Corticosteroids Appear to Prevent Coronary Abnormalities in Kawasaki Disease

By Will Boggs, MD

August 21, 2020

NEW YORK (Reuters Health) - Addition of corticosteroids to initial intravenous immunoglobulin (IVIG) treatment appears to reduce the rate of coronary-artery abnormalities in high-risk patients with Kawasaki disease, according to a nationwide survey from Japan.

"Clinical trials in Japan have previously demonstrated that the initial use of corticosteroids in combination with the standard IVIG treatment was more effective in preventing development of coronary-artery abnormalities among select patients," said Dr. Ryusuke Ae of Jichi Medical University, in Tochigi, Japan, and the Centers for Disease Control and Prevention, in Atlanta.

"However, a multicenter, randomized trial in the United States did not reach the same conclusion," he told Reuters Health by email.

For the current study, Dr. Ae and colleagues used data derived from the 21st and 24th nationwide Kawasaki disease surveys in Japan to compare the effectiveness of standard treatment with IVIG and aspirin versus corticosteroids added to standard treatment in preventing coronary-artery abnormalities in patients with high-risk Kawasaki disease.

After applying selection criteria and matching steps to patients from 115 hospitals, 1,593 patients with Kawasaki disease in the combination-treatment group and the same number of controls in the standard-treatment group were selected for inclusion in 1,000 sample iterations of a logistic regression analysis.

The median number of patients who developed coronary-artery abnormalities was 47% lower in the combination-treatment group (4.6%) than in the standard-treatment group (8.8%), a significant reduction.

The median treatment-failure rate was also significantly lower with combination treatment (14.1%) than with standard treatment (21.7%), the researchers report in the Journal of the American Heart Association.

Secondary analyses that controlled for potential unmeasured confounding yielded similar results.

"Our study, along with others, supports the conclusion that coronary-artery complications can be reduced or prevented in many severe cases with early intensification of standard treatment, such as use of a combination of IVIG and corticosteroid," Dr. Ae said.

"Clinicians should consider combination treatment with multiple-dose corticosteroids for high-risk Kawasaki disease patients," he said. "Early diagnosis and prompt treatment are important for children with Kawasaki disease to prevent development of cardiac complications."

Dr. Ae continued, "Recent studies have indicated that infliximab may also be effective in combination with initial IVIG treatment for treating Kawasaki disease. Further research is needed to compare this treatment regimen with combination multiple-dose corticosteroid treatment to determine which is more effective in preventing development of coronary-artery abnormalities in high-risk patients with Kawasaki disease."

"Multisystem inflammatory syndrome in children (MIS-C) is a new condition associated with the COVID-19 pandemic where different body parts can become inflamed, including the heart, lungs, kidneys, brain, skin, eyes, or gastrointestinal organs," he added. "Children with MIS-C may present with Kawasaki disease-like features, and may have a fever and various symptoms, including abdominal (gut) pain, vomiting, diarrhea, neck pain, rash, bloodshot eyes, or feeling extra tired. Currently, there is limited information available about other risk factors, pathogenesis, clinical course (particularly the long-term consequences of the illness), and treatment for MIS-C. As with Kawasaki disease, treatments have consisted primarily of supportive care and directed care against the underlying inflammatory process. In published reports of the treatments that many institutions have been using, anti-inflammatory measures have included the frequent use of IVIG and steroids. However, formal treatment trials would be necessary to determine the extent to which the results of our study may or may not apply to US cases of Kawasaki disease or to MIS-C."

Dr. Masaru Miura of Tokyo Metropolitan Children's Medical Center, who earlier reported the efficacy and safety of IVIG plus prednisolone in patients with Kawasaki disease, told Reuters Health by email, "In Japan, corticosteroids have been used to treat patients with positive risk scores predicting unresponsiveness to immunoglobulin therapy. However, the risk scores are not useful in the United States and Europe; in the United States, it is suggested that coronary-artery dilation on echocardiography (based on the Z-scores of diameters) before treatment is a risk factor for coronary-artery-aneurysm complications, and these patients may benefit from the concomitant use of corticosteroids."

"Corticosteroids should be used aggressively in the initial treatment for Kawasaki disease patients who are at risk for coronary aneurysms," said Dr. Miura, who was not involved in the new study. "Early administration of corticosteroids is also recommended as an additional treatment for those unresponsive to initial immunoglobulin therapy."

SOURCE: Journal of the American Heart Association, online August 19, 2020.