% CI, 0.89-2.97; P = .11)
In a subset analysis of 167 children with complete KD, there was nearly a 2-fold difference in the odds of recrudescent fever with low-dose aspirin (OR, 1.87; 95% CI, 0.82-4.23; P = .14), this difference did not reach statistical significance
Summary
Kawasaki disease (KD) is an acute systemic vasculitis of unknown cause with the potential for serious sequelae, including coronary artery abnormalities, in 15% to 25% of untreated patients.[1,2] With timely initiation of treatment, the risk of coronary artery abnormalities is greatly reduced. In the United States, the standard of care for initial treatment of KD is high-dose intravenous immunoglobulin, along with acetylsalicylic acid (aspirin).[1] the role and dose of intravenous immunoglobulin, 2 g/kg, are well established and have been shown to significantly reduce the risk of coronary artery abnormalities,[3,4,5,6,7,8] the optimal dose of aspirin is unclear, resulting in significant practice variation.[1,5,9,10]. Aspirin is used as an anti-inflammatory agent, while at lower doses it has antithrombotic effects. Both of these actions are thought to be useful in the initial stages of KD. Multiple studies have shown no difference in coronary artery abnormality risk between low- and high-dose aspirin,[9,12,13] the effect on recrudescent fever, especially in the US population, is understudied.[3,4,14] We sought to evaluate whether the dose of aspirin was associated with recrudescent fever, hypothesizing that, given its the antiinflammatory properties, high-dose aspirin would be associated with a decrease in recrudescent fever compared with low-dose aspirin in children with KD
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