Regimen effective for preventing aneurysm in children with refractory Kawasaki disease

By Liz Meszaros, MDLinx
Published April 14, 2018

Key Takeaways

A safe, effective strategy for preventing coronary artery aneurysm (CAA) in children with refractory Kawasaki disease incorporates first-, second-, and third-line treatment with intravenous methylprednisolone (IVMP), IV immunoglobulin (IVIG), and infliximab (IFX). The researchers from Japan who developed and tested the strategy published their results in The Journal of Pediatrics.

Kawasaki disease is a systemic vasculitis that occurs primarily in children, with 80% of cases occurring between ages 6 months to 4 years old. It occurs most often in Japan. In the United States, children of Asian or Asian American background are most affected, with about 1,800 new cases of Kawasaki disease being diagnosed annually. The etiology of Kawasaki disease is, as yet, unknown but it is a major cause of heart disease in children, according to the American Heart Association.

“Although remarkable progress has been made in the treatment of acute-phase Kawasaki disease since the introduction of high-dose IVIG treatment,1 3% to 5% of children with Kawasaki disease still suffer from cardiovascular lesions, especially coronary artery aneurysm. In particular, if a coronary artery aneurysm develops, it becomes a risk factor for acute coronary syndrome,” noted the authors, led by Takasuke Ebato, MD, Department of Pediatrics, Kitasato University, Kanagawa, Japan.

Dr. Ebato and fellow researchers undertook this study to assess the clinical usefulness and safety of their strategy for refractory Kawasaki disease, which they defined as an Egami score of ≥3.

Of 365 children with Kawasaki disease treated at Kitasato University Hospital from April 2007 to April 2016, 71 patients were diagnosed with refractory disease (median age: 2.4 years; 39 males).

All patients were treated with IVMP (30 mg/kg, 2 hours, 1 dose) and IVIG (2 g/kg, 24 hours).

Treatment resistance was defined as a persistent fever at 36 hours after treatment.

“Under our treatment strategy, we believe that a fever will break out again if the suppression of Kawasaki disease vasculitis is insufficient, allowing us to provide a more appropriate additional treatment,” noted the authors.

Patients resistant to first-line treatment received additional IVIG. Those resistant to second-line treatment were treated with IFX if they had been vaccinated with Bacillus Calmette-Guérin 6 months or more earlier, or plasma exchange if they were not.

In accordance with American Heart Association guidelines and Japanese Ministry of Health, Labor, and Welfare criteria, Dr. Ebato and fellow researchers assessed coronary artery lesions at the time of diagnosis, at 1 month, and finally at 1 year after diagnosis

First-line therapy was effective in 81.6% of patients and second-line in 69.2%. Four patients received third-line therapy, three of whom were treated with infliximab and one with plasma exchange.

At diagnosis and before initial treatment, 18 patients (25.3%) had evidence of coronary artery abnormalities. At 1 month, 13 of these patients demonstrated coronary artery dilatation. After treatment, 17 showed improvements in coronary artery status, with z scores all less than 2.5. A z score of 5 or more was considered evidence of a CAA.

The remaining patient underwent additional therapy with IVIG and responded with a z score of less than 2.5 in the left anterior descending artery; however, dilation in the right coronary artery (RCA) remained at more than 2.5 but less than 5. One year later, RCA dilation was improved, with a z score of less than 2.5.

No patient developed CAA or CAA of 4 mm or greater.

Side effects due to IVMP included transient hypothermia, transient hypertension, and heart rate deceleration. No side effects occurred in patients treated with IFX or plasma exchange.

“The combination of IVIG treatment and IVMP treatment as the initial treatment was effective for 83.8% of patients even with refractory Kawasaki disease. We believe that this was the reason for our good results. In addition, patients with treatment resistance were able to be identified without the antipyretic action of steroids, which allowed us to administer additional therapy at the appropriate time. We were also able to prevent the onset of CAA, because all treatments were administered within 14 days after the onset of Kawasaki disease, which is when coronary artery lesions are most likely to occur,” noted Dr. Ebato and colleagues.

“Our strategy for treatment of refractory Kawasaki disease was found to be safe. Future studies will be needed to confirm these results,” they concluded.


  1. Newburger JW, Takahashi M, Beiser AS, et al. A single intravenous infusion of gamma globulin as compared with four infusions in the treatment of acute Kawasaki syndrome. N Engl J Med. 1991;324:1633-1639.
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