Kawasaki disease is an acute vasculitis of childhood that leads to coronary artery aneurysms in ≈25% of untreated cases. It has been reported worldwide and is the leading cause of acquired heart disease in children in developed countries.a multidisciplinary writing group of experts was convened to review and appraise available evidence and practice-based opinion, as well as to provide updated recommendations for diagnosis, treatment of the acute illness, and long-term management by AHA.
These recommendations provide updated and best evidence-based guidance to healthcare providers who diagnose and manage Kawasaki disease, but clinical decision making should be individualized to specific patient circumstances.
Key Points: Epidemiology
- The cause is unknown.
- The estimated incidence in North America is ≈25 cases per 100 000 children <5 years of age per year.
- The highest relative risk is in Asian children, especially of Japanese ancestry.
- The ratio of males to females is ≈1.5:1.
- KD affects predominantly, but not exclusively, young children.
- It is most common in winter and early spring in North America.
- Predisposing factors have been reported inconsistently.
- Nonspecific symptoms are common in the 10 days before diagnosis.
- In Japan, the recurrence rate is ≈3%, and the relative risk in siblings is 10-fold higher.
- The case fatality rate is <0.1% in Japan.
- Coronary artery aneurysms from KD account for 5% of acute coronary syndromes (ACS) in adults <40 years of age.
Key Points: Pathology
- KD vasculopathy primarily involves muscular arteries and is characterized by 3 linked processes: (1) necrotizing arteritis; (2) subacute/chronic vasculitis; and (3) LMP.
- Large or giant coronary artery aneurysms ≥8 mm in diameter or with a Z score ≥10 do not “resolve,” “regress,” or “remodel.” They rarely rupture and virtually always contain thrombi (the oldest of which may calcify) that can become occlusive.
- Aneurysms with markedly damaged but partially preserved media may develop decreases in lumen diameter over time as the result of LMP or thrombi and can become progressively stenotic.
- Atherosclerotic features are not characteristic of KD vasculopathy even in late deaths or transplants.
- Pericarditis and myocarditis result from subacute/chronic inflammation, which is usually concentrated around coronary arteries.
Key Points: Consider KD in the Differential Diagnosis of Certain Infants or Children
- Infants <6 months old with prolonged fever and irritability
- Infants with prolonged fever and unexplained aseptic meningitis
- Infants or children with prolonged fever and unexplained or culture-negative shock
- Infants or children with prolonged fever and cervical lymphadenitis unresponsive to antibiotic therapy
- Infants or children with prolonged fever and retropharyngeal or parapharyngeal phlegmon unresponsive to antibiotic therapy.
Recommendations for Cardiovascular Assessment for Diagnosis and Monitoring During the Acute Illness
- Echocardiography should be performed when the diagnosis of KD is considered, but unavailability or technical limitations should not delay treatment (Class I; Level of Evidence B).
- Coronary arteries should be imaged, and quantitative assessment of luminal dimensions, normalized as Z scores adjusted for body surface, should be performed (Class I; Level of Evidence B).
- For uncomplicated patients, echocardiography should be repeated both within 1 to 2 weeks and 4 to 6 weeks after treatment (Class I; Level of Evidence B).
- For patients with important and evolving coronary artery abnormalities (Z score >2.5) detected during the acute illness, more frequent echocardiography (at least twice per week) should be performed until luminal dimensions have stopped progressing to determine the risk for and presence of thrombosis (Class I; Level of Evidence B).
- To detect coronary artery thrombosis, it may be reasonable to perform echocardiography for patients with expanding large or giant aneurysms twice per week while dimensions are expanding rapidly and at least once weekly in the first 45 days of illness, and then monthly until the third month after illness onset, because the failure to escalate thromboprophylaxis in time with the rapid expansion of aneurysms is a primary cause of morbidity and mortality (Class IIa; Level of Evidence C).
Recommendations for Initial Treatment With IVIG and ASA
- Patients with complete KD criteria and those who meet the algorithm criteria for incomplete KD should be treated with high-dose IVIG (2 g/kg given as a single intravenous infusion) within 10 days of illness onset but as soon as possible after diagnosis (Class I; Level of Evidence A).
- It is reasonable to administer IVIG to children presenting after the 10th day of illness (ie, in whom the diagnosis was missed earlier) if they have either persistent fever without other explanation or coronary artery abnormalities together with ongoing systemic inflammation, as manifested by elevation of ESR or CRP (CRP >3.0 mg/dL) (Class IIa; Level of Evidence B).
- Administration of moderate- (30–50 mg·kg−1·d−1) to high-dose (80–100 mg·kg−1·d−1) ASA is reasonable until the patient is afebrile, although there is no evidence that it reduces coronary artery aneurysms (Class IIa; Level of Evidence C).
- IVIG generally should not be administered to patients beyond the tenth day of illness in the absence of fever, significant elevation of inflammatory markers, or coronary artery abnormalities (Class III; Level of Evidence C).
- The ESR is accelerated by IVIG therapy and therefore should not be used to assess response to IVIG therapy. A persistently high ESR alone should not be interpreted as a sign of IVIG resistance (Class III; Level of Evidence C).
Recommendations for Adjunctive Therapies for Primary Treatment
- Single-dose pulse methylprednisolone should not be administered with IVIG as routine primary therapy for patients with KD (Class III; Level of Evidence B).
- Administration of a longer course of corticosteroids (eg, tapering over 2–3 weeks), together with IVIG 2 g/kg and ASA, may be considered for treatment of high-risk patients with acute KD, when such high risk can be identified in patients before initiation of treatment (Class IIb; Level of Evidence B).
Recommendations for Additional Therapy in the IVIG-Resistant Patient
- It is reasonable to administer a second dose of IVIG (2 g/kg) to patients with persistent or recrudescent fever at least 36 hours after the end of the first IVIG infusion (Class IIa; Level of Evidence B).
- Administration of high-dose pulse steroids (usually methylprednisolone 20–30 mg/kg intravenously for 3 days, with or without a subsequent course and taper of oral prednisone) may be considered as an alternative to a second infusion of IVIG or for retreatment of patients with KD who have had recurrent or recrudescent fever after additional IVIG (Class IIb; Level of Evidence B).
- Administration of a longer (eg, 2–3 weeks) tapering course of prednisolone or prednisone, together with IVIG 2 g/kg and ASA, may be considered in the retreatment of patients with KD who have had recurrent or recrudescent fever after initial IVIG treatment (Class IIb; Level of Evidence B).
- Administration of infliximab (5 mg/kg) may be considered as an alternative to a second infusion of IVIG or corticosteroids for IVIG-resistant patients (Class IIb, Evidence Level C).
- Administration of cyclosporine may be considered in patients with refractory KD in whom a second IVIG infusion, infliximab, or a course of steroids has failed (Class IIb; Level of Evidence C).
- Administration of immunomodulatory monoclonal antibody therapy (except TNF-α blockers), cytotoxic agents, or (rarely) plasma exchange may be considered in highly refractory patients who have failed to respond to a second infusion of IVIG, an extended course of steroids, or infliximab (Class IIb; Level of Evidence C).
Recommendations for Prevention of Thrombosis During the Acute Illness
- Low-dose ASA (3–5 mg·kg−1·d−1) should be administered to patients without evidence of coronary artery changes until 4 to 6 weeks after onset of illness (Class I; Level of Evidence C).
- For patients with rapidly expanding coronary artery aneurysms or a maximum Zscore of ≥10, systemic anticoagulation with LMWH or warfarin (international normalized ratio target 2.0–3.0) in addition to low-dose ASA is reasonable (Class IIa; Level of Evidence B).
- For patients at increased risk of thrombosis, for example, with large or giant aneurysms (≥8 mm or Z score ≥10) and a recent history of coronary artery thrombosis, “triple therapy” with ASA, a second antiplatelet agent, and anticoagulation with warfarin or LMWH may be considered (Class IIb; Level of Evidence C).
- Ibuprofen and other nonsteroidal anti-inflammatory drugs with known or potential involvement of cyclooxygenase pathway may be harmful in patients taking ASA for its antiplatelet effects (Class III; Level of Evidence B).
Recommendations for Treatment of Coronary Artery Thrombosis
- Coronary artery thrombosis with actual or impending occlusion of the arterial lumen should be treated with thrombolytic therapy or, in patients of sufficient size, by mechanical restoration of coronary artery blood flow at cardiac catheterization (Class I; Level of Evidence C).
- Thrombolytic agents should be administered together with low-dose ASA and low-dose heparin, with careful monitoring for bleeding (Class I; Level of Evidence C).
- Treatment of coronary artery thrombosis with substantial thrombus burden and high risk of occlusion with a combination of reduced-dose thrombolytic therapy and abciximab may be considered (Class IIb; Level of Evidence C).
Recommendations for Risk Stratification of Coronary Artery Abnormalities
- It is reasonable to use echocardiographic coronary artery luminal dimensions converted to BSA-adjusted Z scores to determine risk stratification (Class IIa; Level of Evidence B).
- It is reasonable to incorporate both maximal and current coronary artery involvement in risk stratification (Class IIa; Level of Evidence C).
- It is reasonable to incorporate the presence of additional features other than coronary artery luminal dimensions into decisions regarding risk stratification (Class IIa; Level of Evidence C).
For full Guidelines click on the link: https://doi.org/10.1161/CIR.0000000000000484
Dr. Kamal Kant Kohli
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