Kawasaki Disease

Kawasaki disease is an acute, self-limited vasculitis of unknown etiology that primarily affects young children
It is also known as mucocutaneous lymph node syndrome
The illness was first described by Tomisaku Kawasaki in Japan in 1967
It is a leading cause of acquired heart disease in children in developed countries

Kawasaki disease is most common in children younger than 5 years of age
The peak incidence is between 18 and 24 months of age
It is rare in children younger than 6 months and older than 8 years
Males are affected more often than females
It is more common in children of Asian descent, particularly those of Japanese and Korean ethnicity
Incidence rates are highest in Japan
There are seasonal variations; in North America and Japan, Kawasaki disease is more common in the winter and early spring

The cause of Kawasaki disease is unknown
Infectious, environmental, and genetic factors are hypothesized to play a role
Several infectious agents have been investigated, including viruses, bacteria, and fungi, but no single pathogen has been consistently identified
Superantigens have been proposed as potential triggers, as they can cause widespread T-cell activation and cytokine release
Genetic susceptibility is suggested by the increased incidence in certain ethnic groups and the higher concordance rate in monozygotic twins compared to dizygotic twins
Several genes involved in immune regulation and inflammation have been identified as potential susceptibility genes

Kawasaki disease primarily affects medium-sized arteries, especially the coronary arteries
The acute phase is characterized by widespread inflammation of the blood vessels, leading to vasculitis
Endothelial cell activation and dysfunction are prominent features
Inflammatory cells, including neutrophils, lymphocytes, and macrophages, infiltrate the vessel walls
Matrix metalloproteinases (MMPs) are produced, which degrade the extracellular matrix and contribute to vessel wall damage
Coronary artery aneurysms (CAA) are a major complication
Thrombosis can occur within the aneurysms, leading to myocardial infarction
In the subacute phase, inflammation gradually subsides, but the risk of thrombosis and stenosis remains
In the chronic phase, the inflammation is resolved, but the damaged vessels may develop stenosis or remain aneurysmal

The diagnosis of Kawasaki disease is based on clinical criteria
Fever is a universal finding, typically lasting for at least 5 days
Incomplete or atypical cases may present with fewer classic features
The principal clinical features:
Conjunctival injection (bilateral, non-exudative)
Mucous membrane changes (e.g., injected or fissured lips, strawberry tongue)
Peripheral extremity changes (e.g., edema, erythema, desquamation of the fingers and toes)
Rash (primarily truncal; polymorphous, non-vesicular)
Cervical lymphadenopathy (often unilateral and >1.5 cm in diameter)
Other common symptoms:
Irritability is a prominent feature, especially in infants
Cardiac involvement, including myocarditis, pericarditis, and coronary artery abnormalities
Arthritis or arthralgia
Gastrointestinal symptoms such as abdominal pain, vomiting, and diarrhea
Aseptic meningitis
Uveitis
Hydrops of the gallbladder
Hepatic dysfunction
Respiratory symptoms

There is no specific diagnostic test for Kawasaki disease, and diagnosis relies on clinical criteria
The American Heart Association (AHA) guidelines provide a framework for diagnosis
According to AHA criteria, diagnosis requires fever for at least 5 days plus at least four of the five principal clinical features
If fewer than four criteria are present, the patient is considered to have incomplete Kawasaki disease
Incomplete Kawasaki disease is more common in infants and may be challenging to diagnose
Laboratory findings:
Elevated acute phase reactants, such as erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP)
Leukocytosis with neutrophilia
Thrombocytosis
Anemia
Elevated liver enzymes
Hypoalbuminemia
Sterile pyuria
Echocardiography to assess coronary artery abnormalities

Many infectious and inflammatory conditions can mimic Kawasaki disease
These include:
Viral infections (e.g., adenovirus, measles, Epstein-Barr virus)
Bacterial infections (e.g., streptococcal infections, staphylococcal infections)
Scarlet fever
Toxic shock syndrome
Stevens-Johnson syndrome
Drug reactions
Juvenile idiopathic arthritis
Clinicians must carefully consider the clinical and laboratory findings to differentiate Kawasaki disease from other conditions

The primary goals of treatment are to reduce inflammation and prevent coronary artery abnormalities
Intravenous immunoglobulin (IVIG) and aspirin are the mainstays of therapy
IVIG is administered as a single dose
High-dose aspirin is given initially to reduce inflammation; once the fever subsides, the aspirin dose is reduced to an antiplatelet dose
Corticosteroids may be considered in patients who are at high risk, or unresponsive to initial IVIG therapy
Additional therapies, such as infliximab or plasma exchange, may be used in refractory cases
Patients with coronary artery aneurysms require long-term management to prevent thrombosis and ischemia
This may include antiplatelet agents, anticoagulants, and lifestyle modifications

With prompt diagnosis and treatment, the prognosis for children with Kawasaki disease is generally good
Most patients recover without long-term sequelae
Coronary artery aneurysms (CAA) are present despite treatment in a subset of patients
Large or giant aneurysms are more likely to cause long-term complications, such as myocardial infarction, sudden death, or ischemia
The long-term cardiovascular risk in patients with a history of Kawasaki disease is not fully understood, and ongoing monitoring is recommended
Patients with coronary artery abnormalities should be followed by a cardiologist throughout their lives
Lifestyle modifications, such as smoking cessation and regular exercise, are recommended to reduce cardiovascular risk