Understanding Kawasaki Disease in Children

 

Kawasaki disease (KD) is named after the Japanese pediatrician Tomisaku Kawasaki who in 1967 described 50 cases of infants with persistent fever, accompanied by rash, lymphadenopathy, edema, conjunctival injection, redness and cracking of the lips, "strawberry tongue," and convalescent desquamation.

Kawasaki Disease, also known as mucocutaneous lymph node syndrome, is a self-limited medium-sized vasculitis that primarily affects children. It is the leading cause of acquired heart disease in children in developed countries. Let’s break down the key points:

Classic KD (Typical KD)

Clinical diagnosis based on at least 4 of 5 clinical criteria.

Typically occurs in children aged 6 months to 6 years.

Criteria include:

• Fever lasting ≥ 4 days.
• Presence of at least 4 of the following features:
• Polymorphous rash (desquamation, morbilliform, erythema multiforme).
• Cervical lymphadenopathy (usually unilateral, ≥ 1.5 cm).
• Changes in lips/oral mucosa (strawberry tongue/ulcerations).
• Extremity changes (swelling, erythema).
• Nonexudative conjunctivitis with limbic sparing.

Diagnosis is clinical, but lab studies (elevated white blood cell count, inflammation markers, liver enzymes) can assist.

Incomplete KD (Atypical KD)

Challenging diagnosis.

Patients lack atypical features but have fewer classic features.

Criteria: 5 days of fever and 2-3 clinical features.

Infants ≤ 6 months are at higher risk for coronary artery lesions.

Treatment and Timing

Intravenous immunoglobulin (IVIG) reduces coronary artery disease risk (from 25% to 4%) if appropriately timed.

Early treatment is essential to prevent cardiac abnormalities.

Emergency Care of Kawasaki Disease (KD)

Patients often arrive in the emergency room with prolonged fevers. A thorough history and physical exam are crucial to differentiate KD from other illnesses.

Classic KD (Typical KD):

Diagnosed clinically.

Emergency center (EC) management involves obtaining labs, echocardiogram, and administering intravenous immunoglobulin (IVIG).

Incomplete KD (Atypical KD):

More challenging to diagnose.

Patients without elevated inflammatory markers are less likely to have KD, but clinical judgment matters.

Clinical Criteria for Classic KD:

Fever lasting ≥ 4 consecutive days (measured over 38°C).

At least 4 clinical symptoms suggestive of KD (e.g., mucositis, rash, large lymph nodes).

Fever alone doesn’t confirm Classic KD.

Other Considerations:

Viral and bacterial illnesses (e.g., influenza, adenovirus, strep pharyngitis) can trigger KD.

Age matters: Classic KD usually occurs between 6 months and 6 years, while Incomplete KD can happen at any age.

Consult an Infectious Disease specialist if the diagnosis is uncertain.

Multisystem Inflammatory Syndrome in Children (MIS-C)

In 2020, institutions noted severe inflammatory syndrome resembling KD in pediatric patients with recent COVID-19 infection.

MIS-C should be considered in patients with KD-like features and a history of COVID infection.

Inpatient management for Kawasaki Disease (KD)

Primary Treatment:

IVIG (Intravenous Immunoglobulin):

Administer high-dose IVIG (2g/kg) as a single infusion within 10 days of illness onset.

Do not delay treatment for echocardiogram or specialty consultation.

IVIG Beyond 10 Days:

Generally avoid administering IVIG beyond the tenth day of illness unless specific criteria are met:

Persistent fever without other explanation.

Coronary artery abnormalities with ongoing systemic inflammation (elevated ESR or CRP >3 mg/dL).

Avoid Routine Methylprednisolone with IVIG:

Single-dose pulse methylprednisolone is not recommended as routine primary therapy.

Consider Corticosteroids for High-Risk Patients:

Consider longer corticosteroid course (tapering over 2–3 weeks) along with IVIG and Aspirin (ASA) for high-risk patients.

High-risk criteria: infants <6 months, patients with large or giant aneurysms.

No consensus on prediction scores for IVIG resistance in North America.

ASA Administration:

Reasonably administer moderate (30–50 mg/kg/day) to high-dose (80–100 mg/kg/day) ASA until the patient is afebrile.

Evidence does not conclusively show reduction in coronary artery aneurysms.

Transition to Low-Dose ASA:

Consider transitioning to low-dose ASA (3-5 mg/kg once daily) upon discharge or when the patient returns to baseline.

If no improvement within 7 days, immediate follow-up with a physician is recommended.

IVIG-resistant patients in the context of Kawasaki Disease (KD)

IVIG Resistance:

Defined as persistent or recrudescent fever at least 36 hours and <7 days after the first IVIG infusion.

Treatment options:

Second IVIG Infusion:

Administer pooled polyclonal IG (2 g/kg) intravenously.

IVIG + Steroid:

Administer IVIG (2 g/kg) intravenously along with methylprednisolone (2 mg/kg/day) intravenously divided every 8 hours until afebrile.

Then switch to oral prednisone or prednisolone until C-reactive protein (CRP) normalizes, followed by a taper over 2–3 weeks.

Infliximab:

Monoclonal antibody against TNF-α.

Single infusion: 5 mg/kg intravenously over 2 hours.

Additional Options:

Cyclosporine:

Consider in refractory KD patients who have failed other treatments.

Immunomodulatory Monoclonal Antibodies (except TNF-α blockers), Cytotoxic Agents, or Plasma Exchange:

Rarely considered for highly refractory patients who haven’t responded to previous treatments.

Echocardiography Recommendations

Perform echocardiography when considering KD diagnosis.

Unavailability or technical limitations should not delay treatment.

Image coronary arteries and assess luminal dimensions using Z scores adjusted for body surface area.

Classification of coronary artery abnormalities:

• No involvement: Always Z-score <2.
• Dilation only: Z-score 2 to <2.5.
• Small aneurysm: Z-score >2.5 to <5.
• Medium aneurysm: Z-score >5 to <10 with absolute dimension <8 mm.
• Large or giant aneurysm: Z-score >10 or absolute dimension >8 mm.

Positive Echocardiogram for Kawasaki Disease (KD) Includes:

Left anterior descending (LAD) or right coronary artery Z-score >2.5.

Any coronary artery aneurysm.

Three or more of the following:

Decreased left ventricular function.

Mitral regurgitation.

Pericardial effusion.

Left anterior descending (LAD) or right coronary artery Z-score between 2 and <2.5.

Note that other cardiac lesions associated with KD (e.g., valvular disease, myocarditis) should be discussed with cardiology and infectious disease specialists. 

Discharge Criteria & Follow-Up

Patient should be afebrile for >24 hours and show improved clinical status (less irritability, adequate hydration, and voiding).

Ensure all medications are sent to the pharmacy in advance.

Arrange consultations and follow-up appointments.

Recommend influenza vaccine (unless contraindicated) to prevent Reye’s Syndrome.

Avoid ibuprofen in children with coronary aneurysms taking aspirin.

Address transportation issues for families.

Ensure family understands follow-up instructions and when to seek immediate medical attention.

No live vaccines within 11 months after IVIG administration (e.g., MMR, varicella).

Follow-up:

Primary Care Physician within 1 week.

Cardiology outpatient follow-up (echocardiogram) in 1-2 weeks.

Infectious Disease follow-up in 1-2 weeks.

Documentation

Document concerns for KD:

Note if the patient is at higher risk (e.g., infants ≤ 6 months).

Explain why the patient is considered at higher risk (e.g., age-related factors).

Consider Other Diagnoses:

1. Dehydration:

Document at least 2 symptoms related to dehydration (e.g., capillary refill time, absent tears, dry mucous membranes, weight loss).

2. Acute kidney injury:

Consider and document any signs or symptoms suggestive of kidney dysfunction.

3. Transaminitis:

Be alert for elevated liver enzymes and document accordingly.

(Note: Please follow your hospital protocol for the diagnosis and management of Kawasaki Disease. The information in this blog is derived from the references below)

References:

https://www.cdc.gov/kawasaki/about/index.html

Owens AM, Plewa MC. Kawasaki Disease. [Updated 2023 Jun 26]. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2024 Jan-. Available from: https://www.ncbi.nlm.nih.gov/books/NBK537163/

LiJiang MDa†, et al COVID-19 and multisystem inflammatory syndrome in children and adolescents, The Lancet Infectious Diseases, Volume 20, Issue 11, November 2020, Pages e276-e288

McCrindle, B., Rowley, A., Newburger, J., et al. (2017). Diagnosis, treatment, and long-term management of Kawasaki disease: A scientific statement for health professionals from the American Heart Association. Circulation, 135, e927. http://circ.ahajournals.org/content/early/2017/03/29/CIR.0000000000000484

Newburger, J., Takahashi, M., Gerber, M., et al. (2004). Diagnosis, treatment, and long-term management of Kawasaki disease: A statement for health professionals from the committee on rheumatic fever, endocarditis and Kawasaki disease, council on cardiovascular disease in the young, American Heart Association. Circulation, 110(17), 2748. http://circ.ahajournals.org/content/110/17/2747.ful