What's new in Kawasaki disease?

DR. MILANA is assistant professor and DR. CHANDRAN is associate professor in the department of pediatrics at the State University of New York at Stony Brook.

Staff editors: KAREN BARDOSSI, Senior Editor, and JOHN BARANOWSKI, Editor, Contemporary Pediatrics.

The authors, manuscript reviewers, and staff editors have nothing to disclose in regard to affiliations with, or financial interests in, any organization that may have an interest in any part of this article.

A 14-year study in Japan reported a seasonal distribution, with bimodal peaks in January and June and July and a nadir in October.³ In this country, however, most cases occur in late winter and early spring.² The seasonality of the disease, along with its age distribution and tendency to cluster in communities, suggest a possible infectious cause. However, no causative agent has been definitively identified. A familial occurrence has been noted⁴ , suggesting that KD may have a genetic component as well. Current thinking is that KD results from "one or more widely distributed infectious agents, which evoke an abnormal immunological response in genetically susceptible persons."⁵

KD can be difficult to diagnose and challenging to manage over the long term. Newly revised guidelines offer a helpful approach to evaluating the child who does not meet all the classical clinical criteria for KD. They also outline long-term treatment strategies to prevent complications, chiefly myocardial infarction.

What happens in Kawasaki disease?

KD is an acute febrile illness that arises from systemic vasculitis. It has three distinct clinical phases: the acute phase, subacute phase, and convalescent phase. The acute phase, which usually lasts one or two weeks, is marked by fever and other signs and symptoms of acute inflammation. In the subacute phase, which occurs two to four weeks after the onset of symptoms, the fever resolves, but irritability, loss of appetite, and conjunctivitis usually persist. Periungual desquamation with accompanying thrombocytosis and development of coronary artery aneurysms are characteristic of this phase.

The convalescent phase occurs six to eight weeks after the onset of illness. At this point, all signs and symptoms resolve, and laboratory values consistent with acute inflammation start to normalize.

KD affects mainly medium-sized arteries, with a particular predilection for the coronary arteries. It has replaced acute rheumatic fever as the most common cause of acquired heart disease in children in the U.S.⁶ Aneurysms also may occur in the celiac, mesenteric, femoral, renal, and other arteries.⁷

In the acute phase of the disease, the endothelial and smooth-muscle cells become edematous with inflammatory infiltration of the vessel walls. The infiltration starts with neutrophils, but eventually switches to macrophages, lymphocytes, and plasma cells. Immunoglobulin A (IgA) plasma cells are prominent in the infiltrate. During this process, the vessel loses its structural integrity and weakens, resulting in dilatation of the artery or formation of aneurysms. As the vessel heals, lesions become fibrotic and stenotic, leading to formation of scars. Reduced blood flow within coronary aneurysms predisposes the area to chronic thrombus formation. Stenotic areas may also develop at the inlet and outlet of the aneurysm. The combination of low blood flow and stenosis activates platelets and leads to formation of thrombi.

Risk factors for developing aneurysms include male gender, age younger than 1 year or older than 5 years, persistent fevers refractory to treatment, anemia, hypoalbuminemia, and a high level of C-reactive protein (CRP) on presentation. African Americans have a decreased likelihood of developing coronary artery aneurysms.⁸