Kawasaki disease

Standard treatment

• IVIG 2 g/kg as a single infusion over 8–12 hours — standard of care, administer as soon as diagnosis is made [1][7]
• Aspirin:
  • Acute phase: moderate dose (30–50 mg/kg/day) or high dose (80–100 mg/kg/day) until afebrile 48–72 hours [1][4]
  • Antiplatelet phase: low dose (3–5 mg/kg/day) once daily for 6–8 weeks minimum [1-2]
  • Emerging evidence suggests low-dose aspirin alone may be non-inferior for coronary outcomes [4][9]

Adjunctive/rescue therapies

• Adjunctive corticosteroids (prednisolone 2 mg/kg/day, max 60 mg, tapered over 15 days) for high-risk patients — conditionally recommended by ACR [2][10]
• IVIG-resistant KD: second dose of IVIG, or infliximab, anakinra, cyclosporine, or IV methylprednisolone pulse [2]
• Giant aneurysms (Z ≥10): systemic anticoagulation (LMWH or warfarin) + antiplatelet agent [8]

Contraindications/cautions

• NSAIDs inhibit aspirin's antiplatelet effect — avoid concurrent use during aspirin therapy [1]
• Live vaccines (MMR, varicella) must be deferred 11 months after IVIG [1]
• Reye syndrome risk: monitor for influenza/varicella while on aspirin; consider holding aspirin during active influenza or varicella and substituting clopidogrel if needed
• Hemolytic anemia with IVIG: dose-dependent, higher risk in blood types A, B, AB; consider lean body mass dosing in obese patients [1-2]

Vital signs

• High fever (often ≥39–40°C), typically remitting-relapsing
• Tachycardia; hypotension in KD shock syndrome

Focused exam findings

• Eyes: bilateral bulbar conjunctival injection, limbus-sparing, non-exudative [2][6]
• Oral: erythematous, cracked/fissured lips; strawberry tongue; diffuse oropharyngeal erythema [2]
• Skin: polymorphous rash (maculopapular, erythroderma, or erythema multiforme–like); perineal erythema with early desquamation is highly suggestive [6]
• Extremities (acute): erythema and edema of hands/feet, painful induration of palms/soles
• Extremities (subacute, weeks 2–3): periungual desquamation of fingers and toes [2]
• Neck: unilateral cervical lymphadenopathy ≥1.5 cm [2]
• Cardiac: gallop rhythm, murmur of mitral regurgitation, distant heart sounds (effusion)
• BCG site: erythema/induration at inoculation site [5]

Recommended initial labs

• CBC with differential: leukocytosis (WBC ≥15,000), neutrophil predominance; thrombocytosis (platelets ≥450,000) typically after day 7; anemia for age [3][6]
• CRP and ESR: elevated (CRP ≥3 mg/dL, ESR ≥40 mm/hr); note ESR is unreliable after IVIG [1][7]
• CMP: hypoalbuminemia (≤3 g/dL), elevated ALT/AST, hyponatremia [3]
• Urinalysis: sterile pyuria (≥10 WBC/hpf, leukocyte esterase negative) [6]
• BNP/NT-proBNP: elevated in myocardial involvement; higher levels more suggestive of MIS-C [1][4]
• Troponin: if myocarditis suspected
• Blood type: important before IVIG — types A, B, AB at higher risk for hemolytic anemia [1]

For incomplete KD evaluation (AHA algorithm): ≥3 of the following supportive labs: anemia, thrombocytosis after day 7, hypoalbuminemia, elevated ALT, leukocytosis ≥15,000, sterile pyuria [6]

Repeat echocardiography schedule

• During hospitalization and before discharge if high-risk features or IVIG resistance [1]
• 1–2 weeks post-discharge [1]
• 4–6 weeks after onset if prior echos abnormal [1]
• If CA Z-score ≥2.5: at least twice weekly until dimensions stabilize [1]

Advanced imaging (for established CAA)

• CT coronary angiography or cardiac MRI for older children/adolescents with known aneurysms
• Invasive coronary angiography for giant aneurysms or suspected stenosis [1]

When imaging is unnecessary: patients with normal echos at diagnosis and 1–2 weeks post-discharge who responded to therapy — 98.6% remain normal at 4–6 weeks, and further cardiac follow-up may not be needed [1]

Diagnostic scoring/criteria

The AHA diagnostic criteria calculator can assist in classification:

• Kobayashi score, Egami score, Sano score: Japanese risk scores for IVIG resistance prediction — poor sensitivity/specificity in non-Japanese populations [2][4]
• North American CAA risk score (Son et al.): baseline Z-score ≥2.0 (2 points), age <6 months (1 point), Asian race (1 point), CRP ≥13 mg/dL (1 point) — low (0–1), moderate (2), high (3–5) risk groups [11]

Point-of-care considerations

• Bedside echocardiography for coronary assessment in the ED
• IL-17 family cytokines (IL-17A, IL-17C, IL-17F) show promise as diagnostic biomarkers distinguishing KD from other febrile illnesses (AUC 0.91–0.95), though not yet widely available clinically [13]

Severity stratification

• Complete KD: ≥5 days fever + ≥4/5 principal features [2][4]
• Incomplete KD: ≥5 days fever + 2–3 features + supportive labs or echo findings — carries equal or greater CAA risk [2]
• KD shock syndrome: hemodynamic instability requiring volume resuscitation ± vasopressors [1]
• IVIG-resistant KD: persistent/recrudescent fever ≥36 hours post-IVIG (~10–20% of patients) [4]

Complications: CAA (including giant aneurysms), coronary thrombosis, MI, myocarditis, valvulitis (mitral regurgitation), MAS, hydrops of the gallbladder, sensorineural hearing loss

Initial stabilization

• IV access, fluid resuscitation if dehydrated or in shock
• Antipyretics (acetaminophen preferred over ibuprofen to avoid NSAID-aspirin interaction)

Standard therapy (administer as soon as diagnosis is made — do not wait for echo):

• IVIG 2 g/kg single infusion over 8–12 hours [1][7]
• Aspirin 30–50 mg/kg/day divided q6h until afebrile 48–72 hours, then 3–5 mg/kg/day once daily for minimum 6–8 weeks [1-2][4]

IVIG-resistant KD (fever ≥36 hours post-IVIG)

• Second IVIG dose (2 g/kg) — but consider hemolysis risk in non-type O blood [2]
• Alternatives: infliximab (5 mg/kg IV), IV methylprednisolone pulse (30 mg/kg × 1–3 days), anakinra, cyclosporine [2]

Giant aneurysms (Z ≥10 or ≥8 mm)

• Systemic anticoagulation (LMWH or warfarin) + antiplatelet therapy [8]
• Frequent echocardiograms for thrombus surveillance [8]

The following figure from Newburger et al. illustrates the comprehensive management algorithm from diagnosis through long-term risk-stratified follow-up:

Admission criteria

• All patients meeting complete or incomplete KD criteria
• Unexplained prolonged fever in infants <6 months
• KD shock syndrome → ICU admission

Discharge criteria

• Afebrile ≥48 hours after IVIG completion
• Clinically improving, tolerating oral intake
• Echocardiogram obtained and follow-up plan established
• Parents educated on fever monitoring and return precautions

Specialist consultation triggers

• Pediatric cardiology: all confirmed/suspected KD cases for echocardiography [2]
• Pediatric rheumatology: IVIG-resistant or refractory KD, suspected MAS [2]
• Pediatric infectious disease: diagnostic uncertainty, concern for MIS-C or other mimics

Follow-up timing

• 1–2 weeks post-discharge: repeat echocardiogram and clinical assessment [1]
• 4–6 weeks: echocardiogram if prior imaging abnormal; if all echos normal and patient responded to therapy, further cardiac follow-up may not be needed [1]
• Patients with CAA: follow-up per AHA risk stratification — ranges from annual to biannual cardiology visits with advanced imaging for those with persistent aneurysms [7][14]

Daily fever monitoring for 1–2 weeks post-discharge — parents should be instructed on proper temperature measurement and told to contact the physician immediately if fever recurs [2]

Return precautions — seek immediate care for

• Recurrence of fever (>38°C) after discharge → urgent echocardiogram needed [1-2]
• New rash, conjunctival injection, or mucocutaneous changes
• Chest pain, shortness of breath, or signs of heart failure
• Pallor, jaundice, dark urine (hemolytic anemia post-IVIG)
• Excessive irritability or lethargy

Patient/parent counseling

• KD is part of the child's permanent medical history — ensure it is documented [7]
• Low-dose aspirin continues for minimum 6–8 weeks; avoid ibuprofen while on aspirin
• Defer live vaccines (MMR, varicella) for 11 months after IVIG [1]
• Contact physician if child is exposed to influenza or varicella while on aspirin (Reye syndrome risk)
• Expected recovery: most children recover fully; periungual desquamation in weeks 2–3 is expected and not a sign of worsening
• Long-term: patients with no coronary involvement can be discharged from cardiology at 4–6 weeks; those with aneurysms require lifelong cardiology follow-up [7][14]