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Kawasaki Disease Workup

  • Author: Noah S Scheinfeld, JD, MD, FAAD; Chief Editor: Russell W Steele, MD  more...
 
Updated: Sep 13, 2015
 

Approach Considerations

No specific laboratory test is used to diagnose Kawasaki disease; however, certain abnormalities coincide with various stages. Acute-phase reactants (ie, erythrocyte sedimentation rate [ESR], C-reactive protein levels [CRP], and alpha1-antitrypsin levels) are almost universally elevated at first; they usually return to baseline 6-10 weeks after the onset of the illness.

More recently, 2 urine proteins hold promise as biomarkers of Kawasaki disease: meprin A or filamin C. These 2 biomarkers were diagnostically superior to ESR or CRP.[6, 7] Investigators identified more than 190 proteins that were present only in children with Kawasaki disease, including the proteins associated with endothelial and myocardial cell injury (filamin C) and immune regulators (meprin A).[6, 7]

Elevated macrophage migration factor (MIF) and Interleukin-6 (IL-6) may be useful markers in the acute stages of Kawasaki disease. The serum complement level is normal or elevated.

On complete blood counts (CBCs), mild-to-moderate normochromic anemia is observed in the acute stage. The white blood cell count (WBC) is moderate to high (50% of patients have a WBC greater than 15,000/µL), with a left shift, which is a predominant sign of immature and mature granulocytes.

During the subacute stage, thrombocytosis is the outstanding marker. The platelet count begins to rise in the second week and continues to rise during the third week. Platelet counts average 700,000/μL, but levels as high as 2 million have been observed. Thrombocytopenia is associated with severe coronary artery disease and myocardial infarction (MI); rarely, it may be associated with disseminated intravascular coagulation.

Serum cholesterol, high-density lipoprotein, and apolipoprotein A levels are decreased; these values tend to persist beyond clinical resolution of the disease. Hypoalbuminemia may be present and is often associated with more severe and prolonged illness.

In the convalescent stage, the levels of platelets and other markers begin to return to values within the reference range. Laboratory values may require 6-8 weeks to normalize.

Normal results on some studies can help narrow the differential diagnosis. levels of antineutrophil cytoplasmic antibodies, antiendothelial cell antibodies, antinuclear antibody, and rheumatoid factors are all within the reference range. Culture results are all negative. On rapid antigen testing, results for adenovirus are negative. Urinalysis may show mild-to-moderate sterile pyuria of urethral origin and proteinuria.

Cardiac imaging, electrocardiography, and cardiac biomarkers

Echocardiography is the study of choice to evaluate for coronary artery aneurysms (CAAs), in both fully manifested and suspected incomplete cases of Kawasaki disease. Serial echocardiograms should be obtained, preferably at the time of Kawasaki disease diagnosis, at 2 weeks, and at 6-8 weeks after the onset of the illness. These may need to be performed more frequently in high-risk patients.[66, 71, 8]

Magnetic resonance imaging (MRI), magnetic resonance angiography (MRA), and ultrafast computed tomography (CT) scanning are other noninvasive tests that can be used to evaluate coronary artery abnormalities. However, larger studies are required to evaluate their reliability.

On electrocardiography (ECG), tachycardia, prolonged PR interval, ST-T wave changes, and decreased voltage of R waves may indicate myocarditis. Q waves or ST-T wave changes may indicate myocardial infarction. Cardiac enzyme levels (eg, creatine kinase [CK], creatine kinase myocardial band [CK-MB], cardiac troponin, lactate dehydrogenase [LD-1 >LD-2]) are elevated during a myocardial infarction.

A select group of patients may require cardiac catheterization and angiography. Coronary CT angiography and magnetic resonance angiography may also prove beneficial in the evaluation and follow-up of the coronary arteries.[72, 73] Cardiac angiography provides a more detailed study of the arteries, but it is associated with greater risks of rupture, especially when performed in the acute phase of the illness; it should be limited to select cases.

Studies for selected patients

Liver function studies and serum lipase measurement may be indicated in selected cases. On liver function testing, serum transaminase values are mildly elevated in 40% of affected patients. Elevated alanine aminotransferase (ALT) levels can indicate a more serious course. Bilirubin values are elevated in 10% of affected patients.

A chest radiograph should be obtained to assess baseline findings, exclude cardiomegaly or subclinical pneumonitis, or confirm clinical suspicion of chronic heart failure.

Gallbladder ultrasonography may be necessary if liver or gallbladder dysfunction is suspected. Acute distention of the gallbladder (hydrops) is identified on abdominal ultrasonography in 15% of patients. Gallbladder hydrops usually resolves without surgical intervention.

Obtain a scrotal sonogram in males to evaluate for epididymitis. Although epididymitis is generally an inflammatory process that affects boys aged 9-14 years, it can be observed in younger boys with Henoch-Schönlein purpura and Kawasaki disease.

Arthrocentesis may be indicated in patients with joint involvement. Joint fluid analysis in affected patients typically shows numerous white blood cells, ranging from 125,000-300,000/µL, with normal glucose levels and negative culture results.

Lumbar puncture may be indicated in patients with clinical signs suggesting meningitis. In children who undergo lumbar puncture, 50% show evidence of aseptic meningitis with a predominance of mononuclear cells, along with normal glucose and protein levels.

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Diagnosis of Incomplete Kawasaki Disease

In some cases, patients have many of the typical clinical features of Kawasaki disease but not as many as are required to meet standard diagnostic criteria. Hence, the term "incomplete" rather than "atypical" is used to describe these cases. Incomplete cases usually occur in children younger than 6 months. In this setting, fever plus only 3 features can establish the diagnosis. The rationale is that treatment is safe and effective and that failure to diagnose Kawasaki disease may have a significant negative impact on outcome.

For the diagnosis of incomplete Kawasaki disease, the American Academy of Pediatrics (AAP)/American Heart Association (AHA) recommend that when fever plus 2 or 3 of the typical features are present for 5 days or more and when patient characteristics suggest possible Kawasaki disease, a C-reactive protein (CRP) level and erythrocyte sedimentation rate (ESR) should be obtained.[66] If the CRP level is less than 3 mg/dL and the ESR is more than 40 mm/hr, the child is monitored and actions taken as appropriate.

If the CRP is 3 mg/dL or higher and the ESR is 40 mm/hr or more, the next step is to measure albumin, alanine aminotransferase (ALT), platelets, and WBC count and test the urine for pyuria. Abnormal limits include the following:

  • Albumin < 3 g
  • Anemia for age
  • Elevated ALT level
  • Platelets >450,000 (after 7 d)
  • WBC count >12,000
  • Presence of pyuria

If 3 or more supplemental laboratory criteria are positive, a diagnosis of Kawasaki disease is made. The child should have an echocardiogram and be treated.

If fewer than 3 supplemental laboratory criteria are positive, a cardiac echocardiogram should be performed. If the echocardiogram is negative but fever persists, a repeat echocardiogram may be performed. If the echocardiogram is negative and the fever abates, Kawasaki disease is unlikely. If the echocardiogram is positive, the child is treated for Kawasaki disease.

Newberger questioned the suitability of laboratory findings as evidence of inflammation, noting that in some cases, the clinical criteria are not all present on any given day. Conversely, some patients with an inflammatory disorder did not meet the clinical case definition but developed coronary artery abnormalities consistent with Kawasaki disease.[74]

The results of one study noted that patients with incomplete Kawasaki disease realized a longer median interval from symptom onset to diagnosis and were less likely to be treated with IV immunoglobulin than those patients with complete Kawasaki disease. However, no significant differences between the two groups were noted in demographics, clinical and laboratory characteristics, and coronary artery abnormalities.[75]

A French group has suggested adding another diagnostic category, "uncertain Kawasaki disease”, for children with 5 days of fever, fewer than 4 classic signs, normal echocardiographic findings, and an inflammatory syndrome that does not meet AHA criteria. These researchers found that children in this category did well when treated with IVIG and aspirin.[76]

Hinze et al reported a case of Kawasaki disease in a 3-month-old boy manifested by typical signs and CAAs but without fever. They commented on the difficulty in making the diagnosis in young infants.[77] Case reports of other unusual presentations (eg, GI bleeding, lupuslike illness in a recurrent case, arthritis, rhabdomyolysis) have been published. Such presentations appear to be very uncommon.[33]

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Echocardiography

Echocardiography is the study of choice to evaluate for CAAs during the acute stage. In order of highest to lowest frequency, the involvement of the coronary arteries is as follows:

  1. Proximal left anterior descending and right coronary artery
  2. Left main coronary artery
  3. Left circumflex artery
  4. Distal right coronary artery
  5. Posterior descending artery

In addition to evaluating the coronary arteries for dilation and thrombosis, the baseline echocardiogram is also performed to evaluate for other cardiac involvement. This includes aortic root dilation, depressed contractility, ventricular and valvular function, and pericardial effusion.

Diffuse dilatation of coronary lumina can be observed in 50% of patients by the 10th day of illness. In children, ensure that pediatric cardiologists perform this study because they are familiar with coronary artery diameters. Coronary artery dimensions must be adjusted for body surface area to accurately identify dilation. A basic rule is that if the internal diameter of a segment is greater than 1.5 times that of an adjacent segment, then dilation probably exists.

The echocardiogram should be repeated in the second or third week and again 1 month after all other laboratory results have normalized. Echocardiograms may need to be performed more frequently in high-risk patients.[66, 71, 8] If by 8 weeks the patient exhibits no coronary involvement, follow-up echocardiography is recommended at 1 year. If the echocardiographic findings are abnormal at any point, refer the child to a pediatric cardiologist for a complete cardiac workup and follow-up care.

In a study that examined echocardiograms obtained at diagnosis and 1 and 5 weeks after diagnosis from 198 patients, Printz et al concluded that noncoronary cardiac abnormalities were associated with coronary artery dilation and laboratory evidence of inflammation within the first 5 weeks after the diagnosis of Kawasaki disease.[78] Left ventricular (LV) systolic dysfunction was noted in 20% of patients and coronary artery dilation in 29%. Mitral regurgitation was present in 27% of patients and aortic root dilation in 8%.

One group of authors recommended that the initial echocardiogram be performed in the emergency department. The same group identified a pulmonary artery aneurysm in one case and noted that this had never been found before.[76]

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MRA and CT

Free-breathing 3-dimensional (3D) coronary MRA accurately defines CAA in patients with Kawasaki disease. This technique may provide a noninvasive alternative when the image quality of transthoracic echocardiography is insufficient, thereby reducing the need for serial radiographic coronary angiography in this patient group.

In a small study that used multislice spiral CT in 16 adolescents and young adults with Kawasaki disease, CT was 100% sensitive in the detection of coronary artery aneurysms but only 87.5% sensitive for the detection of significant stenosis or occlusion. False-positive results occurred secondary to severe calcification in 5 arteries and cardiac motion artifact in 2. Specificity was therefore 92.5%.[79]

In another small study, electron beam CT (EBCT) was used to determine whether coronary artery calcifications could be used as a marker of future coronary artery events. The authors felt that EBCT may be useful for risk stratification in long-term management of patients with Kawasaki disease.[80]

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Histologic Findings

Biopsy is rarely performed to make the diagnosis; therefore, most specimens are obtained from autopsies or from patients who have had diseased arterial segments removed during bypass operations. Early findings show acute destruction of the media of the vessels by neutrophils, with loss of elastic fibers. Later, the infiltrate is replaced by lymphocytes, monocytes, and fibroblasts involved in arterial remodeling. Chronic lesions show intimal proliferation, neoangiogenesis, and vascular occlusion.

Weedon summarized the reported findings of Kawasaki disease as follows[81] :

  • Features are nonspecific
  • Lymphocytes and mononuclear cells manifest in a perivascular fashion
  • Edema of the papillary dermis may be present
  • Pustules with small intraepidermal and subcorneal abscesses unrelated to eccrine ducts may be present
  • One report noted subtle vascular alterations, subendothelial edema, focal endothelial cell necrosis, and vascular deposition of minute quantities of fibrinoid material

More definite reports have noted the internal vascular changes of Kawasaki disease. Destruction of vascular layers and infiltration of inflammatory cells in blood vessels are observed.

Upon ultrastructural examination, myocardial changes reveal hypertrophy, various degrees of degeneration, proliferation and abnormality of mitochondria, infiltration of a small number of lymphocytes, and fibrosis. Coronary microvascular lesions are characterized by the following:

  • Microvascular dilatation
  • Endothelial cell injury
  • Platelet aggregation with thrombosis
  • Stenotic lumen with thickened walls in the small arterioles
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Laboratory Studies

 Elevated blood triglycerides and hypercoagulationare characterize Kawasaki disease.[82] .  Soluble LR11 is a new biomarker helps define vascular lesions following Kawasaki disease.[83]

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Contributor Information and Disclosures
Author

Noah S Scheinfeld, JD, MD, FAAD Assistant Clinical Professor, Department of Dermatology, Weil Cornell Medical College; Consulting Staff, Department of Dermatology, St Luke's Roosevelt Hospital Center, Beth Israel Medical Center, New York Eye and Ear Infirmary; Assistant Attending Dermatologist, New York Presbyterian Hospital; Assistant Attending Dermatologist, Lenox Hill Hospital, North Shore-LIJ Health System; Private Practice

Noah S Scheinfeld, JD, MD, FAAD is a member of the following medical societies: American Academy of Dermatology

Disclosure: Serve(d) as a speaker or a member of a speakers bureau for: Abbvie<br/>Received income in an amount equal to or greater than $250 from: Optigenex<br/>Received salary from Optigenex for employment.

Coauthor(s)

Steven J Parrillo, DO, FACOEP, FACEP Clinical Adjunct Professor, Medical Director and Faculty, Disaster Medicine and Management Masters Program, Philadelphia University College of Health Sciences; Associate Professor, Clinical and Educational Scholarship Track, Jefferson Medical College of Thomas Jefferson University; Director, Division of EMS and Disaster Medicine, Albert Einstein Healthcare Network

Steven J Parrillo, DO, FACOEP, FACEP is a member of the following medical societies: American College of Emergency Physicians, American College of Osteopathic Emergency Physicians, American Osteopathic Association, World Association for Disaster and Emergency Medicine

Disclosure: Nothing to disclose.

Paul R Ogershok, MD Allergist, Allergy, Asthma, and Immunology Clinic, Southwest Regional Medical Center

Paul R Ogershok, MD is a member of the following medical societies: American Academy of Allergy Asthma and Immunology, American Academy of Pediatrics, American College of Allergy, Asthma and Immunology, Pennsylvania Medical Society, West Virginia State Medical Association

Disclosure: Nothing to disclose.

Elena L Jones, MD Clinical Assistant Professor of Dermatology, Columbia University College of Physicians and Surgeons; Clinic Chief, Department of Dermatology, St Luke's-Roosevelt Hospital Center

Disclosure: Nothing to disclose.

Chief Editor

Russell W Steele, MD Clinical Professor, Tulane University School of Medicine; Staff Physician, Ochsner Clinic Foundation

Russell W Steele, MD is a member of the following medical societies: American Academy of Pediatrics, American Association of Immunologists, American Pediatric Society, American Society for Microbiology, Infectious Diseases Society of America, Louisiana State Medical Society, Pediatric Infectious Diseases Society, Society for Pediatric Research, Southern Medical Association

Disclosure: Nothing to disclose.

Acknowledgements

Jeffrey Glenn Bowman, MD, MS Consulting Staff, Highfield MRI, Columbus, Ohio

Disclosure: Nothing to disclose.

Lawrence H Brent, MD Associate Professor of Medicine, Jefferson Medical College of Thomas Jefferson University; Chair, Program Director, Department of Medicine, Division of Rheumatology, Albert Einstein Medical Center

Lawrence H Brent, MD is a member of the following medical societies: American Association for the Advancement of Science, American Association of Immunologists, American College of Physicians, and American College of Rheumatology

Disclosure: Genentech Honoraria Speaking and teaching; Genentech Grant/research funds Other; Amgen Honoraria Speaking and teaching; Pfizer Honoraria Speaking and teaching; Abbott Immunology Honoraria Speaking and teaching; Takeda Honoraria Speaking and teaching; UCB Speaking and teaching; Omnicare Consulting fee Consulting; Centocor Consulting fee Consulting

Herbert S Diamond, MD Professor of Medicine, Temple University School of Medicine; Chairman Emeritus, Department of Internal Medicine, Western Pennsylvania Hospital

Herbert S Diamond, MD is a member of the following medical societies: Alpha Omega Alpha, American College of Physicians, American College of Rheumatology, American Medical Association, and Phi Beta Kappa

Disclosure: Merck Ownership interest Other; Smith Kline Ownership interest Other; Zimmer Ownership interest Other

Joseph Domachowske, MD Professor of Pediatrics, Microbiology and Immunology, Department of Pediatrics, Division of Infectious Diseases, State University of New York Upstate Medical University

Joseph Domachowske, MD is a member of the following medical societies: Alpha Omega Alpha, American Academy of Pediatrics, American Society for Microbiology, Infectious Diseases Society of America, Pediatric Infectious Diseases Society, and Phi Beta Kappa

Disclosure: Nothing to disclose.

Kristine M Lohr, MD, MS Professor, Department of Internal Medicine, Center for the Advancement of Women's Health and Division of Rheumatology, Director, Rheumatology Training Program, University of Kentucky College of Medicine

Kristine M Lohr, MD, MS is a member of the following medical societies: American College of Physicians and American College of Rheumatology

Disclosure: Nothing to disclose.

Catherine V Parrillo, DO, FACOP, FAAP, Retired, Clinical Assistant Professor, Department of Pediatrics, Philadelphia College of Osteopathic Medicine

Catherine V Parrillo, DO, FACOP, FAAP, is a member of the following medical societies: American Academy of Pediatrics, American College of Osteopathic Pediatricians, and American Osteopathic Association

Disclosure: Nothing to disclose

Francisco Talavera, PharmD, PhD Adjunct Assistant Professor, University of Nebraska Medical Center College of Pharmacy; Editor-in-Chief, Medscape Drug Reference

Disclosure: Medscape Reference Salary Employment

Martin Weisse, MD Program Director, Associate Professor, Department of Pediatrics, West Virginia University

Martin Weisse, MD is a member of the following medical societies: Ambulatory Pediatric Association, American Academy of Pediatrics, and Pediatric Infectious Diseases Society

Disclosure: Nothing to disclose.

Mary L Windle, PharmD Adjunct Associate Professor, University of Nebraska Medical Center College of Pharmacy; Editor-in-Chief, Medscape Drug Reference

Disclosure: Nothing to disclose.

Grace M Young, MD Associate Professor, Department of Pediatrics, University of Maryland Medical Center

Grace M Young, MD is a member of the following medical societies: American Academy of Pediatrics and American College of Emergency Physicians

Disclosure: Nothing to disclose.

References
  1. 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].

  2. Wolff AE, Hansen KE, Zakowski L. Acute Kawasaki disease: not just for kids. J Gen Intern Med. 2007 May. 22(5):681-4. [Medline]. [Full Text].

  3. Han RK, Sinclair B, Newman A, Silverman ED, Taylor GW, Walsh P, et al. Recognition and management of Kawasaki disease. CMAJ. 2000 Mar 21. 162(6):807-12. [Medline]. [Full Text].

  4. Gedalia A. Kawasaki disease: 40 years after the original report. Curr Rheumatol Rep. 2007 Aug. 9(4):336-41. [Medline].

  5. Satou GM, Giamelli J, Gewitz MH. Kawasaki disease: diagnosis, management, and long-term implications. Cardiol Rev. 2007 Jul-Aug. 15(4):163-9. [Medline].

  6. 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.

  7. 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].

  8. Wood L, Tulloh R. Kawasaki disease: diagnosis, management and cardiac sequelae. Expert Rev Cardiovasc Ther. 2007 May. 5(3):553-61. [Medline].

  9. 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].

  10. 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].

  11. 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].

  12. 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].

  13. 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].

  14. Baker AL, Lu M, Minich LL, Atz AM, Klein GL, Korsin R, et al. Associated symptoms in the ten days before diagnosis of Kawasaki disease. J Pediatr. 2009 Apr. 154(4):592-595.e2. [Medline]. [Full Text].

  15. 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].

  16. 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].

  17. Rowley AH, Shulman ST. Pathogenesis and management of Kawasaki disease. Expert Rev Anti Infect Ther. 2010 Feb. 8(2):197-203. [Medline]. [Full Text].

  18. 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].

  19. 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].

  20. Leung DY, Schlievert PM, Meissner HC. The immunopathogenesis and management of Kawasaki syndrome. Arthritis Rheum. 1998 Sep. 41(9):1538-47. [Medline].

  21. 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].

  22. 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].

  23. Ogawa S. Biomarker. Nihon Rinsho. 2014 Sep. 72(9):1578-84. [Medline].

  24. Onouchi Y. Susceptibility genes for Kawasaki disease. Nihon Rinsho. 2014 Sep. 72(9):1554-60. [Medline].

  25. 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].

  26. 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].

  27. 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].

  28. Burns JC, Glodé MP. Kawasaki syndrome. Lancet. 2004 Aug 7-13. 364(9433):533-44. [Medline].

  29. Melish ME, Hicks RV. Kawasaki syndrome: clinical features. Pathophysiology, etiology and therapy. J Rheumatol Suppl. 1990 Sep. 24:2-10. [Medline].

  30. 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].

  31. 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].

  32. 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].

  33. Pinna GS, Kafetzis DA, Tselkas OI, Skevaki CL. Kawasaki disease: an overview. Curr Opin Infect Dis. 2008 Jun. 21(3):263-70. [Medline].

  34. 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].

  35. 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].

  36. 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].

  37. 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.:

  38. 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].

  39. 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].

  40. 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].

  41. Dergun M, Kao A, Hauger SB, Newburger JW, Burns JC. Familial occurrence of Kawasaki syndrome in North America. Arch Pediatr Adolesc Med. 2005 Sep. 159(9):876-81. [Medline]. [Full Text].

  42. Burns JC, Cayan DR, Tong G, Bainto EV, Turner CL, Shike H, et al. Seasonality and temporal clustering of Kawasaki syndrome. Epidemiology. 2005 Mar. 16(2):220-5. [Medline]. [Full Text].

  43. 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].

  44. 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].

  45. 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:

  46. 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].

  47. 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].

  48. 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].

  49. 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].

  50. 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].

  51. 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].

  52. 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].

  53. Royle JA, Williams K, Elliott E, Sholler G, Nolan T, Allen R, et al. Kawasaki disease in Australia, 1993-95. Arch Dis Child. 1998 Jan. 78(1):33-9. [Medline]. [Full Text].

  54. Harnden A, Alves B, Sheikh A. Rising incidence of Kawasaki disease in England: analysis of hospital admission data. BMJ. 2002 Jun 15. 324(7351):1424-5. [Medline]. [Full Text].

  55. 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].

  56. Nakamura Y. Epidemiology of Kawasaki disease. Nihon Rinsho. 2014 Sep. 72(9):1536-41. [Medline].

  57. 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].

  58. 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].

  59. 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].

  60. 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].

  61. Choi JY, Park SY, Choi KH, Park YH, Lee YH. Clinical characteristics of Kawasaki disease with sterile pyuria. Korean J Pediatr. 2013 Jan. 56(1):13-8. [Medline]. [Full Text].

  62. 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].

  63. 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].

  64. 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].

  65. 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].

  66. 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].

  67. 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].

  68. 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].

  69. Turnier JL, Anderson MS, Heizer HR, Jone PN, Glodé MP, Dominguez SR. Concurrent Respiratory Viruses and Kawasaki Disease. Pediatrics. 2015 Aug 24. [Medline].

  70. 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.

  71. 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].

  72. 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].

  73. 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].

  74. Newburger JW, Fulton DR. Kawasaki disease. Curr Opin Pediatr. 2004 Oct. 16(5):508-14. [Medline].

  75. 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].

  76. 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].

  77. Hinze CH, Graham TB, Sutherell JS. Kawasaki disease without fever. Pediatr Infect Dis J. 2009 Oct. 28(10):927-8. [Medline].

  78. 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].

  79. 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].

  80. 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].

  81. Weedon R. Kawasaki Syndrome: The vasculopathic reaction pattern In:. Pathology. 2002:238-9:

  82. 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].

  83. 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].

  84. 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].

  85. 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].

  86. 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].

  87. 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].

  88. 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].

  89. 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].

  90. 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].

  91. 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].

  92. 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].

  93. 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].

  94. 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].

  95. 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].

  96. 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].

  97. Douglas D. IVIG Plus Prednisolone Promising in Refractory Kawasaki Disease. Medscape. Mar 18 2013. [Full Text].

  98. 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].

 
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Patchy generalized macular erythema, which is also typical of some viral exanthems.
Peeling and erythema of the fingertips.
Strawberry tongue.
Pediatrics, Kawasaki disease. Note the appearance of the hand and lips. Photo courtesy of Sam Richardson, MD.
Clinical manifestations and time course of Kawasaki disease.
Oral manifestations of Kawasaki disease: red lips and strawberry tongue.
 
 
 
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