Kawasaki Disease Treatment & Management
- Author: Noah S Scheinfeld, JD, MD, FAAD; Chief Editor: Russell W Steele, MD more...
The principal goal of treatment for Kawasaki disease is to prevent coronary artery disease and to relieve symptoms. Full doses of intravenous immunoglobulin (IVIG) are the mainstay of treatment.[5, 8, 9]
Admit all patients to the hospital for administration of IVIG and for observation until fever is controlled. Closely monitor cardiovascular function. Once the fever resolves, clinically significant heart failure or myocardial dysfunction is unlikely.
Aspirin has traditionally been part of the standard treatment of this disorder. Although some authors have suggested that aspirin is no longer needed, most experts use high-dose aspirin for a variable period, followed by lower-dose aspirin for its antiplatelet effects. Aspirin is used in patients with small coronary artery aneurysms (CAAs). Dipyridamole is indicated in patients with larger CAAs.
The appropriate treatment of patients who fail to respond to IVIG remains unclear. Severe Kawasaki disease that is resistant to IVIG may benefit from intravenous pulse corticosteroid therapy or infliximab infusion.
Transfer patients with suspected Kawasaki disease to a facility that has clinicians experienced in the care of these patients and a pediatric or adult cardiologist to evaluate the echocardiogram. Some authorities recommend transferring patients who have documented coronary artery aneurysms to a tertiary pediatric facility.
The following clinical guidelines are relevant for management of Kawasaki disease:
National Collaborating Centre for Women's and Children's Health - Feverish illness in children: assessment and initial management in children younger than 5 years
American College of Chest Physicians Evidence-Based Clinical Practice Guidelines - Antithrombotic therapy in neonates and children. American College of Chest Physicians evidence-based clinical practice guidelines (8th edition)
American College of Cardiology/American Heart Association Task Force on Practice Guidelines - 2008 focused update incorporated into the ACC/AHA 2006 guidelines for the management of patients with valvular heart disease. A report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines (Writing Committee to Revise the 1998 Guidelines for the Management of Patients with Valvular Heart Disease)
Emergency Department Care
Any young child who presents to the emergency department (ED) with symptoms of early or acute-stage Kawasaki disease should be evaluated to rule out sepsis or meningitis. Although the diagnosis may seem obvious, other life-threatening diseases must be ruled out. The ED physician must consider the possibility that a child has an incomplete case and proceed with the evaluation listed above. Intravenous access and cardiac monitoring should be established.
Depending on the institution, anti-inflammatory therapy may need to begin in the ED. Arrangements for admission must take into consideration the potential for multiple problems. This is not a routine pediatric illness. Accordingly, transferring the patient to a pediatric referral center may be prudent.
IVIG relieves acute inflammation and has been shown to reduce the rate of coronary aneurysms from greater than 25% in untreated patients to 1-5% in treated patients. Maximal benefits are seen when IVIG is given within the first 10 days of the illness. Some controversy exists about the ideal time to begin IVIG, but it is given most often from days 5-7.
In the past, IVIG was given as a lower dose over 4 days (400 mg/kg/day), but newer studies have shown that high single doses are more effective. In current practice, the dose is 2 g/kg intravenously over 10-12 hours.
In patients in whom the standard treatment fails (approximately 10-15%) and who continue to have fever 36 hours after the initial dose of IVIG, a second treatment with IVIG at the original dose is recommended. A small subgroup of patients fails to respond to a second dose of IVIG.
A study in an ethnically diverse population in San Diego, California, found that patients with IVIG resistance tended to have higher percent bands; higher concentrations of C-reactive protein, alanine aminotransferase, and gamma-glutamyl transferase; lower platelet counts; and lower age-adjusted hemoglobin concentrations. They were also more likely to have aneurysms. However, a proposed scoring system to predict IVIG resistance proved insufficiently accurate to be clinically useful.
In a review from Singapore by Sittiwangkul et al, initial treatment with IVIG (2 g/kg) failed to elicit a response in 13% of patients. The diagnosis in 2 patients with IVIG-resistant Kawasaki disease was delayed, and giant aneurysms developed. Patients with a high erythrocyte sedimentation rate (ESR) were at an increased risk of IVIG-resistant Kawasaki disease. Patients with IVIG-resistant Kawasaki disease had a higher prevalence of coronary artery lesions at the acute phase and 2 months after onset.
Treatment of IVIG-Resistant Disease
Patients in whom a second dose of IVIG therapy fails can be treated with corticosteroids. Intravenous pulse methylprednisolone may be given at 30 mg/kg for 2-3 hours administered once daily for 1-3 days.
An alternative treatment is infliximab (Remicade) at 5 mg/kg, which is a chimeric mouse-human monoclonal antibody directed against soluble and membrane bound tumor necrosis factor-alpha. Several studies have found infliximab to be useful in treating Kawasaki disease that is refractory to IVIG.[87, 88] Burns et al reported that infliximab was as effective as a second dose of IVIG in patients who did not respond to a first dose of IVIG.
43 patients with KD who were initially treatment resistant to intravenous immunoglobulin (IVIG) had researchers randomized the 43 to get either a first does infliximab (n=11) or second dose of IVIG (n=32). IVIG retreatment gave 65.6% (21) patients a response while infliximab gave 90.9% (10)patients aresponse. Infliximab provided less days of hospitalization and a shorter duration of fever. Adverse events and coronary artery meterics resembled each other in the two groups.
Other alternative therapies for resistant cases include cyclophosphamide with and without methotrexate; however, the effectiveness of these latter treatments is still uncertain because they have been used in only a small number of cases. The following are adjunctive therapies for patients who do not respond to conventional therapies.
Ulinastatin is a human trypsin inhibitor purified from human urine. It has been used only in Japan for refractory cases of Kawasaki disease and is believed to function by inhibiting neutrophil elastase and prostaglandin H2 synthase at the mRNA level.
In the future, by identifying a genetic signature for this group, more aggressive therapies, such as anticytokine therapy, plasmapheresis, or cyclosporin A, may be used to reduce the risk of coronary complications.[43, 33]
Aspirin has a synergistic effect with IVIG and has long been a standard part of therapy for Kawasaki disease. However, its use has been called into question. Some studies suggest that high- or medium-dose aspirin may have no effect on the response rate to IVIG, duration of fever, or incidence of coronary artery aneurysms despite treatment before or after 5 days of therapy.
Randomized controlled trial outcomes are insufficient to indicate whether children with this disorder should continue to receive salicylate as part of the treatment regimen. Baumer et al concluded that no randomized clinical trials of adequate quality have been performed and that current evidence is insufficient to support the use of salicylate in children with Kawasaki disease as part of their treatment regimen.
Nevertheless, most experts use high-dose aspirin for a variable period, followed by lower-dose aspirin for its antiplatelet effects. High-dose aspirin (80-100 mg/kg/d orally in 4 divided doses) is given in the acute phase for its anti-inflammatory effects. It is continued until day 14 of the illness or until the patient has been afebrile for 48-72 hours.
Once the patient has remained afebrile for 48-72 hours, low-dose aspirin is initiated for its antiplatelet activity. The dose is 3-5 mg/kg/day for a total of 6-8 weeks as long as the patient shows no evidence of coronary abnormalities. For patients who have aneurysms, aspirin should be continued until the aneurysm resolves or should be continued indefinitely.
Patients who remain on long-term, low-dose aspirin should receive an annual influenza vaccine. Additionally, the risks of developing Reye syndrome during an active infection with influenza or varicella should be addressed.
The pediatrician or cardiologist who provides the long-term care monitors aspirin therapy and decides whether to use warfarin or heparin.
Patients on prolonged aspirin therapy must be instructed that concomitant use of ibuprofen antagonizes the irreversible effect of platelet inhibition by aspirin and should be avoided during therapy. Contact activities or high-impact sports should be avoided in patients on prolonged antiplatelet therapy.
Clopidogrel (Plavix) may be briefly substituted for aspirin in patients who develop influenza or varicella. This agent can also be used in patients allergic to aspirin.
Other Adjunctive Agents
In addition to their use in treatment of IVIG-resistant Kawasaki disease, corticosteroids have been proposed as part of primary therapy. This indication is controversial, however. Research results have been inconsistent, as follows:
In a multicenter prospective randomized trial in Japan, the combination of corticosteroids and IVIG significantly decreased coronary artery abnormalities, duration of fever, C-reactive protein levels, and initial treatment failure 
A randomized trial in the United States in which a single pulsed dose of methylprednisolone (30 mg/kg) was added to conventional therapy saw a reduction in the ESR at 1 week, but no difference in coronary artery abnormalities 
In a meta-analysis of 4 studies and 447 patients, Athappan et al concluded that the addition of steroids to standard therapy with IVIG and aspirin decreased the rate of re-treatment but did not decrease the incidence of coronary aneurysms or adverse events 
The roles of other adjunctive therapies, including pentoxifylline and abciximab, have not yet been definitively determined. Pentoxifylline acts as an anti-inflammatory agent by inhibiting tumor necrosis factor-alpha and may reduce the incidence of aneurysms. Abciximab is a platelet glycoprotein IIb/IIIa receptor inhibitor and has been used in conjunction with standard therapies in patients with Kawasaki disease and giant aneurysms.
A selection of ongoing, recruiting, and completed clinical trials is as follows:
Consultation with a pediatric cardiologist may be required if coronary artery aneurysms are identified or if other cardiac complications develop. Consult a pediatric or adult cardiologist for the following:
Children or adults with clinically significant coronary artery disease
Determining the appropriate timing of subsequent echocardiographic studies
Anticoagulation in patients with large aneurysms
To determine whether other studies to assess cardiac function (eg, stress testing, coronary artery angiography) are required
Consult a pediatric or adult infectious disease specialist to rule out infectious disease as a cause of fever. Consult a pediatric or adult rheumatologist to rule out other causes of vasculitis and connective tissue diseases. Consult a pediatric dermatologist to rule out other conditions that can manifest with fever and a rash. Pediatric cardiothoracic surgery assistance may be needed in the pediatric ICU for those patients who need bypass surgery.
Reevaluate all patients within 1 week of hospital discharge. Schedule the patient for repeat echocardiography 21-28 days after the onset of fever. If baseline echocardiographic studies and those obtained at 3-4 weeks do not show any evidence of coronary aneurysms, further echocardiography is usually unnecessary, as are activity restrictions or medications beyond 3 months after the initial illness. However, a repeat echocardiogram at 1 year and a cardiovascular risk assessment at 5-year intervals are optimal.
Ensure that a patient with coronary artery aneurysms (CAAs) or other cardiac abnormalities receives further care, as dictated by a cardiologist. Although 55% of patients who have identified coronary lesions during the acute phase of the disease typically show regression or reduction in these lesions within 1-2 years, these patients may still be at an increased risk for future atherosclerotic lesions.
Patients who develop coronary aneurysms should remain on aspirin therapy at least until the abnormalities resolve. Depending on the severity of the aneurysm, the patient will need biannual echocardiography, a cardiac stress test, a risk assessment with lipid evaluation, and possibly an angiogram if noninvasive tests suggest ischemia.
Cardiac stress testing is typically performed 1-5 years after the illness resolves in patients who had CAAs. It is used to assess the existence and functional consequences of coronary artery disease, and helps determine recommendations for physical activity.
Kawasaki T. [Acute febrile mucocutaneous syndrome with lymphoid involvement with specific desquamation of the fingers and toes in children]. Arerugi. 1967 Mar. 16(3):178-222. [Medline].
Gedalia A. Kawasaki disease: 40 years after the original report. Curr Rheumatol Rep. 2007 Aug. 9(4):336-41. [Medline].
Satou GM, Giamelli J, Gewitz MH. Kawasaki disease: diagnosis, management, and long-term implications. Cardiol Rev. 2007 Jul-Aug. 15(4):163-9. [Medline].
Henderson D. Kawasaki Disease Diagnosed by Urine Proteins? Medscape Medical News. December 26, 2012. Available at http://www.medscape.com/viewarticle/776728. Accessed: January 8, 2013.
Kentsis A, Shulman A, Ahmed S, Brennan E, Monuteaux MC et al. Urine proteomics for discovery of improved diagnostic markers of Kawasaki disease. EMBO Mol Med. 2012 Dec 20. [Medline].
Wood L, Tulloh R. Kawasaki disease: diagnosis, management and cardiac sequelae. Expert Rev Cardiovasc Ther. 2007 May. 5(3):553-61. [Medline].
Newburger JW, Takahashi M, Burns JC, Beiser AS, Chung KJ, Duffy CE, et al. The treatment of Kawasaki syndrome with intravenous gamma globulin. N Engl J Med. 1986 Aug 7. 315(6):341-7. [Medline].
Salguero JS, Durán DG, Peracaula CS, Iznardi CR, Tardío JO. [Refractory Kawasaki disease with coronary aneurysms treated with infliximab]. An Pediatr (Barc). 2010 Nov. 73(5):268-71. [Medline].
Kawamura Y, Kanai T, Takeshita S, Nonoyama S. Use of the urinary trypsin inhibitor ulinastatin for acute Kawasaki disease. Nihon Rinsho. 2014 Sep. 72(9):1650-3. [Medline].
Melish ME, Hicks RM, Larson EJ. Mucocutaneous lymph node syndrome in the United States. Am J Dis Child. 1976 Jun. 130(6):599-607. [Medline].
Newburger JW, Taubert KA, Shulman ST, Rowley AH, Gewitz MH, Takahashi M, et al. Summary and abstracts of the Seventh International Kawasaki Disease Symposium: December 4-7, 2001, Hakone, Japan. Pediatr Res. 2003 Jan. 53(1):153-7. [Medline].
Rizk SR, El Said G, Daniels LB, Burns JC, El Said H, Sorour KA, et al. Acute Myocardial Ischemia in Adults Secondary to Missed Kawasaki Disease in Childhood. Am J Cardiol. 2014 Nov 29. [Medline].
Son MB, Gauvreau K, Ma L, Baker AL, Sundel RP, Fulton DR, et al. Treatment of Kawasaki disease: analysis of 27 US pediatric hospitals from 2001 to 2006. Pediatrics. 2009 Jul. 124(1):1-8. [Medline].
Burns JC, Shimizu C, Shike H, Newburger JW, Sundel RP, Baker AL, et al. Family-based association analysis implicates IL-4 in susceptibility to Kawasaki disease. Genes Immun. 2005 Aug. 6(5):438-44. [Medline]. [Full Text].
Lee TJ, Chun JK, Yeon SI, Shin JS, Kim DS. Increased serum levels of macrophage migration inhibitory factor in patients with Kawasaki disease. Scand J Rheumatol. 2007 May-Jun. 36(3):222-5. [Medline].
Leung DY, Schlievert PM, Meissner HC. The immunopathogenesis and management of Kawasaki syndrome. Arthritis Rheum. 1998 Sep. 41(9):1538-47. [Medline].
Pietra BA, De Inocencio J, Giannini EH, Hirsch R. TCR V beta family repertoire and T cell activation markers in Kawasaki disease. J Immunol. 1994 Aug 15. 153(4):1881-8. [Medline].
Wang CL, Wu YT, Liu CA, Kuo HC, Yang KD. Kawasaki disease: infection, immunity and genetics. Pediatr Infect Dis J. 2005 Nov. 24(11):998-1004. [Medline].
Ogawa S. Biomarker. Nihon Rinsho. 2014 Sep. 72(9):1578-84. [Medline].
Onouchi Y. Susceptibility genes for Kawasaki disease. Nihon Rinsho. 2014 Sep. 72(9):1554-60. [Medline].
Hua W, Izurieta HS, Slade B, Belay ED, Haber P, Tiernan R, et al. Kawasaki disease after vaccination: reports to the vaccine adverse event reporting system 1990-2007. Pediatr Infect Dis J. 2009 Nov. 28(11):943-7. [Medline].
Miron D, Fink D, Hashkes PJ. Kawasaki disease in an infant following immunisation with hepatitis B vaccine. Clin Rheumatol. 2003 Dec. 22(6):461-3. [Medline].
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 Oct. 21(10):976-8. [Medline].
Burns JC, Glodé MP. Kawasaki syndrome. Lancet. 2004 Aug 7-13. 364(9433):533-44. [Medline].
Melish ME, Hicks RV. Kawasaki syndrome: clinical features. Pathophysiology, etiology and therapy. J Rheumatol Suppl. 1990 Sep. 24:2-10. [Medline].
Leung DY, Meissner HC, Fulton DR, Murray DL, Kotzin BL, Schlievert PM. Toxic shock syndrome toxin-secreting Staphylococcus aureus in Kawasaki syndrome. Lancet. 1993 Dec 4. 342(8884):1385-8. [Medline].
Yanagawa H, Nakamura Y, Yashiro M, Ojima T, Tanihara S, Oki I, et al. Results of the nationwide epidemiologic survey of Kawasaki disease in 1995 and 1996 in Japan. Pediatrics. 1998 Dec. 102(6):E65. [Medline].
Yanagawa H, Yashiro M, Nakamura Y, Kawasaki T, Kato H. Epidemiologic pictures of Kawasaki disease in Japan: from the nationwide incidence survey in 1991 and 1992. Pediatrics. 1995 Apr. 95(4):475-9. [Medline].
Pinna GS, Kafetzis DA, Tselkas OI, Skevaki CL. Kawasaki disease: an overview. Curr Opin Infect Dis. 2008 Jun. 21(3):263-70. [Medline].
Caquard M, Parlier G, Siret D. [Family observation of Kawasaki disease: 2 cases in sister and brother]. Arch Pediatr. 2006 May. 13(5):453-5. [Medline].
Burns JC, Shimizu C, Gonzalez E, Kulkarni H, Patel S, Shike H, et al. Genetic variations in the receptor-ligand pair CCR5 and CCL3L1 are important determinants of susceptibility to Kawasaki disease. J Infect Dis. 2005 Jul 15. 192(2):344-9. [Medline]. [Full Text].
Uehara R, Yashiro M, Nakamura Y, Yanagawa H. Clinical features of patients with Kawasaki disease whose parents had the same disease. Arch Pediatr Adolesc Med. 2004 Dec. 158(12):1166-9. [Medline].
Mason WH, Takahashi M, Schneider T. Recurrence of Kawasaki disease in a large urban cohort in the United States. In: Takahashi M, Taubert K, eds. Proceedings of the Fourth International Symposium on Kawasaki Disease. Dallas, Tex: American Heart Association; 1993:21-6.:
Kato S, Kimura M, Tsuji K, Kusakawa S, Asai T, Juji T, et al. HLA antigens in Kawasaki disease. Pediatrics. 1978 Feb. 61(2):252-5. [Medline].
Matsuda I, Hattori S, Nagata N, Fruse A, Nambu H. HLA antigens in mucocutaneous lymph node syndrome. Am J Dis Child. 1977 Dec. 131(12):1417-8. [Medline].
Onouchi Y, Tamari M, Takahashi A, Tsunoda T, Yashiro M, Nakamura Y, et al. A genomewide linkage analysis of Kawasaki disease: evidence for linkage to chromosome 12. J Hum Genet. 2007. 52(2):179-90. [Medline].
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 Jan. 40(1):35-42. [Medline]. [Full Text].
Breunis WB, Biezeveld MH, Geissler J, Kuipers IM, Lam J, Ottenkamp J, et al. Polymorphisms in chemokine receptor genes and susceptibility to Kawasaki disease. Clin Exp Immunol. 2007 Oct. 150(1):83-90. [Medline]. [Full Text].
Mamtani M, Matsubara T, Shimizu C, et al. Association of CCR2-CCR5 haplotypes and CCL3L1 copy number with Kawasaki Disease, coronary artery lesions, and IVIG responses in Japanese children. PLoS One. Jul 7 2010;5(7):e11458:
Taniuchi S, Masuda M, Teraguchi M, Ikemoto Y, Komiyama Y, Takahashi H, et al. Polymorphism of Fc gamma RIIa may affect the efficacy of gamma-globulin therapy in Kawasaki disease. J Clin Immunol. 2005 Jul. 25(4):309-13. [Medline].
Holman RC, Belay ED, Christensen KY, Folkema AM, Steiner CA, Schonberger LB. Hospitalizations for Kawasaki syndrome among children in the United States, 1997-2007. Pediatr Infect Dis J. 2010 Jun. 29(6):483-8. [Medline].
Falcini F, Ozen S, Magni-Manzoni S, Candelli M, Ricci L, Martini G, et al. Discrimination between incomplete and atypical Kawasaki syndrome versus other febrile diseases in childhood: results from an international registry-based study. Clin Exp Rheumatol. 2012 Sep-Oct. 30:799-804. [Medline].
Burns JC, Mason WH, Hauger SB, Janai H, Bastian JF, Wohrley JD, et al. Infliximab treatment for refractory Kawasaki syndrome. J Pediatr. 2005 May. 146(5):662-7. [Medline].
Yanagawa H, Nakamura Y, Yashiro M, Uehara R, Oki I, Kayaba K. Incidence of Kawasaki disease in Japan: the nationwide surveys of 1999-2002. Pediatr Int. 2006 Aug. 48(4):356-61. [Medline].
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 Sep. 26(9):821-3. [Medline].
Huang GY, Ma XJ, Huang M, Chen SB, Huang MR, Gui YH, et al. Epidemiologic pictures of Kawasaki disease in Shanghai from 1998 through 2002. J Epidemiol. 2006 Jan. 16(1):9-14. [Medline].
Lin YT, Manlhiot C, Ching JC, Han RK, Nield LE, Dillenburg R, et al. Repeated systematic surveillance of Kawasaki disease in Ontario from 1995 to 2006. Pediatr Int. 2010 Oct. 52(5):699-706. [Medline].
Nakamura Y. Epidemiology of Kawasaki disease. Nihon Rinsho. 2014 Sep. 72(9):1536-41. [Medline].
Stankovic K, Miailhes P, Bessis D, Ferry T, Broussolle C, Sève P. Kawasaki-like syndromes in HIV-infected adults. J Infect. 2007 Dec. 55(6):488-94. [Medline].
Pannaraj PS, Turner CL, Bastian JF, Burns JC. Failure to diagnose Kawasaki disease at the extremes of the pediatric age range. Pediatr Infect Dis J. 2004 Aug. 23(8):789-91. [Medline].
Manlhiot C, Yeung RS, Clarizia NA, Chahal N, McCrindle BW. Kawasaki disease at the extremes of the age spectrum. Pediatrics. 2009 Sep. 124(3):e410-5. [Medline].
Kim T, Choi W, Woo CW, Choi B, Lee J, Lee K, et al. Predictive risk factors for coronary artery abnormalities in Kawasaki disease. Eur J Pediatr. 2007 May. 166(5):421-5. [Medline].
Gupta-Malhotra M, Gruber D, Abraham SS, Roman MJ, Zabriskie JB, Hudgins LC, et al. Atherosclerosis in survivors of Kawasaki disease. J Pediatr. 2009 Oct. 155(4):572-7. [Medline].
Kitamura S, Tsuda E, Kobayashi J, Nakajima H, Yoshikawa Y, Yagihara T, et al. Twenty-five-year outcome of pediatric coronary artery bypass surgery for Kawasaki disease. Circulation. 2009 Jul 7. 120(1):60-8. [Medline].
Yeo Y, Kim T, Ha K, Jang G, Lee J, Lee K, et al. Incomplete Kawasaki disease in patients younger than 1 year of age: a possible inherent risk factor. Eur J Pediatr. 2009 Feb. 168(2):157-62. [Medline].
Wilder MS, Palinkas LA, Kao AS, Bastian JF, Turner CL, Burns JC. Delayed diagnosis by physicians contributes to the development of coronary artery aneurysms in children with Kawasaki syndrome. Pediatr Infect Dis J. 2007 Mar. 26(3):256-60. [Medline]. [Full Text].
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 Oct 26. 110(17):2747-71. [Medline].
Nomura Y, Arata M, Koriyama C, Masuda K, Morita Y, Hazeki D, et al. A severe form of Kawasaki disease presenting with only fever and cervical lymphadenopathy at admission. J Pediatr. 2010 May. 156(5):786-91. [Medline].
Ulloa-Gutierrez R, Acón-Rojas F, Camacho-Badilla K, Soriano-Fallas A. Pustular rash in Kawasaki syndrome. Pediatr Infect Dis J. 2007 Dec. 26(12):1163-5. [Medline].
Turnier JL, Anderson MS, Heizer HR, Jone PN, Glodé MP, Dominguez SR. Concurrent Respiratory Viruses and Kawasaki Disease. Pediatrics. 2015 Aug 24. [Medline].
Boggs W. Concurrent Respiratory Viruses Common in Children With Kawasaki Disease. http://www.medscape.com/viewarticle/850157. Available at http://www.medscape.com/viewarticle/850157. August 31, 2015; Accessed: September 14, 2015.
Belay ED, Maddox RA, Holman RC, Curns AT, Ballah K, Schonberger LB. Kawasaki syndrome and risk factors for coronary artery abnormalities: United States, 1994-2003. Pediatr Infect Dis J. 2006 Mar. 25(3):245-9. [Medline].
Goo HW, Park IS, Ko JK, Kim YH. Coronary CT angiography and MR angiography of Kawasaki disease. Pediatr Radiol. 2006 Jul. 36(7):697-705. [Medline].
Mavrogeni S, Papadopoulos G, Douskou M, Kaklis S, Seimenis I, Baras P, et al. Magnetic resonance angiography is equivalent to X-ray coronary angiography for the evaluation of coronary arteries in Kawasaki disease. J Am Coll Cardiol. 2004 Feb 18. 43(4):649-52. [Medline].
Newburger JW, Fulton DR. Kawasaki disease. Curr Opin Pediatr. 2004 Oct. 16(5):508-14. [Medline].
Manlhiot C, Christie E, McCrindle BW, Rosenberg H, Chahal N, Yeung RS. Complete and incomplete Kawasaki disease: two sides of the same coin. Eur J Pediatr. 2011 Dec 3. [Medline].
Heuclin T, Dubos F, Hue V, Godart F, Francart C, Vincent P, et al. Increased detection rate of Kawasaki disease using new diagnostic algorithm, including early use of echocardiography. J Pediatr. 2009 Nov. 155(5):695-9.e1. [Medline].
Hinze CH, Graham TB, Sutherell JS. Kawasaki disease without fever. Pediatr Infect Dis J. 2009 Oct. 28(10):927-8. [Medline].
Printz BF, Sleeper LA, Newburger JW, Minich LL, Bradley T, Cohen MS, et al. Noncoronary cardiac abnormalities are associated with coronary artery dilation and with laboratory inflammatory markers in acute Kawasaki disease. J Am Coll Cardiol. 2011 Jan 4. 57(1):86-92. [Medline].
Kanamaru H, Sato Y, Takayama T, Ayusawa M, Karasawa K, Sumitomo N, et al. Assessment of coronary artery abnormalities by multislice spiral computed tomography in adolescents and young adults with Kawasaki disease. Am J Cardiol. 2005 Feb 15. 95(4):522-5. [Medline].
Dadlani GH, Gingell RL, Orie JD, Roland JM, Najdzionek J, Lipsitz SR, et al. Coronary artery calcifications in the long-term follow-up of Kawasaki disease. Am Heart J. 2005 Nov. 150(5):1016. [Medline].
Weedon R. Kawasaki Syndrome: The vasculopathic reaction pattern In:. Pathology. 2002:238-9:
Chen X, Zhao ZW, Li L, Chen XJ, Xu H, Lou JT, et al. Hypercoagulation and elevation of blood triglycerides are characteristics of Kawasaki disease. Lipids Health Dis. 2015 Dec 30. 14(1):166. [Medline].
Watanabe K, Suzuki H, Jiang M, Haniu H, Numano F, Hoshina S, et al. Soluble LR11 is a novel biomarker for vascular lesions late after Kawasaki disease. Atherosclerosis. 2015 Dec 29. 246:94-97. [Medline].
Uehara R, Yashiro M, Oki I, Nakamura Y, Yanagawa H. Re-treatment regimens for acute stage of Kawasaki disease patients who failed to respond to initial intravenous immunoglobulin therapy: analysis from the 17th nationwide survey. Pediatr Int. 2007 Aug. 49(4):427-30. [Medline].
Tremoulet AH, Best BM, Song S, Wang S, Corinaldesi E, Eichenfield JR, et al. Resistance to intravenous immunoglobulin in children with Kawasaki disease. J Pediatr. 2008 Jul. 153(1):117-21. [Medline]. [Full Text].
Sittiwangkul R, Pongprot Y, Silvilairat S, Phornphutkul C. Management and outcome of intravenous gammaglobulin-resistant Kawasaki disease. Singapore Med J. 2006 Sep. 47(9):780-4. [Medline].
Zulian F, Zanon G, Martini G, Mescoli G, Milanesi O. Efficacy of infliximab in long-lasting refractory Kawasaki disease. Clin Exp Rheumatol. 2006 Jul-Aug. 24(4):453. [Medline].
Stenbøg EV, Windelborg B, Hørlyck A, Herlin T. The effect of TNFalpha blockade in complicated, refractory Kawasaki disease. Scand J Rheumatol. 2006 Jul-Aug. 35(4):318-21. [Medline].
Burns JC, Best BM, Mejias A, Mahony L, Fixler DE, Jafri HS, et al. Infliximab treatment of intravenous immunoglobulin-resistant Kawasaki disease. J Pediatr. 2008 Dec. 153(6):833-8. [Medline]. [Full Text].
Youn Y, Kim J, Hong YM, Sohn S. Infliximab as the First Retreatment in Patients with Kawasaki Disease Resistant to Initial Intravenous Immunoglobulin. Pediatr Infect Dis J. 2015 Dec 15. [Medline].
Hsieh KS, Weng KP, Lin CC, Huang TC, Lee CL, Huang SM. Treatment of acute Kawasaki disease: aspirin's role in the febrile stage revisited. Pediatrics. 2004 Dec. 114(6):e689-93. [Medline].
Baumer JH, Love SJ, Gupta A, Haines LC, Maconochie I, Dua JS. Salicylate for the treatment of Kawasaki disease in children. Cochrane Database Syst Rev. 2006 Oct 18. CD004175. [Medline].
Inoue Y, Okada Y, Shinohara M, Kobayashi T, Kobayashi T, Tomomasa T, 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):336-341. [Medline].
Newburger JW, Sleeper LA, McCrindle BW, Minich LL, Gersony W, Vetter VL, et al. Randomized trial of pulsed corticosteroid therapy for primary treatment of Kawasaki disease. N Engl J Med. 2007 Feb 15. 356(7):663-75. [Medline].
Athappan G, Gale S, Ponniah T. Corticosteroid therapy for primary treatment of Kawasaki disease - weight of evidence: a meta-analysis and systematic review of the literature. Cardiovasc J Afr. 2009 Jul-Aug. 20(4):233-6. [Medline].
Phillips B. Review: corticosteroids with intravenous immunoglobulin reduced the incidence of coronary artery aneurysm formation in patients with Kawasaki disease. Arch Dis Child Educ Pract Ed. 2013 Feb 7. [Medline].
Douglas D. IVIG Plus Prednisolone Promising in Refractory Kawasaki Disease. Medscape. Mar 18 2013. [Full Text].
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. J Pediatr. Aug 2013. 163(2):521-526.e1. [Medline].