Kawasaki Disease Overview

Kawasaki Disease

• Kawasaki Disease is a systemic vasculitis affecting small and medium-sized arteries, especially coronary arteries.
• It predominantly affects children between 1 and 5 years old with a higher incidence in males and those of Asian ethnicity.
• Japanese children have a 10-fold higher incidence compared to Caucasian children.
• Kawasaki Disease is the leading cause of acquired heart disease in children in developed countries.

Pathogenesis

• The exact cause of Kawasaki Disease is unknown, but it is thought to be triggered by an infectious agent in a genetically predisposed individual.
• The infection likely enters the bloodstream and then the tissues, leading to an aberrant immune response.
• The immune response involves a switch from B lymphocytes to IgA plasma cells, suggesting stimulation by an intracellular pathogen.
• Coronary artery aneurysm formation is attributed to inflammatory cytokines and enzymes released by infiltrating neutrophils and mononuclear cells, which destroy collagen and elastin fibers.

Clinical Manifestations

• Kawasaki Disease presents in stages:
  • Acute Febrile Stage:
    • Fever lasting at least 5 days, typically above 39°C.
    • Conjunctivitis (non-exudative, bilateral) in over 90% of cases.
    • Polymorphous rash, particularly on the groin and trunk.
    • Edema or erythema of the hands and feet.
    • Cervical lymphadenopathy (above 1.5 cm diameter, often unilateral).
    • Mucosal involvement including strawberry tongue, dry, fissured lips, pharyngeal or lip mucosa injection.
    • Myocarditis or pericarditis may also be present.
  • Subacute Stage: Fever, rash, and lymphadenopathy resolve.
    • Desquamation (peeling) of the skin occurs, particularly around the nails.
    • Coronary artery aneurysms typically develop in this stage.
  • Convalescent Stage: Signs and symptoms of inflammation recede.
    • Acute phase markers normalize.
    • Coronary artery aneurysms may enlarge.
  • Chronic Stage: Aneurysms may resolve, but sometimes persist into adulthood.

Diagnosis

• Kawasaki Disease is a clinical diagnosis requiring fever and at least 4 out of 5 of the following clinical findings:
  • Conjunctivitis
  • Rash
  • Edema or erythema of hands and feet
  • Cervical lymphadenopathy
  • Mucosal involvement
• Incomplete or atypical Kawasaki Disease diagnosis is made if only 2 or 3 criteria are present.
• Laboratory values can aid in diagnosis:
  • Anemia
  • Platelet count above 450,000/µL after 7 days of fever
  • Hypoalbuminemia
  • Elevated alanine aminotransferase
  • White blood cell count above 15,000/µL
  • Urine with more than 10 white blood cells/high-power field.
• Echocardiography is the primary imaging modality to assess coronary artery abnormalities.

Echocardiographic Findings

• Z-scores are used to describe the diameter of the coronary artery relative to the average diameter in a child of the same body surface area.
• Positive for coronary abnormalities if:
  • Z-score of 2.5 or more in the left anterior descending or right coronary arteries.
  • Visible coronary artery aneurysm.
  • Three or more suggestive features like decreased left ventricular function, mitral regurgitation, pericardial effusion, or a z-score of 2 to 2.5 in the left anterior descending or right coronary arteries.
• Z-score interpretation:
  • Less than 2: Normal
  • 2 to 2.5: Dilatation only
  • 2.5 to 5: Small Aneurysm
  • 5 to 10: Medium Aneurysm
  • More than 10: Large or Giant Aneurysm

Treatment

• Intravenous immunoglobulins (IVIG) are the mainstay of treatment, indicated if:
  • Patient is within 10 days of fever onset.
  • Patient is beyond 10 days of fever with ongoing fever or elevated inflammatory markers.
• Aspirin is often used concurrently with IVIG, continued for at least 4 to 6 weeks or longer if the z-score hasn't returned to normal.
• Steroids or anti-TNF-alpha agents (e.g., infliximab) can be used in patients not responding to IVIG.

Follow-Up

• Follow-up depends on the z-score.
  • Patients with a z-score below 2 at all times discontinue aspirin therapy after 4 to 6 weeks and undergo cardiovascular risk assessment at that time and again at one year.
  • Patients with giant aneurysms receive:
    • Aspirin therapy
    • Anticoagulation medication (e.g., warfarin or low molecular weight heparin)
    • Regular assessments throughout the first year and every 3-6 months thereafter
    • Stress echocardiography every 6-12 months
    • Consideration for angiography during the first year and every 1-5 years afterwards
    • Avoidance of high-intensity activities
    • Some patients may also require dual antiplatelet therapy (aspirin and clopidogrel).
• Beta-blockers may be initiated in some high-risk cases.
• Treatment is scaled down based on aneurysm regression.

Prognosis

• The overall prognosis for patients with Kawasaki Disease is excellent with treatment.
• While coronary artery aneurysms can be a significant complication leading to myocardial infarction and sudden cardiac death, most patients recover well.
• The development of coronary artery aneurysms is the greatest long-term risk factor.