Highlights & Basics
- Kawasaki disease is the second most common vasculitis in childhood (the most common being IgA vasculitis).
- Presents with an acute self-limiting febrile illness usually in young children, and is the leading cause of acquired heart disease in children ages under 5 years in the developed world.
- Classic features include fever, rash, conjunctivitis, lymphadenopathy, changes to the lips or oral mucosal, and peripheries, with initial swelling and erythema followed by desquamation in the second week.
- The most serious sequelae is coronary artery aneurysm, affecting 20% to 25% of untreated patients and 19% of treated patients in the UK, with even higher coronary artery aneurysm complication rates in those ages under 1 year.
- Current standard treatment includes intravenous immune globulin (IVIG), alongside aspirin. There remains clinical equipoise if up-front corticosteroids reduce coronary artery aneurysms in unselected cases, but they are usually added for high-risk cases as well as patients with Kawasaki shock syndrome.
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McCrindle BW, Rowley AH, Newburger JW, et al; American Heart Association. Diagnosis, treatment, and long-term management of Kawasaki disease: a scientific statement for health professionals from the American Heart Association. Circulation. 2017 Apr 25;135(17):e927-99.[Abstract][Full Text]
Kawasaki T, Kosaki T, Okawa S, et al. A new infantile acute febrile mucocutaneous lymph node syndrome (MLNS) prevailing in Japan. Pediatrics. 1974 Sep;54(3):271-6.[Abstract]
de Graeff N, Groot N, Ozen S, et al. European consensus-based recommendations for the diagnosis and treatment of Kawasaki disease - the SHARE initiative. Rheumatology (Oxford). 2019 Apr 1;58(4):672-82.[Abstract][Full Text]
Gorelik M, Chung SA, Ardalan K, et al. 2021 American College of Rheumatology/Vasculitis Foundation guideline for the management of Kawasaki disease. Arthritis Care Res (Hoboken). 2022 Apr;74(4):538-48.[Abstract]
Newburger JW, Takahashi M, Beiser AS, et al. A single intravenous infusion of gamma globulin as compared with four infusions in the treatment of acute Kawasaki syndrome. N Engl J Med. 1991 Jun 6;324(23):1633-9.[Abstract]
Lei WT, Chang LS, Zeng BY, et al. Pharmacologic interventions for Kawasaki disease in children: A network meta-analysis of 56 randomized controlled trials. EBioMedicine. 2022 Apr;78:103946.[Abstract][Full Text]
McCrindle BW, Rowley AH, Newburger JW, et al; American Heart Association. Diagnosis, treatment, and long-term management of Kawasaki disease: a scientific statement for health professionals from the American Heart Association. Circulation. 2017 Apr 25;135(17):e927-99.[Abstract][Full Text]
1. McCrindle BW, Rowley AH, Newburger JW, et al; American Heart Association. Diagnosis, treatment, and long-term management of Kawasaki disease: a scientific statement for health professionals from the American Heart Association. Circulation. 2017 Apr 25;135(17):e927-99.[Abstract][Full Text]
2. Kawasaki T. Acute febrile mucocutaneous syndrome with lymphoid involvement with specific desquamation of the fingers and toes in children [in Japanese]. Arerugi. 1967 Mar;16(3):178-222.[Abstract]
3. Mason WH, Takahashi M. Kawasaki syndrome. Clin Infect Dis. 1999 Feb;28(2):169-85.[Abstract]
4. Callinan LS, Holman RC, Vugia DJ, et al. Kawasaki disease hospitalization rate among children younger than 5 years of age in California, 2003-2010. Pediatr Infect Dis J. 2014 Jul;33(7):781-3.[Abstract]
5. Tulloh RMR, Mayon-White R, Harnden A, et al. Kawasaki disease: a prospective population survey in the UK and Ireland from 2013 to 2015. Arch Dis Child. 2019 Jul;104(7):640-6.[Abstract]
6. Lin MT, Wu MH. The global epidemiology of Kawasaki disease: Review and future perspectives. Glob Cardiol Sci Pract. 2017 Oct 31;2017(3):e201720.[Abstract][Full Text]
7. Holman RC, Curns AT, Belay ED, et al. Kawasaki syndrome hospitalizations in the United States, 1997 and 2000. Pediatrics. 2003 Sep;112(3 Pt 1):495-501.[Abstract]
8. Holman RC, Belay ED, Clarke MJ, et al. Kawasaki syndrome among American Indian and Alaska native children. Pediatr Infect Dis J. 1999 May;18(5):451-5.[Abstract]
9. Yanagawa H, Nakamura Y, Ojima T, et al. Changes in epidemic patterns of Kawasaki disease in Japan. Pediatr Infect Dis J. 1999 Jan;18(1):64-6.[Abstract]
10. 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(3):239-45.[Abstract][Full Text]
11. Hata A, Onouchi Y. Susceptibility genes for Kawasaki disease: toward implementation of personalized medicine. J Hum Genet. 2009 Feb;54(2):67-73.[Abstract]
12. Brogan P, Burns JC, Cornish J, et al. Lifetime cardiovascular management of patients with previous Kawasaki disease. Heart. 2020 Mar;106(6):411-420.[Abstract][Full Text]
13. Yanagawa H, Yashiro M, Nakamura Y, et al. Nationwide surveillance of Kawasaki disease in Japan, 1984 to 1993. Pediatr Infect Dis J. 1995 Jan;14(1):69-71.[Abstract]
14. Dominguez SR, Anderson MS, Glode MP, et al. Blinded case-control study of the relationship between human coronavirus NL63 and Kawasaki syndrome. J Infect Dis. 2006 Dec 15;194(12):1697-701.[Abstract]
15. Abinun M, Cant AJ. Toxic shock syndrome toxin-secreting Staphylococcus aureus in Kawasaki syndrome. Lancet. 1994 Jan 29;343(8892):300.[Abstract]
16. Meissner HC, Leung DY. Superantigens, conventional antigens and etiology of Kawasaki syndrome. Pediatr Infect Dis J. 2000 Feb;19(2):91-4.[Abstract]
17. Leung DY, Meissner HC, Fulton DR, et al. Toxic shock syndrome toxin-secreting Staphylococcus aureus in Kawasaki syndrome. Lancet. 1993 Dec 4;342(8884):1385-8.[Abstract]
18. Rowley AH. Kawasaki disease: novel insights into etiology and genetic susceptibility. Annu Rev Med. 2011 Feb 18;62:69-77.[Abstract]
19. Hata A, Onouchi Y. Susceptibility genes for Kawasaki disease: toward implementation of personalized medicine. J Hum Genet. 2009 Feb;54(2):67-73.[Abstract]
20. Khor CC, Davila S, Breunis WB, et al. Genome-wide association study identifies FCGR2A as a susceptibility locus for Kawasaki disease. Nat Genet. 2011 Nov 13;43(12):1241-6.[Abstract]
21. Xie X, Shi X, Liu M. The roles of genetic factors in Kawasaki disease: a systematic review and meta-analysis of genetic association studies. Pediatr Cardiol. 2018 Feb;39(2):207-25.[Abstract]
22. Rowley AH, Shulman ST. New developments in the search for etiologic agent of Kawasaki disease. Curr Opin Pediatr. 2007 Feb;19(1):71-4.[Abstract]
23. Dajani AS, Taubert KA, Gerber MA, et al. Diagnosis and therapy of Kawasaki disease in children. Circulation. 1993 May;87(5):1776-80.[Abstract]
24. Takahashi K, Oharaseki T, Naoe S, et al. Neutrophilic involvement in the damage to coronary arteries in acute stage of Kawasaki disease. Pediatr Int. 2005 Jun;47(3):305-10.[Abstract]
25. Senzaki H. The pathophysiology of coronary artery aneurysms in Kawasaki disease: role of matrix metalloproteinases. Arch Dis Child. 2006 Oct;91(10):847-51.[Abstract][Full Text]
26. Suzuki A, Miyagawa-Tomita S, Komatsu K, et al. Immunohistochemical study of apparently intact coronary artery in a child after Kawasaki disease. Pediatr Int. 2004 Oct;46(5):590-6.[Abstract]
27. Onouchi Y, Tamari M, Takahashi A, et al. A genomewide linkage analysis of Kawasaki disease: evidence for linkage to chromosome 12. J Hum Genet. 2007;52(2):179-90.[Abstract]
28. Satou GM, Giamelli J, Gewitz MH. Kawasaki disease: diagnosis, management, and long-term implications. Cardiol Rev. 2007 Jul-Aug;15(4):163-9.[Abstract]
29. Kawasaki T, Kosaki T, Okawa S, et al. A new infantile acute febrile mucocutaneous lymph node syndrome (MLNS) prevailing in Japan. Pediatrics. 1974 Sep;54(3):271-6.[Abstract]
30. Kuemmerle-Deschner JB, Hansmann S, Wulffraat NM, et al. Recommendations for collaborative paediatric research including biobanking in Europe: a Single Hub and Access point for paediatric Rheumatology in Europe (SHARE) initiative. Ann Rheum Dis. 2018 Mar;77(3):319-327.[Abstract]
31. de Graeff N, Groot N, Ozen S, et al. European consensus-based recommendations for the diagnosis and treatment of Kawasaki disease - the SHARE initiative. Rheumatology (Oxford). 2019 Apr 1;58(4):672-82.[Abstract][Full Text]
32. Manlhiot C, Millar K, Golding F, et al. Improved classification of coronary artery abnormalities based only on coronary artery z-scores after Kawasaki disease. Pediatr Cardiol. 2009 Dec 19;31(2):242-9.[Abstract]
33. Saguil A, Fargo M, Grogan S. Diagnosis and management of Kawasaki disease. Am Fam Physician. 2015 Mar 15;91(6):365-71.[Abstract][Full Text]
34. Wen JX, Bai X, Niu Y, et al. Diagnostic accuracy of N-terminal pro-brain natriuretic peptide for Kawasaki disease: An updated systematic review and meta-analysis. Int J Clin Pract. 2021 Nov;75(11):e14538.[Abstract]
35. Colomba C, La Placa S, Saporito L, et al. Intestinal involvement in Kawasaki disease. J Pediatr. 2018 Nov;202:186-93.[Abstract][Full Text]
36. Lee KY, Rhim JW, Kang JH. Kawasaki disease: laboratory findings and an immunopathogenesis on the premise of a "protein homeostasis system". Yonsei Med J. 2012 Mar;53(2):262-75.[Abstract][Full Text]
37. Gorelik M, Chung SA, Ardalan K, et al. 2021 American College of Rheumatology/Vasculitis Foundation guideline for the management of Kawasaki disease. Arthritis Care Res (Hoboken). 2022 Apr;74(4):538-48.[Abstract]
38. Dorfman AL, Geva T, Samyn MM, et al. SCMR expert consensus statement for cardiovascular magnetic resonance of acquired and non-structural pediatric heart disease. J Cardiovasc Magn Reson. 2022 Jul 21;24(1):44.[Abstract][Full Text]
39. Smith MT, Lester-Smith D, Zurynski Y, et al. Persistence of acute rheumatic fever in a tertiary children's hospital. J Paediatr Child Health. 2011 Apr;47(4):198-203.[Abstract]
40. Bansal N, Azeka E, Neunert C, et al. Multisystem inflammatory syndrome associated with COVID-19 anti-thrombosis guideline of care for children by action. Pediatr Cardiol. 2021 Oct;42(7):1635-39.[Abstract][Full Text]
41. Henderson LA, Canna SW, Friedman KG, et al. American College of Rheumatology clinical guidance for multisystem inflammatory syndrome in children associated with SARS-CoV-2 and hyperinflammation in pediatric COVID-19: Version 2. Arthritis Rheumatol. 2021 Apr;73(4):e13-29.[Abstract][Full Text]
42. Marchesi A, Rigante D, Cimaz R, et al. Revised recommendations of the Italian Society of Pediatrics about the general management of Kawasaki disease. Ital J Pediatr. 2021 Jan 25;47(1):16.[Abstract][Full Text]
43. Oates-Whitehead RM, Baumer JH, Haines L, et al. Intravenous immunoglobulin for the treatment of Kawasaki disease in children. Cochrane Database Syst Rev. 2003 Oct 20;(4):CD004000.[Abstract][Full Text]
44. Newburger JW, Takahashi M, Beiser AS, et al. A single intravenous infusion of gamma globulin as compared with four infusions in the treatment of acute Kawasaki syndrome. N Engl J Med. 1991 Jun 6;324(23):1633-9.[Abstract]
45. Chiang MH, Liu HE, Wang JL. Low-dose or no aspirin administration in acute-phase Kawasaki disease: a meta-analysis and systematic review. Arch Dis Child. 2021 Jul;106(7):662-8.[Abstract]
46. Lei WT, Chang LS, Zeng BY, et al. Pharmacologic interventions for Kawasaki disease in children: A network meta-analysis of 56 randomized controlled trials. EBioMedicine. 2022 Apr;78:103946.[Abstract][Full Text]
47. Riyad C, Brogan P. A practical approach to refractory Kawasaki disease. Paediatrics and Child Health. 2022 Nov 17;32(12):476-9.
48. Tremoulet AH, Best BM, Song S, et al. Resistance to intravenous immunoglobulin in children with Kawasaki disease. J Pediatr. 2008 Jul;153(1):117-21.[Abstract][Full Text]
49. Zheng X, Li J, Yue P, et al. Is there an association between intravenous immunoglobulin resistance and coronary artery lesion in Kawasaki disease?-Current evidence based on a meta-analysis. PLoS One. 2021;16(3):e0248812.[Abstract][Full Text]
50. Sleeper LA, Minich LL, McCrindle BM, et al; Pediatric Heart Network Investigators. Evaluation of Kawasaki disease risk-scoring systems for intravenous immunoglobulin resistance. J Pediatr. 2011 May;158(5):831-35.e3.[Abstract][Full Text]
51. Davies S, Sutton N, Blackstock S, et al. Predicting IVIG resistance in UK Kawasaki disease. Arch Dis Child. 2015 Apr;100(4):366-8.[Abstract]
52. Jakob A, von Kries R, Horstmann J, et al. Failure to predict high-risk Kawasaki disease patients in a population-based study cohort in Germany. Pediatr Infect Dis J. 2018 Sep;37(9):850-5.[Abstract]
53. Green J, Wardle AJ, Tulloh RM. Corticosteroids for the treatment of Kawasaki disease in children. Cochrane Database Syst Rev. 2022 May 27;5(5):CD011188.[Abstract][Full Text]
54. Eleftheriou D, Levin M, Shingadia D, et al. Management of Kawasaki disease. Arch Dis Child. 2014 Jan;99(1):74-83.[Abstract][Full Text]
55. Newburger JW, Sleeper LA, McCrindle BW; Pediatric Heart Network Investigators. Randomized trial of pulsed corticosteroid therapy for primary treatment of Kawasaki disease. N Engl J Med. 2007 Feb 15;356(7):663-75.[Abstract][Full Text]
56. Inoue Y, Okada Y, Shinohara M, et al. A multicenter prospective randomized trial of corticosteroids in primary therapy for Kawasaki disease: clinical course and coronary artery outcome. J Pediatr. 2006 Sep;149(3):336-41.[Abstract]
57. 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. 2012 Apr 28;379(9826):1613-20.[Abstract]
58. Furukawa T, Kishiro M, Akimoto K, et al. Effects of steroid pulse therapy on immunoglobulin-resistant Kawasaki disease. Arch Dis Child. 2008 Feb;93(2):142-6.[Abstract]
59. Okada K, Hara J, Maki I, et al. Pulse methylprednisolone with gammaglobulin as an initial treatment for acute Kawasaki disease. Eur J Pediatr. 2009 Feb;168(2):181-5.[Abstract]
60. Sundel RP, Baker AL, Fulton DR, et al. Corticosteroids in the initial treatment of Kawasaki disease: report of a randomized trial. Pediatr. 2003 Jun;142(6):611-6.[Abstract]
61. Chen S, Dong Y, Yin Y, et al. Intravenous immunoglobulin plus corticosteroid to prevent coronary artery abnormalities in Kawasaki disease: a meta-analysis. Heart. 2013 Jan;99(2):76-82.[Abstract]
62. Newburger JW. Kawasaki disease: medical therapies. Congenit Heart Dis. 2017 Sep;12(5):641-3.[Abstract]
63. Burns JC, Mason WH, Hauger SB, et al. Infliximab treatment for refractory Kawasaki syndrome. J Pediatr. 2005 May;146(5):662-7.[Abstract]
64. Burns JC, Roberts SC, Tremoulet AH, et al. Infliximab versus second intravenous immunoglobulin for treatment of resistant Kawasaki disease in the USA (KIDCARE): a randomised, multicentre comparative effectiveness trial. Lancet Child Adolesc Health. 2021 Dec;5(12):852-861.[Abstract][Full Text]
65. Yamaji N, da Silva Lopes K, Shoda T, et al. TNF-alpha blockers for the treatment of Kawasaki disease in children. Cochrane Database Syst Rev. 2019 Aug 16;8(8):CD012448.[Abstract][Full Text]
66. Li X, Tang Y, Ding Y, et al. Higher efficacy of infliximab than immunoglobulin on Kawasaki disease, a meta-analysis. Eur J Pharmacol. 2021 May 15;899:173985.[Abstract]
67. Chan H, Chi H, You H, et al. Indirect-comparison meta-analysis of treatment options for patients with refractory Kawasaki disease. BMC Pediatr. 2019 May 17;19(1):158.[Abstract][Full Text]
68. Crayne CB, Mitchell C, Beukelman T. Comparison of second-line therapy in IVIg-refractory Kawasaki disease: a systematic review. Pediatr Rheumatol Online J. 2019 Nov 27;17(1):77.[Abstract][Full Text]
69. Nomura O, Fukuda S, Ota E, et al. Monoclonal antibody and anti-cytokine biologics for Kawasaki disease: A systematic review and meta-analysis. Semin Arthritis Rheum. 2021 Oct;51(5):1045-56.[Abstract]
70. Sonoda K, Mori M, Hokosaki T, et al. Infliximab plus plasma exchange rescue therapy in Kawasaki disease. J Pediatr. 2014 May;164(5):1128-32.e1.[Abstract]
71. Koné-Paut I, Tellier S, Belot A, et al. Phase II open label study of anakinra in intravenous immunoglobulin-resistant Kawasaki disease. Arthritis Rheumatol. 2021 Jan;73(1):151-61.[Abstract]
72. Wardle AJ, Connolly GM, Seager MJ, et al. Corticosteroids for the treatment of Kawasaki disease in children. Cochrane Database Syst Rev. 2017 Jan 27;(1):CD011188.[Abstract][Full Text]
73. Burns JC, Best BM, Mejias AJ, et al. Infliximab treatment of intravenous immunoglobulin-resistant Kawasaki disease. J Pediatr. 2008 Dec;153(6):833-8.[Abstract][Full Text]
74. Sonoda K, Mori M, Hokosaki T, et al. Infliximab plus plasma exchange rescue therapy in Kawasaki disease. J Pediatr. 2014 May;164(5):1128-32.e1. [Abstract]
75. de Ferranti SD, Steinberger J, Ameduri R, et al. Cardiovascular risk reduction in high-risk pediatric patients: a scientific statement from the American Heart Association. Circulation. 2019 Mar 26;139(13):e603-34.[Abstract][Full Text]
76. Suda K, Tahara N, Honda A, et al. Statin reduces persistent coronary arterial inflammation evaluated by serial ¹⁸fluorodeoxyglucose positron emission tomography imaging long after Kawasaki disease. Int J Cardiol. 2014 Oct 22;179:61-2.[Abstract]
77. Amarilyo G, Koren Y, Brik Simon D, et al. High-dose aspirin for Kawasaki disease: outdated myth or effective aid? Clin Exp Rheumatol. 2017 Mar-Apr;35 Suppl 103(1):209-12.[Abstract]
78. Jia X, Du X, Bie S, et al. What dose of aspirin should be used in the initial treatment of Kawasaki disease? A meta-analysis. Rheumatology (Oxford). 2020 Aug 1;59(8):1826-33.[Abstract][Full Text]
79. Beiser AS, Takahasha M, Baker AL, et al. A predictive instrument for coronary artery aneurysms in Kawasaki disease. US Multicenter Kawasaki Disease Study Group. Am J Cardiol. 1998 May 1;81(9):1116-20.[Abstract]
80. Mori M, Imagawa T, Yasui K, et al. Predictors of coronary artery lesions after intravenous gamma-globulin treatment in Kawasaki disease. J Pediatr. J Pediatr. 2000 Aug;137(2):177-80.[Abstract]
81. Fukunishi M, Kikkawa M, Hamana K, et al. Prediction of non-responsiveness to intravenous high-dose gamma-globulin therapy in patients with Kawasaki disease at onset. J Pediatr. 2000 Aug;137(2):172-6.[Abstract]
82. Nakamura Y, Yashiro M, Uehara R, et al. Use of laboratory data to identify risk factors of giant coronary aneurysms due to Kawasaki disease. Pediatr Int. 2004 Feb;46(1):33-8.[Abstract]
83. Marquez J, Gedalia O, Candia L, et al. Kawasaki disease: clinical spectrum of 88 patients in a high-prevalence African-American population. J Natl Med Assoc. 2008 Jan;100(1):28-32.[Abstract]
84. Gersony WM. The adult after Kawasaki disease: the risks for late coronary events. J Am Coll Cardiol. 2009 Nov 17;54(21):1921-3.[Abstract][Full Text]
85. Friedman KG, Gauvreau K, Hamaoka-Okamoto A, et al. Coronary artery aneurysm in Kawasaki disease: risk factors for progressive disease and adverse cardiac events in US population. J Am Heart Assoc. 2016 Sep 15;5(9):e003289.[Abstract][Full Text]
86. Burns JC, El-Said H, Tremoulet AH, et al. Management of myocardial infarction in children with giant coronary artery aneurysms after Kawasaki disease. J Pediatr. 2020 Jun;221:230-4.[Abstract][Full Text]
87. Tsuda E, Hamaoka K, Suzuki H, et al. A survey of the 3-decade outcome for patients with giant aneurysms caused by Kawasaki disease. Am Heart J. 2014 Feb;167(2):249-58.[Abstract]
88. García-Pavón S, Yamazaki-Nakashimada MA, Báez M, et al. Kawasaki disease complicated with macrophage activation syndrome: a systematic review. J Pediatr Hematol Oncol. 2017 Aug;39(6):445-51.[Abstract]
89. McCrindle BW, Rowley AH, Newburger JW, et al; American Heart Association. Diagnosis, treatment, and long-term management of Kawasaki disease: a scientific statement for health professionals from the American Heart Association. Circulation. 2017 Apr 25;135(17):e927-99.[Abstract][Full Text]
