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Kawasaki Syndrome
Michael A. Davis, MD
Kawasaki syndrome (KS) is an acute, febrile, self-limited, infectious, multisystem vasculitis, which occurs in young children. Fever is often prolonged and coronary aneurysms may lead to myocardial infarction and death.
Epidemiology
KS has a peak incidence between 1 and 2 years of age. The disease is rare in children older than 8 years old, and it is uncommon before 3 months of age.
Boys are affected more often than girls by a ratio of 1.5 to 1. Japanese and Korean children are at greatest risk (145 per 100,000).
The rate for European children is 9 per 100,000, and the rate for African children is 20 per 100,000.
Pathophysiology
KS is a multisystem vasculitis with a predilection for the coronary arteries. KS is probably caused by an infectious agent, based on the acute febrile exanthematous character of the disorder and the occurrence of epidemics.
During the first 10 days of illness, an inflammatory infiltrate appears in the coronary arteries, with pancarditis and pericarditis. Death during this phase is usually caused by an arrhythmia, although fatal heart failure may sometimes occur.
Ten to 40 days from the onset of fever, the most common cause of death in untreated children is myocardial infarction caused by coronary aneurysms.
After 40 days, healing and stenosis of the post-aneurysmal coronary artery develops.
Clinical Manifestations
Abrupt onset of high but remittent fever between 38 and 41 degrees C is characteristic of KS.
Within 2 to 5 days, the child develops other diagnostic signs of KS: Conjunctival injection, mouth changes, an erythematous rash, changes in the hands and feet, and unilateral cervical lymphadenopathy.
Eye involvement consists of conjunctival injection and, often, photophobia.
The lips are initially bright red, progressing over 3 days to swelling, cracking, and bleeding. Prominent papillae on the tongue create a strawberry appearance, and the oral cavity and pharynx is diffusely erythematous.
The skin rash is deeply erythematous with slightly raised margins, varying in size from 2 to 3 mm papules to large plaques covering several centimeters. The rash often is urticarial and may be intensely pruritic. The rash frequently affects the face, often forming a mask-like area around the eyes, nose, and mouth. It may be distributed more prominently on the trunk or on the extremities.
Firm, indurative edema of the hands and feet and diffuse red-purple discoloration of palms and soles develop. The edema is sharply demarcated at the wrists and around the sides of the hands and feet.
Ten to 20 days after the onset of fever, in early convalescence, desquamation starts just under the fingernails and toenails and proceeds to involve the entire palm and sole.
Cervical lymph node involvement occurs in 50% of patients, manifesting as sudden onset of a firm swelling on one side of the neck.
Kawasaki Disease: Diagnostic Criteria |
I. Fever for >5 days (usually >102EF) II. At least four of five features A. Bilateral conjunctival injection (bulbar. non-purulent) B. Cervical adenitis (unilateral >1.5 cm diameter, non-fluctuant) C. Rash (truncal. perineal accentuation, polymorphous but non-vesicular) D. Inflamed oral mucosae (fissured lips, strawberry tongue) E. Hands and feet inflammation (periungual peeling around 14-21 days) III. No alternate diagnosis IV. Fever plus 3/5 criteria are diagnostic when coronary abnormalities are present |
Associated Features
Extreme irritability and emotional lability is common.
Mild cerebrospinal fluid pleocytosis occurs in 25%. The CSF cell count is between 50 and 150/mm3 and is mononuclear. Protein levels are normal to slightly elevated, and glucose level is normal.
Urethritis is present in 60% and is characterized by sterile pyuria. Red blood cells may be detected.
Severe abdominal pain occurs in 20% in the first few days, and it may be associated with elevated amylase and lipase levels.
Liver involvement occurs in 40%; 10% have a bilirubin level >2 mg/dL. The direct fraction is elevated.
Cardiac Manifestations
Sixty percent have tachycardia with gallop rhythm, and 20% have congestive heart failure. Thirty percent have a pericardial effusion, and 30% have tricuspid insufficiency.
Prolongation of the PR interval and first-degree heart block are very common, but more significant arrhythmias are rare. Eighteen to 25% of patients will develop coronary artery aneurysms.
Differential Diagnosis
The differential diagnosis of KS includes staphylococcal toxic shock syndrome, scarlatiniform erythroderma, streptococcal scarlet fever, staphylococcal scalded skin syndrome, measles, febrile viral exanthems, hypersensitivity reactions (Stevens-Johnson syndrome), and juvenile rheumatoid arthritis. Bacterial cultures should be drawn in order to exclude bacterial infection.
KS should be considered in all young children who have a fever of unknown origin or fever and severe lymphadenopathy, rash, conjunctival injection, hand and feet changes, and mouth changes.
Laboratory Findings
Erythrocyte sedimentation rate, C-reactive protein, and alpha-1-antitrypsin are elevated. White blood cell (WBC) count is elevated, with a polymorphonuclear cell predominance.
Platelet counts are elevated, peaking at 650,000-2,000,000/mm3 between days 10-20.
Mild-to-moderate anemia usually is present. Bilirubin is elevated in 10%, and liver enzymes are moderately elevated in the first week in 40%. Hypoalbuminemia is common. Urinalysis shows pyuria in 60%.
Treatment of Kawasaki Syndrome
Intravenous Gamma Globulin. As soon as KS is diagnosed, a baseline echocardiogram is obtained and IVIG 2 g/kg is given in an 8- to 12-hour infusion. Heart rate and blood pressure should be monitored periodically during the infusion.
Aspirin
High dose aspirin therapy is started on the same day as IVIG. The aspirin dosage is 100 mg/kg/day until a few days after defervescence or until the 14th day of illness. This is followed by a daily dose of 3 to 5 mg/kg (one half to one 81-mg tablet) until the ESR and platelet counts return to normal, usually after 8 weeks.
Serum salicylate levels should be obtained if symptoms of toxicity (vomiting, hyperpnea, lethargy) or liver function abnormalities develop. To decrease the risk of Reye syndrome, aspirin therapy should be interrupted if varicella or influenza develop during the follow-up phase.
Cardiac Evaluation and Monitoring
Serial echocardiograms should monitor the coronary arteries, valves, and ventricles.
Electrocardiography is useful in the acute stage to evaluate heart block or myocarditis, QRS amplitude reduction, T wave changes, or QT interval changes.
Patients who are afebrile for 24 hours and who have stable cardiovascular function may be discharged. A repeat echocardiography is completed 3-6 weeks after the onset of fever.
Prognosis
KS usually is self-limited; however, cardiac damage may be serious. Twenty percent of all patients not treated with IVIG develop coronary artery aneurysms, appearing 7 days to 4 weeks after the onset of KS.
The risk of coronary aneurysms is reduced to 3% when IVIG is given. Patients who have coronary artery abnormalities are at risk for myocardial infarction, sudden death, and myocardial ischemia for at least 5 years; however, regression of aneurysms is usual. §