Background—Kawasaki disease is an acute self-limited vasculitis of childhood that is characterized by fever, bilateral nonexudative conjunctivitis, erythema of the lips and oral mucosa, changes in the extremities, rash, and cervical lymphadenopathy. Coronary artery aneurysms or ectasia develop in 15% to 25% of untreated children and may lead to ischemic heart disease or sudden death. Methods and Results—A multidisciplinary committee of experts was convened to revise the American Heart Association recommendations for diagnosis, treatment, and long-term management of Kawasaki disease. The writing group proposes a new algorithm to aid clinicians in deciding which children with fever for 5 days and 4 classic criteria should undergo echocardiography, receive intravenous gamma globulin (IVIG) treatment, or both for Kawasaki disease. The writing group reviews the available data regarding the initial treatment for children with acute Kawasaki disease, as well for those who have persistent or recrudescent fever despite initial therapy with IVIG, including IVIG retreatment and treatment with corticosteroids, tumor necrosis factor- antagonists, and abciximab. Long-term management of patients with Kawasaki disease is tailored to the degree of coronary involvement; recommendations regarding antiplatelet and anticoagulant therapy, physical activity, follow-up assessment, and the appropriate diagnostic procedures to evaluate cardiac disease are classified according to risk strata. Conclusions—Recommendations for the initial evaluation, treatment in the acute phase, and long-term management of patients with Kawasaki disease are intended to assist physicians in understanding the range of acceptable approaches for caring for patients with Kawasaki disease. The ultimate decisions for case management must be made by physicians in light of the particular conditions presented by individual patients. (Circulation. 2004;110:2747-2771.)

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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

Background. Kawasaki disease is an acute self-limited vasculitis of childhood that is characterized by fever, bilateral nonexudative conjunctivitis, erythema of the lips and oral mucosa, changes in the extremities, rash, and cervical lymphadenopathy. Coronary artery aneurysms or ectasia develop in ∼15% to 25% of untreated children and may lead to ischemic heart disease or sudden death.
 Methods and Results. A multidisciplinary committee of experts was convened to revise the American Heart Association recommendations for diagnosis, treatment, and long-term management of Kawasaki disease. The writing group proposes a new algorithm to aid clinicians in deciding which children with fever for ≥5 days and ≤4 classic criteria should undergo electrocardiography, receive intravenous gamma globulin (IVIG) treatment, or both for Kawasaki disease. The writing group reviews the available data regarding the initial treatment for children with acute Kawasaki disease, as well for those who have persistent or recrudescent fever despite initial therapy with IVIG, including IVIG retreatment and treatment with corticosteroids, tumor necrosis factor-α antagonists, and abciximab. Long-term management of patients with Kawasaki disease is tailored to the degree of coronary involvement; recommendations regarding antiplatelet and anticoagulant therapy, physical activity, follow-up assessment, and the appropriate diagnostic procedures to evaluate cardiac disease are classified according to risk strata.
 Conclusions. Recommendations for the initial evaluation, treatment in the acute phase, and long-term management of patients with Kawasaki disease are intended to assist physicians in understanding the range of acceptable approaches for caring for patients with Kawasaki disease. The ultimate decisions for case management must be made by physicians in light of the particular conditions presented by individual patients.

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

Background The long-term consequences of the cardiovascular sequelae in Kawasaki disease remain uncertain. Methods and results We identified 594 consecutive children with acute Kawasaki disease between 1973 and 1983, and this cohort was followed up for 10 to 21 years (mean, 13.6 years). In all patients, we evaluated coronary lesions by coronary angiography just after the acute stage. One hundred and forty-six patients (24.6%) were diagnosed as having coronary aneurysms. A second angiogram was performed 1 to 2 years later in all 146 patients who previously had coronary aneurysms, which demonstrated that 72 (49.3%) of these 146 had regression in the coronary aneurysm. A third angiogram was performed for 62 patients, a fourth for 29, and a fifth for 17. By 10 to 21 years after the onset of the illness, stenosis in the coronary aneurysm had developed in 28 patients. Myocardial infarction occurred in 11 patients, 5 of whom died. In the 26 patients with giant coronary aneurysms, stenotic lesions developed in 12, and no regression occurred. The 448 patients with normal findings at the first angiogram subsequently never developed any abnormal cardiac findings. Systemic artery aneurysms developed in 13 patients (2.2%), and valvular heart disease appeared in 7 (1.2%). Conclusions The incidence of coronary aneurysm in acute Kawasaki disease was 25%, 55% of which showed regression. During follow-up, ischemic heart disease developed in 4.7% and myocardial infarction in 1.9%. Death occurred in 0.8%.

Long-term Consequences of Kawasaki Disease A 10- to 21-Year Follow-up Study of 594 Patients

Background. Treatment of acute Kawasaki syndrome with a four-day course of intravenous gamma globulin, together with aspirin, has been demonstrated to be safe and effective in preventing coronary-artery lesions and reducing systemic inflammation. We hypothesized that therapy with a single, very high dose of gamma globulin would be at least as effective as the standard regimen. Methods. We conducted a multicenter, randomized, controlled trial involving 549 children with acute Kawasaki syndrome. The children were assigned to receive gamma globulin either as a single infusion of 2 g per kilogram of body weight over 10 hours or as daily infusions of 400 mg per kilogram for four consecutive days. Both treatment groups received aspirin (100 mg per kilogram per day through the 14th day of illness, then 3 to 5 mg per kilogram per day). Results. The relative prevalence of coronary abnormalities, adjusted for age and sex, among patients treated with the four-day regimen, as compared with those treated with...

https://www.nejm.org/doi/pdf/10.1056/NEJM199106063242305

A Single Intravenous Infusion of Gamma Globulin as Compared with Four Infusions in the Treatment of Acute Kawasaki Syndrome

Background Deep hypothermia with either total circulatory arrest or low-flow cardiopulmonary bypass is used to support vital organs during heart surgery in infants. We compared the developmental and neurologic sequelae of these two strategies one year after surgery. Methods Infants with D-transposition of the great arteries who underwent an arterial-switch operation were randomly assigned to a method of support consisting predominantly of circulatory arrest or a method consisting predominantly of low-flow bypass. Developmental and neurologic evaluations and magnetic resonance imaging (MRI) were performed at one year of age. Results Of the 171 patients enrolled in the study, 155 were evaluated. After adjustment for the presence or absence of a ventricular septal defect, the infants assigned to circulatory arrest, as compared with those assigned to low-flow bypass, had a lower mean score on the Psychomotor Development Index of the Bayley Scales of Infant Development (a 6.5-point deficit, P = 0.01) and a hig...

https://www.nejm.org/doi/pdf/10.1056/NEJM199503023320901

Developmental and Neurologic Status of Children after Heart Surgery with Hypothermic Circulatory Arrest or Low-Flow Cardiopulmonary Bypass

Cortical hyperostosis following long-term administration of prostaglandin E1 in infants with cyanotic congenital heart disease

Accurate evaluation of the extent of coronary artery lesions complicating Kawasaki disease is clinically important in patient management. Based on a total of 188 coronary angiograms and retrospective follow-up observations, the condition of coronary aneurysms was quantitatively graded as: 0 (normal)—no significant enlargement in any portion of the coronary artery; I (mild)—aneurysmal dilatation of the coronary artery evident but localized, with a maximal diameter of less than 4.0 mm; II (moderate)—maximal diameter of coronary aneurysms between 4.0 and 8.0 mm, regardless of body size; III (severe)—giant aneurysms, with the maximal diameter greater than 8.0 mm. Most mild coronary aneurysms regressed to normal within a short time, and the patient's prognosis was good. The course of grade II aneurysms varied, depending on initial angiographic coronary diameter, but all were eventually reduced in coronary size. In contrast, grade III aneurysms usually progressed to become obstructive or stenotic coronary lesions, or the large aneurysm persisted. Follow-up observations revealed that the course of coronary artery disease depended on the size and distribution of aneurysms at initial angiography. This grading of the severity of coronary lesions may provide useful criteria for predicting the prognosis of patients with Kawasaki disease.

Repeated quantitative angiograms in coronary arterial aneurysm in Kawasaki disease.

Subclinical changes in brain morphology following cardiac operations as reflected by computed tomographic scans of the brain

The beneficial effect of immunoglobulin in preventing coronary artery aneurysms in patients with Kawasaki disease is recognized, but immunoglobulin should be selectively given to patients at high risk for coronary lesions. The present study was designed to present a scoring method to evaluate the severity of Kawasaki disease in terms of coronary artery disease based on clinical and early laboratory findings. Seventy-eight patients who were admitted at 4 to 7 days of illness and who had received aspirin alone during the acute febrile period were separated into 2 groups according to significant coronary artery involvement, and possible related factors to the discrimination of the 2 groups were studied using multivariate analysis. Age at onset, C-reactive protein and platelet count contributed significantly to the discrimination, and from these 3 items a simple scoring system was devised to predict patients at high risk for coronary lesions. Retrospective study using this scoring method indicated that significant coronary artery disease was more often seen in patients predicted to be at high risk treated with aspirin, while no patients who received immunoglobulin had coronary lesions of moderate or severe degree. Thus, the present scoring method provides simple but clinically useful criteria for predicting patients at high risk of coronary artery disease, and immunoglobulin therapy for selected patients may reduce the significant coronary artery complications of Kawasaki disease.

Ken Ueda

Papers

Cortical hyperostosis following long-term administration of prostaglandin E1 in infants with cyanotic congenital heart disease

Repeated quantitative angiograms in coronary arterial aneurysm in Kawasaki disease.

Subclinical changes in brain morphology following cardiac operations as reflected by computed tomographic scans of the brain

Scoring method for identifying patients with Kawasaki disease at high risk of coronary artery aneurysms.

Extrathoracically adjustable pulmonary artery banding.