Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Review
. 2018 Dec 11:6:374.
doi: 10.3389/fped.2018.00374. eCollection 2018.

The Epidemiology and Pathogenesis of Kawasaki Disease

Anne H Rowley  1 , Stanford T Shulman  1
Affiliations
Review

The Epidemiology and Pathogenesis of Kawasaki Disease

Anne H Rowley et al. Front Pediatr. .

Abstract

Epidemiologic and clinical features of Kawasaki Disease (KD) strongly support an infectious etiology. KD is worldwide, most prominently in Japan, Korea, and Taiwan, reflecting increased genetic susceptibility among Asian populations. In Hawaii, KD rates are 20-fold higher in Japanese ethnics than in Caucasians, intermediate in other ethnicities. The age distribution of KD, highest in children < 2 yo, lower in those < 6 months, is compatible with infection by a ubiquitous agent resulting in increasing immunity with age and with transplacental immunity, as with some classic viruses. The primarily winter-spring KD seasonality and well-documented Japanese epidemics with wave-like spread also support an infectious trigger. We hypothesize KD pathogenesis involves an RNA virus that usually causes asymptomatic infection but KD in a subset of genetically predisposed children. CD8 T cells, oligoclonal IgA, and upregulation of cytotoxic T cell and interferon pathway genes in the coronaries in fatal KD also support a viral etiology. Cytoplasmic inclusion bodies in ciliated bronchial epithelium identified by monoclonal antibodies made from oligoclonal IgA heavy chains also supports a viral etiology. Recent availability of "second generation" antibodies from KD peripheral blood plasmablasts may identify a specific viral antigen. Thus, we propose an unidentified ("new") RNA virus infects bronchial epithelium usually causing asymptomatic infection but KD in a subset of genetically predisposed children. The agent persists in inclusion bodies, with intermittent respiratory shedding, entering the bloodstream via macrophages targeting coronaries. Antigen-specific IgA plasma cells and CD8 T cells respond but coronaries can be damaged. IVIG may include antibody against the agent. Post infection, 97-99% of KD patients are immune to the agent, protected against recurrence. The agent can spread either from those with asymptomatic primary infection in winter-spring or from a previously infected contact who intermittently sheds the agent.

Keywords: coronary; etiology; kawasaki; pathogenesis; pediatric.

PubMed Disclaimer

Figures

Figure 1
Figure 1
A proposed model of KD pathogenesis.
See this image and copyright information in PMC

References

    1. Makino N, Nakamura Y, Yashiro M, Sano T, Ae R, Kosami K, et al. Epidemiological observations of Kawasaki disease in Japan, 2013-2014. Pediatr Int. (2018) 60:581–7. 10.1111/ped.13544 - DOI - PubMed
    1. Kim GB, Han JW, Park YW, Song MS, Hong YM, Cha SH, et al. Epidemiologic features of Kawasaki disease in South Korea: data from nationwide survey, 2009-2011. Pediatr Infect Dis J. (2014) 33:24–7. 10.1097/INF.0000000000000010 - DOI - PubMed
    1. Lin MC, Lai MS, Jan SL, Fu YC. Epidemiologic features of Kawasaki disease in acute stages in Taiwan, 1997-2010: effect of different case definitions in claims data analysis. J Chin Med Assoc. (2015) 78:121–6. 10.1016/j.jcma.2014.03.009 - DOI - PMC - PubMed
    1. Holman RC, Belay ED, Christensen KY, Folkema AM, Steiner CA, Schonberger LB. Hospitalizations for Kawasaki syndrome among children in the United States, 1997-2007. Pediatr Infect Dis J. (2010) 29:483–8. 10.1097/INF.0b013e3181cf8705 - DOI - PubMed
    1. Yanagawa H, Nakamura Y, Kawasaki T, Shigematsu I. Nationwide epidemic of Kawasaki disease in Japan during winter of 1985-86. Lancet (1986) 2:1138–9. 10.1016/S0140-6736(86)90541-6 - DOI - PubMed