What are the symptoms and treatment of Kawasaki disease?

Kawasaki Disease: Symptoms and Treatment

Clinical Symptoms

Kawasaki disease is diagnosed by fever lasting at least 5 days plus at least 4 of 5 principal clinical features: bilateral nonexudative conjunctival injection, oral mucosal changes, polymorphous rash, extremity changes, and cervical lymphadenopathy. 1

Fever Characteristics

• High-spiking fever typically exceeding 39-40°C (102.2-104°F) is the hallmark feature 2, 1
• Without treatment, fever persists for an average of 11 days, though it can last several weeks 2, 1
• Diagnosis can be made with only 4 days of fever when all other principal features are present, particularly with hand/foot swelling 1

The Five Principal Clinical Features

Oral Mucosal Changes:

• Erythema and cracking of lips 1
• Strawberry tongue 1
• Erythema of oral and pharyngeal mucosa 2

Bilateral Conjunctival Injection:

• Nonexudative and primarily bulbar with limbal sparing 2, 1
• Photophobia and eye pain are typically absent 2

Polymorphous Rash:

• Most commonly presents as diffuse maculopapular eruption 1
• Can vary in appearance 2

Extremity Changes:

• Erythema of palms and soles in acute phase 1
• Periungual desquamation (peeling beginning under nail beds) typically occurs 1-3 weeks after fever onset 2, 1
• Edema of hands and feet 2

Cervical Lymphadenopathy:

• Usually unilateral and ≥1.5 cm diameter 1
• This is the least common of the five principal features 1

Other Important Clinical Findings

Neurological:

• Extreme irritability exceeding that of other febrile illnesses 2
• Aseptic meningitis in children who undergo lumbar puncture 2

Gastrointestinal:

• Hepatitis, diarrhea, vomiting, abdominal pain 2
• Gallbladder hydrops 2

Genitourinary:

• Urethritis (common) 2
• Sterile pyuria that can be mistaken for urinary tract infection 2

Musculoskeletal:

• Arthralgia and arthritis affecting small interphalangeal joints and large weight-bearing joints 2, 1

Incomplete (Atypical) Kawasaki Disease

Consider incomplete Kawasaki disease in children with fever ≥5 days AND only 2-3 principal features, or infants with fever ≥7 days without explanation. 1

• Infants <6 months may present with only prolonged fever and irritability, yet have the highest risk of coronary abnormalities 1
• Older children and adolescents often have delayed diagnosis and higher prevalence of coronary artery abnormalities 1
• When incomplete disease is suspected with elevated inflammatory markers (CRP ≥3.0 mg/dL and/or ESR ≥40 mm/hr), check for supplemental laboratory criteria including anemia, thrombocytosis after day 7, albumin <3.0 g/dL, elevated ALT, WBC ≥15,000/mm³, or urine ≥10 WBC/hpf 2

Common Diagnostic Pitfalls

• Fever and pyuria in infants can be mistakenly attributed to urinary tract infection, with subsequent rash and conjunctival injection blamed on antibiotic reaction 2
• Irritability and culture-negative CSF pleocytosis may be misdiagnosed as aseptic meningitis 2
• Cervical lymphadenitis as the primary manifestation can be misdiagnosed as bacterial adenitis 2
• Prominent gastrointestinal symptoms may lead to surgical admission with other findings overlooked 2

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Treatment

Early treatment with intravenous immunoglobulin (IVIG) 2 g/kg as a single infusion plus high-dose aspirin (80-100 mg/kg/day divided into four doses) within 10 days of fever onset significantly reduces coronary artery abnormality risk. 3, 4

Initial Treatment Protocol

• IVIG should be administered as early as possible within the first 10 days of fever onset 3, 4
• High-dose aspirin (80-100 mg/kg/day divided into four doses) is given concurrently with IVIG and continued until the patient is afebrile for at least 48 hours 3, 4
• After fever resolution, reduce aspirin to low-dose (3-5 mg/kg/day as a single daily dose) and continue until 6-8 weeks after disease onset if no coronary abnormalities are present 3, 4
• Fever typically resolves within 36 hours after IVIG completion; persistence indicates IVIG resistance requiring further therapy 1

Management of IVIG-Resistant Disease (10-20% of patients)

First-line for IVIG resistance:

• A second dose of IVIG (2 g/kg as a single infusion) 3, 4

Second-line options for persistent fever after second IVIG:

• High-dose pulse methylprednisolone (20-30 mg/kg IV for 3 days) 3, 4
• Infliximab (5 mg/kg IV over 2 hours) 3, 4

Third-line for highly refractory cases:

• Cyclosporine 4-6 mg/kg/day orally (monitor for hyperkalemia, which occurred in 32% of patients in trials) 4

Long-term Antiplatelet/Anticoagulation Management

For patients without coronary abnormalities:

• Low-dose aspirin (3-5 mg/kg/day) continued until 6-8 weeks after disease onset 3, 4

For patients with small coronary aneurysms:

• Low-dose aspirin indefinitely 4

For patients with moderate aneurysms (4-6 mm):

• Low-dose aspirin plus clopidogrel 1 mg/kg/day (max 75 mg/day) 4

For patients with giant aneurysms (≥8 mm):

• Low-dose aspirin plus warfarin (target INR 2.0-3.0) or aspirin plus therapeutic doses of low-molecular-weight heparin 3, 4
• The highest risk for coronary artery thrombosis occurs within the first 3 months, with peak incidence in the first 15-45 days 3, 4

Monitoring

• Frequent echocardiography and ECG evaluation during the first 3 months after diagnosis are recommended, especially for patients with giant coronary aneurysms 3, 4
• Transthoracic echocardiography is the diagnostic imaging modality of choice to screen for coronary aneurysms 5

Critical Treatment Caveats

• Incomplete Kawasaki disease (fever plus fewer than 4 classic criteria) should still be treated if there is evidence of coronary artery abnormalities or elevated inflammatory markers 3, 4
• Delaying treatment beyond 10 days increases the risk of coronary artery abnormalities 4
• Incomplete Kawasaki disease is more common in children under 1 year, who paradoxically have higher rates of coronary aneurysms if not treated 4
• Measles and varicella immunizations should be deferred for 11 months after high-dose IVIG administration 3, 4
• Annual influenza vaccination is recommended for children on long-term aspirin therapy 3, 4
• Ibuprofen should be avoided in children taking aspirin for its antiplatelet effects as it antagonizes the irreversible platelet inhibition induced by aspirin 4

Prognosis

• Coronary artery aneurysms or ectasia develop in 15-25% of untreated children and may lead to myocardial infarction, sudden death, or ischemic heart disease 2
• Kawasaki disease is the leading cause of acquired heart disease among children in developed countries 2