Kawasaki Disease Research

Kawasaki disease (KD) is an acute inflammatory disease characterized by persistent high-grade fever along with certain mucosal and dermatological changes, and generally presents with varying degrees of multi-organ system manifestations including acute vasculitis, myocarditis, pulmonary infiltrates as well as aseptic meningitis mostly in young children and infants below 5 years of age. This phenomenon was first described in Japan where its annual incidence has been substantially higher compared with other geographical regions. Pathogenetically, a substantial immune response induced by specific antigens including viruses possibly accounts for KD evolution mostly through an acute autoinflammatory reaction characterized by a plenitude of activated circulating neutrophils and augmented proinflammatory pathways including interleukin (IL)-1 and IL-6 cascades. The most dreaded clinical manifestation appears to be the ‘coronary arteritis’ potentially complicated by subsequent ‘coronary artery aneurysm (CAA)’ formation. Morphologically, CAA in the setting of KD is defined as an ‘ectatic coronary segment’ with a diameter of >1.5 times that of the reference segment or an echocardiographic Z score of >2.5. In this context, harnessing Z score (that universally signifies standard deviation from the avarage) allows adjustment for certain variables including body surface area. Therefore, one should not exclusively rely on numerical values (including aneurysm diameter) to define CAAs in children due to the significant variation in their body sizes (and hence; coronary artery diameters at baseline). Importantly, coronary artery involvement, besides being an ominous sign, also confirms the diagnosis of KD in cases with incomplete or ambiguous findings. Temporally, CAA evolution in the setting of KD has been universally regarded as an early-onset phenomenon, and is well known to be associated with the severity of the disease course, and in particular; with the failure to initiate disease-modifying strategies including intravenous immunoglobulin (IVIG), etc.in a timely manner. In particular, classical CAAs in the setting of KD have a male gender predilection with an incidence of 25% that has declined to around 4% with the initiation of proper management strategies.

Biomarkers that tell us whether a coronary aneurysm is growing in size or spontaneously regressing. Research into these aspects is being conducted in close collaboration with a reference center in China, where most cases of Kawasaki disease occur (Department for Pediatric Cardiology, Shaanxi Provincial People's Hospital, Xiatong University, Xi'an, China, Chief: Prof. Jiao Fuyong).