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

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 factorantagonists, 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. Pediatrics 2004;114:1708–1733; AHA Scientific Statements, vasculitis, therapy, aneurysm, diagnosis. ABBREVIATIONS. MI, myocardial infarction; CI, confidence interval; Ig, immunoglobulin; TNF, tumor necrosis actor; 2D, 2-dimensional; 2DE, 2-dimensional echocardiography; IVIG, intravenous immunoglobulin; ESR, erythrocyte sedimentation rate; CRP, C-reactive protein; LV, left ventricular; RCA, right coronary artery; LAD, left anterior descending coronary artery; LMCA, left main coronary artery; LCX, left circumflex coronary artery; IVUS, intravascular ultrasound; MRA, magnetic resonance angiography; CT, computed tomography; MRI, magnetic resonance imaging; IL, interleukin; INR, international normalized ratio; tPA, tissue plasminogen activator; ECG, electrocardiogram. Kawasaki disease is an acute, self-limited vasculitis of unknown etiology that occurs predominantly in infants and young children. First described in Japan in l967 by Tomisaku Kawasaki, the disease is now known to occur in both endemic and community-wide epidemic forms in the Americas, Europe, and Asia in children of all races.1 Kawasaki disease 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 with the disease and may lead to myocardial infarction (MI), sudden death, or ischemic heart disease.2,3 In the United States, Kawasaki disease has surpassed acute rheumatic fever as the leading cause of acquired heart disease in children.4 Treatment of Kawasaki disease in the acute phase is directed at reducing inflammation in the coronary artery wall and preventing coronary thrombosis, whereas long-term therapy in individuals who develop coronary aneurysms is aimed at preventing myocardial ischemia or infarction. A new feature of these recommendations is an This report was approved by the American Heart Association Science Advisory and Coordinating Committee on June 16, 2004. This report was copublished in the October 26, 2004 issue of Circulation. The guidance in this report does not indicate an exclusive course of treatment or serve as a standard of medical care. Variations, taking into account individual circumstances, may be appropriate. doi:10.1542/peds.2004-2182 PEDIATRICS (ISSN 0031 4005). Copyright © 2004 by the American Academy of Pediatrics. 1708 PEDIATRICS Vol. 114 No. 6 December 2004 by guest on January 21, 2015 pediatrics.aappublications.org Downloaded from algorithm for the evaluation and treatment of patients in whom incomplete or atypical Kawasaki disease is suspected (refer to “Criteria for Treatment of Kawasaki Disease” later in this statement and Fig 1). We attempt to summarize the current state of knowledge of the management of patients with Kawasaki disease. The recommendations are evidence based and derived from published data wherever possible. The levels of evidence on which recommendations are based are classified as follows: level A (highest), multiple randomized clinical trials; level B (intermediate), limited number of randomized trials, nonrandomized studies, and observational registries; and level C (lowest), primarily expert consensus. Fig 1. Evaluation of suspected incomplete Kawasaki disease. (1) In the absence of gold standard for diagnosis, this algorithm cannot be evidence based but rather represents the informed opinion of the expert committee. Consultation with an expert should be sought anytime assistance is needed. (2) Infants 6 months old on day 7 of fever without other explanation should undergo laboratory testing and, if evidence of systemic inflammation is found, an echocardiogram, even if the infants have no clinical criteria. (3) Patient characteristics suggesting Kawasaki disease are listed in Table 1. Characteristics suggesting disease other than Kawasaki disease include exudative conjunctivitis, exudative pharyngitis, discrete intraoral lesions, bullous or vesicular rash, or generalized adenopathy. Consider alternative diagnoses (see Table 2). (4) Supplemental laboratory criteria include albumin 3.0 g/dL, anemia for age, elevation of alanine aminotransferase, platelets after 7 days 450 000/mm3, white blood cell count 15 000/mm3, and urine 10 white blood cells/high-power field. (5) Can treat before performing echocardiogram. (6) Echocardiogram is considered positive for purposes of this algorithm if any of 3 conditions are met: z score of LAD or RCA 2.5, coronary arteries meet Japanese Ministry of Health criteria for aneurysms, or 3 other suggestive features exist, including perivascular brightness, lack of tapering, decreased LV function, mitral regurgitation, pericardial effusion, or z scores in LAD or RCA of 2–2.5. (7) If the echocardiogram is positive, treatment should be given to children within 10 days of fever onset and those beyond day 10 with clinical and laboratory signs (CRP, ESR) of ongoing inflammation. (8) Typical peeling begins under nail bed of fingers and then toes. AMERICAN ACADEMY OF PEDIATRICS 1709 by guest on January 21, 2015 pediatrics.aappublications.org Downloaded from Recommendations for 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. Where published data do not define well the best medical practices, our report provides practical interim recommendations. Ultimately, management decisions must be individualized to a patient’s specific circumstances.