Exploring Kawasaki Disease

Studies have identified certain demographic features of children at high risk for resistance to treatment with immune intravenous globulin (IVIG) with the concomitant risk of coronary artery aneurysms. Risk factors include male sex, age younger than 6 months and older than 9 years, Asian/Pacific Islander race and Hispanic ethnicity, as well as laboratory findings at the time of diagnosis, including leukocytosis, thrombo­cytopenia, hypoalbuminemia, hyponatremia, trans­aminitis and an elevated C-reactive protein.

Risk scores to identify children at risk for IVIG resistance have been constructed and tested in Japanese populations by Kobayashi et al,³ Sano et al4 and Egami et al.⁵ Unfortunately, these risk scores do not appear to successfully identify North American children at risk for IVIG resistance.⁶

Etiology

As mentioned above, the etiology of KD remains unknown. The hallmark symptoms of fever and rash mimic an infectious disease, and discrete seasonal peaks with clustering of cases in geographic areas suggest a transmittable vector.⁷

Further, the epidemiology of KD is consistent with an infectious agent, because it is highly unusual for two populations to have KD: very young babies who may be protected by maternal antibodies via placental transfer, and adults who have presumably seen multiple infectious agents and are immune. However, an infectious agent has been searched for exhaustively. To date no single culprit has been found.

Other theories of the pathogenesis of KD include the possibility of superantigen activity, because children can present with hypotension if myocarditis is significant and there is erythroderma present. However, studies of toxins made by Staphylococcus aureus and Streptococcus pyogenes acting as superantigens have varied in regard to conclusive evidence of such.

Genome-wide association studies have identified polymorphisms in the ITPKC gene (a T cell regulator),⁸ in B lymphoid tyrosine kinase9 and in a high-affinity receptor for immunoglobulin G (FCGR2A) in patients with KD.10 The functional single-nucleotide polymorphisms in the ITPKC gene have been associated with IVIG resistance and worse coronary artery outcomes.

An alternative hypothesis for the pathogenesis of KD is that multiple environmental and/or infectious triggers may lead to a stereotyped inflammatory cascade with the characteristic features of KD as a final common pathway.

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Figure 1: Evaluation of Suspected Incomplete Kawasaki Disease. Source: Reprinted with permission. Circulation. 2004;110:2747–2771. ©2004 American Heart Association, Inc.

Clinical Features & Diagnosis

The diagnosis of KD relies on a case definition (Table 1), because reliable diagnostic testing has not yet been discovered. It should be noted that not all features of KD may be present simultaneously, and a thorough history of the course of the illness is required. All features of KD will resolve, typically within 11–12 days, even in the absence of treatment.