Kawasaki Disease Guideline Highlights Rheumatology Angles

Heidi Splete

March 23, 2022

All Kawasaki disease (KD) patients should be treated first with intravenous immunoglobulin, according to an updated guideline issued jointly by the American College of Rheumatology and the Vasculitis Foundation.

Dr Mark Gorelik

KD has low mortality when treated appropriately, guideline first author Mark Gorelik, MD, assistant professor of pediatrics at Columbia University, New York, and colleagues wrote.

The update is important at this time because new evidence continues to emerge in the clinical management of KD, Gorelik said in an interview.

"In addition, this guideline approaches Kawasaki disease from a perspective of acting as an adjunct to the already existing and excellent American Heart Association guidelines by adding information in areas that rheumatologists may play a role," Gorelik said. "This is specifically regarding patients who may require additional therapy beyond standard IVIg, such as patients who may be at higher risk of morbidity from disease and patients who have refractory disease," he explained.

The guideline, published in Arthritis & Rheumatology, includes 11 recommendations, 1 good practice statement, and 1 ungraded position statement. The good practice statement emphasizes that all patients with KD should be initially treated with IVIg.

The position statement advises that either nonglucocorticoid immunosuppressive therapy or glucocorticoids may be used for patients with acute KD whose fever persists despite repeated IVIg treatment. No clinical evidence currently supports the superiority of either nonglucocorticoid immunosuppressive therapy or glucocorticoids; therefore, the authors support the use of either based on what is appropriate in any given clinical situation. Although optimal dosage and duration of glucocorticoids have yet to be determined in a U.S. population, the authors described a typical glucocorticoid dosage as starting prednisone at 2 mg/kg per day, with a maximum of 60 mg/day, and dose tapering over 15 days.

The 11 recommendations consist of 7 strong and 4 conditional recommendations. The strong recommendations focus on prompt treatment of incomplete KD, treatment with aspirin, and obtaining an echocardiogram in patients with unexplained macrophage activation syndrome or shock. The conditional recommendations support using established therapy promptly at disease onset, then identifying cases in which additional therapy is needed.

Gorelik highlighted four clinical takeaways from the guideline. First, "patients with higher risk for complications do exist in Kawasaki disease, and that these patients can be treated more aggressively," he said. "Specifically, patients with aneurysms seen at first ultrasound, and patients who are under 6 months, are more likely to have progressive and/or refractory disease; these patients can be treated with an adjunctive short course of corticosteroids."

Second, "the use of high-dose aspirin for patients with Kawasaki disease does not have strong basis in evidence. While aspirin itself of some dose is necessary for patients with Kawasaki disease, use of either high- or low-dose aspirin has the same outcome for patients, and a physician may choose either of these in practice," he said.

Third, "we continue to recommend that refractory patients with Kawasaki disease be treated with a second dose of IVIg; however, there are many scenarios in which a physician may choose either corticosteroids [either a single high dose of >10 mg/kg, or a short moderate-dose course of 2 mg/kg per day for 5-7 days] or a biologic agent such as infliximab. ... These are valid choices for therapy in patients with refractory Kawasaki disease," he emphasized.

Fourth, "physicians should discard the idea of treating before [and conversely, not treating after] 10 days of fever," Gorelik said. "Patients with Kawasaki disease should be treated as soon as the diagnosis is made, regardless of whether this patient is on day 5, day 12, or day 20 of symptoms."

Update Incorporates Emerging Evidence

Potential barriers to implementing the guideline in practice include the challenge of weaning doctors from practices that are habitual in medicine, Gorelik said. "One of these is the use of high-dose aspirin for Kawasaki disease; a number of studies have shown over the past decade or more that high-dose aspirin has no greater effect than lower-dose aspirin for Kawasaki disease. Despite all of these studies, the use of high-dose aspirin continued. High-dose aspirin for Kawasaki disease was used in the era prior to use of IVIg as an anti-inflammatory agent. However, it has poor efficacy in this regard, and the true benefit for aspirin is for anticoagulation for patients at risk of a clot, and this is just as effective in lower doses. Expressing this in a guideline could help to change practices by helping physicians understand not only what they are guided to do, but why."

Additional research is needed to better identify high-risk patients in non-Japanese populations, he noted. "While studies from Japan suggest that higher-risk patients can be identified based on various parameters, these have not been well replicated in non-Japanese populations. Good research that identifies which patients may be more at risk in other populations would be helpful to more precisely target high-risk therapy."

Other research needs include a clearer understanding of the best therapies for refractory patients, Gorelik said. "One area of the most difficulty was determining whether patients with refractory disease should have repeated IVIg or a switch to glucocorticoids and biologic agents. Some of this research is underway, and some was published just as these guidelines were being drawn, and this particular area is one that is likely to change significantly. While currently we recommend a repeated dose of IVIg, it is likely that over the very near term, the use of repeated IVIg in KD will be curtailed" because of concerns such as the relatively high rate of hemolysis. Research to identify which therapy has a noninferior effect with a superior risk profile is needed; such research "will likely result in a future iteration of these guidelines specifically related to this question," he concluded.

The KD guideline is the final companion to three additional ACR/VF vasculitis guidelines that were released in July 2021. The guideline research received no outside funding. The researchers had no financial conflicts to disclose.

This article originally appeared on MDedge.com, part of the Medscape Professional Network.

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