• An idiopathic, multisystem disease of young children characterized by vasculitis of the small- and medium-sized blood vessels.
• Diagnosis of Kawasaki disease requires a fever for greater than 5 days and four of the following criteria:
  • Non-exudative conjunctival injection
  • Polymorphous, non-vesicular rash
  • Mucosal involvement of the upper respiratory tract that may include erythema, fissures of the lips, crusting of the lips and mouth, or a strawberry tongue. Exudative pharyngitis and discrete oral lesions (e.g., vesicles, etc.) are rare.
  • Edema or erythema of the hands and feet
  • Cervical adenopathy of at least 1.5 cm in diameter, which is often unilateral.
• Atypical Kawasaki disease
  • Patients may present with less than four of the five diagnostic criteria and still develop aneurysms.
  • Atypical disease is more common in children less than 1 year of age.

• Etiology is uncertain.
• Association with recent use of rug cleaners or having had rugs shampooed has not been substantiated.

• Median age of cases is 2.3 years with 80% of cases in children less than 4 years of age, 5% of cases in children greater than 10 years of age, and almost unheard of in children over age 15. Recurrence is low, approximately 0.8%.
• In the United States, incidence seems to be increasing, approximately 11% per year in the period 1984–1990.

• Aneurysms usually first noted 12 to 28 days after onset of the disease. Rarely appear greater than 28 days after onset.
• Aneurysms may thrombose leading to myocardial infarction and death.
• Aneurysms may rupture rarely in patients.
• A pancarditis is often present in the first 10 days of the illness. Pericardial effusions may accompany this.

• Without treatment with intravenous immunoglobulin (IVIG) 15% to 25% of patients develop coronary aneurysms.
• Use of IVIG decreased the incidence of coronary artery aneurysms 4–8%.
• Death occurs secondary to cardiac disease in 0.3% to 2% of cases; approximately 10% is related to early myocarditis, and the remainder due to myocardial infarctions.
• Myocardial infarction can occur several years after the initial illness.
• Patients who are younger than 1 year, older than 8 years, male, and whose fevers persist for greater than 14 days are more likely to develop aneurysms.
• Mortality rates are much higher in males and patients who develop giant coronary artery aneurysms (diameter of greater than 8 mm).

• Diarrhea and abdominal pain may be seen.
• Patients may develop arthralgias or even frank arthritis.
• Pancarditis may present as myocardial dysfunction early in the course of disease with signs of congestive heart failure.
• Infantile periarteritis nodosa (PAN) is a previously described entity in which the pathological findings of coronary artery aneurysms are indistinguishable from those seen in Kawasaki disease. Most patients with PAN do not have the other findings of Kawasaki disease.

• Infections
  • Measles and group A b-hemolytic streptococcal infections most closely resembled Kawasaki disease and accounted for 83% of patients referred who did not have Kawasaki disease.
  • Severe staphylococcal infections with toxin release (e.g., toxic shock syndrome) may also resemble Kawasaki disease, although there is usually renal involvement (extremely rare in Kawasaki disease) and low platelets.
  • Other infections that must be considered include adenovirus, Epstein-Barr virus, roseola, enterovirus, Rocky Mountain spotted fever, and leptospirosis.
• Immunological
  • Juvenile rheumatoid arthritis and unusual variants of acute rheumatic fever.
  • Hypersensitivity reactions and Stevens-Johnson syndrome.
  • In Stevens-Johnson syndrome the conjunctivitis is more likely to be exudative, the rash is more likely to be vesicular with crusting, and there is often a history of drug ingestion.

• Acute phase (1–2 weeks from onset):
  • Highly febrile, irritable, toxic appearing
  • Fever usually greater than 40°C and may be as high as 41.6°C
  • Oral changes usually quickly follow and also may last 1 to 2 weeks.
  • Rash prone to occur in perineal area
  • Edema and erythema of the feet are usually painful and limit ambulation.
• Subacute phase (from 2 to 8 weeks after onset)
  • Without treatment gradual improvement occurs; fever decreases and there is desquamation of the perineal area, palms, soles, and/or periungual areas.
  • Coronary artery aneurysms often appear during the early portion of this phase and acute myocardial infarction may be seen.
  • May have persistent arthritis or arthralgias
• Convalescent phase (from months to years after)
  • Resolution of remaining symptoms
  • Laboratory values return to normal (see subsequent text).
  • Aneurysms may resolve or patients may have persistent aneurysms, persistent cardiac dysfunction, or even myocardial infarction.

Finding: High, unremitting fevers that last 1 to 2 weeks.
Significance: Fever

Finding: Rash is polymorphous and not vesicular.
Significance: Seen in 99% of cases; predilection for perineum. Often prominent on trunk, usually maculopapular, may coalesce and may be petechial.

Finding: Conjunctivitis
Significance: Bilateral and non-exudative (96% of cases).

Finding: Oral changes may be erythema, fissures, and crusting of lips, diffuse oropharyngeal erythema, or the presence of a strawberry tongue or any combination of these findings.
Significance: Usually not exudative.

Finding: Extremity changes may include erythema of the palms and soles and/or induration of the hands and feet (99% of cases).
Significance: Desquamation, especially periungual, usually occurs in subacute phase. Transverse grooves across the fingernails (Beau lines) may be seen 2 to 3 months after onset.

Finding: Adenopathy is usually cervical and often unilateral.
Significance: Least often seen of the major criteria (75–82% of cases). May be fleeting and easily missed.

Finding: Aseptic meningitis
Significance: Is common and patients are extremely irritable and may show signs of encephalopathy or ataxia.

Finding: Pancarditis during the acute phase
Significance: May present with tachycardia, gallop rhythms, muffled heart sounds, signs of congestive heart failure, and murmurs consistent with aortic or mitral insufficiency.

Finding: Abdominal exam
Significance: Patients may have a right upper quadrant mass (hydrops of gall bladder), diarrhea, hepatosplenomegaly, or jaundice.

Finding: Meatitis and vulvitis
Significance: May be seen in association with urethritis and sterile pyuria.

Finding: Arthralgias are common; frank arthritis is seen in approximately one-third of patients.
Significance: May involve large and small joints; is non-deforming. Onset may be as late as second or third week. Usually resolves in approximately 1 month.

• During acute phase, slit lamp examination may reveal anterior uveitis in approximately 80% of Kawasaki disease cases.

Test: White blood cell count
Significance: Usually increased with a left shift; greater than 20,000 in 50% of cases and greater than 30,000 in 15%.

Test: Increased erythrocyte sedimentation rate
Significance: Often greater than 100 mm.

Test: Platelet count
Significance: Platelets may be low, normal, or high at presentation but increase rapidly after the second week of illness; during subacute phase platelet counts may increase to 1 to 2 × 10⁶.

Test: Other laboratory abnormalities include:

Test: ECG
Significance: During acute phase may show prolonged pr interval, decreased QRS voltage, flat T waves, and ST changes.

Test: Chest x-ray
Significance: May show dilated heart during acute phase.

Test: Echocardiogram
Significance: During acute phase can show a decreased shortening fraction and effusion. Aneurysms may be detected as early as 6 days into the illness, and peak onset is between 3 to 4 weeks.

Test: Increased BUN or creatinine
Significance: If laboratory indicators of renal involvement are present, then illnesses other than Kawasaki disease should be considered (e.g., toxic shock syndrome).

• Intravenous immunoglobulin (IVIG)
  • Usual dose is 2 g/kg as a one-time dose over 10 hours.
  • Efficacy of IVIG after the tenth day of illness is unclear.
  • Patients who fail to respond to an initial dose of IVIG or who have a recrudescence of their symptoms should be retreated (up to two-thirds may have a good response to repeat doses).
  • Side effects: Patients may develop signs of fluid overload and congestive heart failure.
• Aspirin
  • High-dose aspirin was the mainstay of therapy; still used in conjunction with IVIG, although no data look at IVIG with aspirin versus IVIG alone.
  • Usual initial dose is 80 to 100 mg/kg/d in divided doses. High dose required to overcome malabsorption of aspirin seen during acute phase of Kawasaki disease.
• Corticosteroids are contraindicated; may actually increase the rate of coronary artery aneurysms.

• Aspirin is continued at high dose until day 14 of the illness or when the child has been afebrile for 48 hours.
• Aspirin dose is then decreased to 30 mg kg/d until 4 weeks after onset and additionally decreased to 3 to 10 mg/kg/d for 6 to 8 weeks or until the platelet count returns to normal.
• If there are coronary artery abnormalities dypyridamole at 3 to 5 mg/kg/d should be added to the aspirin for its vasodilatory effect. Aspirin and dypyridamole should be continued for 1 year or until coronary artery aneurysms resolve.

• Children with Kawasaki disease should be kept at bedrest until the second or third week of illness or when they have been afebrile for over 72 hours due to the possibility of myocardial involvement during the acute phase.
• Isolation of patients is not indicated.
• Even asymptomatic patients should be restricted from strenuous activities.

• The natural course is a gradual improvement during the subacute phase.
• With IVIG children usually defervesce and show significant resolution of clinical symptoms within 2 to 3 days of treatment (70–80%).
• Two-thirds of patients who receive a repeat dose of IVIG will respond to this dose.

• White blood cell count, platelet count, and ESR should be followed weekly to biweekly until they return to normal.
• Weekly echocardiograms should be done to rule out the development of coronary artery aneurysms from weeks 2 to 6 of the illness.
• If aneurysms are present, cardiology follow-up should include coronary artery catheterization and imaging at some time (usually 8–12 weeks after onset of illness).
• Symptoms of cardiac insufficiency (fatigue, chest pain, dyspnea on exertion, etc.) ECG, CXR, echocardiogram, and exercise myocardial perfusion studies should be done at regular intervals.

Q: Do coronary artery aneurysms associated with Kawasaki disease ever resolve?
A: Most coronary artery aneurysms do resolve. Even some giant aneurysms (those greater than 8 mm in diameter) will resolve; there is concern, however, that even if aneurysms resolve, these patients may be at risk for the early development of atherosclerosis.

Melish ME. Kawasaki syndrome. Pediatr Rev 1996;17:153–162.

Momenah T, Sanatini S, Potts J, et al. Kawasaki disease in the older child. Pediatrics 1998;102(1):e7.

Rosenfeld EA, Corydon KE, Shulman ST. Kawasaki disease in infants less than one year of age. J Pediatr 1995;126:524–529.

Shulman ST, DeInocencio J, Hirsch R. Kawasaki disease. Pediatr Clin North Am 1995;42:1205–1222.