High-Risk Kawasaki Disease: Role of Adjunctive Corticosteroids

Source: Wang AP, Khan H, Dong S, et al. Primary adjunctive corticosteroids in the acute management of high-risk Kawasaki disease in a North American cohort. J Pediatr Infect Dis Soc. 2024;13(12):626-632; doi: 10.1093/jpids/piae112.Investigators from the Ann & Robert H. Lurie Children’s Hospital and Northwestern University, both Chicago, IL, conducted a retrospective study to assess the effectiveness of a standard corticosteroid regimen as an adjunct to intravenous immunoglobulin (IVIG) therapy in a North American population of high-risk children with Kawasaki disease (KD). In the RAISE study in Japan, a standardized course of corticosteroids was associated with reduced coronary artery (CA) abnormalities. Based on the results of that study, a modified RAISE (mRAISE) corticosteroid regimen was implemented as a primary adjunctive therapy in high-risk KD patients treated at Lurie Children’s Hospital beginning in 2017. The regimen consists of IV methylprednisolone 2 mg/kg/day for 5 days, followed by oral prednisone 2 mg/kg/day for 5 days, and then a taper over 10 days. For the current study, data on children with high-risk KD treated with the mRAISE regimen from 2017– 2023 and those treated between 2010 and 2016 without the corticosteroid regimen were analyzed. Standardized criteria were used to classify a patient at high risk for being classified as high-risk. The medical records of study children were reviewed and demographic and clinical data abstracted. Some study patients treated before 2017 received limited corticosteroids in a non-standardized fashion. The primary study outcome was maximum CA z-score (z-Max). Other outcomes included increase in CA z-scores >2 standard deviations (SD), decrease in z-score >2 SD from z-Max, and need for retreatment with IVIG. Outcomes were compared between those in the mRAISE corticosteroid and the non-mRAISE groups. Separate analyses were conducted comparing outcomes between the mRAISE group and those who received no corticosteroids.Data were analyzed on 221 children with high-risk KD, including 83 treated with the mRAISE regimen and 138 in the non-mRAISE group; 82 patients in the non-mRAISE group received no corticosteroids. Among those in the mRAISE group, the median z-Max was 1.80, which was not significantly different from z-MAX in children in the non-mRAISE group (1.84; P = 0.47), or in the subgroup who received no corticosteroids (2.08; P = 0.50). There also were no differences between those treated with the mRAISE protocol and the non-mRAISE group or those not receiving any corticosteroids for the other CA outcomes. IVIG retreatment was required in 9 (11%) children in the mRAISE group and 45 (33%) for those in the non-mRAISE group (P <0.001).The authors conclude that use of a specific regimen of corticosteroids was not associated with reduced CA abnormalities in a North American population of high-risk children with KD.Dr Philip has disclosed no financial relationship relevant to this commentary. This commentary does not contain a discussion of an unapproved/investigative use of a commercial product/device.KD is the leading cause of acquired heart disease in children in the developed world. Timely initiation of IVIG therapy has reduced the incidence of coronary artery aneurysms (CAA), which are associated with long-term morbidity and mortality.1 Risk factors for CAA include higher baseline CA dimension, young age, IVIG resistance, Asian race, and late treatment.2 In Japanese children with a high risk of IVIG resistance, the adjunctive use of corticosteroids/cyclosporine has reduced the incidence of CAA in randomized clinical trials.3In the current single-center retrospective study that included all high-risk KD patients, the effect of primary adjunctive corticosteroid therapy with IVIG on CA outcomes was evaluated and compared with those who did not primarily receive the corticosteroid protocol. While there was no significant difference in CA outcomes identified with the use of adjunctive corticosteroids, there was a significantly lower IVIG resistance rate in this cohort. The United States has been experiencing critical national shortages in IVIG. The use of adjunctive corticosteroids in high-risk KD patients may decrease their need for IVIG and potentially increase the availability of IVIG.The lack of alignment with other studies on CA outcomes may be secondary to the variances in race and disease. (See AAP Grand Rounds. 2024;51[1]:5.)4 in different population subsets. Other limitations were the retrospective nature of the study, which accounted for the variation in aspirin dosing between eras, though one should have expected a higher resistance rate with lower aspirin dosing/anti-inflammatory therapy. One also may argue that the overlap in diagnosis with the advent of COVID and multisystem inflammatory syndrome in children (MIS-C) may have impacted the results. (See AAP Grand Rounds. 2025;53[3]:27.)5Primary adjunctive therapy with corticosteroids in high-risk KD lowers IVIG resistance.