Kawasaki disease: Epidemiology and etiology
- Robert Sundel, MD
Robert Sundel, MD
- Section Editor — Pediatric Rheumatology
- Associate Professor of Pediatrics
- Harvard Medical School
- Section Editors
- Marisa Klein-Gitelman, MD, MPH
Marisa Klein-Gitelman, MD, MPH
- Section Editor — Pediatric Rheumatology
- Chief, Division of Rheumatology
- Ann & Robert H. Lurie Children's Hospital of Chicago
- Professor of Pediatrics
- Northwestern University Feinberg School of Medicine
- Sheldon L Kaplan, MD
Sheldon L Kaplan, MD
- Editor-in-Chief — Pediatrics
- Section Editor — Pediatric Infectious Diseases
- Professor and Vice Chairman for Clinical Affairs
- Baylor College of Medicine
Kawasaki disease (KD, previously called mucocutaneous lymph node syndrome) is one of the most common vasculitides of childhood, particularly in East Asia. It is typically a self-limited condition, with fever and other acute inflammatory manifestations lasting for an average of 12 days if not treated. The underlying etiology is unknown.
KD can cause a variety of cardiovascular complications, including coronary artery aneurysms, cardiomyopathy with depressed myocardial contractility and heart failure, myocardial infarction, arrhythmias, and peripheral arterial occlusion. These complications may cause significant morbidity and mortality, particularly in children who are inadequately treated. The frequency of aneurysm development and mortality has dramatically decreased as a result of intravenous immune globulin therapy. Early diagnosis is critical to achieve the optimal treatment result.
The epidemiology and etiology of KD are reviewed here. The clinical features, diagnosis, treatment, and cardiac sequelae are presented separately. Incomplete KD is also discussed separately. (See "Kawasaki disease: Clinical features and diagnosis" and "Kawasaki disease: Initial treatment and prognosis" and "Cardiovascular sequelae of Kawasaki disease" and "Incomplete (atypical) Kawasaki disease".)
KD is one of the most common vasculitides of childhood .
Geographic variation — The incidence of KD is greatest in children who live in East Asia or are of Asian ancestry living in other parts of the world [2-5]. The incidence in underdeveloped countries is largely unknown and ascertainment may be incomplete. KD is particularly difficult to diagnose in areas where measles is still prevalent since the presentation is similar [6,7]. Many nations around the world have demonstrated an increase in the number of children diagnosed with KD since the early to mid 2000s. It is not clear, however, whether this represents an actual increase in the incidence of the disease, increased awareness of the condition, or a greater tendency to classify children with incomplete clinical features as having KD.
- Burns JC, Glodé MP. Kawasaki syndrome. Lancet 2004; 364:533.
- Holman RC, Curns AT, Belay ED, et al. Kawasaki syndrome hospitalizations in the United States, 1997 and 2000. Pediatrics 2003; 112:495.
- Kao AS, Getis A, Brodine S, Burns JC. Spatial and temporal clustering of Kawasaki syndrome cases. Pediatr Infect Dis J 2008; 27:981.
- Son MB, Gauvreau K, Ma L, et al. Treatment of Kawasaki disease: analysis of 27 US pediatric hospitals from 2001 to 2006. Pediatrics 2009; 124:1.
- Wu MH, Lin MT, Chen HC, et al. Postnatal Risk of Acquiring Kawasaki Disease: A Nationwide Birth Cohort Database Study. J Pediatr 2017; 180:80.
- Davaalkham D, Nakamura Y, Baigalmaa D, et al. Kawasaki disease in Mongolia: results from 2 nationwide retrospective surveys, 1996-2008. J Epidemiol 2011; 21:293.
- Badoe EV, Neequaye J, Oliver-Commey JO, et al. Kawasaki disease in ghana: case reports from Korle Bu teaching hospital. Ghana Med J 2011; 45:38.
- Kawasaki T. [Acute febrile mucocutaneous syndrome with lymphoid involvement with specific desquamation of the fingers and toes in children]. Arerugi 1967; 16:178.
- Nakamura Y, Yashiro M, Uehara R, et al. Epidemiologic features of Kawasaki disease in Japan: results of the 2007-2008 nationwide survey. J Epidemiol 2010; 20:302.
- Huang WC, Huang LM, Chang IS, et al. Epidemiologic features of Kawasaki disease in Taiwan, 2003-2006. Pediatrics 2009; 123:e401.
- Du ZD, Zhao D, Du J, et al. Epidemiologic study on Kawasaki disease in Beijing from 2000 through 2004. Pediatr Infect Dis J 2007; 26:449.
- Holman RC, Belay ED, Christensen KY, et al. Hospitalizations for Kawasaki syndrome among children in the United States, 1997-2007. Pediatr Infect Dis J 2010; 29:483.
- Harnden A, Mayon-White R, Perera R, et al. Kawasaki disease in England: ethnicity, deprivation, and respiratory pathogens. Pediatr Infect Dis J 2009; 28:21.
- Bar-Meir M, Haklai Z, Dor M. Kawasaki disease in Israel. Pediatr Infect Dis J 2011; 30:589.
- Yanagawa H, Nakamura Y, Yashiro M, et al. Results of the nationwide epidemiologic survey of Kawasaki disease in 1995 and 1996 in Japan. Pediatrics 1998; 102:E65.
- Fischer TK, Holman RC, Yorita KL, et al. Kawasaki syndrome in Denmark. Pediatr Infect Dis J 2007; 26:411.
- Yanagawa H, Yashiro M, Nakamura Y, et al. Epidemiologic pictures of Kawasaki disease in Japan: from the nationwide incidence survey in 1991 and 1992. Pediatrics 1995; 95:475.
- Tomiyama J, Hasegawa Y, Kumagai Y, et al. Acute febrile mucocutaneous lymph node syndrome (Kawasaki disease) in adults: case report and review of the literature. Jpn J Med 1991; 30:285.
- Stockheim JA, Innocentini N, Shulman ST. Kawasaki disease in older children and adolescents. J Pediatr 2000; 137:250.
- Cai Z, Zuo R, Liu Y. Characteristics of Kawasaki disease in older children. Clin Pediatr (Phila) 2011; 50:952.
- Gomard-Mennesson E, Landron C, Dauphin C, et al. Kawasaki disease in adults: report of 10 cases. Medicine (Baltimore) 2010; 89:149.
- Hirata S, Nakamura Y, Yanagawa H. Incidence rate of recurrent Kawasaki disease and related risk factors: from the results of nationwide surveys of Kawasaki disease in Japan. Acta Paediatr 2001; 90:40.
- Uehara R, Yashiro M, Nakamura Y, Yanagawa H. Kawasaki disease in parents and children. Acta Paediatr 2003; 92:694.
- Dergun M, Kao A, Hauger SB, et al. Familial occurrence of Kawasaki syndrome in North America. Arch Pediatr Adolesc Med 2005; 159:876.
- Takahashi K, Oharaseki T, Yokouchi Y. Pathogenesis of Kawasaki disease. Clin Exp Immunol 2011; 164 Suppl 1:20.
- Burgner D, Harnden A. Kawasaki disease: what is the epidemiology telling us about the etiology? Int J Infect Dis 2005; 9:185.
- Amano S, Hazama F, Kubagawa H, et al. General pathology of Kawasaki disease. On the morphological alterations corresponding to the clinical manifestations. Acta Pathol Jpn 1980; 30:681.
- Jennette JC, Falk RJ. The role of pathology in the diagnosis of systemic vasculitis. Clin Exp Rheumatol 2007; 25:S52.
- Naoe S, Takahashi K, Masuda H, Tanaka N. Kawasaki disease. With particular emphasis on arterial lesions. Acta Pathol Jpn 1991; 41:785.
- Popper SJ, Shimizu C, Shike H, et al. Gene-expression patterns reveal underlying biological processes in Kawasaki disease. Genome Biol 2007; 8:R261.
- Brown TJ, Crawford SE, Cornwall ML, et al. CD8 T lymphocytes and macrophages infiltrate coronary artery aneurysms in acute Kawasaki disease. J Infect Dis 2001; 184:940.
- Rowley AH, Shulman ST, Spike BT, et al. Oligoclonal IgA response in the vascular wall in acute Kawasaki disease. J Immunol 2001; 166:1334.
- Rowley AH, Baker SC, Shulman ST, et al. Cytoplasmic inclusion bodies are detected by synthetic antibody in ciliated bronchial epithelium during acute Kawasaki disease. J Infect Dis 2005; 192:1757.
- Rowley AH, Baker SC, Shulman ST, et al. RNA-containing cytoplasmic inclusion bodies in ciliated bronchial epithelium months to years after acute Kawasaki disease. PLoS One 2008; 3:e1582.
- Mason WH, Jordan SC, Sakai R, et al. Circulating immune complexes in Kawasaki syndrome. Pediatr Infect Dis 1985; 4:48.
- Rowley AH, Eckerley CA, Jäck HM, et al. IgA plasma cells in vascular tissue of patients with Kawasaki syndrome. J Immunol 1997; 159:5946.
- Burns JC, Cayan DR, Tong G, et al. Seasonality and temporal clustering of Kawasaki syndrome. Epidemiology 2005; 16:220.
- Yanagawa H, Nakamura Y, Yashiro M, et al. A nationwide incidence survey of Kawasaki disease in 1985-1986 in Japan. J Infect Dis 1988; 158:1296.
- de Jonge RC, van Furth AM, Wassenaar M, et al. Predicting sequelae and death after bacterial meningitis in childhood: a systematic review of prognostic studies. BMC Infect Dis 2010; 10:232.
- Wang SC, Chang LY, Hsueh PR, et al. Campylobacter enteritis in children in northern Taiwan--a 7-year experience. J Microbiol Immunol Infect 2008; 41:408.
- Oliver JE, Silman AJ. Why are women predisposed to autoimmune rheumatic diseases? Arthritis Res Ther 2009; 11:252.
- Benseler SM, McCrindle BW, Silverman ED, et al. Infections and Kawasaki disease: implications for coronary artery outcome. Pediatrics 2005; 116:e760.
- Rowley AH, Baker SC, Shulman ST, et al. Ultrastructural, immunofluorescence, and RNA evidence support the hypothesis of a "new" virus associated with Kawasaki disease. J Infect Dis 2011; 203:1021.
- Uehara R, Yashiro M, Nakamura Y, Yanagawa H. Clinical features of patients with Kawasaki disease whose parents had the same disease. Arch Pediatr Adolesc Med 2004; 158:1166.
- Fujita Y, Nakamura Y, Sakata K, et al. Kawasaki disease in families. Pediatrics 1989; 84:666.
- Yeung RS. Kawasaki disease: update on pathogenesis. Curr Opin Rheumatol 2010; 22:551.
- McCrindle BW, Rowley AH, Newburger JW, et al. Diagnosis, Treatment, and Long-Term Management of Kawasaki Disease: A Scientific Statement for Health Professionals From the American Heart Association. Circulation 2017; 135:e927.
- Onouchi Y, Gunji T, Burns JC, et al. ITPKC functional polymorphism associated with Kawasaki disease susceptibility and formation of coronary artery aneurysms. Nat Genet 2008; 40:35.
- Kuo HC, Yang KD, Juo SH, et al. ITPKC single nucleotide polymorphism associated with the Kawasaki disease in a Taiwanese population. PLoS One 2011; 6:e17370.
- Breunis WB, Biezeveld MH, Geissler J, et al. Vascular endothelial growth factor gene haplotypes in Kawasaki disease. Arthritis Rheum 2006; 54:1588.
- Burgner D, Davila S, Breunis WB, et al. A genome-wide association study identifies novel and functionally related susceptibility Loci for Kawasaki disease. PLoS Genet 2009; 5:e1000319.
- Breunis WB, Davila S, Shimizu C, et al. Disruption of vascular homeostasis in patients with Kawasaki disease: involvement of vascular endothelial growth factor and angiopoietins. Arthritis Rheum 2012; 64:306.
- Burns JC, Shimizu C, Gonzalez E, et al. Genetic variations in the receptor-ligand pair CCR5 and CCL3L1 are important determinants of susceptibility to Kawasaki disease. J Infect Dis 2005; 192:344.
- Khor CC, Davila S, Shimizu C, et al. Genome-wide linkage and association mapping identify susceptibility alleles in ABCC4 for Kawasaki disease. J Med Genet 2011; 48:467.
- Tsai FJ, Lee YC, Chang JS, et al. Identification of novel susceptibility Loci for kawasaki disease in a Han chinese population by a genome-wide association study. PLoS One 2011; 6:e16853.
- Kim JJ, Hong YM, Sohn S, et al. A genome-wide association analysis reveals 1p31 and 2p13.3 as susceptibility loci for Kawasaki disease. Hum Genet 2011; 129:487.
- Khor CC, Davila S, Breunis WB, et al. Genome-wide association study identifies FCGR2A as a susceptibility locus for Kawasaki disease. Nat Genet 2011; 43:1241.
- Onouchi Y, Ozaki K, Burns JC, et al. A genome-wide association study identifies three new risk loci for Kawasaki disease. Nat Genet 2012; 44:517.
- Lee YC, Kuo HC, Chang JS, et al. Two new susceptibility loci for Kawasaki disease identified through genome-wide association analysis. Nat Genet 2012; 44:522.
- Mutter J, Yeter D. Kawasaki's disease, acrodynia, and mercury. Curr Med Chem 2008; 15:3000.
- Woon PY, Chang WC, Liang CC, et al. Increased risk of atopic dermatitis in preschool children with kawasaki disease: a population-based study in taiwan. Evid Based Complement Alternat Med 2013; 2013:605123.
- Rodó X, Ballester J, Cayan D, et al. Association of Kawasaki disease with tropospheric wind patterns. Sci Rep 2011; 1:152.