Dissecting Kawasaki disease: a state-of-the-art review

Abstract

Kawasaki disease (KD) is a pediatric vasculitis with coronary artery aneurysms (CAA) as its main complication. The diagnosis is based on the presence of persistent fever and clinical features including exanthema, lymphadenopathy, conjunctival injection, and changes to the mucosae and extremities. Although the etiology remains unknown, the current consensus is that it is likely caused by an (infectious) trigger initiating an abnormal immune response in genetically predisposed children. Treatment consists of high dose intravenous immunoglobulin (IVIG) and is directed at preventing the development of CAA. Unfortunately, 10–20% of all patients fail to respond to IVIG and these children need additional anti-inflammatory treatment. Coronary artery lesions are diagnosed by echocardiography in the acute and subacute phases. Both absolute arterial diameters and z-scores, adjusted for height and weight, are used as criteria for CAA. Close monitoring of CAA is important as ischemic symptoms or myocardial infarction due to thrombosis or stenosis can occur. These complications are most likely to arise in the largest, so-called giant CAA. Apart from the presence of CAA, it is unclear whether KD causes an increased cardiovascular risk due to the vasculitis itself. Conclusion: Many aspects of KD remain unknown, although there is growing knowledge on the etiology, treatment, and development and classification of CAA. Since children with previous KD are entering adulthood, long-term follow-up is increasingly important. What is known: • Kawasaki disease (KD) is a pediatric vasculitis with coronary artery damage as its main complication. • Although KD approaches its 50th birthday since its first description, many aspects of the disease remain poorly understood. What is new: • In recent years, multiple genetic candidate pathways involved in KD have been identified, with recently promising information about the ITPKC pathway. • As increasing numbers of KD patients are reaching adulthood, increasing information is available about the long-term consequences of coronary artery damage and broader cardiovascular risk.

Complete Kawasaki disease (KD) with peculiar skin manifestations

“…All these mucosal and cutaneous manifestations in addition to fever lasting longer than 5 days were consistent with the diagnosis of a complete form of Kawasaki disease (KD) 1. Moreover, C-reactive protein and erythrocyte sedimentation rate were increased, as well as α2-globulin fraction of serum proteins.…”

Kawasaki Disease

“…Various susceptibility genes have been identified to have association with KD. These includes inositol 1,4,5-trisphosphate 3-kinase C (ITPKC), Caspase-3 calcium release-activated calcium modulator 1 (ORAI1), and CD 40 [19][20][21]. Knowledge about these susceptibility genes may provide new insights in etiopathogenesis of KD.…”

Plaque psoriasis following Kawasaki disease and varicella

“…It is believed that an infectious agent induces an abnormal immune response in genetically predisposed individuals 2. Infection with varicella zoster virus (VZV) has been associated with KD in a few reports 3–9…”