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Table of Contents   
INVITED COMMENT  
Year : 2012  |  Volume : 5  |  Issue : 2  |  Page : 133-134
Finding Kawasaki disease


Department of Pediatrics, University of California San Diego School of Medicine, La Jolla, CA, USA

Click here for correspondence address and email

Date of Web Publication11-Aug-2012
 

How to cite this article:
Burns JC. Finding Kawasaki disease. Ann Pediatr Card 2012;5:133-4

How to cite this URL:
Burns JC. Finding Kawasaki disease. Ann Pediatr Card [serial online] 2012 [cited 2019 Aug 18];5:133-4. Available from: http://www.annalspc.com/text.asp?2012/5/2/133/99613


What lessons can we learn from the study of Kawasaki disease (KD) around the globe? Epidemiologic tools have traditionally been used to determine the etiology of infectious diseases, but, 50 years later, the application of these approaches to the study of KD has only yielded limited insights. [1],[2] Although KD is the most common cause of acquired heart disease in children in countries where rheumatic heart disease has waned, the etiology remains a mystery. [3] The current paradigm is that KD is an immunologic reaction to an environmental trigger in genetically susceptible children. [4] Genes in pathways that modulate calcium signaling, activation of FCγ receptors, prostaglandin secretion, and myofibroblast transformation have been implicated in host susceptibility and coronary artery aneurysm formation. [5],[6],[7],[8],[9] Recent genome-wide association studies from Asia have uncovered genetic influences specific to Asian populations that may contribute to the increased incidence of KD in children of Asian descent. [6],[10] However, while progress has been made in understanding genetic susceptibility, progress on etiology has proved a more daunting task. The lack of well-preserved autopsy tissues and the inaccessibility of the coronary arteries, the main target of inflammation, have certainly impeded progress. Recently, new clues from the study of KD epidemiology may help us focus the search for the KD trigger.


   Explaining the Large Epidemics in Japan Top


Epidemiologists often focus on outbreaks or epidemics in their search for clues to etiology. Investigation of KD outbreaks in the USA variously suggested an association with carpet cleaning, residence near a body of water, humidifier use in the child's room, and antecedent respiratory infection. [11],[12],[13] However, none of these observations has been consistently replicated. The observations about seasonality and clustering of cases were first made by Yanagawa and colleagues in Japan in the 1980s. [14] A later refinement of those observations clearly established the seasonality of KD in Japan and in the Western US. [15] Temporospatial clustering of KD cases was also observed, which suggested an environmental exposure acting on a regional scale. [16] In Japan, three large nationwide epidemics were observed in 1979, 1982, and 1986. A new analysis of atmospheric variables in relation to these epidemics has uncovered a potential new clue: winds blowing from Central Asia in a southwesterly direction across Japan were highly associated with the dramatic peaks in KD activity, while a reversal of wind direction coincided with the cessation of the epidemics. [17],[18] Further analyses demonstrated that the annual peaks in KD disease activity in Japan, Hawaii, and southern California also coincided with this tropospheric wind pattern. These observations raise several questions. First, will study of these wind patterns allow predictions of peak and trough KD activity in a given region? Second, from analysis of these wind patterns, can we make estimates of the incubation period between environmental exposure and onset of fever? Clearly, knowing when to look would help the search for the etiologic agent. Third, is it possible that these large-scale tropospheric wind currents associated with KD are actually carrying aerosols harboring the agent? If so, then determining the source regions of these aerosols would provide clues as to where to look for the agent. Experiments are in progress to attempt to answer these questions.

Old disease or new disease

To better focus our search for the etiology of KD, it would be very helpful to know if this is an old or newly emergent agent. Time series of KD cases from different countries suggest that, at least in some parts of Asia, KD is newly emergent. In Japan, where meticulous hospital records allowed this type of retrospective inquiry, it seems quite clear that the clinical entity of KD did not exist prior to World War II. [19],[20],[21] In India, this question framed a debate that was filmed in different parts of the country (YouTube, "Kawasaki Disease in India"). [22],[23] In the West, infantile periarteritis nodosa (IPN), a vasculitis of young infants, was clearly observed in Western Europe, South America, and the USA as early as the turn of the last century. [24] Although IPN and KD are pathologically indistinguishable, it is difficult to determine whether they share a common etiology. [25] To answer this question, it would be helpful to have additional time series from countries around the globe and for researchers to attempt to find "the first case" in their region. Interviews with senior pediatricians, review of hospital and clinic records, and review of autopsy cases with coronary artery aneurysms can be productive avenues to pursue. As morbidity and mortality from vaccine-preventable diseases falls in different parts of the world, KD seems to emerge. But, whether this is due to increased awareness with increased case ascertainment or is due to rising numbers of cases is a matter of debate. One aspect on which we can all agree is that tracking and reporting KD from different countries, as in the article from Pakistan in this issue of the Annals, [26] will contribute to our understanding of how KD operates in different parts of the globe and may improve our search for the etiologic agent.

 
   References Top

1.Uehara R, Belay ED. Epidemiology of Kawasaki disease in Asia, Europe, and the United States. J Epidemiol 2012;22:79-85.  Back to cited text no. 1
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2.Pitzer VE, Burgner D, Viboud C, Simonsen L, Andreasen V, Steiner CA, et al. Modelling seasonal variations in the age and incidence of Kawasaki disease to explore possible infectious aetiologies. Proc Biol Sci 2012;279:2736-43.  Back to cited text no. 2
[PUBMED]    
3.Taubert KA, Rowley AH, Shulman ST. Nationwide survey of Kawasaki disease and acute rheumatic fever. J Pediatr 1991;119:279-82.  Back to cited text no. 3
[PUBMED]    
4.Rowley AH. Kawasaki disease: Novel insights into etiology and genetic susceptibility. Annu Rev Med 2011;62:69-77.  Back to cited text no. 4
[PUBMED]    
5.Onouchi Y, Gunji T, Burns JC, Shimizu C, Newburger JW, Yashiro M, et al. Itpkc functional polymorphism associated with Kawasaki disease susceptibility and formation of coronary artery aneurysms. Nat Genet 2008;40:35-42.  Back to cited text no. 5
[PUBMED]    
6.Onouchi Y, Ozaki K, Burns JC, Shimizu C, Terai M, Hamada H, et al. A genome-wide association study identifies three new risk loci for Kawasaki disease. Nat Genet 2012;44:517-21.  Back to cited text no. 6
[PUBMED]    
7.Khor CC, Davila S, Breunis WB, Lee YC, Shimizu C, Wright VJ, et al. Genome-wide association study identifies FCGR2A as a susceptibility locus for Kawasaki disease. Nat Genet 2011;43:1241-6.  Back to cited text no. 7
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8.Shimizu C, Jain S, Davila S, Hibberd ML, Lin KO, MolkaraD, et al. Transforming growth factor-beta signaling pathway in patients with Kawasaki disease. Circ Cardiovasc Genet 2011;4:16-25.  Back to cited text no. 8
    
9.Khor CC, Davila S, Shimizu C, Sheng S, Matsubara T, Suzuki Y, et al. Genome-wide linkage and association mapping identify susceptibility alleles in abcc4 for Kawasaki disease. J Med Genet 2011;48:467-72.  Back to cited text no. 9
[PUBMED]    
10.Lee YC, Kuo HC, Chang JS, Chang LY, Huang LM, Chen MR, et al. Two new susceptibility loci for Kawasaki disease identified through genome-wide association analysis. Nat Genet 2012;44:522-5.  Back to cited text no. 10
[PUBMED]    
11.Patriarca PA, Rogers MF, Morens DM, Schonberger LB, Kaminski RM, Burns JC, et al. Kawasaki syndrome: Association with the application of rug shampoo. Lancet 1982;2:578-80.  Back to cited text no. 11
[PUBMED]    
12.Rauch AM, Kaplan SL, Nihill MR, Pappas PG, Hurwitz ES, Schonberger LB. Kawasaki syndrome clusters in harris county, texas, and eastern north carolina. A high endemic rate and a new environmental risk factor. Am J Dis Child 1988;142:441-4.  Back to cited text no. 12
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13.Treadwell TA, Maddox RA, Holman RC, Belay ED, Shahriari A, Anderson MS, et al. Investigation of Kawasaki syndrome risk factors in colorado. Pediatr Infect Dis J 2002;21:976-8.  Back to cited text no. 13
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14.Nakamura Y, Yanagawa I, Kawasaki T. Temporal and geographical clustering of Kawasaki disease in Japan. Prog Clin Biol Res 1987;250:19-32.  Back to cited text no. 14
[PUBMED]    
15.Burns JC, Cayan DR, Tong G, Bainto EV, Turner CL, Shike H, et al. Seasonality and temporal clustering of Kawasaki syndrome. Epidemiology 2005;16:220-5.  Back to cited text no. 15
    
16.Kao AS, Getis A, Brodine S, Burns JC. Spatial and temporal clustering of Kawasaki syndrome cases. Pediatr Infect Dis J 2008;27:981-5.  Back to cited text no. 16
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17.Rodo X, Ballester J, Cayan D, Melish ME, Nakamura Y, Uehara R, et al. Association of Kawasaki disease with tropospheric wind patterns. Sci Rep 2011;1:152.  Back to cited text no. 17
    
18.Frazer J. Blowing in the wind. Nature 2012;484:21-3.  Back to cited text no. 18
    
19.Kato H. Is Kawasaki disease a new disease?--A pathological perspective. Circ J 2012;76:821-2.  Back to cited text no. 19
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20.Shibuya N, Shibuya K, Kato H, Yanagisawa M. Kawasaki disease before Kawasaki at tokyo university hospital. Pediatrics 2002;110:e17.  Back to cited text no. 20
[PUBMED]    
21.Takahashi K, Oharaseki T, Yokouchi Y, Yamada H, Shibuya K, Naoe S. A half-century of autopsy results--Incidence of pediatric vasculitis syndromes, especially Kawasaki disease. Circ J 2012;76:964-70.  Back to cited text no. 21
[PUBMED]    
22.Kushner HI, Macnee R, Burns JC. Impressions of Kawasaki syndrome in India. Indian Pediatr 2006;43:939-42.  Back to cited text no. 22
[PUBMED]    
23.Kushner HI, Macnee RP, Burns JC. Kawasaki disease in India: Increasing awareness or increased incidence? Perspect Biol Med 2009;52:17-29.  Back to cited text no. 23
[PUBMED]    
24.Kushner HI, Bastian JF, Turner CL, Burns JC. The two emergencies of Kawasaki syndrome and the implications for the developing world. Pediatr Infect Dis J 2008;27:377-83.  Back to cited text no. 24
[PUBMED]    
25.Landing BH, Larson EJ. Are infantile periarteritis nodosa with coronary artery involvement and fatal mucocutaneous lymph node syndrome the same? Comparison of 20 patients from north america with patients from Hawaii and Japan. Pediatrics 1977;59:651-62.  Back to cited text no. 25
[PUBMED]    
26.Akhtar S, Alam MM, Atiq MA, Cardiac involvement in Kawasaki disease in Pakistani children. Annals Ped Cardiol 2012;5:129-32.  Back to cited text no. 26
    

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Correspondence Address:
Jane C Burns
Department of Pediatrics, University of California San Diego School of Medicine, 9500 Gilman Dr, La Jolla, CA 92093-0641
USA
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Source of Support: None, Conflict of Interest: None


PMID: 23129900

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