Springer Nature is making SARS-CoV-2 and COVID-19 research free. View research | View latest news | Sign up for updates

Advances in Kawasaki disease

  • 245 Accesses

  • 56 Citations


Recent studies have increased our understanding of the etiopathogenesis of Kawasaki disease (KD). The inflammatory infiltrate in KD coronary artery aneurysms has been shown to consist of CD8 T lymphocytes, macrophages, and IgA plasma cells, consistent with an immune response to an intracellular pathogen with a mucosal portal of entry. The identification of an oligoclonal IgA response in the vascular wall and the detection of a KD-associated antigen in inflamed KD tissues using a synthetic antibody derived from KD oligoclonal IgA antibodies have provided new approaches to identification of the etiologic agent. Highly effective therapy has evolved for KD, even in the absence of identification of the etiologic agent. The existence of incomplete KD cases remains a significant diagnostic dilemma for the clinician. Conclusion: the development of a diagnostic test, more specific therapy, and ultimate prevention of this potentially fatal illness of childhood are dependent upon continued advances in determining the etiopathogenesis of this fascinating disorder.

This is a preview of subscription content, log in to check access.



Kawasaki disease


intravenous immunoglobulin


  1. 1.

    Abe J, Kotzin BL, Jujo K, Melish ME, Glode MP, Kohsaka T, Leung DYM (1992) Selective expansion of T cells expressing T-cell receptor variable regions Vbeta2 and Vbeta8 in Kawasaki disease. Proc Natl Acad Sci 89: 4066–4070

  2. 2.

    Amano S, Hazama F, Hamashima Y (1979) Pathology of Kawasaki disease. I. Pathology and morphogenesis of the vascular changes. Jpn Circ J 43: 633–643

  3. 3.

    Amano S, Hazama F, Hamashima Y (1979) Pathology of Kawasaki disease. II. Distribution and incidence of the vascular lesions. Jpn Circ J 43: 741–748

  4. 4.

    Amano S, Hazama F, Kubagawa H, Tasaka K, Haebara H, Hamashima Y (1980) General pathology of Kawasaki disease. Acta Pathol Jpn 30: 681–694

  5. 5.

    American Academy of Pediatrics (2003) Report of the Committee on Infectious Diseases. Red Book, 26th edn.

  6. 6.

    Bell DM, Brink EW, Nitzkin JL, Hall CB, Wulff H, Berkowitz ID, Feorino PM, Holman RC, Huntley CL, Meade RH, Anderson LJ, Cheesman SH, Fiumara NJ, Gilfillan RF, Keim DE, Modlin JF (1981) Kawasaki Syndrome: description of two outbreaks in the United States. N Engl J Med 304: 1568–1575

  7. 7.

    Brown TJ, Crawford SE, Cornwall M, Garcia F, Shulman ST, Rowley AH (2001) CD8+ T cells and macrophages infiltrate coronary artery aneurysms in acute Kawasaki disease. J Infect Dis 184: 940–943

  8. 8.

    Burns JC, Shimizu C, Shike H, Bastian JF, Buchanan JA, Yuan J, Newburger J, Sundel RS, Dergun M, Cantor RM (2003) Candidate genes for susceptibility to Kawasaki Disease: analysis of preferentially transmitted alleles inpatient/parent triads. Pediatr Res 53: 325A

  9. 9.

    Burns JC, Bastian JF, Mason WH, Janais H, Hauger SB, Wohrley JD (2003) Treatment of refractory Kawasaki syndrome with infliximab. 41st Annual Meeting of Infectious Diseases Society of America, San Diego, CA, Abstract 803

  10. 10.

    Choi IH, Chwae YJ, Shim WP, Kim DS, Kwon DH, Kim JD, Kim SJ (1997) Clonal expansion of CD8+ T cells in Kawasaki disease. J Immunol 159: 481–486

  11. 11.

    Curtis N, Zheng R, Lamb JK, Levin M (1995) Evidence for a superantigen mediated process in Kawasaki disease. Arch Dis Child 72: 308–311

  12. 12.

    Dajani AS, Taubert KA, Gerber MA, Shulman ST, Ferrieri P, Freed M (1993) Diagnosis and therapy of Kawasaki disease in children. Circulation 87: 1776–1780

  13. 13.

    Dale RC, Saleem MA, Daw S, Dillon MJ (2000) Treatment of severe complicated Kawasaki disease with oral prednisolone and aspirin. J Pediatr 137: 723–726

  14. 14.

    Dean AG, Melish ME, Hicks R (1982) An epidemic of Kawasaki syndrome in Hawaii. J Pediatr 100: 552–557

  15. 15.

    Durongpisitkul K, Soongswang J, Laohaprasitiporn D, Nana A, Prachuabmoh C, Kangkagate C (2003) Immunoglobulin failure and retreatment in Kawasaki disease. Pediatr Cardiol 24: 145–148

  16. 16.

    Freeman AF, Crawford SE, Finn LS, Lopez-Andreu JA, Ferrando-Monleon S, Perez-Tamarit D, Cornwall M, Shulman ST, Rowley AH (2003) Inflammatory pulmonary nodules in Kawasaki disease. Pediatr Pulmonol 36: 102–106

  17. 17.

    Fujiwara H, Fujiwara T, Kao T, Ohshio G, Hamashima Y (1986) Pathology of Kawasaki disease in the healed stage. Relationships between typical and atypical cases of Kawasaki disease. Acta Pathol Jpn 36: 857–867

  18. 18.

    Furukawa S, Matsubara T, Umezawa Y, Motohashi T, Ino T, Yabuta K (1994) Pentoxifylline and intravenous gamma globulin combination therapy for acute Kawasaki disease. Eur J Pediatr 153: 663–667

  19. 19.

    Furusho K, Kamiya T, Nakano H, Kiyosawa N, Shinomiya K, Hayashidera T (1984) High-dose intravenous gamma globulin for Kawasaki disease. Lancet 2: 1055–1058

  20. 20.

    Gavin PJ, Crawford SE, Shulman ST, Garcia FL, Rowley AH (2003) Systemic arterial expression of matrix metalloproteinases 2 and 9 in acute Kawasaki disease. Arterioscler Thromb Vasc Biol 23: 576–581

  21. 21.

    Han RK, Silverman ED, Newman A, McCrindle BW (2000) Management and outcome of persistent or recurrent fever after initial intravenous gamma globulin therapy in acute Kawasaki disease. Arch Pediatr Adolesc Med 154: 694–699

  22. 22.

    Hashino K, Ishii M, Lemura M, Akagi T, Kato H (2001) Re-treatment for immune globulin-resistant Kawasaki disease: a comparative study of additional immune globulin and steroid pulse therapy. Pediatr Int 43: 211–217

  23. 23.

    Hirao J, Hibi S, Andoh T, Ichimura T (1997) High levels of circulating interleukin-4 and interleukin-10 in Kawasaki disease. Int Arch Allergy Immunol 112: 152–156

  24. 24.

    Kawasaki T (1967) Acute febrile mucocutaneous syndrome with lymphoid involvement with specific desquamation of the fingers and toes in children (in Japanese). Jpn J Allerg 16: 178–222

  25. 25.

    Koren G, Lavi S, Rose V, Rowe R (1986) Kawasaki disease: review of risk factors for coronary aneurysms. J Pediatr 108: 388–392

  26. 26.

    Kusakawa S, Heiner DC (1976) Elevated levels of imunoglobulin E in the acute febrile mucocutaneous lymph node syndrome. Pediatr Res 10: 108–111

  27. 27.

    Landing BH, Larson EJ (1977) 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 59: 651–662

  28. 28.

    Larkin SM, Williams DN, Osterholm MT, Tofte RW, Posalaky Z (1982) Toxic shock syndrome: clinical, laboratory, and pathologic findings in nine fatal cases. Ann Internal Med 96: 858–864

  29. 29.

    Leung DYM, Siegel RL, Grady S, Krensky A, Meade R, Reinherz EL, Geha RS (1982) Immunoregulatory abnormalities in mucocutaneous lymph node syndrome. Clin Immunol Immunopathol 23: 100–112

  30. 30.

    Leung DYM, Meissner HC, Fulton DR, Murray DL, Kotzin BL, Schlievert PM (1993) Toxic shock syndrome toxin-secreting Staphylococcus aureus in Kawasaki syndrome. Lancet 342: 1385–1388

  31. 31.

    Leung DY, Meissner HC, Shulman ST, Mason WH, Gerber MA, Glode MP, Myones BL, Wheeler JG, Ruthazer R, Schlievert PM (2002) Prevalence of superantigen-secreting bacteria in patients with Kawasaki disease. J Pediatr 140: 742–746

  32. 32.

    Lin CY, Hwang B (1987) Serial immunologic studies in patients with mucocutaneous lymph node syndrome (Kawasaki disease). Ann Allergy 59: 291–297

  33. 33.

    Lin CY, Lin CC, Hwang B, Chiang B (1992) Serial changes of serum interleukin-6, interleukin-8, and tumor necrosis factor alpha among patients with Kawasaki disease. J Pediatr 121: 924–926

  34. 34.

    Linderholm M, Ahlm C, Settergren B, Waage A, Tarnvik A (1996) Elevated plasma levels of tumor necrosis factor (TNF)-alpha, soluble TNF receptors, interleukin (IL)-6, and IL-10 in patients with hemorrhagic fever with renal syndrome. J Infect Dis 173: 38–43

  35. 35.

    Mancia L, Wahlstrom J, Schiller B, Chini L, Elinder G, D’Argenio P,Gigliotti D, Wigzell H, Rossi P, Grunewald J (1998) Characterization of the T-cell receptor V-beta repertoire in Kawasaki disease. Scand J Immunol 48: 443–449

  36. 36.

    Melish ME, Hicks RM, Larson EJ (1976) Mucocutaneous lymph node syndrome in the United States. Am J Dis Child 130: 599–607

  37. 37.

    Melish ME, Parsonett J, Marchette N (1994) Kawasaki syndrome (KS) is not caused by toxic shock syndrome toxin-1 (TSST-1)+ staphylococci. Pediatr Res 35: 187A

  38. 38.

    Newburger JW, Takahashi M, Burns JC, Beiser AS, Duffy CE, Glode MP (1986) The treatment of Kawasaki syndrome with intravenous gamma globulin. N Engl J Med 315: 341–347

  39. 39.

    Newburger JW, Takahashi M, Beiser AS, Burns JC, Bastian J, Chung KJ, Colan SD, Duffy CE, Fulton DR, Glode MP, Mason WH, Meissner HC, Rowley AH, Shulman ST, Reddy V, Sundel RP, Wiggins JW, Colton T, Melish ME, Rosen FS (1991) A single intravenous infusion of gamma globulin as compared with four infusions in the treatment of acute Kawasaki syndrome. N Engl J Med 324: 1633–1639

  40. 40.

    Peters RJ, Mehta SR, Fox KA, Zhao F, Lewis BS, Kopecky SL (2003) Effects of aspirin dose when used alone or in combination with clopidogrel in patients with acute coronary syndromes: observations from the Clopidogrel in Unstable angina to prevent Recurrent Events (CURE) study. Circulation 108: 1682–1687

  41. 41.

    Pietra BA, DeInocencio J, Giannini EH, Hirsch R (1994) TCR Vbeta family repertoire and T cell activation markers in Kawasaki disease. J Immunol 153: 1881–1888

  42. 42.

    Rosenfeld EA, Corydon K, Shulman ST (1995) Kawasaki disease in infants under one year of age. J Pediatr 126: 4

  43. 43.

    Rowley AH, Gonzalez-Crussi F, Gidding SS, Duffy CE, Shulman ST (1987) Incomplete Kawasaki syndrome with coronary artery disease. J Pediatr 110: 409–413

  44. 44.

    Rowley AH, Eckerley CA, Jack H-M, Shulman ST, Baker SC (1997) IgA plasma cells in vascular tissue of patients with Kawasaki syndrome. J Immunol 159: 5946–5955

  45. 45.

    Rowley AH, Shulman ST, Mask CA, Finn LS, Terai M, Baker SC, Galliani CA, Takahashi K, Naoe S, Kalelkar MB, Crawford SE (2000) IgA plasma cell infiltration of proximal respiratory tract, pancreas, kidney, and coronary artery in acute Kawasaki disease. J Infect Dis 182: 1183–1191

  46. 46.

    Rowley AH, Shulman ST, Spike BT, Mask CA, Baker SC (2001) Oligoclonal IgA response in the vascular wall in acute Kawasaki disease. J Immunol 166: 1334–1343

  47. 47.

    Rowley AH, Guzman-Cottrill JA, Garcia FL, Crawford SE, Shulman ST (2003) Synthetic Kawasaki Disease (KD) antibodies bind to acute fatal KD tissues. Ped Res 53: 308A

  48. 48.

    Shulman ST (2003) Kawasaki disease. In: Feigin RD, Cherry JD, Demmler GJ, Kaplan SL (eds) Textbook of pediatric infectious diseases, 5th edn. Saunders, Philadelphia, pp 1055–1074

  49. 49.

    Shulman ST (2003) Is there a role for corticosteroids in Kawasaki Disease? J Pediatr 142: 601–603

  50. 50.

    Shulman ST, Melish M, Inoue O, Kato H, Tomita S (1993) Immunoglobulin allotypic markers in Kawasaki disease. J Pediatrics 122: 84–86

  51. 51.

    Sundel RP, Baker AL, Fulton DR, Newburger JW (2003) Corticosteroids in the initial treatment of Kawasaki disease: report of a randomized trial. J Pediatr 142: 611–616

  52. 52.

    Takagi N, Kihara M, Yamaguchi S, Tamura K, Yabana M, Tokita Y (1995) Plasma exchange in Kawasaki disease. Lancet 346: 1307

  53. 53.

    Taubert KA, Rowley AH, Shulman ST (1991) Nationwide survey of Kawasaki disease and acute rheumatic fever. J Pediatr 119: 279-282

  54. 54.

    Terai M, Shulman ST (1997) Prevalence of coronary artery abnormalities in Kawasaki disease is highly dependent on gamma globulin dose but independent of salicylate dose. J Pediatr 131: 888–893

  55. 55.

    Terai M, Kohno Y, Niwa K, Toba T, Sakurai N, Nakajima H (1987) Imbalance among T-cell subsets in patients with coronary arterial aneurysms in Kawasaki disease. Am J Cardiol 60: 555–559

  56. 56.

    Terai M, Miwa K, Williams T, Kabat W, Fukuyama M, Okajima Y, Igarashi H, Shulman ST (1995) The absence of evidence of staphylococcal toxin involvement in the pathogenesis of Kawasaki disease. J Infect Dis 172: 558–561

  57. 57.

    Ueno Y, Takano N, Kanegane H, Yokoi T, Yachie A, Miyawaki T, Taniguchi N (1989) The acute phase nature of interleukin 6: studies in Kawasaki disease and other febrile illnesses. Clin Exp Immunol 76: 337–342

  58. 58.

    Wallace CA, French JW, Kahn SJ, Sherry DD (2000) Initial intravenous gamma globulin treatment failure in Kawasaki disease. Pediatrics 105: E78

  59. 59.

    Williams RV, Wilke VM, Tani LY, Minich LL (2002) Does abciximab enhance regression of coronary aneurysms resulting from Kawasaki disease? Pediatrics 109: E4

  60. 60.

    Wright DA, Newburger JW, Baker A, Sundel RP (1996) Treatment of immune globulin-resistant Kawasaki disease with pulsed doses of corticosteroids. J Pediatr 128: 146–149

  61. 61.

    Yanagawa H, Nakamura Y, Yashiro M, Oki I, Hirata S, Zhang T (2001) Incidence survey of Kawasaki disease in 1997 and 1998 in Japan. Pediatrics 107: E33

Download references

Author information

Correspondence to Stanford T. Shulman.

Rights and permissions

Reprints and Permissions

About this article

Cite this article

Shulman, S.T., Rowley, A.H. Advances in Kawasaki disease. Eur J Pediatr 163, 285–291 (2004).

Download citation


  • Kawasaki disease
  • Review