Kawasaki disease

Definition

Kawasaki disease (KD), also known as mucocutaneous lymph node syndrome, is an acute, self-limited vasculitis predominantly affecting medium-sized arteries, with a particular predilection for the coronary arteries. It primarily affects children under 5 years of age and is a leading cause of acquired heart disease in this population.

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Epidemiology

• Most common in children aged 6 months to 5 years.

• Higher incidence in boys than girls (ratio ~1.5:1).

• Higher prevalence in East Asian populations (Japan, Korea, Taiwan).

• Seasonal peaks often occur in winter and early spring.

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Etiology and Pathophysiology

• Exact cause unknown; likely an abnormal immune response to an infectious trigger in genetically susceptible individuals.

• Involves activation of the immune system, leading to widespread inflammation of blood vessel walls (panvasculitis) and damage to the endothelium.

• Coronary artery involvement can result in aneurysms, thrombosis, or stenosis.

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Diagnostic Criteria

Diagnosis is clinical, based on fever and associated features.

Classic Kawasaki Disease

• Fever ≥5 days (mandatory)

• Plus ≥4 of the following:

  1. Bilateral non-purulent conjunctivitis

  2. Oral changes: cracked red lips, strawberry tongue, diffuse oropharyngeal erythema

  3. Peripheral extremity changes: erythema and edema of hands/feet in acute phase; periungual peeling in subacute phase

  4. Polymorphous rash: maculopapular, urticarial, or erythema multiforme-like

  5. Cervical lymphadenopathy: usually unilateral, ≥1.5 cm diameter

Incomplete Kawasaki Disease

• Fever ≥5 days plus 2–3 clinical features, supported by laboratory and echocardiographic findings.

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Phases of Disease

1. Acute Phase (1–2 weeks)

   • High fever, irritability, mucocutaneous inflammation, rash, lymphadenopathy.

   • Myocarditis and pericarditis may occur.

2. Subacute Phase (2–6 weeks)

   • Resolution of fever.

   • Desquamation of fingers/toes, arthralgia, thrombocytosis.

   • Highest risk for coronary artery aneurysm formation.

3. Convalescent Phase (6–8 weeks)

   • Clinical recovery; inflammatory markers normalize.

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Complications

• Cardiac: coronary artery aneurysms (15–25% untreated; <5% treated), myocardial infarction, arrhythmias, heart failure.

• Non-cardiac: arthritis, sensorineural hearing loss, hydrops of the gallbladder.

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Investigations

Laboratory

• Elevated ESR and CRP.

• Leukocytosis (acute phase), thrombocytosis (subacute phase).

• Mild to moderate anemia.

• Elevated liver enzymes, hypoalbuminemia.

Imaging

• Echocardiography: recommended at diagnosis, at 2 weeks, and at 6–8 weeks to assess for coronary artery changes.

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Management

Goals of Therapy

• Reduce inflammation.

• Prevent coronary artery aneurysms.

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First-Line Treatment

1. Intravenous Immunoglobulin (IVIG)

• Dose: 2 g/kg as a single infusion over 8–12 hours.

• Administer within the first 10 days of illness (ideally within 7 days) to reduce risk of coronary artery complications.

• May repeat if fever persists ≥36 hours after first dose.

2. Aspirin (Acetylsalicylic acid)

• Acute phase: 30–50 mg/kg/day orally in 4 divided doses until afebrile for 48–72 hours.

• Antiplatelet phase: 3–5 mg/kg/day orally once daily for 6–8 weeks or longer if coronary abnormalities persist.

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Adjunctive or Second-Line Therapies

• Corticosteroids:

  • Indicated for high-risk patients or IVIG-resistant KD.

  • Example: Methylprednisolone 2 mg/kg/day IV in divided doses or as pulse therapy 30 mg/kg/day for 1–3 days.

• Infliximab (anti-TNF):

  • Dose: 5 mg/kg IV over 2 hours; option for IVIG-resistant cases.

• Cyclosporine:

  • Dose: 3–5 mg/kg/day orally in 2 divided doses; in refractory cases.

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Long-Term Management

• Cardiology follow-up for coronary artery status.

• Physical activity restriction if coronary abnormalities are present.

• Lifelong antiplatelet or anticoagulation therapy in patients with persistent large aneurysms.

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Prognosis

• With timely IVIG and aspirin, mortality is <0.2%.

• Most children recover fully if treated early.

• Coronary aneurysms may persist or cause late complications in a minority of cases.

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Prevention and Patient Education

• No vaccine or specific prevention.

• Parents should monitor for fever recurrence or cardiac symptoms.

• Annual influenza vaccination is recommended for patients on long-term aspirin to reduce risk of Reye’s syndrome.