New Hope for Treatment of Rare Pediatric Disease

Feb 25, 2014, 1:00 PM

About 19 in every 100,000 American children under the age of five suffers from an inflammatory illness called Kawasaki Disease (KD) that can cause irreversible damage to the heart. If diagnosed early, it can usually be treated effectively, and children can be returned to health in just a few days. But between 10 and 20 percent of treated patients suffer from a persistent fever, or one that recurs after treatment, and they are at elevated risk of developing coronary artery aneurysms. A new study, led by Robert Wood Johnson Foundation (RWJF) Harold Amos Medical Faculty Development Program Scholar Adriana H. Tremoulet, MD, MAS, and published yesterday in The Lancet, offers new hope for patients with KD.

The symptoms of KD include prolonged fever associated with a rash, swollen neck glands, red eyes, swollen red lips, a condition physicians call strawberry tongue, and swollen hands and feet with peeling skin. Current treatment is infusion of intravenous immunoglobulin (IVIG) and aspirin. The IVIG carries the pooled antibodies from the blood plasma of more than 100,000 donors, and in the KD patient, it decreases the inflammation that causes heart damage. The treatment usually works, but some patients’ IVIG-resistance puts them at greater risk and in need of further treatment.

Tremoulet, a pediatric infectious disease specialist at Rady Children’s Hospital in San Diego, conducted a Phase III trial in which a synthetic antibody called infliximab was added to the standard IVIG and aspirin treatment. While the protocol did not affect the patients’ resistance, it had important positive results. “In our study,” Tremoulet said, “we demonstrated that a single dose of infliximab is safe in children with Kawasaki Disease and that this treatment reduced the inflammation in the body overall as well as in the arteries of the heart faster than just using standard treatment with intravenous immunoglobulin.”

She has been at the forefront of another important effort around KD: the development of a straightforward diagnostic test for the disease, a project funded by an RWJF grant. It is currently diagnosed by its symptoms. But not all patients exhibit all symptoms, and the diagnosis is sometimes missed, with dangerous results. Tremoulet and colleagues have developed an algorithm that uses blood work and biomarkers to identify the disease. (Read more about Tremoulet’s work to develop the diagnostic tool.)

She notes that the clinical trial reported in her Lancet paper is noteworthy not just for its promise of progress on the disease. “Few randomized clinical trials are done in pediatrics,” she observes, “and I strongly believe that studies such as ours are critical to providing better care for children.”

Read an abstract of Tremoulet’s article in The Lancet.

This commentary originally appeared on the RWJF Human Capital Blog. The views and opinions expressed here are those of the authors.