assessed and the patient should be monitored closely with serial echocardiograms until KD is diagnosed or until the patient is afebrile and well appearing for 48 hours TABLE 101.19 ECHOCARDIOGRAPHIC CRITERIA SUGGESTIVE OF KAWASAKI DISEASE Echocardiogram considered positive if any of the three criteria are met I z score of LAD or RCA of ≥2.5 II Coronary arteries meet Japanese Ministry of Health criteria for aneurysms III If three or more suggestive features are present Lack of tapering Decreased LV function Mitral regurgitation Pericardial effusion z scores in LAD or RCA of 2–2.5 LAD, left anterior descending coronary artery; RCA, right coronary artery; LV, left ventricle Management IVIG If the clinical criteria are fulfilled, or partial clinical criteria are met with supportive supplemental laboratory criteria, then treatment should be initiated Recommended initial therapy includes IVIG and aspirin within the first 10 days of the illness; treatment with IVIG within this time frame significantly shortens disease duration and minimizes the incidence of complications Overall, prompt diagnosis and appropriate therapy prevent aneurysm formation in approximately 95% of children and result in rapid symptomatic improvement in about 90% Studies in Japan were the first to suggest relative protection from coronary artery aneurysms when IVIG is administered early in the course of KD Since then, further trials in the United States and Japan have confirmed this finding and documented the safety of high-dose infusions of immunoglobulin At present, a single large infusion of IVIG (2 g/kg) administered over to 12 hours is the standard of care for KD This is somewhat more effective than multiple smaller infusions, and it also significantly shortens the duration of hospitalization Therapy with IVIG also has other benefits Treatment results in a reduced prevalence of giant aneurysms, the most serious form of coronary abnormality caused by the disease It also accelerates normalization of abnormalities of left ventricular systolic function and contractility Finally, high-dose IVIG reduces fever and laboratory indices of inflammation, suggesting a rapid, generalized anti-inflammatory effect in addition to specific cardioprotective effects Despite its advantages, IVIG is an expensive and potentially toxic intervention The greatest long-term concern is the possible transmission of blood-borne pathogens Elaborate sterilization procedures, including lyophilization, pasteurization, and addition of solvent detergents, are generally effective in rendering the product free of infectious agents There have been no cases of infections transmitted by IVIG since current purification practices were initiated in 1995 Overall, significant toxicity is rare, and benefits clearly outweigh risks in children with confirmed KD Aspirin Aspirin was the first medication to be used for treatment of KD, both for its antiinflammatory and its antithrombotic effects High-dose (>80 mg/kg/day) and low-dose regimens (30 mg/kg/day) in four divided doses are still used in conjunction with IVIG during the acute phase of the illness despite the fact that meta-analyses demonstrate no additive protection from coronary artery aneurysms from aspirin Once fever has resolved for 48 hours, patients are generally switched to antiplatelet doses of aspirin (3 to mg/kg/day) Unless coronary artery abnormalities are detected by echocardiogram, aspirin is discontinued once laboratory studies return to normal, usually within months of the onset of KD The risks of aspirin appear to be similar to those reported in other settings: transaminitis, chemical hepatitis, transient hearing loss, and, rarely, Reye syndrome These risks may even be increased in KD: Aspirin-binding studies have suggested that the hypoalbuminemia of children with KD predisposes them to toxic levels of free salicylate despite measured (bound) levels within the therapeutic range At least one case of Reye syndrome has been reported after days of aspirin therapy for KD Alternative antipyretic and anti-inflammatory agents, such as ibuprofen, may be used for treatment of arthralgias, and aspirin should be rapidly discontinued whenever intercurrent illness with varicella or influenza is possible Influenza vaccine should be given to the patient and household contacts at the time of diagnosis according to seasonal recommendations For those patients who are unable to tolerate aspirin, other antiplatelet agents (e.g., clopidogrel) should be considered Adjunctive Therapy With Corticosteroids New evidence has emerged supporting the use of glucocorticoids for the primary treatment of KD in patients who carry risk factors that could lead to resistance with IVIG In 2017, the AHA recognized that use of adjunctive therapy with glucocorticoids may be beneficial for patients considered to be at high risk for developing CAA and/or at increased risk of resistance to IVIG Among Japanese children, there are clearly delineated criteria to define those patients as high-risk For non-Japanese children, there are no validated criteria to identify children before treatment Some experts recommend adding glucocorticoids to non-Japanese children with the following criteria: enlarged CAA at presentation (LAD or RCA CA z score of ≥2.5 on baseline echo), age ≤6 months, Kawasaki shock syndrome, and KD presenting with MAS There is no consensus for the ideal course of steroids One regimen used is IV methylprednisolone at mg/kg/day divided BID for the duration of IV access, with a transition to oral prednisolone mg/kg/day divided BID The decision to treat primary KD with adjunctive agents should be decided in consultation with physicians who have expertise in managing patients with KD The use of corticosteroids in refractory KD is discussed below Adjunctive Therapy With Tumor Necrosis Factor Inhibition Modulation of proinflammatory cytokines, such as TNF-α, has impacted the treatment of rheumatologic conditions including vasculitis Elevated levels of TNF-α are increased in the acute phase of KD Some recent studies suggest that use of biologic response modifiers or biologics for adjunctive therapy of primary KD may show promise A 2019 retrospective study showed a benefit among a high-risk group of patients with KD with CAA (z score ≥2.5, but