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Kawasaki
disease is a vasculitis, sometimes involving the coronary arteries,
that tends to occur in infants and children between ages 1 and 8
yr. It is characterized by prolonged fever, exanthem, conjunctivitis,
mucous membrane inflammation, and lymphadenopathy. Coronary
artery aneurysms may develop and rupture or cause MI. Diagnosis
is by clinical criteria; once the disease is diagnosed, echocardiography
is performed. Treatment is aspirin and IV immune globulin. Coronary
thrombosis may require fibrinolysis or percutaneous interventions.
Kawasaki disease (KD) is a vasculitis of medium-sized arteries, most significantly the coronary arteries, which are involved in about 20% of untreated patients. Early manifestations include acute myocarditis with heart failure, arrhythmias, endocarditis, and pericarditis. Coronary artery aneurysms may subsequently form. Giant coronary artery aneurysms (> 8 mm internal diameter on echocardiogram), though rare, have the greatest risk of producing cardiac tamponade, thrombosis, or infarction. KD is the leading cause of acquired heart disease in children. Extravascular tissue may also become inflamed, including the upper respiratory tract, pancreas, biliary tract, and kidneys.
The etiology is unknown, but the epidemiology and clinical presentation suggest an infection or an abnormal immunologic response to an infection in genetically predisposed children. Children of Japanese descent have a particularly high incidence, but KD occurs worldwide. In the US, 3000 to 5000 cases occur annually. The male:female ratio is about 1.5:1. Eighty percent of patients are < 5 yr (peak, 18 to 24 mo). Cases in teenagers, adults, and infants < 4 mo are rare. Cases occur year-round, but most often in spring or winter. Clusters have been reported in communities without clear evidence of person-to-person spread. About 2% of patients have recurrences, typically months to years later.
Symptoms and Signs
The illness tends to progress in stages, beginning with fever lasting at least 5 days, usually remittent and > 39° C, associated with irritability, occasional lethargy, or intermittent colicky abdominal pain. Usually within a day or two of fever onset, bilateral bulbar conjunctival injection appears without exudate. Within 5 days, a polymorphous, erythematous macular rash appears, primarily over the trunk, often with accentuation in the perineal region. The rash may be urticarial, morbilliform, erythema multiforme, or scarlatiniform. It is accompanied by injected pharynx; reddened, dry, fissured lips; and a red strawberry tongue. During the 1st week, pallor of the proximal portion of the fingernails or toenails (leukonychia partialis) may occur. Erythema or a purple-red discoloration and variable edema of the palms and soles usually appear on about the 3rd to 5th day. Although edema may be slight, it is often tense, hard, and nonpitting. Periungual, palmar, and plantar and perineal desquamation begins on about the 10th day. The superficial layer of the skin sometimes comes off in large casts, revealing new normal skin. Tender, nonsuppurative cervical lymphadenopathy (≥ 1 node, ≥ 1.5 cm in size) is present throughout the course in about 50% of patients. The illness may last from 2 to 12 wk or longer. Incomplete or atypical cases can occur, especially in younger infants, who have higher risk of developing coronary artery disease. These findings manifest in about 90% of patients.
Other less specific findings indicate involvement of many systems. Arthritis or arthralgias (mainly involving large joints) occur in about 1⁄3 of patients. Other clinical features include urethritis, aseptic meningitis, hepatitis, otitis, vomiting, diarrhea, hydrops of the gallbladder, and anterior uveitis.
Cardiac manifestations usually begin in the subacute phase of the syndrome about 1 to 4 wk after onset, as the rash, fever, and other early acute clinical symptoms begin to subside.
Diagnosis
Diagnosis is by clinical criteria (see Table 3: Miscellaneous Disorders in Infants and Children: Criteria for Diagnosis of Kawasaki Disease ). Similar symptoms can result from scarlet fever, staphylococcal exfoliative syndromes, measles, drug reactions, and juvenile RA; less common mimics are leptospirosis and Rocky Mountain spotted fever.
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Table 3
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Criteria for
Diagnosis of Kawasaki Disease
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Diagnosis is made if fever of ≥ 5 days has occurred and 4 of the following 5 criteria are noted:
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1. Bilateral nonexudative conjunctival injection
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2. Changes in the lips, tongue, or oral mucosa (injection, drying, fissuring, red strawberry tongue)
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3. Changes in the peripheral extremities (edema, erythema, desquamation)
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4. Polymorphous truncal exanthem
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5. Cervical lymphadenopathy (at least one node ≥ 1.5 cm in diameter)
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Laboratory tests are not diagnostic but may be obtained to exclude other disorders. Patients generally undergo CBC, antinuclear antibody (ANA), rheumatoid factor (RF), ESR, and throat and blood culture. Leukocytosis, often with a marked increase in immature cells, is common acutely. Other hematologic findings include a mild normocytic anemia, thrombocytosis (≥ 450,000/μL) in the 2nd or 3rd wk of illness, and elevated ESR or C-reactive protein. ANA, RF, and cultures are negative. Other abnormalities, depending on the organ systems involved, include sterile pyuria, elevated liver enzymes, proteinuria, and CSF pleocytosis.
Consultation with a pediatric cardiologist is important. At diagnosis, ECG and echocardiography are performed; because abnormalities may not appear until later, these tests are repeated at 2 to 3 wk, 6 to 8 wk, and perhaps at 6 to 12 mo after onset. ECG may show arrhythmias, decreased voltage, or left ventricular hypertrophy. Echocardiography should detect coronary artery aneurysms, valvular regurgitation, pericarditis, or myocarditis. Coronary arteriography is occasionally useful in patients with aneurysms and abnormal stress testing.
Prognosis
Without therapy, mortality may approach 1%, usually occurring within 6 wk of onset. The mortality rate is < 0.01% in the US with adequate therapy. Long duration of fever increases cardiac risk. Deaths most commonly result from cardiac complications and can be sudden and unpredictable: > 50% occur within 1 mo of onset, 75% within 2 mo, and 95% within 6 mo but may occur as long as 10 yr later. Effective therapy reduces acute symptoms and, more importantly, the incidence of coronary artery aneurysms from 20% to < 5%. In the absence of coronary artery disease, the prognosis for complete recovery is excellent. About 2⁄3 of coronary aneurysms regress within 1 yr, although it is unknown whether residual coronary stenosis remains. Giant coronary aneurysms are less likely to regress and require more intensive follow-up and therapy.
Treatment
Children should be treated by or in close consultation with an experienced pediatric cardiologist and/or pediatric infectious disease specialist. Therapy is started as soon as possible, optimally within the 1st 10 days of illness, with a combination of high-dose immune globulin IV (IGIV), a single dose of 2 g/kg given over 10 to 12 h, and oral high-dose aspirin , 20 to 25 mg/kg po qid. The aspirin dose is reduced to 3 to 5 mg/kg once/day after the child has been afebrile for 4 to 5 days; some authorities prefer to continue high-dose aspirin until the 14th day of illness. Aspirin metabolism is erratic during acute KD, which partially explains the high dose requirements. Some authorities monitor serum aspirin levels during high-dose therapy, especially if therapy is given for 14 days.
Most patients have a brisk response over the 1st 24 h of therapy. A small fraction continues to be ill with fever for several days and requires repeated dosing with IGIV. An alternative regimen, which may lead to slightly slower resolution of symptoms but may benefit those with cardiac dysfunction who could not tolerate the volume of a 2 g/kg IGIV infusion, is IGIV 400 mg/kg once/day for 4 days (again in combination with high-dose aspirin ). The efficacy of IGIV/ aspirin therapy when begun > 10 days after onset of illness is unknown, but therapy should still be considered.
After the child has improved for 4 to 5 days, aspirin 3 to 5 mg/kg/day is continued for at least 8 wk after onset until repeated echocardiographic testing is completed. If there are no coronary artery aneurysms and signs of inflammation are absent (demonstrated by normalization of ESR and platelets), aspirin may be stopped. Because of its antithrombotic effect, aspirin is continued indefinitely for children with coronary artery abnormalities. Children with giant coronary aneurysms may require additional anticoagulant therapy (eg, warfarin , dipyridamole ).
Children who receive IGIV therapy may have a lower response rate to live viral vaccines. Thus, measles-mumps-rubella vaccine should generally be delayed for 11 mo after IGIV administration, and varicella vaccine should be delayed for ≥ 11 mo. If the risk of measles exposure is high, vaccination should proceed, but revaccination (or serologic testing) should be performed 11 mo later.
A small risk of Reye's syndrome exists in children receiving long-term aspirin during outbreaks of influenza or varicella; thus, annual influenza vaccination is indicated for children (≥ 6 mo of age) receiving long-term aspirin therapy. Further, parents of children receiving aspirin should be instructed to contact their child's physician promptly if the child is exposed to or develops symptoms of influenza or varicella. Temporary interruption of aspirin may be considered (with substitution of dipyridamole for children with documented aneurysms).
Last full review/revision November 2005
Content last modified November 2005
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