Kawasaki Disease (KD) is a rare, acute, self-limiting systemic vasculitis predominantly affecting infants and children. It is characterized by a febrile illness with associated mucocutaneous changes, including erythema of the mucous membranes, skin, and tongue, as well as swelling and desquamation of the hands and feet. Coronary artery involvement is the most significant complication of KD, which can lead to long-term cardiovascular issues. The etiology remains unknown, but it is hypothesized to involve genetic susceptibility and environmental triggers.

Epidemiology and Risk Factors

KD most commonly affects children under the age of 5, with a peak incidence at around 1 year of age and a mean age of 2.6 years. It is rare in children older than 8 years, and its incidence shows seasonal variation, peaking during the winter and spring months. KD is more common in boys than girls, and the condition is observed with a higher frequency in children of Asian descent, particularly in Japan. Although the exact cause is unknown, KD is believed to result from an interplay of genetic predisposition and an environmental trigger, potentially an infectious agent.

Clinical Features and Disease Phases

Kawasaki Disease is typically classified into three phases, each with distinct clinical features and implications for management:

• Phase I: Acute Febrile Phase (Days 1-12)

• • • Fever: A high fever (>38.5°C) persists for more than 5 days, which is the hallmark of the disease.
    • Rash: A characteristic rash appears, often beginning on the palms and soles before spreading to the trunk. The rash is typically erythematous, hives-like, or morbilliform (resembling measles), and may also resemble erythema multiforme or scarlet fever.
    • Mucocutaneous Changes: Bilateral conjunctival injection (red eyes) and redness of the lips and mouth (stomatitis) are common. A “strawberry” tongue, characterized by a bright red tongue with prominent papillae, is also seen.
    • Swelling: Swelling of the hands and feet is observed, often with erythema and edema around the nails.
    • Lymphadenopathy: Enlargement of at least one anterior cervical lymph node is characteristic.

• Phase II: Subacute Phase (Days 12-30)

• • • Desquamation: The skin begins to peel, particularly on the hands and feet, starting around the fingertips and toes. This desquamation is often most pronounced on the palms and soles.
    • Cardiovascular Involvement: This is the phase with the highest risk for developing cardiovascular complications, including myocarditis, heart failure, and coronary artery abnormalities (such as aneurysms). Sudden death may occur due to these complications, making this phase the most critical period for intervention.
    • Arthritis and Arthralgia: Joint pain and inflammation may occur during this phase, often affecting the large joints.

• Phase III: Convalescent Phase (Weeks 8-10 and beyond)

• • Resolution of Symptoms: All clinical symptoms typically resolve in this phase, and laboratory values return to normal. However, it is during this phase that patients must be monitored for long-term complications, particularly coronary artery issues, which may manifest months after the initial disease onset.

Diagnostic Criteria

The diagnosis of Kawasaki Disease is primarily clinical, based on the presence of fever lasting for at least 5 days and the involvement of at least four of the following five criteria:

• Bilateral Conjunctival Injection: Redness of both eyes without discharge.
• Cervical Lymphadenopathy: Swelling of at least one lymph node in the anterior cervical chain.
• Skin Rash: Erythematous maculopapular rash, often with a scarlet fever-like appearance, which may have sharply defined borders.
• Mucous Membrane Changes: Erythema and fissuring of the lips, injected pharynx, and a “strawberry tongue.”
• Peripheral Edema and Desquamation: Erythema and swelling of the palms and soles, followed by desquamation, often starting around the nails.

In addition, laboratory tests typically show elevated inflammatory markers (e.g., C-reactive protein, erythrocyte sedimentation rate) and thrombocytosis in the subacute phase.

Cardiovascular Complications

The most serious complications of Kawasaki Disease involve the cardiovascular system, particularly the coronary arteries. Up to 20% of patients develop coronary artery aneurysms, which can lead to long-term risks such as myocardial infarction or stroke. Other vascular complications may include myocarditis, pericarditis, and peripheral vascular occlusion. Early diagnosis and treatment, particularly the use of intravenous immunoglobulin (IVIG), are essential to reduce the risk of these complications.

Management and Treatment

Early recognition and treatment of KD are crucial to prevent cardiovascular sequelae. The primary treatment modalities include:

• Aspirin Therapy:

• • • High-dose aspirin (100 mg/kg/day) is administered during the acute phase of the disease to reduce inflammation and fever. Once the fever resolves, the dose is reduced to a low dose (3-5 mg/kg/day) to prevent thromboembolic complications related to coronary artery aneurysms.

• Intravenous Immunoglobulin (IVIG):

• • • The standard treatment for KD includes a single infusion of high-dose IVIG (2 g/kg) within the first 10 days of illness. IVIG has been shown to reduce the incidence of coronary artery aneurysms and other vascular complications, particularly when administered early in the disease.

• Steroid Therapy:

• • • Corticosteroids may be considered in severe cases or in patients who do not respond to IVIG. Steroids can help to modulate the inflammatory response and reduce the risk of cardiovascular complications.

• Additional Therapies:

• • In refractory cases, additional immunosuppressive therapies such as infliximab (an anti-TNF antibody) may be used to control inflammation and prevent the development of coronary aneurysms.

Prognosis and Long-term Follow-up

The majority of children with KD recover without significant long-term complications. However, up to 20% of patients may experience lasting vascular abnormalities, including coronary artery aneurysms, which can result in myocardial infarction or stroke in later life. Long-term follow-up with serial echocardiograms is recommended for all patients, especially those with evidence of coronary artery involvement. Most children who do not develop coronary artery complications have an excellent prognosis and normal life expectancy.

Conclusion

Kawasaki Disease is an acute systemic vasculitis with significant potential for cardiovascular complications. Early diagnosis and timely treatment with aspirin and IVIG are crucial in preventing long-term sequelae, particularly coronary artery aneurysms. While KD generally resolves without significant long-term problems, it requires vigilant monitoring during the acute and subacute phases to prevent serious complications. Further research is needed to understand the pathogenesis of KD and to optimize treatment strategies.

References

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