Management of Kawasaki disease

Abstract

Kawasaki disease (KD) is an acute self-limiting inflammatory disorder, associated with vasculitis, affecting predominantly medium-sized arteries, particularly the coronary arteries. In developed countries KD is the commonest cause of acquired heart disease in childhood. The aetiology of KD remains unknown, and it is currently believed that one or more as yet unidentified infectious agents induce an intense inflammatory host response in genetically susceptible individuals. Genetic studies have identified several susceptibility genes for KD and its sequelae in different ethnic populations, including FCGR2A, CD40, ITPKC, FAM167A-BLK and CASP3, as well as genes influencing response to intravenous immunoglobulin (IVIG) and aneurysm formation such as FCGR3B, and transforming growth factor (TGF) β pathway genes. IVIG and aspirin are effective therapeutically, but recent clinical trials and meta-analyses have demonstrated that the addition of corticosteroids to IVIG is beneficial for the prevention of coronary artery aneurysms (CAA) in severe cases with highest risk of IVIG resistance. Outside of Japan, however, clinical scores to predict IVIG resistance perform suboptimally. Furthermore, the evidence base does not provide clear guidance on which corticosteroid regimen is most effective. Other therapies, including anti-TNFα, could also have a role for IVIG-resistant KD. Irrespective of these caveats, it is clear that therapy that reduces inflammation in acute KD, improves outcome. This paper summarises recent advances in the understanding of KD pathogenesis and therapeutics, and provides an approach for managing KD patients in the UK in the light of these advances.

Keywords: Infectious Diseases; Rheumatology.

Figure 1

Recommended clinical guideline for the management of Kawasaki disease in the UK. Since risk scores for IVIG resistance perform sub-optimally in non-Japanese patients (Table 3), we cannot recommend their use to define high risk definitively; clinicians may, however, choose to consider the clinical and laboratory parameters listed to identify “high risk” patients. If the Kobayashi risk score is “positive” in a non-Japanese patient (eg,≥ 5) then IVIG resistance is likely; however a score <5 does not reliably exclude IVIG resistance. The aim of treatment is to switch off the inflammatory process that is damaging the coronary arteries as rapidly as possible. In the absence of a strong evidence base favouring a specific corticosteroid regimen, two suggested corticosteroid regimens for high-risk cases are provided for clinicians to choose from. For those on low dose aspirin, we also recommend avoiding the concomitant use of non-steroidal anti-inflammatory drugs (NSAIDs) as these interfere with the anti-platelet effect of low dose aspirin. *Treatment can be commenced before 5 days of fever if sepsis excluded; treatment should also be given if the presentation is > 10 days from fever onset if there are signs of persistent inflammation; **Kobayashi risk score ≥5 points ^aRefer to paediatric cardiologist; ¶ Other specific interventions such as positron emission tomography (PET) scanning, addition of calcium channel blocker therapy, and coronary angioplasty at discretion of paediatric cardiologist. + Other immunomodulators may include ciclosporin. ♥For infants, Z score for internal coronary artery diameter >7 based on Montreal normative data: http://parameterz.blogspot.co.uk/2010/11/montreal-coronary-artery-z-scores.html.