Ophthalmology – Kawasaki Disease

Basics

Description

Kawasaki disease (KD) is an acute, systemic medium-vessel vasculitis occurring predominantly in infants and young children.

Its greatest clinical importance is the risk of coronary artery abnormalities, particularly coronary artery aneurysms.

Classic Kawasaki disease is characterized by fever plus characteristic mucocutaneous findings:

• Bilateral nonexudative conjunctival injection
• Oral and lip changes
• Cervical lymphadenopathy
• Changes of the hands and feet
• Polymorphous rash

From an ophthalmic perspective, bilateral conjunctival injection is one of the principal diagnostic features, while mild anterior uveitis is also relatively common.

Epidemiology

Kawasaki disease occurs worldwide but has its highest incidence among children of East Asian ancestry, particularly in Japan.

Most affected children are younger than 5 years.

Other epidemiologic features include:

• Male predominance
• Peak occurrence during infancy and early childhood
• Seasonal variation in many regions

The disease is uncommon in very young neonates and older children, although it can occur at any pediatric age.

Risk Factors

Important factors include:

• Genetic susceptibility
• Young age
• Male sex
• Asian ancestry
• Family history of Kawasaki disease

A delay in diagnosis and treatment increases the risk of coronary artery complications.

Prolonged or persistent fever is also associated with greater cardiovascular risk.

Genetics

Kawasaki disease has a genetic component, but inheritance is complex.

Several susceptibility loci have been identified, including polymorphisms involving ITPKC.

Genetic susceptibility probably interacts with environmental or infectious triggers to produce the inflammatory response.

Etiology

The exact cause remains unknown.

The leading concept is that an unidentified environmental or infectious trigger produces an abnormal immune response in a genetically susceptible child.

Kawasaki disease itself is not considered a conventional contagious infection.

Pathophysiology

Kawasaki disease produces systemic vasculitis, with particularly important involvement of medium-sized muscular arteries.

The inflammatory process progresses through several stages.

Initially, there is:

• Neutrophilic infiltration
• Vascular edema
• Endothelial injury

This is followed by infiltration with:

• T lymphocytes
• Plasma cells
• Monocytes
• Macrophages

Inflammatory enzymes, including matrix metalloproteinases, can damage the arterial media and internal elastic lamina.

This weakening of the arterial wall can result in coronary artery dilation and aneurysm formation.

Later, healing may produce fibrosis, vascular remodeling, stenosis, or thrombosis.

Clinical Diagnosis

Kawasaki disease is primarily a clinical diagnosis.

The classic presentation consists of prolonged fever accompanied by the characteristic clinical features.

Fever

Fever is typically:

• High
• Persistent
• Often ≥39°C
• Poorly responsive to routine antipyretics

Untreated fever may persist for one to several weeks.

Major Clinical Features

1. Bilateral Conjunctival Injection

This is the major ophthalmic feature.

Typical findings are:

• Bilateral
• Bulbar
• Nonpurulent
• Nonexudative
• Usually painless

The conjunctival redness generally occurs without the thick discharge typical of bacterial conjunctivitis.

2. Oral and Oropharyngeal Changes

Typical findings include:

• Bright red lips
• Dry or cracked lips
• Diffuse oral mucosal erythema
• Strawberry tongue

Oral ulceration and exudative tonsillitis are not typical and should suggest alternative diagnoses.

3. Cervical Lymphadenopathy

Usually:

• Nonpurulent
• Cervical
• Often unilateral

At least one lymph node may be markedly enlarged.

This is generally the least frequently encountered of the classic diagnostic features.

4. Extremity Changes

During the acute phase:

• Erythema of palms and soles
• Edema of hands and feet

During the subacute phase:

• Periungual desquamation of fingers and toes

Peeling typically begins approximately 1–3 weeks after disease onset.

5. Polymorphous Rash

A generalized rash commonly involves the trunk and extremities.

It may have several appearances but is generally nonvesicular.

Perineal erythema and subsequent desquamation may also occur.

Ocular Manifestations

Conjunctival Injection

Bilateral nonexudative conjunctival injection is one of the defining clinical manifestations of Kawasaki disease.

It usually resolves as the systemic inflammatory process improves.

Anterior Uveitis

Kawasaki disease can produce a mild bilateral anterior uveitis.

Slit-lamp examination may demonstrate:

• Anterior chamber cells
• Mild flare

The uveitis is generally:

• Mild
• Transient
• Bilateral
• Self-limited

It usually improves as the systemic disease is treated.

Topical corticosteroids are usually unnecessary, although ophthalmic treatment may be required when inflammation is more significant.

Other Ocular Manifestations

Less common manifestations include:

• Superficial punctate keratitis
• Choroiditis
• Optic disc swelling
• Other posterior segment inflammatory abnormalities

Severe ocular disease is unusual.

Associated Systemic Findings

Kawasaki disease may also produce:

• Marked irritability
• Arthritis or arthralgia
• Myocarditis
• Pericarditis
• Gastrointestinal symptoms
• Abdominal pain
• Vomiting
• Diarrhea
• Hepatitis
• Gallbladder hydrops
• Sterile pyuria
• Aseptic meningitis
• Otitis media

The major concern remains cardiovascular involvement.

Coronary Artery Disease

The most important complication is coronary artery involvement.

Possible abnormalities include:

• Coronary dilation
• Coronary aneurysm
• Giant coronary aneurysm
• Coronary thrombosis
• Coronary stenosis
• Myocardial ischemia
• Myocardial infarction

Untreated Kawasaki disease has a substantial risk of coronary artery abnormalities.

Prompt treatment with IVIG dramatically reduces this risk.

Diagnostic Testing

There is no single laboratory test that confirms Kawasaki disease.

Laboratory investigations support the diagnosis and help assess disease severity.

Common abnormalities include:

• Elevated CRP
• Elevated ESR
• Leukocytosis with neutrophilia
• Normocytic anemia
• Elevated hepatic transaminases
• Hypoalbuminemia
• Sterile pyuria

Platelet counts may initially be normal.

During the subacute phase, thrombocytosis commonly develops.

Cardiac Evaluation

Echocardiography

Echocardiography is essential for evaluating:

• Coronary artery dimensions
• Coronary aneurysms
• Ventricular function
• Pericardial effusion
• Other cardiac abnormalities

Importantly, a normal early echocardiogram does not exclude Kawasaki disease.

Serial cardiac imaging is determined by the patient’s coronary findings and clinical course.

Ophthalmic Examination

Routine ophthalmologic consultation is not necessary for every uncomplicated case.

An ophthalmic examination is particularly appropriate when there is:

• Suspected anterior uveitis
• Significant photophobia
• Reduced vision
• Persistent ocular inflammation
• Atypical ocular manifestations

Slit-lamp examination can detect mild anterior chamber inflammation that is not obvious externally.

Differential Diagnosis

Important differential diagnoses include:

• Adenovirus infection
• Scarlet fever
• Toxic shock syndrome
• Measles
• Drug hypersensitivity reactions
• Stevens–Johnson syndrome
• Systemic juvenile idiopathic arthritis
• Other systemic vasculitides
• Bacterial cervical lymphadenitis

Adenovirus can be particularly confusing because both conditions can produce fever and conjunctival injection.

However, exudative conjunctivitis and pharyngitis favor adenovirus rather than classic Kawasaki disease.

Incomplete Kawasaki Disease

Some children do not meet all of the classic clinical criteria but still have Kawasaki disease.

This is known as incomplete Kawasaki disease.

It is especially important to consider in:

• Young infants
• Children with prolonged unexplained fever
• Patients with compatible laboratory abnormalities
• Patients with coronary artery abnormalities

Incomplete disease can still cause serious coronary complications and should not be considered a mild form of Kawasaki disease.

Treatment

Intravenous Immunoglobulin

IVIG is the cornerstone of treatment.

Standard initial therapy is:

IVIG 2 g/kg as a single infusion.

Treatment should be administered promptly once the diagnosis is established.

Early IVIG substantially reduces the risk of coronary artery aneurysm formation.

Aspirin

Aspirin is traditionally given during the acute inflammatory phase, followed by low-dose antiplatelet aspirin.

Low-dose aspirin is generally continued until follow-up confirms the absence of clinically important coronary abnormalities.

Patients with persistent coronary artery abnormalities may require longer antiplatelet therapy.

Exact aspirin dosing and duration should follow current pediatric cardiology/Kawasaki disease protocols.

IVIG-Resistant Disease

Some children have persistent or recurrent fever after initial IVIG.

Depending on the clinical situation, additional treatment may include:

• Repeat IVIG
• Systemic corticosteroids
• Infliximab
• Other immunomodulatory therapy

High-risk children may receive corticosteroids as part of initial therapy rather than waiting for IVIG resistance.

Antithrombotic Therapy

Children with significant coronary aneurysms may require more intensive thrombosis prevention.

Depending on aneurysm size and other risk factors, treatment may include:

• Aspirin
• Additional antiplatelet agents
• Anticoagulation

Management should be directed by pediatric cardiology.

Treatment of Ocular Disease

The conjunctival injection generally requires no specific ocular treatment.

Mild anterior uveitis typically resolves with systemic treatment.

More significant anterior uveitis may occasionally require:

• Topical corticosteroids
• Cycloplegic agents

These should be managed by an ophthalmologist.

Hospital Management

Children with suspected acute Kawasaki disease generally require hospital evaluation and treatment.

Management includes:

• IVIG
• Anti-inflammatory/antiplatelet therapy
• Cardiac assessment
• Laboratory monitoring
• Echocardiography

Fluid management may be necessary in children with significant gastrointestinal symptoms or dehydration.

Follow-Up

Long-term follow-up depends predominantly on coronary artery involvement.

Children without coronary abnormalities generally require substantially less intensive long-term cardiac surveillance than children with persistent aneurysms.

Patients with coronary aneurysms may require:

• Serial echocardiography
• ECG
• Additional coronary imaging
• Stress testing
• Long-term antithrombotic therapy

Large or giant aneurysms require particularly close lifelong cardiology surveillance.

Ophthalmology Follow-Up

Ophthalmic follow-up is primarily indicated when:

• Anterior uveitis is present
• Ocular inflammation persists
• Vision is reduced
• Atypical ocular manifestations develop

Most conjunctival and mild inflammatory ocular manifestations resolve without permanent visual consequences.

Prognosis

With prompt diagnosis and appropriate treatment, the prognosis is generally excellent.

IVIG dramatically decreases the frequency of coronary artery aneurysms.

Long-term prognosis is primarily determined by the presence, size, and persistence of coronary artery abnormalities.

Complications

The major complications are cardiovascular:

• Coronary artery aneurysm
• Coronary thrombosis
• Coronary stenosis
• Myocardial ischemia
• Myocardial infarction
• Arrhythmia
• Rare sudden cardiac death

The key ophthalmology pearl is: bilateral, nonpurulent conjunctival injection in a persistently febrile young child—particularly when accompanied by strawberry tongue, rash, extremity changes, or cervical lymphadenopathy—should immediately raise suspicion for Kawasaki disease.