Residency · Residency · Pediatrics
Acquired Heart Disease: Kawasaki Disease and Myocarditis
Kawasaki Disease
Overview
Kawasaki disease is an acute febrile vasculitis of medium-sized arteries that predominantly affects the coronary arteries. It is the leading cause of acquired heart disease in children in developed countries. Peak incidence occurs between 6 months and 5 years of age (encompassing 80% of cases), and the disease is rare before 3 months or after 10 years. The incidence is higher in children of Asian descent (300 per 100,000 under age 5 in Japan compared to 25 per 100,000 in the United States). The etiology remains unknown but likely involves an infectious trigger in a genetically susceptible host. While the illness is self-limited, 25% of untreated children develop coronary artery aneurysms.
Diagnostic Criteria (Complete Kawasaki Disease)
The diagnosis of complete Kawasaki disease requires fever of 5 or more days plus at least 4 of 5 principal clinical features: bilateral bulbar conjunctival injection (non-exudative, with limbic sparing); oral mucous membrane changes (strawberry tongue, erythematous or cracked lips, oropharyngeal erythema); polymorphous rash (maculopapular, morbilliform, or erythema multiforme-like, but never vesicular); extremity changes (acute erythema and edema of hands and feet, with convalescent periungual desquamation after day 10-14); and cervical lymphadenopathy (at least 1.5 cm, usually unilateral).
Incomplete Kawasaki Disease
Incomplete Kawasaki disease presents with fever of 5 or more days but only 2-3 clinical criteria, supported by laboratory or echocardiographic findings. It is more common in infants under 6 months and older children over 5 years, precisely the populations at highest risk for coronary complications. The AHA algorithm uses supplementary laboratory criteria: CRP of 3 mg/dL or greater or ESR of 40 mm/hr or greater, plus at least 3 of the following: albumin 3 g/dL or less, anemia for age, elevated ALT, platelets greater than 450,000 after day 7, WBC of 15,000 or greater, or sterile pyuria. Echocardiographic findings supporting diagnosis include coronary artery Z-score of 2.5 or greater, decreased LV function, mitral regurgitation, pericardial effusion, or coronary artery brightness with perivascular echogenicity. A low threshold for diagnosis should be maintained in infants with prolonged unexplained fever.
Laboratory Findings
During the acute phase, CRP, ESR, and WBC (with neutrophilia) are elevated, along with liver transaminases, while albumin is low. The subacute phase (weeks 2-3) characteristically shows thrombocytosis with platelets reaching 500,000-1,000,000 or higher. Sterile pyuria reflects urethritis rather than UTI. Normocytic anemia is common. BNP/NT-proBNP may be elevated from myocardial inflammation.
<image>Visual summary of the five principal clinical features of Kawasaki disease showing bilateral non-exudative conjunctival injection, strawberry tongue with cracked erythematous lips, polymorphous trunk rash, erythema and edema of the hands and feet, and unilateral cervical lymphadenopathy, alongside the AHA algorithm for incomplete KD</image>
Treatment
First-Line: IVIG + Aspirin
IVIG is given at 2 g/kg as a single infusion over 10-12 hours, ideally within the first 10 days of illness (by day 7 when possible). This reduces the coronary aneurysm risk from 25% to 3-5%. IVIG can still be given after day 10 if fever persists or aneurysms are present. High-dose aspirin (80-100 mg/kg/day divided four times daily, though 30-50 mg/kg/day is used in Japan with similar outcomes) is given during the acute phase. Once the patient has been afebrile for 48-72 hours, aspirin is switched to low-dose (3-5 mg/kg/day) and continued for a minimum of 6-8 weeks until follow-up echocardiography confirms normal coronaries. If coronary artery aneurysms are present, low-dose aspirin continues indefinitely.
IVIG-Resistant KD
Approximately 10-20% of patients have persistent or recurrent fever more than 36 hours after IVIG completion. Management includes a second dose of IVIG (2 g/kg), corticosteroids (IV methylprednisolone 2 mg/kg/day or pulse methylprednisolone 30 mg/kg as a single dose), infliximab (anti-TNF-alpha at 5 mg/kg IV, increasingly used), or cyclosporine for refractory cases with persistent inflammation.
Adjunctive Corticosteroids (Primary Treatment)
The use of corticosteroids as an initial adjunct to IVIG in high-risk patients remains controversial. Risk scores such as the Kobayashi score identify patients at highest risk of IVIG resistance and coronary aneurysm development. Several meta-analyses suggest adjunctive corticosteroids reduce coronary aneurysm incidence and IVIG resistance in high-risk patients. The current AHA position is to consider adjunctive steroids for high-risk patients while not recommending universal use.
Coronary Artery Aneurysm Classification (Z-Score Based)
| Classification | Z-Score | Absolute Diameter | Antithrombotic Therapy |
|---|---|---|---|
| Normal | <2 | Normal | Low-dose ASA x 6-8 weeks |
| Dilation | 2 to <2.5 | — | Low-dose ASA |
| Small aneurysm | 2.5 to <5 | — | Low-dose ASA (often regresses) |
| Medium aneurysm | 5 to <10 | 4-8 mm | ASA ± anticoagulation |
| Giant aneurysm | ≥10 | ≥8 mm | ASA + warfarin + clopidogrel |
Coronary artery involvement is classified by Z-score: normal (less than 2), dilation (2 to less than 2.5), small aneurysm (2.5 to less than 5), medium aneurysm (5 to less than 10, or absolute diameter 4-8 mm), and giant aneurysm (Z-score 10 or greater, or diameter 8 mm or greater). Giant aneurysms carry the highest risk of thrombosis, stenosis, and myocardial infarction.
Long-Term Management of CAA
Small aneurysms are managed with low-dose aspirin and often regress within 1-2 years. Medium aneurysms require aspirin with consideration of anticoagulation (warfarin or LMWH). Giant aneurysms require aspirin plus warfarin (INR 2-3) plus clopidogrel, with lifelong cardiology follow-up, stress testing, CT angiography, and cardiac catheterization. Activity restrictions are based on aneurysm size and evidence of ischemia. All patients with coronary aneurysms should receive annual influenza vaccination to avoid aspirin-associated Reye syndrome.
Follow-Up Echocardiography
Echocardiography is obtained at diagnosis, at 2 weeks, and at 6-8 weeks. If coronary abnormalities are identified, more frequent imaging follows AHA guidelines. Late aneurysms can develop, and some appear after initially normal echocardiography.
Pediatric Myocarditis
Overview
Myocarditis is inflammation of the myocardium, most commonly from viral infection, with an estimated incidence of 1-2 per 100,000 children per year (likely underestimated). It is a leading cause of sudden unexpected death in young individuals (up to 12% of cases). Presentation ranges from subclinical disease to fulminant heart failure and cardiogenic shock.
Etiology
Viral causes predominate, including enteroviruses (historically Coxsackie B), adenovirus, parvovirus B19, SARS-CoV-2, influenza, EBV, CMV, and HHV-6. Autoimmune and inflammatory causes include systemic lupus, sarcoidosis, and giant cell myocarditis. Toxic causes include anthracyclines, carbon monoxide, and cocaine. Vaccine-associated myocarditis (rare and typically self-limited) occurs predominantly in adolescent males after mRNA COVID-19 vaccination.
Clinical Presentation
A viral prodrome (fever, URI symptoms, GI symptoms) typically precedes cardiac symptoms by days to weeks. Infants present with poor feeding, tachycardia, tachypnea, irritability, and shock, often mimicking sepsis. Older children and adolescents present with chest pain, dyspnea, exercise intolerance, palpitations, and syncope. Fulminant myocarditis causes rapid onset of cardiogenic shock, arrhythmias, and cardiovascular collapse. Paradoxically, fulminant myocarditis may carry a better prognosis than subacute presentation if the patient survives the acute phase, with higher recovery rates.
Diagnostic Workup
Troponin is elevated, often markedly during the acute phase. BNP/NT-proBNP is elevated. ECG may show sinus tachycardia, low voltage QRS, ST-T wave changes, or arrhythmias (VT, heart block). Chest X-ray reveals cardiomegaly and pulmonary edema. Echocardiography demonstrates global or regional LV dysfunction, pericardial effusion, and chamber dilation, though function may initially appear preserved in early presentations.
Cardiac MRI is the gold standard for non-invasive diagnosis, using the Lake Louise criteria: myocardial edema (T2-weighted), hyperemia/capillary leak (early gadolinium enhancement), and necrosis/fibrosis (late gadolinium enhancement), with sensitivity and specificity exceeding 80% in acute myocarditis. Endomyocardial biopsy using Dallas criteria (inflammatory infiltrate with myocyte necrosis) has limited sensitivity due to sampling error and is reserved for unclear diagnosis or rapidly deteriorating patients. Viral PCR from nasopharyngeal swab, stool, and blood may identify the causative agent.
Management
Hemodynamic support is the primary focus. IV milrinone is used for acute decompensation. Beta-blockers should be avoided in the acute phase if the patient is hemodynamically unstable. ECMO for fulminant myocarditis with refractory shock produces excellent outcomes in children (60-80% survival). VAD is deployed if prolonged support is needed. Arrhythmias are managed with antiarrhythmics as needed, and temporary pacing is used for complete heart block.
Immunosuppression is generally not recommended for viral myocarditis. IVIG (1-2 g/kg) is commonly given empirically though evidence is weak. Corticosteroids are reserved for autoimmune or giant cell myocarditis. Activity restriction prohibits competitive sports for a minimum of 3-6 months after recovery, with cardiac MRI-guided return to play. Heart failure medications (ACE inhibitor plus beta-blocker) are initiated once the patient is hemodynamically stable and continued for at least 1 year even if function normalizes.
<image>Cardiac MRI findings in acute myocarditis demonstrating the Lake Louise criteria with T2-weighted images showing myocardial edema, early gadolinium enhancement showing hyperemia, and late gadolinium enhancement showing patchy mid-wall and epicardial enhancement in a pattern typical of viral myocarditis</image>
Prognosis
Overall, 60-70% of patients achieve full recovery of LV function. Fulminant myocarditis, if the patient survives the acute phase, has a recovery rate exceeding 90%. Subacute or chronic myocarditis may progress to dilated cardiomyopathy requiring transplant in 20-30%. Late arrhythmias and sudden death can occur even after apparent recovery, making long-term follow-up essential.
Post-COVID Myocarditis and Return-to-Play
mRNA vaccine-associated myocarditis occurs predominantly in adolescent males aged 12-17, typically after the second dose, with an incidence of approximately 1 in 6,000-18,000 adolescent males. It is typically self-limited with complete recovery. Presentation includes chest pain and troponin elevation, with cardiac MRI often showing mild changes. Management is supportive with NSAIDs, and almost all patients recover within 1-2 weeks. Return to play is individualized with a minimum 3-month restriction from competitive sports, requiring normalization of ECG, echocardiography, cardiac MRI, and exercise stress testing.
Clinical Pearls
Kawasaki disease should be considered in any child with prolonged unexplained fever of 5 or more days; incomplete KD is common and dangerous. Infants under 6 months are at highest risk for both missed diagnosis and coronary complications, warranting a low threshold for evaluation. The thrombocytosis in KD is a subacute finding appearing in weeks 2-3; its absence during the first week does not rule out the diagnosis. In myocarditis, "stable tachycardia" in a febrile child may mask severe ventricular dysfunction, and echocardiography should always be obtained if the resting heart rate is disproportionately elevated. ECMO can be life-saving in fulminant myocarditis and consultation should not be delayed. All children with giant coronary aneurysms from KD require lifelong anticoagulation and cardiology follow-up.
Key Controversy: Adjunctive Corticosteroids in Kawasaki Disease
Meta-analyses suggest benefit (reduced coronary aneurysms, reduced IVIG resistance) in high-risk patients. The RAISE study from Japan demonstrated that pulsed methylprednisolone reduced coronary aneurysms in high-risk patients identified by the Kobayashi score. However, risk scores are population-specific and perform variably across ethnicities. The AHA 2017 statement considers adjunctive corticosteroids "reasonable to consider" in patients judged to be at high risk, but not routine for all KD patients. The experience with MIS-C treatment, where corticosteroids appeared beneficial, has further blurred this controversy.
References
- McCrindle BW, et al. Diagnosis, Treatment, and Long-Term Management of Kawasaki Disease (AHA Scientific Statement). Circulation. 2017;135(17):e927-e999.
- Newburger JW, et al. Diagnosis and Management of Kawasaki Disease. JAMA. 2021;325(4):424.
- Law YM, et al. Diagnosis and Management of Myocarditis in Children (AHA Scientific Statement). Circulation. 2021;144(6):e123-e135.
- Kobayashi T, et al. Efficacy of Immunoglobulin Plus Prednisolone for Prevention of CAA in Kawasaki Disease (RAISE Study). Lancet. 2012;379:1613-1620.
- Caforio ALP, et al. Current State of Knowledge on Aetiology, Diagnosis, Management, and Therapy of Myocarditis. Eur Heart J. 2013;34(33):2636-2648.
- Oster ME, et al. Myocarditis Cases Reported After mRNA-Based COVID-19 Vaccination. JAMA. 2022;327(4):331-340.
