Clinical and Experimental Pediatrics

The Korean Pediatric Society (대한소아청소년과학회)
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Association between Kawasaki disease and acute respiratory viral infections

가와사끼병과 급성 호흡기 바이러스 감염증의 연관성에 관한 연구

  • Cho, Eun Young (Department of Pediatrics, Seoul National University College of Medicine) ;
  • Eun, Byung Wook (Department of Pediatrics, Graduate School of Medicine, Gachon University of Medicine and Science) ;
  • Kim, Nam Hee (Department of Pediatrics, Inje University College of Medicine, Ilsan Paik Hospital) ;
  • Lee, Jina (Department of Pediatrics, Seoul National University College of Medicine) ;
  • Choi, Eun Hwa (Department of Pediatrics, Seoul National University College of Medicine) ;
  • Lee, Hoan Jong (Department of Pediatrics, Seoul National University College of Medicine) ;
  • Choi, Jung Yun (Department of Pediatrics, Seoul National University College of Medicine)
  • 조은영 (서울대학교 의과대학 소아과학교실) ;
  • 은병욱 (가천의과대학교 의학전문대학원 소아과학교실) ;
  • 김남희 (인제대학교 의과대학 소아과학교실) ;
  • 이진아 (서울대학교 의과대학 소아과학교실) ;
  • 최은화 (서울대학교 의과대학 소아과학교실) ;
  • 이환종 (서울대학교 의과대학 소아과학교실) ;
  • 최정연 (서울대학교 의과대학 소아과학교실)
  • Received : 2009.06.29
  • Accepted : 2009.09.11
  • Published : 2009.11.15
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Abstract

Purpose:The etiology of Kawasaki disease (KD) is still unknown. Recently, an association between human coronavirus NL63 (HCoV-NL63) and KD was implicated. Hence, we attempted to determine the association between KD and acute respiratory viral infections. Methods:Nasopharyngeal aspirate samples were obtained from 54 patients diagnosed with KD at the Seoul National University (SNU) Children's Hospital and SNU-Bundang Hospital between October 2003 and September 2006. Viral diagnoses of 11 respiratory viruses were made using multiplex reverse transcriptase-polymerase chain reaction (RT-PCR): respiratory syncytial virus (RSV), adenovirus, rhinovirus (RV), parainfluenza viruses (PIVs) 1 and 3, influenza viruses (IFVs) A and B, human metapneumovirus (HMPV), human bocavirus (HBoV), HCoV OC43/229E, and HCoV-NL63. Clinical data were reviewed retrospectively. Results:The median age was 32 months (6 months-10.4 years). Respiratory symptoms were observed in 37 patients (69%). The following respiratory viruses were identified in 12 patients (22%): RV (n=4), PIV-3 (n=2), HBoV (n=2), and adenovirus, RSV, PIV-1, IFV-A, and HCoV-NL63 (n=1). Co-infection with PIV-3 and RV was observed in one patient. Respiratory symptoms were observed in 7 (58.3%) and 30 (71.4%) patients of the virus-positive and virus-negative groups (P>0.05). Response rate to intravenous immunoglobulin administration was 67% (n=8) and 86% (n=36) in the virus- positive and virus-negative groups (P>0.05). Conclusion:Respiratory symptoms were commonly observed in KD patients but the association between respiratory viruses and KD were not found. Large multicenter-based investigations are required to confirm the association between acute respiratory viral infections and KD.

목 적:가와사끼병은 소아의 후천성 심질환의 가장 흔한 원인이나, 그 원인은 아직 밝혀지지 않았다. 최근 급성 호흡기 감염증의 원인 중 하나인 코로나바이러스(human coronavirus NL63)와 가와사끼병 발병과의 연관성이 제기된 바 있다. 이에 저자들은 급성 호흡기 바이러스 감염증과 가와사끼병의 발병 및 임상적 특징과의 연관성을 연구하고자 하였다. 방 법:2003년 10월부터 2006년 9월까지 서울대학교병원과 분당서울대학교병원에서 가와사끼병으로 진단받은 환자 54명으로부터 비인두 흡인물을 채취하여 총 11가지 호흡기 바이러스(호흡기 세포융합 바이러스, 아데노바이러스, 라이노바이러스, 파라인플루엔자 바이러스 1형 및 3형, 인플루엔자 바이러스 A형 및 B형, 메타뉴모바이러스, 보카바이러스, 코로나바이러스 OC43/229E 및 NL63)를 바이러스 배양검사 혹은 다중 역전사 중합 효소 반응(multiplex RT-PCR)로 검출하였다. 대상 환자들의 임상 양상은 후향적으로 검토하였다. 결 과:대상 환자들의 중앙 연령은 32개월(범위 6개월-10.4세)이었으며, 37례(69%)에서 발병 전에 호흡기 증상이 동반되었다. 호흡기 바이러스는 12례(22%)에서 검출되었으며, 라이노바이러스 4례, 파라인플루엔자 바이러스 3형 2례, 보카바이러스 2례, 그리고 아데노바이러스, 호흡기 세포융합 바이러스, 파라인플루엔자 바이러스 1형, 인플루엔자바이러스 A형, 코로나바이러스 NL63 각각 1례씩 검출되었다. 이 중 파라인플루엔자 바이러스 3형과 라이노바이러스가 중복 검출된 경우가 1례 있었다. 발병 전 호흡기 증상이 동반된 경우는 바이러스 양성군이 7례(58.3%), 음성군이 30례(71.4%)이었고, 정맥내 면역글로불린 1회 치료 후 해열된 경우는 바이러스 양성군이 8례(67%), 음성군이 36례(86%)로 나타났으며, 관상동맥 병변이 2개월 이상 지속된 경우는 바이러스 양성군이 2례(17%), 음성군이 4례(9.5%)이었으나, 모두 통계적으로 유의한 차이는 없었다. 결 론:본 연구에서는 가와사끼병 환자에서 호흡기 증상이 동반되는 경우가 흔하였으나, 특정 호흡기 바이러스와의 인과적 관계는 규명되지 않았다. 본 연구는 소규모 단일기관 연구로서, 향후 대규모 다기관 연구를 통하여 호흡기 바이러스 감염증과 가와사끼병의 연관성 및 예후에 미치는 영향이 검토되어야 할 것으로 보인다.

Keywords

Acknowledgement

Supported by : The Korean Pediatric Society

References

  1. Burns JC, Kushner HI, Bastian JF, Shike H, Shimizu C, Matsubara T, et al. Kawasaki disease: A brief history. Pediatrics 2000;106:E27 https://doi.org/10.1542/peds.106.1.27
  2. Kawasaki T. Acute febrile mucocutaneous syndrome with lymphoid involvement with specific desquamation of the fingers and toes in children. Arerugi 1967;16:178-222
  3. Rowley AH, Shulman ST. Kawasaki syndrome. Clin Microbiol Rev 1998;11:405-14
  4. Rowley AH, Eckerley CA, J$\ddot{a}$ck HM, Shulman ST, Baker SC. IgA plasma cells in vascular tissue of patients with Kawasaki syndrome. J Immunol 1997;159:5946-55
  5. Esper F, Shapiro E, Weibel C, Ferguson D, Landry M, Kahn J. Association between a novel human coronavirus and Kawasaki disease. The Journal of Infectious Diseases 2005;191:499-502 https://doi.org/10.1086/428291
  6. Ebihara T, Endo R, Ma X, Ishiguro N, Kikuta H. Lack of association between New Haven coronavirus and Kawasaki disease. J Infect Dis 2005;192:351-2 https://doi.org/10.1086/430797
  7. Shimizu C, Shike H, Baker SC, Garcia F, van der Hoek L, Kuijpers TW, et al. Human coronavirus NL63 is not detected in the respiratory tracts of children with acute Kawasaki disease. J Infect Dis 2005;192:1767-71 https://doi.org/10.1086/497170
  8. Dominguez SR, Anderson MS, Glodé MP, Robinson CC, Holmes KV. Blinded case-control study of the relationship between human coronavirus NL63 and Kawasaki syndrome. J Infect Dis 2006;194:1697-701 https://doi.org/10.1086/509509
  9. Lehmann C, Klar R, Lindner J, Lindner P, Wolf H, Gerling S. Kawasaki disease lacks association with human coronavirus NL63 and human bocavirus. Pediatr Infect Dis J 2009;28:553-4 https://doi.org/10.1097/INF.0b013e31819f41b6
  10. Newburger JW, Takahashi M, Gerber MA, Gewitz MH, Tani LY, Burns JC, et al. Diagnosis, treatment, and long-term management of Kawasaki disease: a statement for health professionals from the Committee on Rheumatic Fever, Endocarditis and Kawasaki Disease, Council on Cardiovascular Disease in the Young, American Heart Association. Circulation 2004;110: 2747-71 https://doi.org/10.1161/01.CIR.0000145143.19711.78
  11. Lee JA, Kim NH, Kim SJ, Choi EH, Lee HJ. Rapid identification of human adenovirus types 3 and 7 from respiratory specimens via multiplex type-specific PCR. J Clin Microbiol 2005;43: 5509-14 https://doi.org/10.1128/JCM.43.11.5509-5514.2005
  12. Choi EH, Lee HJ, Kim SJ, Eun BW, Kim NH, Lee JA, et al. The association of newly identified respiratory viruses with lower respiratory tract infections in Korean children, 2000-2005. Clin Infect Dis 2006;43:585-92 https://doi.org/10.1086/506350
  13. Research Committee on Kawasaki Disease. Report of subcommittee on standardization of diagnostic criteria and reporting of coronary artery lesions in Kawasaki disease. Tokyo, Japan: Ministry of Health and Welfare 1984
  14. Park YW, Han JW, Park IS, Kim CH, Cha SH, Ma JS, et al. Kawasaki disease in Korea, 2003-2005. Pediatr Infect Dis J 2007;26:821-3 https://doi.org/10.1097/INF.0b013e318124aa1a
  15. Cha SH. Pathogenesis of Kawasaki disease. Korean J Pediatr Infect Dis 2007;14:6-16
  16. Leung DY, Sullivan KE, Brown-Whitehorn TF, Fehringer AP, Allen S, Finkel TH, et al. Association of toxic shock syndrome toxin-secreting and exfoliative toxin-secreting Staphylococcus aureus with Kawasaki syndrome complicated by coronary artery disease. Pediatr Res 1997;42:268-72 https://doi.org/10.1203/00006450-199709000-00004
  17. Matsubara K, Fukaya T. The role of superantigens of group A Streptococcus and Staphylococcus aureus in Kawasaki disease. Curr Opin Infect Dis 2007;20:298-303 https://doi.org/10.1097/QCO.0b013e3280964d8c
  18. Johnson D, Azimi P. Kawasaki disease associated with Klebsiella pneumoniae bacteremia and parainfluenza type 3 virus infection. Pediatr Infect Dis 1985;4:100
  19. Usui D, Ishii Y, Akaike H, Isumi H, Komura H, Kawasaki K, et al. Yersinia pseudotuberculosis type 4a infection meeting the diagnostic criteria for Kawasaki disease complicated by disseminated intravascular coagulation. Kansenshogaku Zasshi 2005;79: 895-9 https://doi.org/10.11150/kansenshogakuzasshi1970.79.895
  20. Khono T, Takase Y, Niki H. Chlamydia infections in Kawasaki disease. Acta Paediatr Jpn 1991;33:408-10 https://doi.org/10.1111/j.1442-200X.1991.tb01575.x
  21. Shike H, Shimizu C, Kanegaye JT, Foley JL, Schnurr DP, Wold LJ, et al. Adenovirus, adeno-associated virus and Kawasaki disease. Pediatr Infect Dis J 2005;24:1011-4 https://doi.org/10.1097/01.inf.0000183769.31951.1e
  22. Nigro G, Zerbini M, Krzysztofiak A, Gentilomi G, Porcaro MA, Mango T, et al. Active or recent parvovirus B19 infection in children with Kawasaki disease. Lancet 1994;343:1260-1 https://doi.org/10.1016/S0140-6736(94)92154-7
  23. Culora GA, Moore IE. Kawasaki disease, Epstein-Barr virus and coronary artery aneurysms. J Clin Pathol 1997;50:161-3 https://doi.org/10.1136/jcp.50.2.161
  24. Takahashi K, Oharaseki T, Wakayama M, Yokouchi Y, Naoe S, Murata H. Histopathological features of murine systemic vasculitis caused by Candida albicans extract-an animal model of Kawasaki disease. Inflamm Res 2004;53:72-7 https://doi.org/10.1007/s00011-003-1225-1
  25. Bell DM, Brink EW, Nitzkin JL, Hall CB, Wulff H, Berkowitz ID, et al. Kawasaki syndrome: description of two outbreaks in the United States. N Engl J Med 1981;304:1568-75 https://doi.org/10.1056/NEJM198106253042603
  26. Rowley AH, Baker SC, Shulman ST, Garcia FL, Guzman- Cottrill JA, Chou P, et al. Detection of antigen in bronchial epithelium and macrophages in acute Kawasaki disease by use of synthetic antibody. J Infect Dis 2004;190:856-65 https://doi.org/10.1086/422648

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