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Kawasaki Disease

Date last published:

Kawasaki Disease is a multi-system vasculitis occurring mainly in children under 5 years old.

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Starship clinical guidelines

Key points

  • Kawasaki Disease is a clinical diagnosis and treatment should be commenced prior to ‘meeting diagnostic criteria’ if there is a strong clinical suspicion.

  • Admit to hospital if Kawasaki Disease is suspected.

  • Prompt recognition and treatment is required to reduce the risk of coronary aneurysm, the rates of which are increasing worldwide even with treatment.

  • All infants under 6 months must be treated aggressively and with more than just IVIG and aspirin – discuss all with paediatric rheumatology and cardiology at Starship and ensure infants have been thoroughly investigated for bacterial and viral infections. Discussion of complex cases and young infants with a paediatric infectious diseases specialist is encouraged.

  • Infants (under 1 year) are particularly high risk for coronary aneurysm and need careful monitoring of fever and CRP following treatment.

  • If risk factors for coronary aneurysm are present (see the risk factors list below), discuss with cardiology and rheumatology early as these patients may require individualized management.

  • In infants with isolated fever for 7 days, Kawasaki Disease should be considered.

Background

Kawasaki Disease is a multi-system vasculitis occurring mainly in children under 5 years old. Eighty-five percent of children with Kawasaki Disease are under 5 years old, but it can occur in older children and adolescents. It is most common in East Asian children, particularly Japanese. It is also more common in children of Pacific Island ethnicity.

The most concerning complication is the development of coronary artery aneurysms, which occurs in 20-25% of cases without treatment. Prompt treatment reduces the risk of aneurysm. However, rates of coronary artery aneurysms, even with treatment, are increasing worldwide, with some studies reporting 30% of infants who have been treated with IVIG still developing a coronary artery aneurysm.

Diagnosis

Kawasaki disease is a clinical diagnosis. Symptoms and signs evolve over days and some symptoms may be present only transiently. Studies show that up to 33% of cases have a confirmed infection and thus Kawasaki Disease still needs to be considered in cases with a “positive” infectious result1. Diagnosis can be challenging as symptoms and clinical signs can overlap with other infectious and inflammatory conditions. There is no single gold standard laboratory test and American Heart Association disease definitions are used to classify cases.

Complete Kawasaki Disease

  • Presence of fever for ≥5 days

    • An experienced clinician can make the diagnosis on day 4 if typical features are present

    • The first day of fever is day 1

  • Presence of 4 or 5 core clinical features (see table below)

Incomplete Kawasaki Disease

  • Presence of fever for ≥5 days

  • Presence of 2 or 3 core clinical features (see table below)

  • CRP > 30 and ESR >40

  • Presence of ≥3 supplemental laboratory features OR echocardiographic features of Kawasaki Disease (see below)

kawasaki criterion

Supplementary laboratory criteria

  • Anaemia for age

  • Albumin <30 g/L

  • White cell count >15 E+9/L

  • Platelets >450 E+9/L (after 7 days)

  • Elevated ALT >45

  • Urine white cells >10 per high powered field

Positive Echocardiogram findings

  • Z score of right coronary artery (RCA) or left anterior descending artery (LAD ≥2.5)

  • Presence of ≥3 suggestive features:

    • Lack of tapering of coronary arteries

    • Perivascular brightness

    • Pericardial effusion

    • Mitral regurgitation

    • Left Ventricular (LV) dysfunction

    • Z score 2.0-2.5

Other possible features

  • Extreme irritability

  • Severe abdominal pain, diarrhoea and vomiting

  • Hepatic dysfunction

  • Gallbladder hydrops

  • Urethritis with sterile pyuria

  • Aseptic meningitis

  • Arthritis/arthralgia

  • Carditis with congestive heart failure

  • Arrhythmia

Incomplete Kawasaki Disease

Incomplete Kawasaki Disease is diagnostically challenging and carries a higher risk of coronary aneurysm.

Incomplete Kawasaki Disease should be considered in children:

  • with fever for 5 or more days

  • under 1 year with unexplained fever and irritability

  • with prolonged fever with shock

  • with cervical adenitis not responding to antibiotic therapy

Below is an adaptation of the American Heart Association diagnostic algorithm for Incomplete Kawasaki Disease (McCrindle et al. 2017).

Image: Kawasaki Disease - 218

Differential diagnoses

  • Viral infections: EBV, CMV, adenovirus, parvovirus, enterovirus, HHV-6

  • Scarlet fever

  • Rheumatic fever (in older children)

  • Stevens-Johnson syndrome

  • Toxic shock syndrome (staph or strep)

  • Sepsis

  • Drug reaction

  • Multi-system Inflammatory Syndrome in Children, associated with SARS-Cov-2 infection

  • Systemic JIA

  • Other vasculitis: polyarteritis nodosa

  • If endemic risk factors: leptospirosis, Rocky Mountain spotted fever

Investigations

There is no single diagnostic test for Kawasaki Disease. Recommend:

  • FBC, CRP, UEC, LFT

  • ESR (note, cannot be interpreted once IVIG has been given)

  • Blood culture

  • Serum to save in laboratory (must be obtained prior to IVIG administration)

  • Urinalysis

  • Nasopharyngeal swab (extended panel) for respiratory pathogens

  • CXR

  • ECG

 

Inpatient Paediatric Cardiology assessment and echocardiogram are indicated if:

  • children under 1 year of age

  • there is persistent fever and inflammation (CRP not improving) >36 hours after IV immunoglobulin (non-responder)

  • the child is treated beyond 10 days of illness (late presenter)

  • there are ECG changes suggestive of myocardial ischaemia

  • there is a murmur of mitral regurgitation

  • there are signs of congestive heart failure

  • the diagnosis is unclear but strongly suspected

Adequate visualization of the coronary arteries is difficult in young, irritable children. The timing and site of the echocardiogram, and the need for sedation, should be discussed with Paediatric Cardiology on a case-by-case basis.

There is no indication for inpatient echocardiography in those who present early, have no risk factors and receive IVIG (<10 days), and respond to IVIG with prompt resolution of fever and falling CRP. This is supported by NZPSU surveillance data (Heaton et al. 2006) and a recent observational study of 162 cases in Tamaki Makaurau (Harrowell et al. 2024; in press).

Coronary Aneurysms

  • Prevention of coronary aneurysms is the priority of treatment.

  • Coronary aneurysms usually appear 2 to 4 weeks into the illness but can be found as early as 3 days. Appearance later than 6 weeks is uncommon.

  • Acute complications of aneurysm can include thrombosis, rupture, stenosis and ischemia. Longer term cardiac morbidity and mortality is also raised (Lee et al. 2022).

Risk factors include:

  • Age <1 year or older than 5 years

  • Fever for > 10 days at presentation

  • Persisting fever and inflammation (CRP) after first dose of IVIG

  • Incomplete Kawasaki Disease

  • Asian ethnicity

  • Pacific ethnicity (unpublished NZ data)

  • Male gender

  • Significant laboratory abnormalities - platelets ≤30 E 10^9/L, albumin≤30 g/L, ALT >100 IU/L, sodium ≤133, liver transaminases (ALT >100), anaemia, CRP >100

Immunomodulatory treatment

Treatment aims to rapidly "switch off" the inflammatory process, minimise coronary artery inflammation and subsequent aneurysm formation. Specific therapy must be given early to be most effective, so it should be given as soon as the diagnosis is strongly suspected.

First lineFirst dose IVIg
Second lineCorticosteroids and/or second dose IVIg
Third lineSeveral agents available - infliximab or anakinra most commonly used
AllAspirin

Intravenous immunoglobulin (IVIG) 2 grams/kg over 10-12 hours

  • This is the primary treatment for all patients with Kawasaki Disease.

  • A second dose of IVIG can be given to children who do not respond to the first dose (ongoing fever / signs of inflammation) after 36 hours although steroids should also be considered then.

  • Infusion rates differ between Privigen and Intragam-P. Please check Starship Clinical Guidelines regarding administration.

  • IVIG should still be administered if the child presents later in their illness (ie. after day 10).

Corticosteroids (discuss with rheumatology)

Corticosteroids are increasingly considered required for children with risk factors for coronary aneurysm, particularly those under 1 year and/or who do not respond to the first dose of IVIG. In some instances, it may be appropriate for corticosteroids to be given alongside the first dose of IVIG or instead of the second dose of IVIG. Use of corticosteroids in KD should be discussed with rheumatology and after excluding infection.

Evidence for the best steroid regimen is lacking. Suggested regimens include:

  • Methylprednisolone 2-10 mg/kg (up to a maximum of 1g daily) once daily for 3 days, followed by oral prednisolone 2 mg/kg/day until day 7 or until CRP normalizes; then wean over the next 2-3 weeks.

  • Note need careful monitoring of blood pressure when diagnosed with Kawasaki Disease, and particularly if also using steroids to treat.

Other treatments (for treatment-refractory KD)

There are a number of additional therapies that can be used for treatment refractory KD. These cases should be discussed with Pediatric Rheumatology. Potential options include, Infliximab, Anakinra, Ciclosporin, Cyclophosphamide and Plasma Exchange.

Aspirin

  • All patients should be commenced on aspirin 3 to 5 mg/kg/day (once daily).

  • Dosing as above (which is low dose) is for antiplatelet effect rather than anti-inflammatory effect.

  • The child should stay on aspirin until they have been reviewed in cardiology clinic. Ongoing need for aspirin or other antiplatelet/anticoagulation medication will be determined by cardiology at follow-up.

  • Aspirin is available in 300 mg soluble tablets and 100 mg enteric-coated tablets. Use soluble tablets dissolved in water to administer part doses and consider enteric coated tablets for older children.

Follow-up

Initially after discharge: Children should remain in hospital until afebrile for 24 hours, clinically improving and inflammatory markers and biochemistry steadily improving. Families should be advised to return to hospital for medical review if fever or other symptoms recur in the days following discharge. For high-risk children, particularly under 1 year, the CRP should be monitored to ensure it is improving and continues to improve (ie. check every 48 hours initially, then weekly until normalized).

4 - 6 weeks after presentation: Cardiology outpatient clinic for clinical review, ECG and echocardiogram.

Further follow-up will be determined in Cardiology clinic.

Subsequent Immunisation

Measles and other live virus vaccines (i.e. varicella) should be deferred for 11 months following high-dose IVIG treatment. Alternatively, a child at high risk of measles could be vaccinated, then re-vaccinated at least 11months after the administration of IVIG. See https://www.tewhatuora.govt.nz/for-health-professionals/clinical-guidance/immunisation-handbook/appendix-6-passive-immunisation

Other routine immunisations should not be interrupted.

Annual influenza vaccination is recommended for children with coronary aneurysms on aspirin.

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