Author Credentials

Rani Shah DO Hisham Hirzallah MD Munes Fares MD Ashwini Mallad MBBS Gudjon Karlsson MD Mehiar El-Hamdani MD, FACC, FSCAI





Background: Kawasaki disease is one of the leading causes of acquired heart disease in children. It is an acute self-limited vasculitis that predominantly affects infants and children younger than 5 years of age. These patients present with nonspecific symptoms, such as fever and lymphadenopathy, making the diagnosis challenging. This disease can have serious and potentially fatal outcomes, and prompt recognition of this disease is vital to the patient’s outcome. We present a complete review of the disease, including the epidemiology, pathophysiology, diagnosis and management of acute Kawasaki disease, the natural history of this disease, and follow up of these patients as they transition into the adult cardiology practice.

Methods: Our systematic review information were collected from articles retrieved from PubMed library. Keywords that were used included; Kawasaki disease, coronary artery disease, coronary artery aneurysm, pediatric coronary artery disease, epidemiology of Kawasaki disease and treatment of Kawasaki disease. We included only relevant to the topic articles. No exclusion criteria were applied.

Conclusions: Kawasaki disease incidence tends to be increasing over the last decade in the united states. Seasonality of the disease has been described in Japan. It is a mysterious disease with unknown etiology, however, multiple hypotheses have been proposed and tested to explain the pathophysiology. As this disease has an associated high morbidity and mortality, prompt recognition and management of this disease is important to the patient’s overall prognosis and survival.

Conflict(s) of Interest

This manuscript has not been published and is not under consideration for publication elsewhere. We have no conflicts of interest to disclose. This article is not supported or funded by any person or institute.

References with DOI

1. Kawasaki T. Acute febrile mucocutaneous syndrome with lymphoid involvement with specific desquamation of the fingers and toes. Jpn J Allergol. 1967;16:178-222.

2. Makino N, Nakamura Y, Yashiro M, et al. Descriptive epidemiology of Kawasaki disease in Japan, 2011-2012: from the results of the 22nd nationwide survey. J Epidemiol. 2015;25:239-45. https://doi.org/10.2188/jea.je20140089

3. Newburger JW, Takahashi M, Gerber MA, et al. Diagnosis, treatment, and long-term management of Kawasaki disease: a statement for health professionals from the committee of 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

4. Yanagawa H, Nakamura Y, Yashiro M, et al. Incidence survey of Kawasaki disease in 1997 and 1998 in Japan. Pediatrics. 2001;107(3). https://doi.org/10.1542/peds.107.3.e33

5. Holman RC, Curns AT, Belay ED, Steiner CA, Schonberger LB. Kawasaki syndrome hospitalizations in the United States, 1997 and 2000. Pediatrics. 2003;112:495–501. https://doi.org/10.1542/peds.112.3.495

6. Maddox RA, Person MK, Joseph LI, et al. Monitoring the occurrence of Kawasaki syndrome in the United States. Proceedings of the Eleventh International Kawasaki Disease Symposium; 3-6 February 2015; Honolulu, Hawaii. Abstract O.03, p. 28.

7. Uehara R, Belay ED. Epidemiology of Kawasaki disease in Asia, Europe, and the United States. J Epidemiol. 2012;22(2):79-85. https://doi.org/10.2188/jea.je20110131

8. Makino N, Nakamura Y, Yashiro M, et al. Descriptive epidemiology of Kawasaki disease in Japan, 2011-2012: from the results of the 22nd nationwide survey. J Epidemiol. 2015;25:239-45. https://doi.org/10.2188/jea.je20140089

9. Park YW, Han JW, Hong YM, et al. Epidemiologic features of Kawasaki disease in Korea, 2006-2008. Pediatr Int. 2011;53:36-9. https://doi.org/10.1111/j.1442-200x.2010.03178.x

10. Saundankar J, Yim D, Itotoh B, et al. The epidemiology and clinical features of Kawasaki disease in Australia. Pediatrics. 2014;133:e1009-14. https://doi.org/10.1542/peds.2013-2936

11. Fujiwara H, Hamashima Y. Pathology of the heart in Kawasaki disease. Pediatrics. 1978;61:100–107.

12. Takahashi K, Oharaseki T, Naoe S, Wakayama M, Yokouchi Y. Neutrophilic involvement in the damage to coronary arteries in acute stage of Kawasaki disease. Pediatr Int. 2005;47: 305–10. https://doi.org/10.1111/j.1442-200x.2005.02049.x

13. Brown TJ, Crawford SE, Cornwall ML, Garcia F, Shulman ST, Rowley AH. CD8 T lymphocytes and macrophages infiltrate coronary artery aneurysms in acute Kawasaki disease. J Infect Dis. 2001;184: 940–3. https://doi.org/10.1086/323155

14. Hoang LT, Shimizu C, Ling L, et al. Global gene expression profiling identifies new therapeutic targets in acute Kawasaki disease. Genome Med. 2014;6:541. https://doi.org/10.1186/s13073-014-0102-6

15. Weyand CM, Goronzy JJ. Immune mechanisms in medium and large-vessel vasculitis. Nat Rev Rheumatol. 2013;9:731–40. https://doi.org/10.1038/nrrheum.2013.161

16. Rasouli M, Heidari B, Kalani M. Downregulation of Th17 cells and the related cytokines with treatment in Kawasaki disease. Immunol Lett. 2014;162:269–75. https://doi.org/10.1016/j.imlet.2014.09.017

17. Ayusawa M, Sonobe T, Uemura S, et al. Revision of diagnostic guidelines for Kawasaki disease (the 5th revised edition). Pediatrics international: official journal of the Japan Pediatric Society. 2005;47(2):232-234. https://doi.org/10.1111/j.1442-200x.2005.02033.x

18. Cox JR, Sallis RE. Recognition of kawasaki disease. The Permanente journal. 2009;13(1):57-61. https://doi.org/10.7812/tpp/08-042

19. Nakamura Y, Yashiro M, Uehara R, et al. Epidemiologic features of Kawasaki disease in Japan: results of the 2009-2010 nationwide survey. Journal of epidemiology. 2012;22(3):216-221. https://doi.org/10.2188/jea.je20110126

20. Kobayashi T, Saji T, Otani T, et al. Efficacy of immunoglobulin plus prednisolone for prevention of coronary artery abnormalities in severe Kawasaki disease (RAISE study): a randomised, open-label, blinded-endpoints trial. Lancet (London, England). 2012;379(9826):1613-1620. https://doi.org/10.1016/s0140-6736(11)61930-2

21. Kobayashi T, Kobayashi T, Morikawa A, et al. Efficacy of intravenous immunoglobulin combined with prednisolone following resistance to initial intravenous immunoglobulin treatment of acute Kawasaki disease. The Journal of pediatrics. 2013;163(2):521-526. https://doi.org/10.1016/j.jpeds.2013.01.022

22. Newburger JW, Takahashi M, Burns JC. Kawasaki Disease. Journal of the American College of Cardiology. 2016;67(14):1738-1749. https://doi.org/10.1016/j.jacc.2015.12.073

23. Manlhiot C, Millar K, Golding F, McCrindle BW. Improved classification of coronary artery abnormalities based only on coronary artery z-scores after Kawasaki disease. Pediatric cardiology. 2010;31(2):242-249. https://doi.org/10.1007/s00246-009-9599-7

24. Takahashi M, Mason W, Lewis AB. Regression of coronary aneurysms in patients with Kawasaki syndrome. Circulation. 1987;75(2):387-94. https://doi.org/10.1161/01.cir.75.2.387

25. Kato H, Sugimura T, Akagi T, Sato N, Hashino K, Maeno Y, et al. Long-term consequences of Kawasaki disease. A 10- to 21-year follow-up study of 594 patients. Circulation. 1996;94(6):1379-85. https://doi.org/10.1161/01.cir.94.6.1379

26. Tatara K, Kusakawa S. Long-term prognosis of giant coronary aneurysm in Kawasaki disease: an angiographic study. J Pediatr. 1987;111(5):705-10. https://doi.org/10.1016/s0022-3476(87)80246-9

27. Sugimura T, Kato H, Inoue O, Takagi J, Fukuda T, Sato N. Vasodilatory response of the coronary arteries after Kawasaki disease: evaluation by intracoronary injection of isosorbide dinitrate. J Pediatr. 1992;121(5 Pt 1):684- 688. https://doi.org/10.1016/s0022-3476(05)81893-1

28. Silva AA, Maeno Y, Hashmi A, Smallhorn JF, Silverman ED, McCrindle BW. Cardiovascular risk factors after Kawasaki disease: a case-control study. J Pediatr. 2001;138(3):400-5. https://doi.org/10.1067/mpd.2001.111430