What is the initial management for pediatric patients with Kawasaki disease?

Management of Kawasaki Disease in Pediatric Patients

All children with Kawasaki disease should receive IVIG 2 g/kg as a single infusion over 10-12 hours combined with high-dose aspirin 80-100 mg/kg/day divided into four doses, initiated as early as possible within the first 10 days of fever onset. 1

Initial Treatment Protocol

Core Therapy

• IVIG 2 g/kg as a single infusion is the cornerstone of treatment, with the highest level of evidence (Grade 1A) supporting its use within 10 days of symptom onset 1
• This regimen reduces coronary artery abnormality risk from 15-25% down to approximately 5% for any abnormality and 1% for giant aneurysms 1, 2
• High-dose aspirin 80-100 mg/kg/day should be given in four divided doses during the acute phase 1

Aspirin Dosing Algorithm

• Continue high-dose aspirin until the patient has been afebrile for 48-72 hours 1
• Then transition to low-dose aspirin 3-5 mg/kg/day as a single daily dose 1
• Continue low-dose aspirin until 6-8 weeks after disease onset if no coronary abnormalities are present 1
• For children who develop coronary abnormalities, aspirin may be continued indefinitely 1

Treatment Beyond Day 10

• IVIG should still be administered to children presenting after 10 days if they have ongoing systemic inflammation with either persistent fever or coronary artery aneurysms 1
• Elevated CRP >3.0 mg/dL together with either persistent fever or coronary abnormalities is an indication for IVIG treatment 1

Management of IVIG-Resistant Disease

Definition and Incidence

• IVIG resistance occurs in 10-20% of patients, defined as persistent or recrudescent fever ≥36 hours after completing initial IVIG infusion 1, 3, 4
• This is a critical risk factor for coronary artery abnormalities requiring escalation of therapy 4

Treatment Algorithm for Resistance

First-line for resistance:

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

Second-line options (if fever persists after second IVIG):

• Methylprednisolone 20-30 mg/kg IV for 3 days, OR 1
• Infliximab 5 mg/kg IV over 2 hours as a single infusion 1
• Both options show similar efficacy in IVIG-resistant cases 1

Third-line therapy (highly refractory cases):

• Cyclosporine 4-6 mg/kg/day orally can be used, though monitor for hyperkalemia which occurred in 32% of patients in trials 1
• Plasma exchange is reserved for patients failing all medical therapies due to significant risks 1

Long-Term Antiplatelet and Anticoagulation Management

Risk-Stratified Approach Based on Coronary Artery Status

No coronary abnormalities:

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

Small coronary aneurysms:

• Low-dose aspirin 3-5 mg/kg/day indefinitely 1

Moderate aneurysms (4-6 mm or Z-score 5-10):

• Low-dose aspirin 3-5 mg/kg/day plus clopidogrel 1 mg/kg/day (max 75 mg/day) 1

Giant aneurysms (≥8 mm or Z-score ≥10):

• Low-dose aspirin 3-5 mg/kg/day plus warfarin with target INR 2.0-3.0 1
• Alternative: Low-dose aspirin plus therapeutic low-molecular-weight heparin for infants or children where warfarin is difficult to regulate 1
• The highest thrombosis risk occurs within the first 3 months, peaking at days 15-45 1

Monitoring and Follow-Up

Echocardiographic Surveillance

• Perform echocardiography at diagnosis, 2 weeks, and 6-8 weeks after treatment initiation 1
• Frequent echocardiography and ECG during the first 3 months after diagnosis, especially for giant aneurysms 1

Laboratory Monitoring

• CRP is more accurate than ESR for monitoring inflammation after IVIG therapy, as IVIG elevates ESR 1

Critical Caveats and Common Pitfalls

Incomplete Kawasaki Disease

• Infants <1 year are at highest risk for incomplete presentations and paradoxically have the highest rates of coronary aneurysms if untreated 1, 5
• Incomplete KD should still be treated if there is evidence of coronary artery abnormalities or elevated inflammatory markers 1

Drug Interactions and Contraindications

• Never use ibuprofen in children taking aspirin for antiplatelet effects, as it antagonizes the irreversible platelet inhibition induced by aspirin 1
• This is particularly critical in children with coronary aneurysms 1

Immunization Considerations

• Defer measles, mumps, rubella, and varicella immunizations for 11 months after high-dose IVIG administration due to interference with vaccine efficacy 1
• Children at high risk of measles exposure may receive vaccination earlier and then be re-immunized at least 11 months after IVIG if serological response is inadequate 1

Reye Syndrome Prevention

• Annual influenza vaccination is mandatory for children on long-term aspirin therapy due to Reye syndrome risk during influenza infection 1
• Reye syndrome risk exists in children receiving salicylates during active varicella or influenza infection 1

Timing Considerations

• While optimal treatment is within the first 10 days, do not withhold treatment solely based on timing if inflammation persists—the goal is preventing coronary damage 1
• Even late treatment provides benefit when inflammation persists 1