What are the symptoms and treatment of Kawasaki disease?

Kawasaki Disease: Symptoms and Treatment

Clinical Symptoms

Classic Kawasaki disease is diagnosed by fever lasting at least 5 days plus at least 4 of 5 principal clinical features: oral mucosal changes, bilateral conjunctival injection, polymorphous rash, extremity changes, and cervical lymphadenopathy. 1

Fever Characteristics

• High-spiking fever typically exceeding 39-40°C (102.2-104°F) is the hallmark feature 1, 2
• Without treatment, fever persists for an average of 1-3 weeks 1
• Fever must be present for at least 5 days (with day of onset = day 1) for diagnosis 2
• Diagnosis can be made with only 4 days of fever when ≥4 principal features are present, particularly with hand/foot swelling 1, 2

The Five Principal Clinical Features

1. Oral Mucosal Changes 1

• Erythema and cracking of lips
• Strawberry tongue appearance
• Erythema of oral and pharyngeal mucosa

2. Bilateral Conjunctival Injection 1

• Nonexudative, primarily bulbar conjunctivitis
• Characteristic limbal sparing (avascular zone around the iris) 1
• Photophobia and eye pain are typically absent 1

3. Polymorphous Rash 1

• Most commonly diffuse maculopapular eruption 1
• May also present as scarlatiniform erythroderma or erythema multiforme-like patterns 1
• Usually extensive, involving trunk and extremities with accentuation in the groin 1
• Bullous, vesicular, and petechial rashes are NOT consistent with Kawasaki disease and should prompt alternative diagnosis 1

4. Extremity Changes 1

• Acute phase: erythema and edema of hands and feet
• Subacute phase: periungual desquamation (typically 2-3 weeks after fever onset)

5. Cervical Lymphadenopathy 1

• Least common of the principal features 1
• Usually unilateral and ≥1.5 cm diameter 1
• Confined to anterior cervical triangle 1

Incomplete (Atypical) Kawasaki Disease

Consider incomplete Kawasaki disease in children with fever ≥5 days AND only 2-3 principal features, or infants with fever ≥7 days without explanation. 2

• Infants <6 months may present with only prolonged fever and irritability, yet have the highest risk of coronary abnormalities 2
• Evaluation should include inflammatory markers (ESR, CRP) and echocardiography 2
• Incomplete disease carries at least as high a risk of coronary complications as classic disease 1

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Treatment Protocol

Initial Treatment (Within 10 Days of Fever Onset)

The American Heart Association recommends IVIG at 2 g/kg as a single infusion combined with high-dose aspirin (80-100 mg/kg/day divided into four doses), administered as early as possible within the first 10 days of fever onset. 3, 4

Aspirin Dosing Algorithm:

1. High-dose aspirin (80-100 mg/kg/day in 4 divided doses) until afebrile for 48-72 hours 3, 4
2. Transition to low-dose aspirin (3-5 mg/kg/day as single daily dose) after fever resolution 3, 4
3. Continue low-dose aspirin for 6-8 weeks if no coronary abnormalities present 3
4. Continue indefinitely if coronary abnormalities develop 3

Critical Timing:

• Treatment within 10 days significantly reduces coronary artery abnormality risk from 15-25% in untreated patients to <5% with treatment 1
• Fever typically resolves within 36 hours after IVIG completion; persistence indicates IVIG resistance 2

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Management of IVIG-Resistant Disease (10-20% of Patients)

IVIG resistance is defined as persistent or recurrent fever ≥36 hours after completion of initial IVIG infusion. 3

Treatment Algorithm for IVIG Resistance:

First-line: Second dose of IVIG (2 g/kg as single infusion) 3, 4

Second-line options if fever persists after 2 doses of IVIG:

• High-dose pulse methylprednisolone (20-30 mg/kg IV for 3 days) 4
• Infliximab (5 mg/kg as single infusion) 4, 5

Third-line for refractory cases:

• Consider cyclosporine or methotrexate after multiple IVIG and steroid failures 5

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Long-Term Anticoagulation Based on Coronary Involvement

Risk-stratified approach based on coronary artery dimensions: 3

No coronary abnormalities:

• Low-dose aspirin for 6-8 weeks only 3, 4

Small coronary aneurysms:

• Low-dose aspirin indefinitely 3

Moderate aneurysms (4-6 mm):

• Low-dose aspirin PLUS second antiplatelet agent 3

Giant aneurysms (≥8 mm):

• Low-dose aspirin PLUS warfarin (target INR 2.0-3.0) 3
• Alternative: aspirin plus therapeutic low-molecular-weight heparin for infants where warfarin regulation is difficult 3

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Monitoring and Follow-Up

Echocardiography timing: 3

• At diagnosis
• 2 weeks after treatment
• 6-8 weeks after treatment
• Frequent monitoring during first 3 months for patients with giant aneurysms 3

Highest thrombosis risk: First 3 months, with peak incidence at 15-45 days 3

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Critical Pitfalls and Caveats

High-Risk Populations:

• Infants <6 months have highest risk of coronary abnormalities despite often presenting with incomplete features 2
• Older children and adolescents often have delayed diagnosis and higher prevalence of coronary abnormalities 2

Vaccination Considerations:

• Defer measles and varicella immunizations for 11 months after high-dose IVIG 3, 4
• Annual influenza vaccination is mandatory for children on long-term aspirin therapy (Reye syndrome risk) 3, 4

Drug Interactions:

• Avoid ibuprofen in children taking aspirin—it antagonizes aspirin's irreversible platelet inhibition 3

Diagnostic Errors:

• Do not dismiss diagnosis if fever spontaneously resolves after 7 days—incomplete disease still requires treatment if other features present 1
• Cervical lymphadenopathy may be the most prominent initial finding, mimicking bacterial lymphadenitis and delaying diagnosis 1