AUTHOR AND EDITOR INFORMATION

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INTRODUCTION

Section 2 of 11  

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Background

Kawasaki disease (KD) (ie, Kawasaki syndrome [KS]) is a febrile illness of childhood. It is a self-limited acute vasculitic syndrome of unknown etiology, first described by Tomisaku Kawasaki in 1967. At that time, he reported 50 children from 1961-1967 who presented with a distinctive clinical illness characterized by fever and rash, which was then thought to be a benign childhood illness.

Several years later, fatalities occurred in Japan among children younger than 2 years. The fatalities occurred when patients were improving or had recovered. Postmortem examinations revealed complete thrombotic occlusion of coronary artery aneurysms with a myocardial infarction (MI) as the immediate cause of death. It soon became evident that, when studied by echocardiography (ECHO), 20-25% of untreated children developed cardiovascular sequelae ranging from asymptomatic coronary artery ectasis or aneurysm formation to giant coronary artery aneurysms with thrombosis, MI, and sudden death. Even today, 15-25% of untreated patients develop coronary artery aneurysms. (The increase from older quotes of 5% is largely based on revised echocardiographic criteria for aneurysmal dilatation).

Although inflammatory infiltrates have been shown in the myocardium, pancreas, kidney, and biliary tract, no significant sequelae persist in those nonvascular tissues. A single report of pulmonary involvement has appeared in the literature. Gallbladder vasculitis (hydrops) is a significant, though uncommon complication.

The syndrome has now surpassed rheumatic fever as the leading cause of acquired heart disease in the United States among children younger than 5 years.

In recent years, much attention has been given to incomplete cases of KD.

Pathophysiology

The etiology is unknown, although many suspect an infectious etiology. Indicators suggesting an infectious etiology include the occurrence of periodic epidemics with geographic spread; the self-limited nature; and the characteristic fever, adenopathy, and eye signs.

Many now believe that many factors (viruses, staphylococci "super antigens") are capable of triggering a final common pathway that results in immune activation. All effective therapies are directed at this immune activity.

Prolonged fever, rash, mucocutaneous involvement, extremity changes, cervical adenopathy, conjunctivitis, and development of coronary artery aneurysms characterize Kawasaki disease.

Treadwell et al have suggested that an association exists between Kawasaki disease and the use of a humidifier in the room of a child with an antecedent respiratory illness.¹

Frequency

United States

Epidemics occur primarily in late winter and spring with 3-year intervals. KD is most commonly observed in children from the middle and upper-middle classes. The estimated number of children hospitalized annually in the United States is about 3000, though more than 4000 admissions occurred in 2006, some of which were incomplete cases.

International

Outside the United States, the disease is most frequently observed in Japan. The prevalence of the disease increased from 1967 to the mid 1980s and has leveled out at 5000-6000 cases per year. Several epidemics have occurred in Japan during the years 1979, 1982, and 1985. The current Japanese incidence is approximately 112 cases per 100,000 population.

Mortality/Morbidity

• The development of coronary artery aneurysms with consequences such as thrombosis or rupture determines the degree of disability. Acute MI has been reported secondary to true coronary artery obstruction. These aneurysms tend to develop approximately 1-2 weeks after onset of symptoms.
• The development of myocarditis, congestive heart failure, pericarditis with pericardial effusion, mitral or aortic insufficiency, and dysrhythmias is observed early in the disease. Later development of aneurysms can be predicted by the severity of the disease. Decreased left ventricular function is present in approximately 50% of all patients with KS. Additionally, arthritis persists in some children.
• The risk of aneurysm is increased in patients who have fever for more than 16 days, who have recurrence of fever after an afebrile period of at least 48 hours, are males, who have cardiomegaly, and especially who are younger than 1 year. Some laboratory values at presentation may also predict a greater likelihood of aneurysm development including hematocrit <35%, thrombocytopenia (<350,000), elevated C-reactive protein (CRP), albumin <3.5g/dL, and WBC >12,000.
• Researchers are beginning to look at the possibility that patients with aneurysms may have an increased risk of premature coronary atherosclerotic disease.

Race

The disease is more common in the Japanese-American population.

Sex

The disease is more common in males than in females, with a male-to-female ratio of 1.5:1.

Age

In the United States, the peak prevalence is in children aged 18-24 months. The Japanese patient population is younger than the patient population in the United States; Kawasaki disease is most frequently observed in infants aged 6-12 months, with equal numbers in the first and second year of life.

Pannaraj et al noted that Kawasaki disease may occur at the extremes of age range, meaning infants younger than 6 months or children older than 5 years and that pediatricians and infectious diseases specialists frequently fail to consider the diagnosis.²

Infants aged 6 months or younger may have maternal antibody protection, but incomplete cases have been reported in that age group.

CLINICAL

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History

Most children present because of concern of a prolonged fever. Diagnosis requires fever of at least 5 days duration (though many believe that the diagnosis can be made earlier in otherwise classic presentations). Parents may note that the fever began abruptly. Antibiotic therapy may have been initiated for other diagnoses, but fever persists. The affected child is usually more irritable than would be expected by the degree of fever.

Key historical clues include the following:

• Fever  
• • At least 5 days in duration
  • Often abrupt in onset
  • Unresponsive to antibiotic therapy, if given
• Irritability - Out of proportion to the degree of fever or other signs (Note that an lumbar puncture (LP) looking for meningitis may demonstrate a pleocytosis). 

Physical

Diagnosis and clinical features of Kawasaki disease

• The diagnosis of classic Kawasaki disease requires fever (>39°C) of at least 5 days' duration and the presence of 4 of the following:  
• • Changes in extremities including erythema, edema, and desquamation. This may limit movement and cause the child to refuse to bear weight. Desquamation of the fingers and toes begins in the periungual region, may involve the palms and soles, and is usually observed 1-2 weeks after the onset of fever. (Occurrence is approximately 75%.)
  • Bulbar conjunctivitis (not associated with exudates) is almost always bilateral. (Occurrence is approximately 85%.)
  • Polymorphous rash (not vesicular) is usually generalized but may be limited to the groin or lower extremities. (Occurrence is approximately 80%.)
  • Cervical lymphadenopathy is usually greater than 1.5 cm and unilateral; it is the least common of all clinical features in US cases, though it is more common in Asia. (US occurrence is approximately 40%.)
  • Changes in the lips and oral cavity include pharyngeal erythema, dry/fissured or swollen lips, and strawberry tongue. (Occurrence is approximately 90%.)
• Clinical features
• • The onset is usually abrupt with a high sustained fever that is unresponsive to antibiotic therapy and lasts for 1 week or longer. In addition, other typical features may be present. 
  • Lips become erythematous and fissured. Bleeding may be noted.
  • The tongue is described as a strawberry tongue because of the diffuse erythema and prominent papillae.
  • The neck may be stiff, possibly leading to a workup for meningitis, especially since many such patients are very irritable. Aseptic meningitis (pleocytosis) may be present in one half of all patients.
  • The primary cardiac involvement is the development of coronary artery aneurysms. Myocarditis and pericarditis with or without effusion may also occur in the acute stage.
  • Other clinical features of the disease may include urethritis, orchitis, arthritis/arthralgia, abdominal pain, vomiting/diarrhea (one third of patients), sterile pyuria (one third of patients), hepatitis, and gallbladder distention.
  • Although rare in the United States, reactions of erythema, induration, and ulcerations may occur at the inoculation site of children who have received the BCG vaccine.

Incomplete cases also occur. (Clinical features are typical, just not present in the numbers required for fully manifested cases). In this setting, usually in children younger than 6 months of age, fever plus only 3 features establishes 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. The American Academy of Pediatrics (AAP)/American Heart Association (AHA) published criteria for the diagnosis in incomplete Kawasaki disease in 2004 in both Pediatrics and Circulation.³ Those articles include a helpful algorithm summarized as follows:

• When fever plus 2 or 3 of the typical features are present for 5 days or more, and patient characteristics suggest possible Kawasaki disease, a c-reactive protein (CRP) and erythrocyte sedimentation rate (ESR) should be obtained. 
• • If CRP level is less than 3 mg/dL and ESR is more than 40 mm/h, the child is monitored and actions taken as appropriate. 
  • If CRP is greater than or equal to 3 mg/dL and ESR is greater than or equal to 40 mm/h, supplemental laboratory studies should be performed. Those studies include albumin, alanine aminotransferase (ALT), platelets, WBC count, and 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, cardiac echocardiogram should be performed. If 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.

Three phases occur, as follows. Some authors add a fourth "chronic" phase.

• Acute febrile phase - 1-2 weeks 
• • The temperature is elevated (>104°F).
  • The child is irritable.
  • Bilateral conjunctivitis and rash are present.
  • The hands and feet develop the erythema and edema that cause the child to refuse to walk. Note that this finding may be the last to develop. Lack of extremity findings may cause consideration of incomplete Kawasaki disease.
  • The tongue and oral mucosa become red and cracked.
  • Hepatic dysfunction may develop.
  • Cardiac complications noted in the first stage include myocarditis and pericarditis.
• Subacute phase - Begins when fever and other signs have abated. This phase should end by the 4th week. 
• • This is characterized by persistent irritability, anorexia, and conjunctival injection.
  • Fever resolution begins this stage. However, persistent fever beyond 2-3 weeks may be an indication of recrudescent Kawasaki disease. (See recrudescent Kawasaki disease below).
  • If fever persists, the outcome is less favorable because of a greater risk of cardiac complications.
  • Thrombocytosis develops, and the platelet count may exceed 1 million/mm³.
  • Desquamation of the fingertips and toes begins at this time.
  • Aneurysm formation may occur during this stage.
  • Children are at greatest risk of sudden death during this phase.
• Convalescent phase - Approximately 4-6 weeks 
• • Begins when all signs of illness have disappeared and continues until acute-phase reactants (ESR, CRP level) have returned to normal.
  • The most significant clinical finding that persists through this phase is the presence of coronary artery aneurysms.         
• Chronic phase
• • This stage is only of clinical importance in patients who have developed cardiac complications.
  • Its duration is of lifetime significance because the aneurysm formed in childhood may rupture in adulthood.
  • In some cases of aneurysms rupturing in adult life, careful reviews of past medical histories have revealed febrile childhood illnesses of unknown etiology.

Causes

The etiology of Kawasaki disease remains unknown. Multiple theories exist, including an infectious etiology, an immunological abnormality, and even the possibility of a link with carpet shampoo. Clinical and epidemiologic features support an infectious etiology, but many authorities believe that an autoimmune component also exists.

One group of authors has suggested a link with tumor necrosis factor-alpha (TNF-alpha).

DIFFERENTIALS

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WORKUP

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Lab Studies

• No specific laboratory test exists; however, certain abnormalities coincide with various stages.
• A mild-to-moderate normochromic anemia is observed in the acute stage along with a moderate to alarmingly elevated WBC count with a left shift.  
• • Many of the acute-phase reactant markers, such as the ESR, CRP level, and serum alpha1-antitrypsin level are elevated. Most authors mention only ESR and CRP.
  • Culture results are all negative.
• During the subacute stage, platelet count elevation is the outstanding marker.  
• • It begins to rise in the second week and continues to rise during the third week.
  • Levels as high as 2 million have been observed.
  • The acute reactive markers remain elevated.
• 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.
• Liver function studies and serum lipase measurement may be indicated in selected cases.

Imaging Studies

• An echocardiogram is the study of choice to demonstrate coronary artery aneurysms in both fully manifested and suspected incomplete cases.  
• During the acute stage, a baseline echocardiogram is important.  
• • The echocardiogram should be repeated in the second or third week and again 1 month after all other laboratory results have normalized.
  • Many centers perform a 1-year echocardiogram, even when the first ones show no aneurysm.
  • If the echocardiogram results are abnormal at any point, the child should be referred to a pediatric cardiologist for a complete cardiac workup and follow-up care.
• Ultrasonography of the gallbladder may be necessary if any suggestion of liver or gallbladder dysfunction is present.
• A chest radiograph should be obtained to assess baseline findings and to confirm clinical suspicion of congestive heart failure.

Other Tests

• An electrocardiogram (ECG) indicates the presence of various conduction abnormalities. Additionally, children with the syndrome may suffer acute infarction.
• One study used multislice spiral CT to assess coronary artery abnormalities in 16 adolescents and young adults with Kawasaki disease. Although the numbers were small, 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%.⁴
• In another small study, electron beam computed tomography (EBCT) was used to determine if coronary artery calcifications could be used as a marker of future coronary artery events. The authors felt that this study may be useful for risk stratification in long-term management of patients with Kawasaki disease.⁵

Procedures

• A select group may require cardiac catheterization.
• Coronary artery bypass grafting and cardiac transplantation have been needed.

TREATMENT

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Prehospital Care

No specific prehospital care exists for Kawasaki disease. Paramedics should assess the need for intravenous access and rhythm monitoring.

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.
• 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.

Consultations

• Pediatrics
• • Consultation with a pediatric cardiologist may be required if coronary artery aneurysms are identified or if other cardiac complications develop.
  • Pediatric cardiothoracic surgery assistance may be needed in the pediatric ICU for those patients who need bypass surgery or a transplant.

MEDICATION

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The medical management of Kawasaki disease primarily involves the use of gamma globulin. Although some have suggested that aspirin is no longer needed, most use high-dose aspirin for a variable period of time, followed by lower-dose aspirin for its antiplatelet effects. 

Some controversy exists about the ideal timing to begin gamma globulin, but this is not an issue that concerns emergency physicians. It is given most often from days 5-7.

Although data are limited, authors of several case reports have suggested a possible role for thrombolysis in those with acute MI as a consequence of thrombus formation in aneurysms. At this time, it seems unlikely that the emergency physician will administer this therapy. Similarly, some have advocated abciximab in those with giant coronary artery aneurysms.

Some have suggested that there is, or may be, a role for corticosteroids. Most have pointed out that not only is there no good data to support a benefit in terms of outcome but also that current therapy with IVIG and aspirin is safe and effective.

Ibuprofen antagonizes aspirin's antiplatelet activity and should be avoided.

Because these children will take aspirin for a variable period of time, vaccination against influenza and varicella must be ensured.

Studies that involved plasma exchange or cyclophosphamide have not shown much promise.

Drug Category: Gamma globulins

These agents can be used to assist in the treatment of inflammation resulting from autoimmune disorders. Much of the pathophysiology in KD involves inflammation. Early and aggressive intervention improves outcome.

Drug Category: Anti-inflammatory agents

These agents systemically interfere with events leading to inflammation. Aspirin is indicated for antiplatelet effect.

FOLLOW-UP

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Further Inpatient Care

• Although some authors advocate a 23-hour observation period, most patients with Kawasaki disease are formally admitted to a pediatric or pediatric cardiology service for aggressive supportive and anti-inflammatory therapy.

Further Outpatient Care

• Careful follow-up care is necessary in the child who has developed cardiac complications.
• • A pediatric cardiologist should provide follow-up care for the child.
  • The long-term implications for coronary artery disease are unknown at this time.

In/Out Patient Meds

• The pediatrician or cardiologist who provides the long-term care monitors aspirin therapy and decides whether or not to use warfarin or heparin.
• Tumor necrosis factor-alpha blockade with infliximab has been advocated by some in cases of refractory KD.

Transfer

• Because of the potential life threats, patients with KD must be admitted to a hospital with a pediatric service.
• Some authorities recommend transferring those patients with documented coronary artery aneurysms to a tertiary pediatric facility.

Deterrence/Prevention

• Since the etiology of KD is unknown, there is no method of deterrence. Therapy is directed at prevention of coronary artery aneurysm formation.

Complications

• The primary complications involve the development and rupture of coronary artery aneurysms. Giant aneurysms may occur and may be resistant to KD therapy. Some recommend coronary artery bypass grafting using arterial grafts that can grow with the child. Transplant has been performed in some children who had large aneurysms in vessels not amenable to bypass.
• Endovascular ultrasonography has shown that some resolved aneurysms are associated with marked intimal thickening.
• Dehydration may result from fever and anorexia.
• Joint inflammation in the acute phase may limit mobility.
• Pancreatitis, hydrops (vasculitis) of the gallbladder, hepatitis, meningitis, and orchitis may complicate care.

Prognosis

• Those patients who do not develop coronary artery aneurysms recover fully. Recurrence is unusual, occurring in only 1-3% of all cases. 
• The severity of aneurysms determines the prognosis in the remainder. More than half of all aneurysms resolve by the 2-year mark. Endovascular ultrasonography has shown that even when aneurysms resolve marked intimal thickening is present. Vessel flow may be abnormal.
• Some believe that giant aneurysms are likely to thrombose or become stenotic. Studies are ongoing. 
• Coronary artery bypass grafting has been required in some children with severe perfusion deficits. Some children have even required cardiac transplantation.

Patient Education

• Parents and other caregivers must understand the need for close pediatric and cardiology follow-up until the disease has fully resolved.

MISCELLANEOUS

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Medical/Legal Pitfalls

• Failure to diagnose the disease is the primary medical/legal pitfall.
• Failure to consider the possibility of incomplete Kawasaki disease could lead to delayed (or missed) diagnosis and treatment with a consequent increased likelihood of coronary artery aneurysms development.

MULTIMEDIA

Section 10 of 11  

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Media file 1:  Pediatrics, Kawasaki disease. Note the appearance of the hand and lips. Photo courtesy of Sam Richardson, MD.
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Media type:  Photo

REFERENCES

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1. 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. Oct 2002;21(10):976-8. [Medline].
2. 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. Aug 2004;23(8):789-91. [Medline].
3. 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. Oct 26 2004;110(17):2747-71. [Medline].
4. 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. Feb 15 2005;95(4):522-5. [Medline].
5. 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. Nov 2005;150(5):1016. [Medline].
6. Barron KS. Kawasaki disease in children. Curr Opin Rheumatol. Jan 1998;10(1):29-37. [Medline].
7. Bernstein DM. Noninfectious conditions causing myocardial damage; diseases of blood vessels. In: Nelson's Textbook of Pediatrics. 15^th ed. 1996:1350-2, 1368.
8. Burns JC. Revisiting steroids in the primary treatment of acute Kawasaki disease. J Pediatr. Sep 2006;149(3):291-2. [Medline].
9. Burns JC, Mason WH, Hauger SB, Janai H, Bastian JF, Wohrley JD, et al. Infliximab treatment for refractory Kawasaki syndrome. J Pediatr. May 2005;146(5):662-7. [Medline].
10. Chantepie A, Mauran P, Lusson JR, Vaillant MC, Bozio A. [Cardiovascular complications of Kawasaki syndrome: results of a French multicenter study]. Arch Pediatr. Jul 2001;8(7):713-9. [Medline].
11. Chung CJ, Stein L. Kawasaki disease: a review. Radiology. Jul 1998;208(1):25-33. [Medline].
12. Curtis N, Levin M. Kawasaki disease thirty years on. Curr Opin Pediatr. Feb 1998;10(1):24-33. [Medline].
13. Daniels K. Anonymity and openness and the recruitment of gamete donors. Part I: semen donors. Hum Fertil (Camb). Sep 2007;10(3):151-8. [Medline].
14. Daniels SR. Steroid treatment for Kawasaki disease. J Pediatrics. Sept 2006;149 (3):336.
15. Feit JR. Kawasaki syndrome: diagnosis and management. R I Med. Jan 1995;78(1):18-20. [Medline].
16. Flynn PA, Engle MA, Ehlers KH. Cardiac issues in the pediatric emergency room. Pediatr Clin North Am. Oct 1992;39(5):955-86. [Medline].
17. Ichida F, Fatica NS, O'Loughlin JE, Klein AA, Snyder MS, Levin AR, et al. Epidemiologic aspects of Kawasaki disease in a Manhattan hospital. Pediatrics. Aug 1989;84(2):235-41. [Medline].
18. 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. Sep 2006;149(3):336-341. [Medline].
19. Italian Society of Pediatrics. The use of intravenous immunoglobulins: recommendations of a consensus conference of the working group of immunology of the Italian Society of Pediatrics. Ann Allergy. Apr 1989;62(4):362-7. [Medline].
20. Kawasaki Disease Symposium. Management of Kawasaki syndrome: a consensus statement prepared by North American participants of the Third International Kawasaki Disease Symposium, Tokyo, Japan, December, 1988. Pediatr Infect Dis J. Oct 1989;8(10):663-7. [Medline].
21. Krendel S, Pollack P, Hanly J. Tissue plasminogen activator in pediatric myocardial infarction. Ann Emerg Med. May 2000;35(5):502-5. [Medline].
22. Laupland KB, Dele Davies H. Epidemiology, etiology, and management of Kawasaki disease: state of the art. Pediatr Cardiol. May-Jun 1999;20(3):177-83. [Medline].
23. Meissner HC, Leung DY. Kawasaki syndrome: where are the answers?. Pediatrics. Sep 2003;112(3 Pt 1):672-6. [Medline].
24. Morgan GJ, MacLeod C, Jenkins J, Stewart C, Craig B. IVIG, aspirin, and Kawasaki disease. J Pediatr. Aug 2003;143(2):280-1; author reply 281. [Medline].
25. Nomura Y, Masuda K, Yoshinaga M, Takei S, Miyata K. Possible relationship between streptococcal pyrogenic exotoxin A and Kawasaki syndrome in patients older than six months of age. Pediatr Infect Dis J. Sep 2003;22(9):794-8. [Medline].
26. Rowley AH. Controversies in Kawasaki syndrome. Adv Pediatr Infect Dis. 1997;13:127-41. [Medline].
27. Rowley AH. The etiology of Kawasaki disease: superantigen or conventional antigen?. Pediatr Infect Dis J. Jan 1999;18(1):69-70. [Medline].
28. Rowley AH, Shulman ST. Kawasaki syndrome. Pediatr Clin North Am. Apr 1999;46(2):313-29. [Medline].
29. Rowley AH, Shulman ST. Kawasaki Disease. In: Behrman RE, Kliegman RM, Jensen HD, eds. Nelson Textbook of Pediatrics. 17^th ed. Philadelphia Pa: WB Saunders Co; 2004:823-6.
30. Saulsbury FT. Comparison of high-dose and low-dose aspirin plus intravenous immunoglobulin in the treatment of Kawasaki syndrome. Clin Pediatr (Phila). Oct 2002;41(8):597-601. [Medline].
31. Schratz LM, Meyer RA, Schwartz DC. Serial intracoronary ultrasound in children: feasibility, reproducibility, limitations, and safety. J Am Soc Echocardiogr. Aug 2002;15(8):782-90. [Medline].
32. Selamet Tierney ES, Newburger JW. Are patients with Kawasaki disease at risk for premature atherosclerosis?. J Pediatr. Sep 2007;151(3):225-8. [Medline].
33. Shulman ST. Is there a role for corticosteroids in Kawasaki disease?. J Pediatr. Jun 2003;142(6):601-3. [Medline].
34. Shulman ST, De Inocencio J, Hirsch R. Kawasaki disease. Pediatr Clin North Am. Oct 1995;42(5):1205-22. [Medline].
35. Sundel RP, Baker AL, Fulton DR, Newburger JW. Corticosteroids in the initial treatment of Kawasaki disease: report of a randomized trial. J Pediatr. Jun 2003;142(6):611-6. [Medline].
36. Tsubata S, Ichida F, Hamamichi Y, Miyazaki A, Hashimoto I, Okada T. Successful thrombolytic therapy using tissue-type plasminogen activator in Kawasaki disease. Pediatr Cardiol. Jul-Aug 1995;16(4):186-9. [Medline].
37. Turbiak T, Reich JL. Bacterial infections - Kawasaki syndrome. In: Rosen P, Braen GR, Dailey R, Levy, Barkin RM, eds. Emergency Medicine: Concepts and Clinical Practice. 3^rd ed. Philadelphia, Pa: Mosby, Inc; 1992:2282.
38. Warren RW, Perez MD, Wilking AP, Myones BL. Pediatric rheumatic diseases. Pediatr Clin North Am. Aug 1994;41(4):783-818. [Medline].
39. Weinstein M. Inflammation at a previous inoculation site: an unusual presentation of Kawasaki disease. CMAJ. Feb 14 2006;174(4):459-60. [Medline].

Article Last Updated: Apr 15, 2008