eMedicine Specialties > Dermatology > Pediatric Diseases

Kawasaki Disease: Differential Diagnoses & Workup

Author: Elizabeth Kline Satter, MD, MPH, Staff Dermatologist and Head of Dermatopathology for Residency Program, Department of Dermatology, Naval Medical Center, San Diego
Contributor Information and Disclosures

Updated: May 8, 2008

Differential Diagnoses

Drug Eruptions
Scarlet Fever
Erythema Multiforme
Staphylococcal Scalded Skin Syndrome
Lyme Disease
Stevens-Johnson Syndrome and Toxic Epidermal Necrolysis
Measles, Rubeola
Toxic Shock Syndrome
Rocky Mountain Spotted Fever

Other Problems to Be Considered

Acrodynia (mercury toxicity)
Group A beta-hemolytic streptococcal infection
Bacteria cervical lymphadenitis
Drug hypersensitivity reaction
Infantile polyarteritis nodosum
Juvenile rheumatoid arthritis (Still disease)
Leptospirosis
Mononucleosis
Parvovirus B19 infection
Staphylococcal or streptococcal scarlet fever
Systemic lupus
Viral meningitis

Workup

Laboratory Studies

  • During the acute phase of the illness, leukocytosis with a predominance of immature and mature granulocytes is common, with 50% of patients having a white blood cell count greater than 15,000/µL.
  • Elevation of acute phase reactants, such as the erythrocyte sedimentation rate (ESR) and C-reactive protein levels, is nearly universal; however, they usually return to baseline 6-10 weeks after the onset of the illness.
  • Elevated macrophage migration factor (MIF) and Interleukin-6 (IL-6) may be useful markers in the acute stages of Kawasaki disease.
  • In the second to third week of the illness, thrombocytosis, with platelet counts ranging from 500,000/µL to greater than 1 million/µL, is common; in uncomplicated cases, values return to baseline 4-8 weeks later. Thrombocytopenia is rare but may be associated with disseminated intravascular coagulation.
  • Normochromic anemia is reported.
  • Serum cholesterol, high-density lipoprotein, and apolipoprotein A levels are decreased; these values tend to persist beyond clinical resolution of the disease.
  • Mild-to-moderate elevations in serum transaminase, bilirubin, and gamma-glutamyl transpeptidase levels are reported.
  • Hypoalbuminemia may be present and is often associated with more severe and prolonged illness.
  • Arthrocentesis in affected patients typically shows numerous white blood cells, ranging from 125,000-300,000/µL, with normal glucose levels and negative culture results.
  • In children who undergo lumbar puncture, 50% show evidence of aseptic meningitis with a predominance of mononuclear cells with normal glucose and protein levels.
  • Sterile pyuria is reported in 33-70% of patients.

Imaging Studies

  • Serial echocardiograms should be obtained, preferably at the time of diagnosis, at 2 weeks, and at 6-8 weeks after the onset of the illness. These may need to be preformed more frequently in high-risk patients.16,21,22
    • If, by 8 weeks, the patient exhibits no coronary involvement, follow-up echocardiography is recommended at 1 year. Patients with significant aneurysms should be followed more closely.
    • Coronary artery dimensions must be adjusted for body surface area to accurately determine if dilation exists. 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. Importantly, evaluate the coronary arteries for dilation and thrombosis, but also evaluate for aortic root dilation, depressed contractility, ventricular and valvular function, and pericardial effusion. In order of highest to lowest frequency, the involvement of the coronary arteries is (1) proximal left anterior descending and right coronary artery, (2) left main coronary artery, (3) left circumflex artery, (4) distal right coronary artery, and (5) posterior descending artery.
  • Magnetic resonance imaging, magnetic resonance angiography, and ultrafast computed tomography scanning are newer noninvasive tests that can be used to evaluate coronary artery abnormalities; however, larger studies are required to evaluate their reliability.
  • 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.

Other Tests

  • Electrocardiographic changes include a prolonged PR interval, abnormal Q waves, nonspecific ST-wave changes, and left ventricular hypertrophy.
  • Cardiac stress testing is typically performed 1-5 years after the illness resolves in patients who had aneurysms. It is used to assess the existence and functional consequences of coronary artery disease. It also helps determine recommendations for physical activity.

Procedures

  • Cardiac catheterization and angioplasty have not been successful, even with the use of high-pressure balloons, because of the dense fibrosis and calcification that occurs in the arterial walls.
  • Surgical management, primarily coronary artery bypass grafts, may be required in patients with obstructive lesions.
  • Cardiac transplantation has been performed in patients with severe cardiac impairment.

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.

More on Kawasaki Disease

Overview: Kawasaki Disease
Differential Diagnoses & Workup: Kawasaki Disease
Treatment & Medication: Kawasaki Disease
Follow-up: Kawasaki Disease
Multimedia: Kawasaki Disease
References
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References

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  3. Kato S, Kimura M, Tsuji K, Kusakawa S, Asai T, Juji T, et al. HLA antigens in Kawasaki disease. Pediatrics. Feb 1978;61(2):252-5. [Medline].

  4. Matsuda I, Hattori S, Nagata N, Fruse A, Nambu H. HLA antigens in mucocutaneous lymph node syndrome. Am J Dis Child. Dec 1977;131(12):1417-8. [Medline].

  5. 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. Aug 2005;6(5):438-44. [Medline].

  6. 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. May-Jun 2007;36(3):222-5. [Medline].

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  11. 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.

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

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

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  20. Leung DY, Meissner HC, Fulton DR, Murray DL, Kotzin BL, Schlievert PM. Toxic shock syndrome toxin-secreting Staphylococcus aureus in Kawasaki syndrome. Lancet. Dec 4 1993;342(8884):1385-8. [Medline].

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  24. 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. Aug 2007;49(4):427-30. [Medline].

  25. Abe J, Kotzin BL, Jujo K, Melish ME, Glode MP, Kohsaka T, et al. Selective expansion of T cells expressing T-cell receptor variable regions V beta 2 and V beta 8 in Kawasaki disease. Proc Natl Acad Sci U S A. May 1 1992;89(9):4066-70. [Medline].

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Further Reading

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Keywords

mucocutaneous lymph node syndrome, Kawasaki's syndrome, Kawasaki's disease, Kawasaki syndrome, KD, infantile polyarteritis nodosa, IPAN, infantile periarteritis nodosa, medium-sized vessel vasculitis, medium vessel vasculitis, vasculitis of medium vessels, periarteritis nodosa

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Contributor Information and Disclosures

Author

Elizabeth Kline Satter, MD, MPH, Staff Dermatologist and Head of Dermatopathology for Residency Program, Department of Dermatology, Naval Medical Center, San Diego
Elizabeth Kline Satter, MD, MPH is a member of the following medical societies: Alpha Omega Alpha and American Medical Women's Association
Disclosure: Nothing to disclose.

Medical Editor

Jean Paul Ortonne, MD, Chair, Department of Dermatology, Professor, Hospital L'Archet, Nice University, France
Jean Paul Ortonne, MD is a member of the following medical societies: American Academy of Dermatology and American Dermatological Association
Disclosure: Nothing to disclose.

Pharmacy Editor

Richard P Vinson, MD, Assistant Clinical Professor, Department of Dermatology, Texas Tech University School of Medicine; Consulting Staff, Mountain View Dermatology, PA
Richard P Vinson, MD is a member of the following medical societies: American Academy of Dermatology, Association of Military Dermatologists, Texas Dermatological Society, and Texas Medical Association
Disclosure: Nothing to disclose.

Managing Editor

Van Perry, MD, Assistant Professor, Department of Medicine, Division of Dermatology, University of Texas Health Science Center
Van Perry, MD is a member of the following medical societies: American Academy of Dermatology and American Society for Laser Medicine and Surgery
Disclosure: Nothing to disclose.

CME Editor

Joel M Gelfand, MD, MSCE, Medical Director, Clinical Studies Unit, Assistant Professor, Department of Dermatology, Associate Scholar, Center for Clinical Epidemiology and Biostatistics, University of Pennsylvania
Joel M Gelfand, MD, MSCE is a member of the following medical societies: Society for Investigative Dermatology
Disclosure: AMGEN Consulting fee Consulting; AMGEN Grant/research funds None; Genentech Consulting fee Consulting; Centocor Consulting fee Consulting; Centocor Grant/research funds None; Covance Consulting fee Consulting; Shire  Consulting

Chief Editor

Dirk M Elston, MD, Director, Department of Dermatology, Geisinger Medical Center
Dirk M Elston, MD is a member of the following medical societies: American Academy of Dermatology
Disclosure: Nothing to disclose.

 
 
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