AUTHOR INFORMATION

Section 1 of 12

Authored by Steven J Parrillo, DO, FACOEP, FACEP, Assistant Professor, Department of Emergency Medicine, Jefferson Medical College; Medical Director of Emergency Medicine, Einstein Elkins Park and Germantown Community Health Services; Chair, Emergency Management Committee, Albert Einstein Medical Center

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

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, and Society for Academic Emergency Medicine

Edited by Jeffrey Glenn Bowman, MD, MS, Consulting Staff, Department of Emergency Medicine, Mercy Springfield Hospital; Mary L Windle, PharmD, Adjunct Assistant Professor, University of Nebraska Medical Center College of Pharmacy, Pharmacy Editor, eMedicine.com, Inc; Grace M Young, MD, Associate Professor, Department of Pediatrics, University of Maryland Medical Center; John Halamka, MD, Chief Information Officer, CareGroup Healthcare System, Assistant Professor of Medicine, Department of Emergency Medicine, Beth Israel Deaconess Medical Center; Assistant Professor of Medicine, Harvard Medical School; and Richard G Bachur, MD, Assistant Professor of Pediatrics, Harvard Medical School; Associate Chief and Fellowship Director, Division of Emergency Medicine, Children's Hospital of Boston

Author's Email:	Steven J Parrillo, DO, FACOEP, FACEP
Editor's Email:	Jeffrey Glenn Bowman, MD, MS

eMedicine Journal, February 14 2007, VOLUME 8, Number 2

INTRODUCTION

Section 2 of 12

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, 20% of untreated patients develop coronary artery aneurysms.

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.

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.

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.

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

Treadwell et al have suggested that there is an association between KS and the use of a humidifier in the room of a child with an antecedent respiratory illness.

Frequency:

• In the US: Epidemics occur primarily in the late winter and spring with 3-year intervals. KS 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.

• Internationally: 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.

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.

• 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 are younger than 1 year, and who have cardiomegaly. Some laboratory values at presentation may also predict a greater likelihood of aneurysm development including low hematocrit levels, thrombocytopenia, and elevated neutrophil/band counts.

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; KD is most frequently observed in infants aged 6-12 months, with equal numbers in the first and second year of life.

Pannaraj et al recently noted that KD 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.

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

CLINICAL

Section 3 of 12

History: Most children present because of concern of a prolonged fever. Diagnosis requires fever of at least 5 days duration (though some believe that experienced clinicians may make the diagnosis 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 aseptic meningitis may coexist.)

Physical:

• The diagnosis of classic Kawasaki disease (KD) requires fever of at least 5 days duration and the presence of 4 of the following (if fever is present with fewer than 4 of the following, the diagnosis is established with ECHO-proven coronary artery disease and exclusion of other diseases with similar clinical features):

• Changes in extremities (eg, erythema, edema, 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.

• Bilateral conjunctivitis (not associated with exudates)

• Polymorphous rash (not vesicular)

• Cervical lymphadenopathy (usually >1.5 cm and unilateral; the least common of all clinical features, occurring in approximately 40%)

• Changes in the lips and oral cavity (eg, pharyngeal erythema, dry/fissured or swollen lips, strawberry tongue)

• 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 may coexist in one half of all patients.

• Cardiac involvement ranges from myocarditis and pericarditis with or without effusion in the acute stage to the development of coronary artery aneurysms later in the course.

• Other clinical features of the disease may include urethritis, arthritis/arthralgia, abdominal pain, vomiting/diarrhea (one third of patients), sterile pyuria (one third of patients), hepatitis, and gallbladder distention.

• Experts now agree that incomplete or atypical cases can and do occur. 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 KD may have a significant negative impact on outcome.

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

• Acute febrile phase (days 1-11)
  • 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.

  • 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 (days 11-21)
  • This is characterized by persistent irritability, anorexia, and conjunctival injection.

  • The fever usually resolves by this stage.

  • If fever has persisted, 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 (days 21-60):
  • Begins when all signs of illness have disappeared and continues until acute phase reactants (erythrocyte sedimentation rate [ESR], C-reactive protein [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.

• 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.

Causes: The etiology of KD 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

Section 4 of 12

Pediatrics, Bacteremia and Sepsis
Pediatrics, Fever
Pediatrics, Meningitis and Encephalitis
Pediatrics, Pharyngitis
Scarlet Fever
Staphylococcal Scalded Skin Syndrome
Tick-Borne Diseases, Rocky Mountain Spotted Fever
Toxic Epidermal Necrolysis
Toxic Shock Syndrome
Toxicity, Mercury

WORKUP

Section 5 of 12

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.

• 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.

Imaging Studies:

• An echocardiogram (ECHO) is the study of choice to demonstrate coronary artery aneurysms.

• During the acute stage, a baseline ECHO is important.

• The ECHO 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 ECHO, even when the first ones show no aneurysm.

• If the ECHO results are abnormal at any point, the child should be referred to a pediatric cardiologist for a complete cardiac workup and follow-up care.

• An ultrasound 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 KD. 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%.

• 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 KD.

Procedures:

• A select group may require cardiac catheterization.

• Coronary artery bypass grafting and cardiac transplantation have been needed.

TREATMENT

Section 6 of 12

Emergency Department Care:

• Any young child presenting to the emergency department (ED) with symptoms of early or acute stage KS should be evaluated to rule out sepsis or meningitis.

• Although the diagnosis of KS 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

Section 7 of 12

The medical management of Kawasaki disease (KD) involves the use of gamma globulin and aspirin as anti-inflammatory agents and long-term anticoagulation. Some controversy exists about the ideal timing to begin gamma-globulin, but that is not an issue that concerns emergency physicians.

Although data are limited, authors of several case reports have suggested a possible role for thrombolysis in those suffering 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, but this is not standard therapy now.

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 Name	Immune globulin, intravenous (Gammagard, Gamimune) -- Generally recommended as the first drug to be used, but it is not the sole therapy. Neutralizes circulating myelin antibodies through anti-idiotypic antibodies; down-regulates proinflammatory cytokines, including INF-gamma; blocks Fc receptors on macrophages; suppresses inducer T and B cells and augments suppressor T cells; blocks complement cascade; promotes remyelination; may increase CSF IgG (10%).
Adult Dose	400 mg/kg/d IV in a single daily infusion for 4 d or single dose of 2 g/kg IV infused over 12 h; may repeat course of therapy in those who do not have an adequate response to initial treatment
Pediatric Dose	Administer as in adults
Contraindications	Documented hypersensitivity; IgA deficiency; anti-IgE/IgG antibodies; severe thrombocytopenia or coagulation disorders
Interactions	Globulin preparation may interfere with immune response to live-virus vaccine (MMR) and reduce efficacy (do not administer within 3 mo of vaccine)
Pregnancy	C - Safety for use during pregnancy has not been established.
Precautions	Flushing of the face, chills, nausea, dyspnea, and tachycardia are the most common adverse effects; less common adverse effects include chest tightness, dizziness, fever, headache, and diaphoresis Check serum IgA before IVIG (use an IgA-depleted product, eg, Gammagard S/D); infusions may increase serum viscosity and thromboembolic events; infusions may increase risk of migraine attacks, aseptic meningitis (10%), urticaria, pruritus, or petechiae (2-30 d postinfusion) Increases risk of renal tubular necrosis in elderly patients and in patients with diabetes mellitus, volume depletion, and preexisting kidney disease; laboratory findings associated with infusions include elevated antiviral or antibacterial antibody titers for 1 mo, 6-fold increase in ESR for 2-3 wk, and apparent hyponatremia

Drug Category: Anti-inflammatory agents -- These agents systemically interfere with events leading to inflammation.

Drug Name	Aspirin (Anacin, Ascriptin, Bayer Aspirin, Bayer Buffered Aspirin) -- Inhibits prostaglandin synthesis, which prevents formation of platelet-aggregating thromboxane A2. Adequate anti-inflammatory therapy requires that aspirin be combined with gamma globulin. Children with coronary artery aneurysms receive aspirin for prolonged periods. First-line therapy with intravenous immunoglobulin. PO absorption of aspirin may decrease in Kawasaki disease to <50% (compared to typical bioavailability of 85-90%). This altered bioavailability may explain why higher doses required to achieve a salicylate serum concentration >20 mg/dL.
Adult Dose	Not established
Pediatric Dose	80-100 mg/kg/d PO divided qid for 2 wk initial; 3-5 mg/kg PO qd for 6-8 wk maintenance Coronary artery abnormalities: 3-5 mg/kg PO qd long term (with or without dipyramidole)
Contraindications	Documented hypersensitivity; liver damage; hypoprothrombinemia; vitamin K deficiency; bleeding disorders; asthma; use in children ( <16 y) with influenza because of association of aspirin with Reye syndrome
Interactions	Effects may decrease with antacids and urinary alkalinizers; corticosteroids decrease salicylate serum levels; additive hypoprothrombinemic effects and increased bleeding time may occur with coadministration of anticoagulants; may antagonize uricosuric effects of probenecid and increase toxicity of phenytoin and valproic acid; doses > 2 g/d may potentiate glucose lowering effect of sulfonylurea drugs
Pregnancy	C - Safety for use during pregnancy has not been established.
Precautions	Pregnancy category D in third trimester; may cause transient decrease in renal function and aggravate chronic kidney disease; avoid use in patients with severe anemia, with history of blood coagulation defects, or taking anticoagulants; caution in asthma; dose is on the borderline of that causing salicylate toxicity, therefore, monitor for toxicity (ie, vomiting, hyperpnea, lethargy, liver dysfunction); monitor salicylate level and maintain at 18-28 mg/dL

Drug Category: Antiplatelet agents -- Besides aspirin, dipyridamole may be used to prevent microthrombus formation.

Drug Name	Dipyridamole (Persantine) -- A platelet-adhesion inhibitor that possibly inhibits RBC uptake of adenosine, itself an inhibitor of platelet reactivity. May inhibit phosphodiesterase activity leading to increased cAMP within platelets and formation of potent platelet activator thromboxane A2.
Adult Dose	75-100 mg PO qid
Pediatric Dose	Not established; limited data indicate 3-6 mg/kg/d PO divided tid
Contraindications	Documented hypersensitivity
Interactions	Theophylline may decrease hypotensive effects; antiplatelet activity of dipyridamole may increase heparin toxicity
Pregnancy	B - Usually safe but benefits must outweigh the risks.
Precautions	Caution in hypotension; has peripheral vasodilating effects

FOLLOW-UP

Section 8 of 12

Further Inpatient Care:

• Patients with Kawasaki disease (KD) are all 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 KS.

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.

Complications:

• The primary complications involve the development and rupture of coronary artery aneurysms.

• Dehydration may result from fever and anorexia.

• Joint inflammation in the acute phase may limit mobility.

MISCELLANEOUS

Section 9 of 12

Medical/Legal Pitfalls:

• Failure to diagnose presence is the primary medical/legal pitfall.

TEST QUESTIONS

Section 10 of 12

CME Question 1: What is the most common cause of acquired heart disease in children in the United States?

A: Stevens-Johnson syndrome
B: Kawasaki disease
C: Acute rheumatic fever
D: Rocky Mountain spotted fever
E: Viral cardiomyopathy

The correct answer is B: In the United States, the peak prevalence is in those aged 18-24 months. Epidemics occur primarily in the late winter and spring with 3-year intervals. It is most commonly observed in children from the middle and upper-middle classes.

CME Question 2: A 9-month-old African American boy presents with a 10-day history of high fever (>103°F). His pediatrician started oral ibuprofen and was seeing him regularly for follow-up care. In the emergency department today, he is irritable and appears dehydrated. His mother confirms that the child has not been eating or drinking well. Examination reveals enlarged tender cervical nodes and dry, swollen lips. What is the most appropriate course of action if Kawasaki disease is suspected?

A: Begin aspirin and discharge to outpatient care.
B: Continue ibuprofen and discharge to outpatient care.
C: Resuscitate with normal saline, begin aspirin, and discharge to outpatient care.
D: Resuscitate with isotonic sodium chloride solution, give one intravenous dose of gamma-globulin, and discharge to outpatient care.
E: Resuscitate with intravenous saline, admit to pediatrics, and begin aspirin and gamma-globulin after pediatric consultation.

The correct answer is E: 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.

Pearl Question 1 (T/F): The peak prevalence of Kawasaki disease in the United States is in children aged 2-4 years.

The correct answer is False: The peak prevalence of Kawasaki disease in the United States is in children aged 18-24 months.

Pearl Question 2 (T/F): Airborne pathogens are the primary cause of morbidity in Kawasaki disease.

The correct answer is False: The etiology of Kawasaki disease remains unknown. Multiple theories include an infectious etiology and immunological abnormality.

Pearl Question 3 (T/F): Persistent fever is one factor that represents an increased risk for the development of aneurysms in patients with Kawasaki disease.

The correct answer is True: Factors include the following: fever that persists for more than 16 days, recurrence of fever after an afebrile period of at least 48 hours, being male and younger than 1 year, and cardiomegaly.

Pearl Question 4 (T/F): Although diagnosis of Kawasaki disease may seem obvious, other life-threatening diseases must be ruled out.

The correct answer is True: Any young child presenting to the emergency department with symptoms of early or acute stage Kawasaki disease should be evaluated to rule out sepsis and meningitis.

PICTURES

Section 11 of 12

Caption: Picture 1. Pediatrics, Kawasaki disease. Note the appearance of the hand and lips. Photo courtesy of Sam Richardson, MD.
	View Full Size Image
	eMedicine Zoom View (Interactive!)
Picture Type: Photo

BIBLIOGRAPHY

Section 12 of 12

• Barron KS: Kawasaki disease in children. Curr Opin Rheumatol 1998 Jan; 10(1): 29-37[Medline].
• Bernstein DM: Noninfectious conditions causing myocardial damage; diseases of blood vessels. In: Nelson's Textbook of Pediatrics. 15th ed. 1996:1350-2, 1368.
• Burns JC, Mason WH, Hauger SB, et al: Infliximab treatment for refractory Kawasaki syndrome. J. Pediatr 2005; 146(5): 662-667[Medline].
• Chantepie A, Mauran P, Lusson JR, et al: [Cardiovascular complications of Kawasaki syndrome: results of a French multicenter study]. Arch Pediatr 2001 Jul; 8(7): 713-9[Medline].
• Chung CJ, Stein L: Kawasaki disease: a review. Radiology 1998 Jul; 208(1): 25-33[Medline].
• Curtis N, Levin M: Kawasaki disease thirty years on. Curr Opin Pediatr 1998 Feb; 10(1): 24-33[Medline].
• Dadlani GH, Gingell RL, Orie, et al: Coronary artery calcifications in the long-term follow-up of Kawasaki disease. Am Heart J 2005; 150(5): 1016-1020[Medline].
• Feit JR: Kawasaki syndrome: diagnosis and management. R I Med 1995 Jan; 78(1): 18-20[Medline].
• Flynn PA, Engle MA, Ehlers KH: Cardiac issues in the pediatric emergency room. Pediatr Clin North Am 1992 Oct; 39(5): 955-86[Medline].
• Ichida F, Fatica NS, O'Loughlin JE, et al: Epidemiologic aspects of Kawasaki disease in a Manhattan hospital. Pediatrics 1989 Aug; 84(2): 235-41[Medline].
• 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 1989 Apr; 62(4): 362-7[Medline].
• Kanamaru H, Sato Y, Takayama T, 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].
• 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 1989 Oct; 8(10): 663-7[Medline].
• Krendel S, Pollack P, Hanly J: Tissue plasminogen activator in pediatric myocardial infarction. Ann Emerg Med 2000 May; 35(5): 502-5[Medline].
• Laupland KB, Dele Davies H: Epidemiology, etiology, and management of Kawasaki disease: state of the art. Pediatr Cardiol 1999 May-Jun; 20(3): 177-83[Medline].
• Meissner HC, Leung DY: Kawasaki syndrome: where are the answers? Pediatrics 2003; 112(3 Pt 1): 672-676[Medline].
• Morgan GJ, MacLeod C, Jenkins J, et al: IVIG, aspirin, and Kawasaki disease. J Pediatr 2003 Aug; 143(2): 280-1; author reply 281[Medline].
• Nomura Y, Masuda K, Yoshinaga M, et al: Possible relationship between streptococcal pyrogenic exotoxin A and Kawasaki syndrome in patients older than six months of age. Pediatr Infect Dis J 2003 Sep; 22(9): 794-8[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].
• Rowley AH, Shulman ST: Kawasaki syndrome. Pediatr Clin North Am 1999 Apr; 46(2): 313-29[Medline].
• Rowley AH: The etiology of Kawasaki disease: superantigen or conventional antigen?. Pediatr Infect Dis J 1999 Jan; 18(1): 69-70[Medline].
• Rowley AH: Controversies in Kawasaki syndrome. Adv Pediatr Infect Dis 1997; 13: 127-41[Medline].
• Rowley AH, Shulman ST: Kawasaki Disease. In: Behrman RE, Kliegman RM, Jensen HD, eds. Nelson Textbook of Pediatrics. 17th ed. Philadelphia Pa: WB Saunders Co; 2004:823-6.
• Saulsbury FT: Comparison of high-dose and low-dose aspirin plus intravenous immunoglobulin in the treatment of Kawasaki syndrome. Clin Pediatr (Phila) 2002; 41(8): 597-601[Medline].
• Schratz LM, Meyer RA, Schwartz DC: Serial intracoronary ultrasound in children: feasibility, reproducibility, limitations, and safety. J Am Soc Echocardiography 2002; 15(8): 782-790[Medline].
• Shulman ST, De Inocencio J, Hirsch R: Kawasaki disease. Pediatr Clin North Am 1995 Oct; 42(5): 1205-22[Medline].
• Shulman ST: Is there a role for corticosteroids in Kawasaki disease?. J Pediatr 2003 Jun; 142(6): 601-3[Medline].
• Sundel RP, Baker AL, Fulton DR, Newburger JW: Corticosteroids in the initial treatment of Kawasaki disease: report of a randomized trial. J Pediatr 2003 Jun; 142(6): 611-6[Medline].
• Treadwell TA, Maddox RA, Homan RC, et al: Investigation of Kawasaki syndrome risk factors in Colorado. Pediatr Infect Dis J 2002; 21(10): 976-978[Medline].
• Tsubata S, Ichida F, Hamamichi Y, et al: Successful thrombolytic therapy using tissue-type plasminogen activator in Kawasaki disease. Pediatr Cardiol 1995 Jul-Aug; 16(4): 186-9[Medline].
• 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. 3rd ed. Philadelphia, Pa: Mosby, Inc; 1992:2282.
• Warren RW, Perez MD, Wilking AP, et al: Pediatric rheumatic diseases. Pediatr Clin North Am 1994 Aug; 41(4): 783-818[Medline].
• Weinstein M: Inflammation at a previous inoculation site: an unusual presentation of Kawasaki disease. CMAJ 2006 Feb 14; 174(4): 459-60[Medline].

eMedicine Journals > Emergency Medicine > Pediatric > Pediatrics, Kawasaki Disease

Please email us with any comments you have on our new chapter format.

Author Information | Introduction | Clinical | Differentials | Workup | Treatment | Medication | Follow-up | Miscellaneous | Test Questions | Pictures | Bibliography