Guide to Kawasaki Disease for Pediatric Patients

A Table for Diagnosis and Management of Kawasaki Disease

Diagnosis Criteria

Criteria	Description	Number of Criteria Required
Fever	Persistent fever lasting ≥ 5 days	1 (mandatory)
Erythematous Rash	Rash on the trunk and extremities, typically maculopapular and not vesicular
Bilateral Non-Exudative Conjunctivitis	Redness of both eyes without pus or discharge, with perilimbal sparing
Extremity Changes	Redness, swelling, and desquamation of hands and feet
Oral Changes	Red, cracked lips, strawberry tongue, and diffuse erythema of the oral and pharyngeal mucosa
Unilateral Cervical Lymphadenopathy	Enlargement of a single lymph node larger than 1.5 cm in diameter
Complete KD Diagnosis	Fever ≥ 5 days + 4 of the 5 clinical criteria listed above	4

Incomplete Kawasaki Disease Lab Criteria

Laboratory Test	Criteria	Number of Criteria Required
ESR or CRP	Elevated ESR (≥ 40 mm/hr) or CRP (≥ 3 mg/dL)	1 (mandatory)
Additional Lab Criteria	If ESR or CRP is elevated, 3 or more of the following:	3 out of 6
- Anemia for age
- White blood cell (WBC) count	≥ 15,000
- Platelet count	≥ 450,000 (typically after the first week)
- Elevated alanine transaminase (ALT)
- Serum albumin	< 3 g/dL
- Urine WBC	≥ 10 cells/high power field (HPF)

Management Dose

Treatment	Dosage	Notes
Intravenous Immunoglobulin (IVIg)	2 g/kg as a single infusion	Administer within the first 10 days of illness to reduce risk of coronary artery aneurysms.
High-Dose Aspirin	80-100 mg/kg/day divided into four doses	Until fever subsides for at least 48 hours.
Moderate-Dose Aspirin	30-50 mg/kg/day	If high-dose aspirin is not tolerated.
Low-Dose Aspirin	3-5 mg/kg/day	Continued for 6-8 weeks if no coronary abnormalities on follow-up echocardiograms.

Refractory KD Management

Treatment	Dosage	Notes
Second IVIg Dose	2 g/kg	For persistent fever ≥ 36 hours after the initial IVIg infusion.
Corticosteroids	Pulse methylprednisolone 30 mg/kg/day for 3 days	Used if refractory to IVIg.
Biologic Agents	Varies (e.g., infliximab, anakinra)	For cases refractory to IVIg and corticosteroids.

Summary Table for Management

Phase	Treatment	Dosage	Duration/Notes
Acute Phase	IVIg	2 g/kg	Single infusion within the first 10 days.
	High-Dose Aspirin	80-100 mg/kg/day (divided into 4 doses)	Until fever subsides for at least 48 hours.
	Moderate-Dose Aspirin	30-50 mg/kg/day	If high-dose aspirin is not tolerated.
Subacute Phase	Low-Dose Aspirin	3-5 mg/kg/day	Continued for 6-8 weeks if no coronary abnormalities.
Refractory KD	Second IVIg Dose	2 g/kg	If persistent fever ≥ 36 hours after initial IVIg.
	Corticosteroids	Pulse methylprednisolone 30 mg/kg/day for 3 days	For refractory cases.
	Biologic Agents	Varies	Used in refractory cases to IVIg and corticosteroids.

Definition

Kawasaki Disease (KD), also known as mucocutaneous lymph node syndrome, is an acute, self-limited vasculitis of medium-sized arteries. It predominantly affects children under the age of 5 and can lead to significant cardiovascular complications, notably coronary artery aneurysms if not promptly treated.

Epidemiology

Kawasaki Disease is most prevalent in children younger than 5 years, with the highest incidence in those under 2 years. In Thailand, the incidence is approximately 15 per 100,000 children. It occurs worldwide but is more common in Asian countries, particularly Japan.

Pathophysiology

The exact etiology of KD remains unknown, though it is believed to be triggered by an infectious agent in genetically predisposed individuals. The disease leads to widespread inflammation of medium-sized arteries, particularly the coronary arteries, causing aneurysms and other cardiovascular complications.

Clinical Presentation

Complete Kawasaki Disease

The diagnosis of complete KD is based on the presence of a fever lasting ≥ 5 days plus at least four of the following five clinical features:

Erythematous Rash:
- Typically, it appears on the trunk and extremities.
- Characteristically maculopapular and not vesicular.
- Rash may be polymorphous, including urticarial, erythema multiforme-like, or scarlatiniform.
Bilateral Non-Exudative Conjunctivitis:
- Redness of both eyes without pus or discharge.
- Perilimbal sparing (the area around the iris is less inflamed).
Extremity Changes:
- Redness and swelling of the hands and feet.
- Desquamation (peeling) of the fingers and toes usually occurs in the subacute phase.
Oral Changes:
- Red, cracked lips, strawberry tongue (red tongue with prominent papillae), and diffuse erythema of the oral and pharyngeal mucosa.
- These changes are often among the earliest symptoms.
Unilateral Cervical Lymphadenopathy:
- Typically, it involves a single lymph node larger than 1.5 cm in diameter.

Incomplete Kawasaki Disease

Incomplete KD should be suspected in children with a prolonged fever (≥ 5 days) and 2-3 of the above clinical criteria. Laboratory findings support the diagnosis:

Elevated Erythrocyte Sedimentation Rate (ESR) ≥ 40 mm/hr or C-Reactive Protein (CRP) ≥ 3 mg/dL.
If either ESR or CRP is elevated, look for three or more of the following lab criteria:
- Anemia for age.
- White blood cell (WBC) count ≥ 15,000.
- Platelet count ≥ 450,000 (typically after the first week).
- Elevated alanine transaminase (ALT).
- Serum albumin < 3 g/dL.
- Urine WBC ≥ 10 cells/high power field (HPF).

In cases where laboratory criteria are not conclusive, an echocardiogram may help diagnose KD by revealing coronary artery abnormalities.

Natural Course

Kawasaki Disease typically progresses through three distinct phases:

Acute Phase (1-2 weeks):
- High fever persisting for ≥ 5 days.
- Rash, conjunctivitis, oral changes, cervical lymphadenopathy, and extremity swelling.
- Laboratory findings may show elevated inflammatory markers (ESR, CRP), sterile pyuria, elevated liver enzymes, and hypoalbuminemia.
Subacute Phase (2-4 weeks):
- Resolution of fever and acute symptoms.
- Desquamation of fingers and toes.
- Thrombocytosis and increased risk of coronary artery aneurysms.
Convalescent Phase (4-8 weeks):
- Symptoms resolve, and lab values normalize.
- Coronary aneurysms may still develop or resolve during this phase.
- Follow-up echocardiography is crucial to monitor coronary artery status.

Diagnosis

Diagnosing KD requires a high index of suspicion, especially in children with prolonged fever and incomplete criteria. The diagnostic approach involves:

Clinical Criteria: As detailed above, considering complete and incomplete KD criteria.
Laboratory Tests:
- Complete Blood Count (CBC): Elevated WBC, anemia, thrombocytosis.
- Inflammatory markers: Elevated ESR and CRP.
- Liver function tests: Elevated ALT.
- Urinalysis: Sterile pyuria.
Echocardiography:
- Essential for all suspected cases to assess coronary artery involvement.
- Repeat echocardiograms are typically performed at diagnosis, 2 weeks, and 6-8 weeks after onset.

Differential Diagnosis

Kawasaki Disease must be differentiated from other febrile illnesses with similar presentations, including:

Multisystem Inflammatory Syndrome in Children (MIS-C):
- Associated with COVID-19.
- Presents with fever, gastrointestinal symptoms, rash, conjunctivitis, and cardiovascular involvement.
- Key differentiators: History of COVID-19 exposure, more prominent gastrointestinal symptoms, and often more severe myocardial involvement.
Scarlet Fever:
- Caused by Group A Streptococcus.
- Features include a sandpaper-like rash, fever, strawberry tongue, and Pastia lines.
- The presence of exudative pharyngitis and positive rapid streptococcal test help differentiate.
Measles:
- Caused by the measles virus.
- Characterized by a maculopapular rash, Koplik spots, conjunctivitis, and cough.
- History of exposure and lack of vaccination are key clues.
Toxic Shock Syndrome:
- Caused by Staphylococcus aureus or Streptococcus pyogenes toxins.
- Features include high fever, diffuse rash, desquamation, hypotension, and multi-organ involvement.
- Differentiated by rapid progression and presence of shock.
Stevens-Johnson Syndrome:
- Severe mucocutaneous reaction often triggered by medications or infections.
- Characterized by extensive mucosal involvement and skin detachment.
- Differentiated by more severe mucocutaneous involvement and targetoid lesions.
Viral Exanthems:
- Various viruses can cause fever and rash, such as enteroviruses and adenoviruses.
- Differentiated by milder clinical course and less consistent laboratory findings.

Management

Specific Treatment

Intravenous Immunoglobulin (IVIg):
- Dosage: 2 g/kg as a single infusion, administered within the first 10 days of illness.
- Benefit: Reduces the risk of coronary artery aneurysms from 20-25% to <5%.
- Administration: Start with a low infusion rate and increase gradually to minimize the risk of adverse reactions. Monitor for signs of anaphylaxis, such as fever, chills, or hypotension.
Aspirin Therapy:
- High-Dose Aspirin: 80-100 mg/kg/day divided into four doses until the fever subsides for at least 48 hours.
- Moderate-Dose Aspirin: 30-50 mg/kg/day may be used if high-dose is not tolerated.
- Low-Dose Aspirin: 3-5 mg/kg/day continued for 6-8 weeks if there are no coronary abnormalities on follow-up echocardiograms.

Refractory KD

IVIg-Resistant KD: Persistent fever ≥ 36 hours after IVIg infusion. Options include:
Second IVIg Dose: 2 g/kg.
Corticosteroids: Pulse methylprednisolone 30 mg/kg/day for 3 days or longer courses based on clinical judgment.
Biologic Agents: Such as infliximab or anakinra, in cases refractory to IVIg and corticosteroids.

Follow-Up and Monitoring

Regular follow-up is critical to monitor for cardiac complications:

Echocardiography: Initial, 2 weeks, and 6-8 weeks post-diagnosis.
Cardiology Consultation: For cases with coronary abnormalities.
Long-Term Follow-Up: For children with coronary artery changes, regular follow-up with a cardiologist is essential.

Vaccination Considerations

Live Vaccines: Postpone for 11 months after IVIg due to potential interference with vaccine efficacy.
Affected Vaccines: JE (Japanese Encephalitis), VZV (Varicella Zoster Virus), MMR (Measles, Mumps, Rubella).
Revaccination: If administered within 14 days before IVIg, revaccinate 11 months later.

Summary

Kawasaki Disease is a serious pediatric condition requiring prompt recognition and intervention to prevent coronary artery complications. The cornerstone of treatment is IVIg and aspirin, with adjustments for refractory cases. Echocardiography and regular follow-up are essential to ensure the resolution of symptoms and monitor for long-term cardiovascular outcomes. Pediatric residents should maintain a high index of suspicion for KD in children with prolonged fever and use a systematic approach to diagnose and manage this condition effectively.