Kawasaki disease seasonality in Venezuela supports an arbovirus infection trigger

Abstract

Kawasaki disease (KD) is an inflammatory disease primarily affecting infants and young children, whose etiology remains uncertain. Observational studies of the overlap between KD outbreaks and seasonal peaks of arboviral infections, suggest the possible role of these pathogens as triggers of KD. In Venezuela, regions with the highest reported arboviral infections simultaneously have the highest incidence of KD. One proposed explanation for this association involves the role of proinflammatory mediators, interleukin‐1 (IL‐1), IL‐6, tumor necrosis factor, and vascular endothelial growth factor as mediators of coronary endothelial damage. The promotion of inflammation and tissue destruction by these cytokines is thought to contribute to the coronary endothelial damage experienced in KD. The utilization of overlapping KD and arboviral infection trends contribute to the comprehension of KD etiology, with improvements in diagnosis, prognosis and treatment.

Emerging evidence of microbial infection in causing systematic immune vasculitis in Kawasaki disease

“…In addition, dengue virus was also identified in the serum of certain KD patients in southern Thailand, and mosquitoes were hypothesized to work with the dengue virus to spread the KD pathogen, thus inducing cell proliferation and morphological changes in endothelial cells and coronary arteritis lesions in KD patients ( Sopontammarak et al, 2008 ). Moreover, regions with the highest reported arboviral infections in Venezuela simultaneously have the highest incidence of KD ( Paniz-Mondolfi et al, 2020 ), demonstrating the critical roles of viral infections in mediating the pathogenesis of KD.…”

Advances in understanding Kawasaki disease‐related immuno‐inflammatory response and vascular endothelial dysfunction

“…The strong immuno‐inflammatory response in acute KD and persistent low‐grade inflammation in chronic KD cause substantial and persistent damage to vascular endothelial cells (VECs) 32 . The production of pro‐inflammatory mediators (e.g., IL‐1, IL‐6, tumor necrosis factor, and vascular endothelial growth factor [VEGF]) promotes inflammation and tissue destruction, which are important causes of coronary artery endothelial injury in patients with KD 33 . The number of early fever days in patients with KD is positively correlated with the risk of VEC dysfunction 34 .…”

“… 32 The production of pro‐inflammatory mediators (e.g., IL‐1, IL‐6, tumor necrosis factor, and vascular endothelial growth factor [VEGF]) promotes inflammation and tissue destruction, which are important causes of coronary artery endothelial injury in patients with KD. 33 The number of early fever days in patients with KD is positively correlated with the risk of VEC dysfunction. 34 CAD is not a determinant of endothelial dysfunction in patients with KD or with a history of KD.…”