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Kawasaki disease

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  • See also

    Intravenous immunoglobulin 
    Febrile child 
    Sepsis – assessment and management

    NB Cases of PIMS-TS – a novel post infectious systemic hyperinflammatory syndrome – have been reported in children in Victoria. See alert

    Key Points

    1. Kawasaki disease (KD) is a clinical diagnosis that requires prompt recognition and management
    2. Consider incomplete KD where there is prolonged fever and no alternative cause found
    3. Infants and adolescents may present with incomplete KD and are at particularly high risk of developing coronary artery aneurysms
    4. Early treatment with intravenous immunoglobulin (IVIg) has been shown to reduce morbidity and mortality

    Background

    KD is the second most common vasculitis in childhood after Henoch Schönlein purpura, and is the most common cause of acquired heart disease in children in high-income countries. Lack of appropriate treatment leads to coronary artery aneurysms (CAA) in approximately 25% of cases.

    • Worldwide distribution, although more common in Asian children
    • Approximately 75% of cases occur under 5 years of age
    • Less common in children <6 months and >5 years; however these children are more likely to develop CAA
    • Can present without all diagnostic criteria (see flowchart below) which can present a significant diagnostic challenge

    Assessment

    History

    Physical findings can present sequentially over a number of days, thus history should include asking about diagnostic features that may have resolved by the time of presentation

    Examination

    Kawasaki disease: Diagnostic criteria
    Fever persisting for 5 days, PLUS 4 of the 5 following criteria:
    • A diagnosis earlier than 5 days can be made with a typical presentation in consultation with an experienced clinician
    • KD can be diagnosed with less than four of the following features if coronary artery abnormalities are present

    Criterion    

    Features

    Conjunctival injection

    Bilateral, non-exudative, painless. Often with limbic sparing (zone around the iris is clear)

    Rash

    Erythematous polymorphous rash occurs in the first few days, involving trunk and extremities
    Variable presentations, most commonly maculopapular, erythema multiforme-like or scarlatiniform
    Bullous, vesicular, or petechial rashes are not typical in KD

    Oral Changes

    Strawberry tongue

    Erythema, dryness, cracking and bleeding of the lips

    Diffuse oropharyngeal erythema
    Exudates are not typical of KD

    Extremity changes

    Hyperaemia and painful oedema of hands and feet that progresses to desquamation from the second week of illness

    Lymphadenopathy
     

    Cervical, most commonly unilateral, tender.  At least one node >1.5cm. Less common feature and seen in older children

       Photographs used with permission from the Kawasaki disease Foundation, Inc

    Common findings in addition to the diagnostic criteria include:

    • neurological: irritability, aseptic meningitis
    • GIT symptoms: abdominal pain, vomiting, diarrhoea, gallbladder hydrops
    • arthralgia / arthritis
    • dysuria
    • inflammation at recent (within 6 months) BCG vaccination site

    KD is a medium vessel vasculopathy; any organ system can be affected

    Incomplete Kawasaki disease

    Consider in a child with a clinical presentation suggestive of KD but not meeting the full diagnostic criteria

    • Requires abnormal investigation results to support the diagnosis (see flowchart)
    • Infants and adolescents often present with an incomplete picture and are at a higher risk for cardiac complications

    Consider incomplete KD in:

    • A child with fever for at least 5 days combined with 2 or 3 of the principal clinical features OR
    • An infant with one/more of the following features:
      • fever ≥7 days +/- irritability without other explanation
      • prolonged fever and unexplained aseptic meningitis
    • A child or infant with prolonged fever and:
      • shock
      • cervical adenitis not responsive to oral antibiotics
    • Incomplete KD can present a significant diagnostic dilemma, however once the diagnosis is made, the treatment for KD and incomplete KD is identical

    Incomplete Kawasaki disease

    Adapted from the American Heart Association (2017).

    Differential diagnosis

    • Group A streptococcal infections: tonsillitis, scarlet fever, acute rheumatic fever
    • Viral infections including EBV, CMV, Adenovirus, HHV-6, SARS-CoV-2
    • Systemic juvenile idiopathic arthritis (JIA)
    • Sepsis
    • Toxic shock syndrome (staphylococcal or streptococcal)
    • Stevens-Johnson syndrome
    • Drug reaction
    • Malignancy

    Management

    Investigations

    There is no diagnostic test for KD. Laboratory tests provide support for diagnosis, assessment of severity, and monitoring of disease and treatment

    • Echocardiogram: discuss with cardiology specific timing of initial and follow-up studies. Suggested schedule:
      • At presentation (this should not delay initiation of treatment)
      • 2 weeks
      • 6 weeks

    Coronary artery lesions should be managed in consultation with paediatric cardiology and haematology services

    • In all patients consider:
      • FBE, CRP, ESR, UEC, LFT (note ESR result unreliable after IVIg administration)
      • Blood culture
      • ASOT
      • Serum to store (prior to IVIg administration)
      • Urinalysis and culture (sterile pyuria)
      • COVID-19 swab
      • ECG

    Common abnormalities include elevation of ESR, CRP and neutrophils. Thrombocytosis is common in the second week of illness.

    Treatment

    1. INTRAVENOUS IMMUNOGLOBULIN (IVIg):  2 g/kg as a single IV infusion on diagnosis
      • IVIg should be given within the first 10 days of illness but should also be given to children diagnosed after 10 days if there is evidence of ongoing fever and/or inflammation
      • A second dose of 2 g/kg IVIg should be given to children who do not respond to the first dose, as demonstrated by persistent or recurrent fevers 36 hours after the end of the first IVIg infusion. Seek specialist advice
      • The National Blood Authority and BloodSTAR coordinate and authorise the use of blood products. IVIg is a product that must be ordered via their website
      • Haemolytic anaemia is an uncommon but recognised adverse effect of IVIg infusion, particularly for children receiving multiple doses. It typically occurs up to a week after IVIg administration
      • Post IVIg vaccination: live vaccines (eg measles and varicella) should be deferred after IVIg administration, see the National Immunisation Handbook. If the child is at high risk of measles, vaccinate and re-vaccinate after the appropriate period
    2. ASPIRIN :  3-5 mg/kg orally as a daily dose until normal echo on follow up (minimum 6 weeks)
      • There is minimal risk of Reye syndrome with low-dose aspirin
      • Avoid non-steroid anti-inflammatory medications whilst on aspirin
    3. CORTICOSTEROIDS: 
      • Evidence for indication and optimal dose/duration of adjunctive steroids in the primary treatment of KD is limited
      • Corticosteroid use in KD should be considered in consultation with specialist advice
      • Consider use in high-risk groups which include
        • Demographics: age <12 months of age, Asian ethnicity
        • Investigation abnormalities: ALT >100 IU/L, albumin ≤30 g/L, sodium ≤133 mmol/L, platelets ≤30 x 109/L, CRP >100 mg/L, anaemia for age
        • Cardiac or coronary artery involvement on echo at presentation
    4. ADDITIONAL TREATMENTS: A number of therapies are available for consideration in patients who are not responsive to initial IVIg. These options should only be used in consultation with local paediatric specialists and include biological medicines such as infliximab

    Consider consultation with local paediatric team when

    • Kawasaki disease is suspected
    • Child does not respond to initial treatment

    Consider transfer when

    • Child has cardiac involvement or timely echocardiography is unavailable locally (in consultation with the paediatric cardiology team)
    • Children requiring care above the level of comfort of the local hospital

    For emergency advice and paediatric or neonatal ICU transfers, see Retrieval Services

    Consider discharge when

    • Afebrile and well at least 36 hours after treatment
    • Children are on a daily dose of aspirin (see treatment point 2 above)
    • A follow-up plan is in place including general paediatric review and repeat echocardiograms planned with cardiology

    Parent information

    RCH Kid’s Health Info: Kawasaki disease
    Sydney Children’s Hospital network fact sheets: Kawasaki disease

    Last Updated January 2021

  • Reference List

    1. American Heart Association. (2017). Diagnosis, treatment, and long-term management of Kawasaki Disease. Circulation, 135. DOI: 10.1161/CIR.0000000000000484
    2. Bernard, R., Whittemore, B., & Scuccimarri, R. (2012). Hemolytic anemia following intravenous immunoglobulin therapy in patients treated for Kawasaki disease: a report of 4 cases. Pediatric Rheumatology Online Journal. 10. doi: 10.1186/1546-0096-10-10
    3. Butters, C., Curtis, N., Burgner, D. P. (2020). Kawasaki disease fact check: Myths, misconceptions and mysteries. J Paediatr Child Health, 56(9), 1343-1345.
    4. Cohen, E. & Sundel, R. (2016). Kawasaki Disease at 50 years. JAMA Paediatrics, 170(11). Pp. 1093 – 1099.
    5. Dallaire, F. et al. (2017). Aspirin dose and prevention of coronary abnormalities in Kawasaki Disease. Paediatrics, 139(6). DOI: e20170098
    6. Dhanrajani, A., Chan, M., Pau, S., Ellsworth, J., Petty, R., & Guzman, J. (2017). Aspirin dose in Kawasaki Disease: the ongoing battle. Arthritis Care & Research, 70(10), pp. 1536-1540. DOI: 10.1002/acr.23504
    7. Guo Yang Ho, L. Curtis, N. (2017). What dose of aspirin should be used in the initial treatment of Kawasaki Disease? Archives of Disease in Childhood, 0, pp 1 – 3. Doi: 10.1136/archdischild-2017-313538
    8. Hedrich, C. M., Schnabel, A., & Hospach, T. (2018). Kawasaki Disease. Frontiers in Pediatrics, 6(198). doi: 10.3389/fped.2018.00198
    9. Ho, L. G. Y., Curtis, N. (2017). What dose of aspirin should be used in the initial treatment of Kawasaki disease? Arch Dis Child, 102(12), 1180-1182
    10. Huuang, X., Huuang, P., Zhang, L., Xie, X., Gong, F., Yuuan, J., & Jin, L. (2018). Is aspirin necessary in the acute phase of Kawasaki disease? Journal of Paediatrics and Child Health, 54, pp. 661-664. doi:10.1111/jpc.13816
    11. Jiang, L., Tang, K., Levin, M., Irfan, O., Morris, S. K. et al. (2020). COVID-19 and multisystem inflammatory syndrome in children and adolescents. Lancet Infectious Diseases. DOI:https://doi.org/10.1016/S1473-3099(20)30651-4
    12. Marchesi, A. et al. (2018). Kawasaki disease: guidelines of the Italian Society of Pediatrics, part I – definition, epidemiology, etiopathogeneis, clinical expression and management of the acute phase. Italian Journal of Pediatrics 44(102). doi.org/10.1186/s13052-018-0536-3
    13. Perth Children’s Hospital clinical practice guidelines. (2018). Kawasaki Disease. https://pch.health.wa.gov.au/For-health-professionals/Emergency-Department-Guidelines/Kawasaki-disease
    14. Phuong, L., K., Chen, K. Y., Burgner, D. P., & Curtis, N. (2020). What paediatricians need to know about the updated 2017 American Heart Association Kawasaki disease guideline. Arch Dis Child 105(1), 10-12
    15. Phuong, L. K., Curtis, N. Gowdie, P., Akikusa, J., & Burgner, D. (2018). Treatment options for resistant Kawasaki Disease. Paediatric Drugs, 20(1), 59-80.
    16. Rigante, D., Andreozzi, L., Fastiggi, M., Bracci, B., Natale, M. F., & Esposito S. (2016). Critical overview of the risk scoring systems to predict non-responsiveness to intravenous immunoglobulin in Kawasaki Syndrome. International Journal of Molecular Sciences, 17 (278). doi:10.3390/ijms17030278
    17. Sevenoaks, L., & Tulloh, R. (2020). Should we use steroids as primary therapy for Kawasaki disease? Archives of Disease in Childhood Published Online First: 03 August 2020. doi: 10.1136/archdischild-2020-319231
    18. Singh, S., Jindal, A. K., & Pilania, R. K. (2018). Diagnosis of Kawasaki disease. International Journal of Rheumatic Diseases, 21, pp. 36-44.
    19. Starship Clinical Guidelines. (2015). Kawasaki Disease. https://www.starship.org.nz/guidelines/kawasaki-disease/
    20. Wardle, A. J., Connolly, G. M., Seager, M. J., & Tulloh, R. M. R. (2017). Corticosteroids for the treatment of Kawasaki disease in children (Review). Cochrane Database of Systematic Reviews. DOI: 10.1002/14651858.CD011188.pub2.
    21. Younger, D. (2019). Epidemiology of the Vasculitides. Neurologic Clinics, 37 (2), pp. 201