What is the management of Kawasaki disease?

Management of Kawasaki Disease

Administer IVIG 2 g/kg as a single infusion combined with high-dose aspirin (80-100 mg/kg/day divided into four doses) as early as possible within the first 10 days of fever onset, ideally within days 5-10 of illness. 1, 2

Initial Treatment Protocol

The cornerstone of acute Kawasaki disease management is IVIG plus aspirin, which reduces coronary artery aneurysm risk from 25% to less than 5%. 3, 4

IVIG Administration

• Dose: 2 g/kg as a single infusion over 10-12 hours 3, 1, 5
• Timing: Administer within the first 10 days of illness, ideally days 5-10 3, 1
• Treatment before day 5 may increase need for IVIG retreatment without additional benefit 3
• For patients presenting after day 10 with persistent fever or aneurysms with ongoing inflammation (elevated ESR/CRP), still administer IVIG 3

Aspirin Regimen

• High-dose phase: 80-100 mg/kg/day divided into four doses until afebrile for 48-72 hours 1, 2, 6
• Low-dose phase: Reduce to 3-5 mg/kg/day as single daily dose after defervescence 3, 1, 2
• Continue low-dose aspirin for 6-8 weeks if no coronary abnormalities develop 1, 2
• Evidence note: High-dose aspirin is associated with 3-times lower odds of IVIG resistance compared to starting with low-dose aspirin 6

Management of IVIG-Resistant Disease

Approximately 10-20% of patients develop persistent or recrudescent fever ≥36 hours after completing initial IVIG infusion. 3, 1, 4

First-Line for IVIG Resistance

• Administer second dose of IVIG 2 g/kg as single infusion 3, 1, 2

Second-Line Options (after two IVIG doses)

Choose one of the following based on availability and institutional experience:

• Methylprednisolone: 20-30 mg/kg IV for 3 days 1, 2
• Infliximab: 5 mg/kg IV over 2 hours (TNF-α inhibitor) 3, 1, 2
• Both show similar efficacy for IVIG-resistant cases 1

Third-Line Options (highly refractory cases)

• Cyclosporine: 4-6 mg/kg/day orally (monitor for hyperkalemia, which occurs in 32% of patients) 1
• Plasma exchange: Reserved for patients failing all medical therapies due to significant risks 3, 1
• Cytotoxic agents (cyclophosphamide) may be considered in exceptional cases, though risks exceed benefits for most patients 3

Long-Term Antiplatelet/Anticoagulation Management

Management is stratified by coronary artery involvement:

No Coronary Abnormalities

• Low-dose aspirin (3-5 mg/kg/day) until 6-8 weeks after disease onset 1, 2

Small Coronary Aneurysms

• Low-dose aspirin indefinitely 1

Moderate Aneurysms (4-6 mm)

• Low-dose aspirin PLUS second antiplatelet agent (clopidogrel 1 mg/kg/day, max 75 mg/day) 1

Giant Aneurysms (≥8 mm)

• Low-dose aspirin PLUS warfarin (target INR 2.0-2.5) 3, 1, 2
• Alternative: Aspirin plus therapeutic low-molecular-weight heparin for infants or when warfarin is difficult to regulate 3, 1
• Consider abciximab (platelet glycoprotein IIb/IIIa inhibitor) in acute/subacute phase with large aneurysms to promote vascular remodeling 3

Rationale: Giant aneurysms create stenosis at inlet/outlet with turbulent low-velocity flow, providing powerful stimulus for thrombosis through platelet activation and endothelial injury 3

Monitoring and Follow-Up

• Frequent echocardiography and ECG during first 3 months after diagnosis, especially for giant aneurysms 1, 2
• Highest thrombosis risk occurs within first 3 months, peaking at days 15-45 1, 2
• Regular physical activity should be encouraged within parameters defined by ischemia/arrhythmia risk 1

Critical Caveats and Pitfalls

Vaccination Considerations

• Defer measles and varicella immunizations for 11 months after high-dose IVIG 3, 1, 2
• If high measles exposure risk, vaccinate earlier and reimmunize at 11 months if inadequate serological response 3
• Annual influenza vaccination is mandatory for children on long-term aspirin therapy 1, 2

Drug Interactions

• Avoid ibuprofen in children taking aspirin for antiplatelet effects—it antagonizes irreversible platelet inhibition 1

Incomplete Kawasaki Disease

• More common in children <1 year, who paradoxically have higher coronary aneurysm rates if untreated 1
• Treat if fever plus 2-3 classic symptoms with elevated CRP/ESR or coronary abnormalities on echocardiography 1, 2

Treatment Timing

• Delaying treatment beyond 10 days increases coronary artery abnormality risk 1
• However, late presenters with persistent fever or aneurysms with ongoing inflammation should still receive IVIG 3

IVIG Product Considerations

• Important manufacturing differences exist between IVIG products, with varying adverse effect profiles 3
• Most studies fail to find significant efficacy differences between brands 3