Leukocytosis in Kawasaki Disease: Impact on Standard Treatment
The presence of leukocytosis (even with jaundice and loose stools) does not alter the standard treatment protocol for Kawasaki disease—proceed immediately with IVIG 2 g/kg as a single infusion plus high-dose aspirin 80-100 mg/kg/day divided into four doses. 1, 2
Standard Treatment Protocol Remains Unchanged
Leukocytosis is an expected laboratory finding in acute Kawasaki disease and represents part of the systemic inflammatory response. 1 The presence of additional features like jaundice and loose stools does not modify the core therapeutic approach:
- Administer IVIG 2 g/kg as a single infusion over 10-12 hours as soon as the diagnosis is established, ideally within the first 10 days of fever onset 1, 2
- Give high-dose aspirin 80-100 mg/kg/day divided into four doses concurrently with IVIG 1
- Continue high-dose aspirin until the patient has been afebrile for 48-72 hours, then transition to low-dose aspirin 3-5 mg/kg/day as a single daily dose 1, 2
Why Leukocytosis Does Not Change Management
The American Heart Association guidelines establish treatment decisions based on clinical diagnostic criteria (fever plus characteristic features) and coronary artery status—not on the degree of leukocytosis or associated gastrointestinal symptoms. 1 IVIG therapy reduces coronary artery abnormality risk from 15-25% down to approximately 5%, regardless of baseline inflammatory markers. 3
Monitoring for IVIG Resistance
While leukocytosis itself does not alter initial treatment, you should monitor closely for IVIG resistance:
- IVIG resistance is defined as persistent or recrudescent fever ≥36 hours after completion of the initial IVIG infusion 2, 3, 4
- If fever persists ≥36 hours post-IVIG, administer a second dose of IVIG 2 g/kg as first-line rescue therapy 2, 3, 4
- After two IVIG doses fail, consider methylprednisolone 20-30 mg/kg IV daily for 3 days or infliximab 5 mg/kg IV as a single infusion 1, 2, 3
Important Caveats Regarding Aspirin
Recent high-quality evidence challenges aspirin's role in preventing coronary complications:
- A 2025 multicenter randomized trial (134 patients) demonstrated non-inferiority of IVIG alone compared to IVIG plus high-dose aspirin for coronary artery lesion reduction 5, 6
- Multiple studies show aspirin does not directly reduce coronary artery abnormality incidence, though it may shorten fever duration 7, 8, 9
However, current American Heart Association guidelines still recommend aspirin as standard therapy, and these should be followed until guidelines are formally updated. 1, 8 The aspirin recommendation is based on its anti-inflammatory effects during acute illness and antiplatelet effects for coronary protection.
Critical Safety Considerations
- Never use ibuprofen concurrently with aspirin, as it antagonizes aspirin's irreversible platelet inhibition 1, 3
- Administer annual influenza vaccination to all children on long-term aspirin to reduce Reye syndrome risk 1, 2
- Defer measles, mumps, rubella, and varicella vaccinations for 11 months after high-dose IVIG due to interference with vaccine efficacy 2, 3, 4
- Use CRP rather than ESR to monitor post-IVIG inflammation, as IVIG artificially elevates ESR 3
Long-Term Management Based on Coronary Status
After initial treatment, management depends on echocardiographic findings at 6-8 weeks:
- No coronary abnormalities: Discontinue low-dose aspirin at 6-8 weeks 2, 3, 4
- Small coronary aneurysms: Continue low-dose aspirin 3-5 mg/kg/day indefinitely 2, 3
- Moderate aneurysms (4-6 mm): Low-dose aspirin plus clopidogrel 1 mg/kg/day (max 75 mg/day) 2, 3
- Giant aneurysms (≥8 mm): Low-dose aspirin plus warfarin (target INR 2.0-3.0) or therapeutic low-molecular-weight heparin 2, 3, 4