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Global incidence of Kawasaki disease: a systematic review

Published online by Cambridge University Press:  08 May 2025

Cho Ryok Kang ,
Jue Seong Lee  and
Young June Choe Open the ORCID record for Young June Choe [Opens in a new window]
Cho Ryok Kang
Affiliation:
Allergy and Immunology Center and Department of Pediatrics, Korea University College of Medicine, Seoul, Korea Department of Nursing, Wonkwang University, Iksan, Korea
Jue Seong Lee
Affiliation:
Allergy and Immunology Center and Department of Pediatrics, Korea University College of Medicine, Seoul, Korea Department of Pediatrics, Korea University College of Medicine and Korea University Anam Hospital, Seoul, Korea
Young June Choe*
Affiliation:
Allergy and Immunology Center and Department of Pediatrics, Korea University College of Medicine, Seoul, Korea Department of Pediatrics, Korea University College of Medicine and Korea University Anam Hospital, Seoul, Korea
*
Corresponding author: Young June Choe; Email: [email protected]
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Abstract

Background:

Kawasaki disease is a systemic vasculitis that primarily affects young children and represents a major cause of acquired heart disease in children in developed countries. The incidence of Kawasaki disease exhibits significant global variation, and the worldwide burden remains limited.

Methods:

A systematic review was conducted to investigate the global incidence of Kawasaki disease in children under 5 years of age. A comprehensive literature search was performed in PubMed, Embase, and KoreaMed up to July 15, 2024. Studies reporting population-level Kawasaki disease incidence were included. Data extraction and quality assessment were performed independently by two reviewers.

Results:

The search yielded 3,197 articles, of which 105 met the inclusion criteria. These studies examined Kawasaki disease incidence in children under 5 years of age across 34 countries, with the majority focusing on the Western Pacific Region and the Region of the Americas. The results demonstrated a wide range of Kawasaki disease incidence globally, with significant geographic variations. The highest incidence rates were observed in Japan, Korea, and Taiwan, with a trend of gradual increase over time.

Conclusions:

This study represents the most comprehensive review of global Kawasaki disease incidence to date. The substantial variation in incidence underscores the need to understand the factors influencing regional differences.

Keywords

Mucocutaneous lymph node syndrome (Kawasaki disease)incidenceglobal healthepidemiologic studiesreview literature as topic
Type
Original Article
Information
Cardiology in the Young , First View , pp. 1 - 12
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Creative Commons
Creative Common License - CCCreative Common License - BY
This is an Open Access article, distributed under the terms of the Creative Commons Attribution licence (https://creativecommons.org/licenses/by/4.0/), which permits unrestricted re-use, distribution and reproduction, provided the original article is properly cited.
Copyright
© The Author(s), 2025. Published by Cambridge University Press

Introduction

Kawasaki disease is an acute systemic vasculitis of unknown aetiology that predominantly affects young children. Reference McCrindle, Rowley and Newburger1 The disease’s hallmark feature is inflammation of medium-sized arteries, with a particular predilection for the coronary arteries. Reference Takahashi, Oharaseki and Yokouchi2 This can lead to coronary artery aneurysms and other cardiovascular complications, making Kawasaki disease the leading cause of acquired heart disease in children in developed countries. Reference Singh, Vignesh and Burgner3 While timely treatment with intravenous immunoglobulin and aspirin significantly reduces the risk of coronary artery involvement, a subset of patients remains unresponsive or develop complications despite treatment. Reference Skochko, Jain and Sun4

The global epidemiology of Kawasaki disease has been characterised by marked geographic and temporal variations, with the highest incidence consistently reported in East Asia, particularly Japan and Korea. Reference Kim5,Reference Burns, Cayan and Tong6 However, a comprehensive understanding of the global burden of Kawasaki disease remains elusive, hindering the development of targeted prevention strategies, optimal allocation of healthcare resources, and a deeper understanding of the disease’s aetiology.

To address this knowledge gap, we conducted a systematic review to investigate the global incidence of Kawasaki disease. By synthesising data from diverse populations and geographic regions, we aim to provide a more comprehensive picture of the worldwide burden of Kawasaki disease, which could inform clinical practice, public health initiatives, and future research directions.

Methods

Search strategy and data sources

A comprehensive literature search was conducted in PubMed, Embase, and KoreaMed by a trained medical librarian (Eun-Ji Kang) from inception up to July 15, 2024. The search strategy, developed initially for MEDLINE using the keywords and MeSH terms, was adapted for other databases. The exact search strategies for PubMed, Embase, and KoreaMed are outlined in Table S1. There were no language restrictions. Reference lists of included articles and relevant literature identified through manual searches were also screened for additional publications. The study protocol has been registered and published with PROSPERO. Reference Schiavo7 This study was exempt from Institutional Review Board approval as a systematic review.

Study selection

Titles and abstracts of identified articles were screened according to the inclusion and exclusion criteria by two reviewers (CRK, YJC). Full-text review was conducted by the same reviewers for all identified articles. Two authors independently reviewed articles for inclusion, resolving disagreements by consensus. Inclusion criteria for selecting articles include studies whose aim is to describe Kawasaki disease incidence in children under 5 years of age in any country or area of a country, including original papers of observational studies, cross-sectional studies, case–control studies, and prospective and retrospective studies. Studies based on Kawasaki disease-relevant ICD-9/ICD-10 codes or guidelines for the diagnosis of Kawasaki disease were included. The exclusion criteria were a) duplicate studies; b) systematic review ± meta-analysis; c) non-original studies including reviews, comments, editorials, case reports, guidelines, and book chapters; d) intervention studies (randomized and clinical controlled trials); e) selected populations of participants with other basic diseases; f) no population-level incidence data of Kawasaki disease; and g) no data available for children under 5 years of age.

Data extraction and quality assessment

Two reviewers (CRK, YJC) independently extracted data on study details, such as first author, publication year, country, study period, study design, data source, and incidence (including incidence rate and admission rate) per 100,000 children under 5 years of age. Discrepancies were resolved through discussion. Studies that met the inclusion criteria were assessed for the risk of bias tool established by Hoy et al. Reference Hoy, Brooks and Woolf8

Results

Study selection

In a systematic search of sources, 3,197 articles were identified. A total of 677 articles were duplicated, and 2,373 were excluded after screening the title and abstract of the articles. After reviewing full-text articles, 42 articles were excluded. Finally, 105 studies were included in the systematic review. Figure 1 shows the identified and retrieved articles in the study.

Figure 1. PRISMA flow diagram.

Study characteristics

The major characteristics of the studies are listed in Table 1. Eligible studies examined Kawasaki disease incidence in children under 5 years of age in 34 countries (Fig 2). A total of 105 studies were published from 1986-2024, mainly concentrated in 2011–2024. The studies were conducted between 1976 and 2021. Dividing the studies by WHO regions, 28 (26.7%) were from the Region of the Americas,Reference Alkanhal, Saunders and Altammar9–Reference Vasudeva, Poku and Thommana36 22 (21.0%) from the European Region,Reference Bar-Meir, Haklai and Dor37–Reference Tulloh, Mayon-White and Harnden58 2 (1.9%) from the Eastern Mediterranean Region,Reference Saffar and Reshidighader59,Reference Shahbaznejad, Hosseininasab and Mahboobi60 2 (1.9%) from the South-East Asia Region,Reference Panamonta, Chaikitpinyo and Durongpisitkul61,Reference Singh and Bhattad62 and 51 (48.6%) from the Western Pacific Region.Reference Abrams, Blase and Belay63–Reference Zhang, Zhang, Liu and Sun113 The majority of studies focused on countries in the Western Pacific Region and the Region of the Americas, and most studies were from the United States (n = 19, 18.1%),Reference Belay, Holman and Clarke11,Reference Belay, Holman, Maddox, Foster and Schonberger12,Reference Bronstein, Dille, Austin, Williams, Palinkas and Burns14–Reference Dawson, Vuong, Ma, Russell, Melish and Bratincsak19,Reference Holman, Belay, Christensen, Folkema, Steiner and Schonberger21–Reference Holman, Shahriari, Effler, Belay and Schonberger26,Reference Lin and Krata28–Reference Okubo, Nochioka, Sakakibara, Testa and Sundel30,Reference Taslakian, Wi and Seol34,Reference Vasudeva, Poku and Thommana36 Japan (n = 18, 17.1%),Reference Abrams, Blase and Belay63–Reference Ae, Makino and Kuwabara65,Reference Iio, Matsubara and Miyakoshi78,Reference Makino, Nakamura and Yashiro89–Reference Makino, Nakamura and Yashiro91,Reference Nakamura, Yashiro, Uehara, Oki, Kayaba and Yanagawa93–Reference Nakamura, Yashiro and Uehara96,Reference Sano, Makino and Aoyama103,Reference Yanagawa, Nakamura and Yashiro106–Reference Yanagawa, Yashiro, Nakamura, Kawasaki and Kato111 Korea (n = 10, 9.5%),Reference Ha, Seo, Kim and Kim72,Reference Kim, Eun and Han79–Reference Kim, Hong, Yoo and Chun82,Reference Lim, Kim, Min, Kim, Lee and Lee84,Reference Oh and Lee98–Reference Park, Han and Park101 and Taiwan (n = 7, 6.7%).Reference Chang, Chang and Lu67,Reference Huang, Lin, Chen, Huang and Wu75–Reference Huang, Lin, Ho, Yan, Lo and Kuo77,Reference Lin, Lai, Jan and Fu85,Reference Lue, Chen and Lin87,Reference Lue, Chen and Lin88 Regarding the methodology, of the total 105 studies, 4 were prospective and 101 were retrospective studies. Among the 101 retrospective studies, 3 were conducted with additional prospective studies, and 29 were conducted together with cross-sectional studies. The quality assessment of each study is shown in Table S2.

Figure 2. Global incidence of Kawasaki disease in children <5 years.

Table 1. Summary of the characteristics of studies included

Incidence of Kawasaki disease in the world

The recent Kawasaki disease incidence in Japan and Korea is the highest worldwide (> 200 per 100,000 children <5 years old). Kawasaki disease incidence is also high in Taiwan and a province (Beijing) of China (> 50 per 1000,000 children <5 years old). For time trends of Kawasaki disease incidence in included studies, the incidence gradually increased in Australia, China, Hong Kong, Japan, Korea, New Zealand, Malaysia, and Taiwan, which are included in the WPR. However, during the COVID-19 pandemic, Kawasaki disease incidence tended to decrease in Japan and Korea. Reference Ae, Makino and Kuwabara65,Reference Oh and Lee98 In the United States, Kawasaki disease incidence differed by administrative region, the incidence in Hawaii was relatively high. There was a slight increase in Kawasaki disease incidence in Canada, Chile, Peru, and the United States, which are included in the AMR. Kawasaki disease incidence in countries included in the European Region, EMR, and South-East Asia Region is nearly constant with low incidence.

Discussion

This systematic review identified 105 studies examining Kawasaki disease incidence in children under 5 years of age from 34 countries. Our review provides the most comprehensive assessment of the global incidence of Kawasaki disease to date. Study findings reveal considerable variation in Kawasaki disease incidence in children under 5 years of age across different populations and geographic regions. The Kawasaki disease incidence in the world reveals substantial variations, highlighting the need for a nuanced understanding of the global burden of Kawasaki disease. The elevated incidence of Kawasaki disease in Japan and Korea, as evidenced in this review, points towards a complex interplay of factors that may contribute to this phenomenon. The prevailing hypothesis suggests a combination of genetic predisposition, environmental influences, and diagnostic practices may be at play. The higher prevalence of certain genetic markers in these populations, particularly specific HLA alleles, suggests a genetic susceptibility to Kawasaki disease. Reference Kwon, Sim and Yu114 The notably higher incidence observed in studies from California and Hawaii, regions with a larger proportion of Asian populations within the United States of America, further suggests the potential influence of genetic factors in Kawasaki disease susceptibility. Reference Callinan, Holman, Vugia, Schonberger and Belay15,Reference Holman, Christensen and Belay23 The rapid industrialisation and improved sanitation in these countries align with the ‘hygiene hypothesis,’ which proposes that reduced exposure to infectious agents in early childhood may increase the risk of immune-mediated diseases like Kawasaki disease. Reference Burgner, Carter, Webster and Kuijpers115 The well-established diagnostic criteria and heightened awareness of Kawasaki disease in Japan and Korea likely contribute to the higher reported incidence, as healthcare professionals in these countries may be more adept at recognising and diagnosing the disease. Reference Yamazaki, Sugawara, Nakajima, Adachi and Hasegawa116 The complex aetiology of Kawasaki disease necessitates further research to elucidate the precise contribution of each factor to the high incidence in Japan and Korea.

The observed temporal trends in Kawasaki disease incidence, as revealed in our systematic review, offer valuable insights into the evolving understanding and recognition of this disease. The general upward trajectory of Kawasaki disease incidence, particularly in the Americas and Europe, likely reflects improved diagnostic capabilities and heightened awareness among healthcare professionals. The increasing familiarity with Kawasaki disease’s clinical presentation and the refinement of diagnostic criteria may have led to more accurate identification and reporting of cases, contributing to the observed rise in incidence. Reference Burns117,Reference Cox and Sallis118 For instance, the gradual increase in Kawasaki disease incidence in the United States, Canada, Chile, and Peru exemplifies this trend. The growing recognition of Kawasaki disease in these regions, coupled with improved diagnostic accuracy, likely plays a significant role in the upward trajectory. Furthermore, the admixture of populations and increased migration may have contributed to the rising incidence in certain regions. Reference Piram119 The introduction of new genetic susceptibilities and environmental exposures through population mixing could potentially influence the occurrence of Kawasaki disease. The relatively high incidence observed in Hawaii, a region known for its diverse population, might be attributed, in part, to this phenomenon. Reference Holman, Christensen and Belay23,Reference Holman, Curns and Belay24,Reference Holman, Shahriari, Effler, Belay and Schonberger26 Conversely, the notable decline in Kawasaki disease incidence in Japan and Korea during the COVID-19 pandemic suggests the potential role of preceding infections in triggering Kawasaki disease. Reference Ae, Makino and Kuwabara65,Reference Oh and Lee98 The reduced circulation of common respiratory viruses during the pandemic might have contributed to this decrease, implying that exposure to certain infections may play a role in the development of Kawasaki disease. The decrease in incidence observed in these countries during the pandemic provides compelling evidence supporting this hypothesis. These temporal trends underscore the dynamic nature of Kawasaki disease epidemiology and highlight the importance of ongoing surveillance and research. The evolving understanding of Kawasaki disease, coupled with the potential influence of population dynamics and infectious triggers, necessitates continuous efforts to monitor and analyse incidence patterns. Such efforts will be crucial for developing effective prevention and treatment strategies and ultimately reducing the global burden of this disease.

This study is the first systematic review to assess the global incidence of Kawasaki disease comprehensively. However, several limitations warrant acknowledgement. Grey literature, which includes unpublished studies, conference abstracts, and reports, was excluded from our review due to the potential for publication bias and the difficulty in assessing the quality of these studies Additionally, the quality of included studies was variable, with quite a few studies demonstrating low methodological rigour. Future research should focus on identifying the specific factors driving the observed geographic and temporal variations in Kawasaki disease incidence. Large-scale, population-based studies with standardised diagnostic criteria and rigorous methodologies are needed to generate more precise estimates for specific populations. Investigations into genetic, environmental, and infectious triggers of Kawasaki disease are crucial for developing targeted prevention and treatment strategies.

Understanding the burden of Kawasaki disease has significant clinical implications. Comprehensive incidence data can inform the allocation of healthcare resources, guide public health interventions, and aid in the design of clinical trials for novel therapies. Recent evidence suggests that Kawasaki disease has surpassed rheumatic fever as the leading cause of acquired heart disease among children globally, not just in developed countries (Pilania RK, et al., Cardiology in the Young, In Press). This highlights the growing burden of Kawasaki disease worldwide and the need for increased awareness and research to address this evolving challenge. Our review highlights the need for further research on the incidence of Kawasaki disease in under-represented regions, such as the Arab world. Also, scarcity of studies from the Eastern Mediterranean Region and the South-East Asia Region suggests that the true incidence of Kawasaki disease in these regions may be underestimated and warrants further investigation. Understanding the regional variations in Kawasaki disease incidence can help tailor diagnostic and treatment algorithms to specific populations, potentially improving patient outcomes. Reference Mohamed, Harahsheh and Choueiter120 Furthermore, recognising the geographic variability in Kawasaki disease incidence can help tailor diagnostic and treatment algorithms to specific populations, potentially improving patient outcomes.

This systematic review highlights the substantial global burden of Kawasaki disease and underscores the significant variation in incidence rates across different populations. It is crucial to recognise and address the regional variations in disease burden. Future research should prioritise elucidating the factors contributing to these variations, ultimately leading to more effective prevention, diagnosis, and management of Kawasaki disease worldwide.

Supplementary material

The supplementary material for this article can be found at https://doi.org/10.1017/S104795112500191X.

Data availability statement

The data that support the findings of this study are available on request from the corresponding author, YJC.

Acknowledgements

The authors thank Eun-Ji Kang from the Medical Library, Korea University, for searching abstracts and articles related to this study.

Author contributions

YJC conceived and designed the study. CRK gathered, processed, and cleaned the data. CRK analysed the data. CRK and YJC had full access to all the data in the study. JSL worked on project administration and methodology. CRK wrote the first draft of the manuscript followed by iterative revision with JSL. All authors substantially contributed to discussion of content and reviewed and edited the manuscript before submission. All authors were involved in the decision to submit and agreed to publish the paper.

Competing interests

All authors declare no competing interests.

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Figure 0

Figure 1. PRISMA flow diagram.

Figure 1

Figure 2. Global incidence of Kawasaki disease in children <5 years.

Figure 2

Table 1. Summary of the characteristics of studies included

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