Kawasaki disease

Last updated 28 Mar 2026 · Vasculitis

Kawasaki Disease

Kawasaki disease (KD) is an acute, self-limiting systemic vasculitis predominantly affecting medium-sized vessels, particularly the coronary arteries, in infants and young children. It is the leading cause of acquired heart disease in children in developed countries, including Australia. Without treatment, coronary artery aneurysms develop in 15–25% of affected children. Early diagnosis and treatment with intravenous immunoglobulin (IVIG) and aspirin reduces aneurysm risk to less than 5%. KD is characterised by prolonged fever with a constellation of clinical features and no specific diagnostic test.

Australian Epidemiology

KD is the most common cause of acquired heart disease in Australian children. Incidence in Australia is approximately 9–15 per 100,000 children under 5 years annually. Higher rates are observed in children of Asian descent (Japanese, Korean, Chinese). Peak age of onset is 6 months to 5 years. Boys are affected 1.5 times more frequently than girls. The cause remains unknown — an infectious trigger in a genetically susceptible host is the leading hypothesis.

Pathophysiology

Vasculitis of Medium Vessels

KD is characterised by acute necrotising vasculitis of medium-sized arteries, with predilection for the coronary arteries. The pathogenesis involves an abnormal immune response — likely triggered by an infectious agent — in genetically susceptible children. Innate immune activation with IL-1β, IL-6, and TNF-α overproduction drives endothelial injury and vascular inflammation. Activated neutrophils and macrophages infiltrate the arterial wall, causing necrosis and aneurysm formation.

Coronary Artery Complications

Coronary artery inflammation causes dilation (z-score ≥2) and aneurysm formation (z-score ≥2.5). Giant aneurysms (internal diameter ≥8 mm) carry high risk of thrombosis, myocardial infarction, and sudden death. The risk of coronary aneurysm is highest in children under 12 months and in IVIG-resistant disease. Coronary artery abnormalities may persist for years and require long-term cardiology follow-up.

Clinical Presentation

Diagnostic Criteria (Classic KD)

Fever ≥5 days PLUS 4 or more of the following principal features:

Bilateral non-exudative conjunctival injection — bulbar conjunctivae, typically limbal sparing
Oral changes — erythematous/cracked lips, strawberry tongue, erythema of oral/pharyngeal mucosa
Polymorphous rash — maculopapular, urticarial, or erythrodermic; trunk and extremities; perineal desquamation
Changes in extremities — erythema/oedema of hands and feet (acute phase); periungual desquamation (subacute, days 10–21)
Cervical lymphadenopathy — usually unilateral, ≥1.5 cm, non-suppurative

Incomplete (Atypical) KD

Fever ≥5 days with fewer than 4 principal features but with compatible laboratory findings and echocardiographic evidence of coronary involvement. Incomplete KD is more common in infants under 12 months and carries a higher risk of coronary aneurysm than classic KD. The American Heart Association algorithm guides diagnosis of incomplete KD.

Other Features

Extreme irritability (particularly in infants), arthritis or arthralgia, abdominal pain, diarrhoea, vomiting, urethritis with sterile pyuria, hepatitis, hydrops of gallbladder, and aseptic meningitis. Macrophage activation syndrome is a rare but life-threatening complication.

Investigations

Essential
Echocardiography
Cornerstone of KD diagnosis and management. Assess coronary artery dimensions (z-scores), left ventricular function, pericardial effusion, and valvular regurgitation. Perform at diagnosis, 2 weeks, and 6–8 weeks. Z-score ≥2 indicates dilation; ≥2.5 indicates aneurysm.
Essential
CRP and ESR
Markedly elevated. CRP >30 mg/L supports KD diagnosis. ESR typically >40 mm/hr. Serial CRP useful to assess IVIG response.
Essential
Full Blood Count
Neutrophilia and leukocytosis in acute phase. Thrombocytosis in subacute phase (days 10–21; platelet count may exceed 1000 × 10⁹/L) is characteristic. Anaemia of inflammation common.
Essential
Urinalysis
Sterile pyuria (WBCs without bacteria) in up to 80% of KD cases. Important diagnostic clue, particularly in infants.
Available
ALT and Albumin
Elevated ALT in 40–60%. Low albumin (<30 g/L) is associated with IVIG resistance and higher coronary risk. Baseline liver function important before IVIG.
Available
Blood Culture and Throat Swab
To exclude bacterial mimics (sepsis, group A streptococcal infection, staphylococcal toxic shock). KD is a diagnosis of exclusion in the context of bacterial infection.

Risk Stratification

LOW RISK

No Coronary Involvement

Classic KD, normal coronary echo, responds to single IVIG dose

IVIG 2 g/kg + aspirin; outpatient follow-up; echo at 2 and 6–8 weeks

MODERATE RISK

Coronary Dilation

Z-score 2–2.5, incomplete KD, IVIG resistance, age <12 months

Repeat IVIG ± infliximab; low-dose aspirin ongoing; cardiology follow-up; anticoagulation consideration

HIGH RISK

Giant Aneurysm

Z-score ≥10 or diameter ≥8 mm; thrombosis risk; myocardial ischaemia

Anticoagulation (warfarin or LMWH) + antiplatelet therapy; urgent paediatric cardiology; long-term surveillance

Risk scoring systems (Kobayashi, Egami, Sano) identify children at high risk of IVIG resistance, allowing more aggressive initial therapy. These scores incorporate clinical and laboratory features including sodium, CRP, ALT, and age at diagnosis.

Treatment Strategy

First-Line: IVIG + Aspirin

Intravenous immunoglobulin (IVIG) 2 g/kg as a single infusion over 10–12 hours is the cornerstone of KD treatment. IVIG significantly reduces coronary aneurysm risk when given within the first 10 days of fever. Treatment after day 10 is still recommended if fever persists or inflammatory markers remain elevated. High-dose aspirin (30–50 mg/kg/day in 4 divided doses) is given during the febrile phase; switch to low-dose aspirin (3–5 mg/kg/day once daily) once afebrile for 48 hours, continuing for 6–8 weeks (or longer if coronary abnormalities persist).

IVIG-Resistant KD

Defined as persistent or recurrent fever ≥36 hours after IVIG completion. Occurs in 10–20% of cases and carries higher coronary risk. Options include a second dose of IVIG 2 g/kg, infliximab 5 mg/kg IV (single dose), or corticosteroids (prednisolone 2 mg/kg/day or IV methylprednisolone pulses). Infliximab has shown equivalent efficacy to second IVIG dose in some studies with faster fever resolution.

Adjunctive Corticosteroids

Corticosteroids (prednisolone 2 mg/kg/day for 2 weeks with taper) combined with IVIG as primary therapy for high-risk patients (Kobayashi score ≥5) reduce aneurysm risk in high-risk Japanese children. Evidence in non-Japanese populations is less robust. Paediatric rheumatology or cardiology guidance recommended before primary corticosteroid use.

Directed Therapy

💉

IVIG (Intravenous Immunoglobulin)

Intragam®, Privigen® · Anti-inflammatory

Adult DoseN/A (paediatric disease)

Paediatric2 g/kg as single infusion

RouteIntravenous infusion over 10–12 hours

FrequencySingle dose; repeat if IVIG-resistant

DurationSingle infusion in acute phase

Renal Adj.Use with caution in renal impairment; use sucrose-free formulation

Hepatic Adj.No adjustment required

PBS StatusPBS Authority Required

💊

Aspirin

Astrix®, Cartia® · Antiplatelet/Anti-inflammatory

Paediatric (Acute)30–50 mg/kg/day in 4 divided doses (febrile phase)

Paediatric (Maintenance)3–5 mg/kg/day once daily (once afebrile × 48 hrs)

RouteOral

Duration (Low Risk)6–8 weeks (until echo normal at 6–8 weeks)

Duration (Aneurysm)Indefinitely while coronary aneurysm persists

PBS Status✓ PBS General Benefit

💉

Infliximab

Remicade®, Inflectra® · TNF-α Inhibitor · IVIG-resistant KD

Paediatric5 mg/kg IV single dose

RouteIntravenous infusion

FrequencySingle dose for IVIG-resistant KD

Renal Adj.No adjustment required

Hepatic Adj.Caution in hepatic impairment

PBS StatusNot PBS listed for KD

Acute Management

Inpatient Management

All children with suspected KD should be admitted to hospital for IVIG administration, monitoring, and echocardiography. IVIG should be given as soon as possible once KD is diagnosed — ideally within the first 10 days of fever. Pre-medication with paracetamol and antihistamine is standard practice. Monitor for IVIG adverse reactions (headache, flushing, rigors). Discontinue live vaccines for 11 months following IVIG administration.

IVIG-Resistant Management Algorithm

Persistent fever ≥36 hours post-IVIG completion: reassess diagnosis; consider blood cultures and echocardiography. Exclude Macrophage Activation Syndrome (MAS). Options in order: (1) Repeat IVIG 2 g/kg; (2) Infliximab 5 mg/kg IV; (3) IV methylprednisolone 30 mg/kg/day × 3 days; (4) Ciclosporin for refractory cases. Discuss all IVIG-resistant cases with paediatric rheumatology and/or cardiology.

Anticoagulation for Giant Aneurysms

Giant coronary aneurysms (z-score ≥10 or diameter ≥8 mm) require anticoagulation to prevent thrombosis. Options include warfarin (target INR 2–3) combined with low-dose aspirin, or low-molecular-weight heparin. Enoxaparin may be preferred in young infants. Management requires paediatric cardiology guidance. Aspirin alone insufficient for giant aneurysms.

Monitoring and Follow-up

Echocardiography Schedule

At Diagnosis

Baseline echocardiography — assess coronary z-scores, LV function, pericardial effusion, valvular regurgitation

Day 14 (2 weeks)

Repeat echo — assess coronary response to IVIG; detect new or evolving aneurysms

Weeks 6–8

Echo — most aneurysms resolve by this time in low-risk cases; assess for persistent coronary abnormalities

6–12 Monthly

Echo annually for patients with persistent coronary abnormalities or aneurysms; cardiology specialist follow-up

Discontinuing Aspirin

Low-dose aspirin can be discontinued at 6–8 weeks if echo is normal and inflammatory markers have normalised. Aspirin should be continued indefinitely in patients with persistent coronary artery abnormalities. Avoid aspirin during active varicella or influenza due to Reye syndrome risk — substitute clopidogrel temporarily if required.

Special Populations

👶 Infants Under 12 Months

Higher Aneurysm RiskInfants under 12 months are at highest risk of coronary aneurysms and IVIG resistance. Maintain high index of suspicion for incomplete KD — diagnostic criteria may not be fully met. Low threshold for echocardiography in febrile infants with unexplained irritability.

Incomplete KDClassic features often absent in infants. Persistent unexplained fever with elevated CRP/ESR and sterile pyuria in an infant warrants echocardiography to evaluate for coronary involvement.

🛡️ KD Shock Syndrome

Haemodynamic InstabilityKD shock syndrome (KDSS) occurs in 5–7% of KD cases. Characterised by hypotension, tachycardia, and haemodynamic instability requiring fluid resuscitation. Higher rates of IVIG resistance, mitral regurgitation, and coronary aneurysms. ICU-level care may be required.

TreatmentAggressive fluid resuscitation + IVIG + high-dose aspirin. Consider corticosteroids as adjunct therapy. Paediatric cardiology and intensivist co-management essential.

Aboriginal and Torres Strait Islander Health Considerations

Aboriginal and Torres Strait Islander Health

Kawasaki disease affects all racial groups, including Aboriginal and Torres Strait Islander children, though precise Australian prevalence data in this population are limited. Febrile illness in young Aboriginal and Torres Strait Islander children in remote communities is common and often infectious in origin, which may make KD recognition more challenging. Access to echocardiography and paediatric specialist services is limited in regional and remote areas, creating potential for delayed diagnosis and treatment.

Diagnostic Challenges

Many features of KD (rash, conjunctivitis, mucositis) overlap with common childhood infections. A prolonged fever (>5 days) with systemic features in any child — regardless of location — should prompt KD consideration. Arrange urgent telehealth paediatric review if KD is suspected in a remote setting.

Echocardiography Access

Echocardiography is essential for KD diagnosis and follow-up but not available in most remote communities. Patient transfer to a regional or metropolitan centre is required for IVIG administration and echocardiography. Expedite transfer to avoid treatment delay beyond day 10 of fever.

IVIG Administration

IVIG requires hospital admission and specialist oversight. Remote community children with suspected KD should be transferred urgently to the nearest facility capable of providing IVIG therapy and paediatric monitoring. Do not delay transfer pending specialist availability.

Follow-up Continuity

Long-term echocardiographic follow-up for children with coronary abnormalities requires coordination between remote health services and paediatric cardiology. Use shared care plans, telehealth review, and patient held records to ensure continuity of cardiac surveillance.

Antimicrobial Stewardship

Antibiotic Use in Kawasaki Disease

KD is not a bacterial infection and antibiotics have no disease-modifying role. However, empirical antibiotics are often commenced in febrile children before KD is recognised. Key stewardship principles:

Discontinue empirical antibiotics once KD is diagnosed and bacterial infection excluded — prolonged antibiotic use increases Clostridioides difficile risk and antibiotic resistance
Blood cultures and throat swabs should be taken before commencing antibiotics in febrile children — negative cultures help support KD diagnosis
Group A streptococcal infection should be excluded (throat swab) as it can mimic KD; treat confirmed streptococcal infection appropriately
Live vaccines (MMR, varicella) must be deferred for 11 months after IVIG administration due to impaired vaccine response
Influenza vaccination recommended annually for children on long-term aspirin (due to Reye syndrome risk from aspirin during influenza)

⚠️

Reye Syndrome: Children on long-term aspirin should receive annual influenza vaccination. During confirmed varicella or influenza infection, temporarily substitute aspirin with clopidogrel to reduce Reye syndrome risk.

References

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McCrindle BW, Rowley AH, Newburger JW, et al. Diagnosis, Treatment, and Long-Term Management of Kawasaki Disease: A Scientific Statement for Health Professionals From the American Heart Association. Circulation. 2017;135(17):e927-e999.
02
Newburger JW, Takahashi M, Gerber MA, et al. Diagnosis, treatment, and long-term management of Kawasaki disease: a statement for health professionals from the Committee on Rheumatic Fever, Endocarditis and Kawasaki Disease. Circulation. 2004;110(17):2747-2771.
03
Eleftheriou D, Levin M, Shingadia D, et al. Management of Kawasaki disease. Arch Dis Child. 2014;99(1):74-83.
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Pilania RK, Bhatt GC, Bhattarai D, Singh S. Kawasaki disease in the developing world. Paediatr Int Child Health. 2020;40(2):87-98.
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Paediatric Society of Australia and New Zealand. Kawasaki Disease Clinical Practice Guidelines. Sydney: PSANZ; 2020. Available from: https://www.racp.edu.au
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Tacke CE, Burgner D, Kuipers IM, et al. Kawasaki disease epidemiology in a prospective, population-based surveillance study in the Netherlands. Arch Dis Child. 2016;101(4):341-347.
07
Kobayashi T, Inoue Y, Takeuchi K, et al. Prediction of intravenous immunoglobulin unresponsiveness in patients with Kawasaki disease. Circulation. 2006;113(22):2606-2612.
08
Tremoulet AH, Jain S, Jaggi P, et al. Infliximab for intensification of primary therapy for Kawasaki disease. Lancet. 2014;383(9930):1731-1738.
09
Burgner D, McMahon JL, Dargaville P, et al. Kawasaki disease in Australia. Arch Dis Child. 2002;86(1):49-52.
10
Oates-Whitehead RM, Baumer JH, Haines L, et al. Intravenous immunoglobulin for the treatment of Kawasaki disease in children. Cochrane Database Syst Rev. 2003;(4):CD004000.