What is the management approach for a patient with prolonged fever and no signs of Kawasaki disease?

Management of Prolonged Fever Without Signs of Kawasaki Disease

For patients with prolonged fever without signs of Kawasaki disease, a systematic evaluation should be performed following the American Heart Association's algorithm for incomplete Kawasaki disease, as this condition can present with minimal clinical features but still carry significant risk of coronary artery abnormalities. 1

Evaluation Algorithm

Initial Assessment

• For children with ≥5 days of unexplained fever:
  • Assess for presence of 2-3 clinical criteria of Kawasaki disease
  • For infants ≤6 months with ≥7 days of unexplained fever, proceed with laboratory evaluation even without clinical criteria 1, 2

Laboratory Evaluation

• Check inflammatory markers:
  • C-reactive protein (CRP)
  • Erythrocyte sedimentation rate (ESR)

If CRP ≥3.0 mg/dL and/or ESR ≥40 mm/hr:

• Perform additional laboratory tests to look for ≥3 of these supplemental findings:
  • Anemia for age
  • Platelet count ≥450,000/mm³ after 7th day of fever
  • Albumin <3.0 g/dL
  • Elevated ALT level
  • WBC count ≥15,000/mm³
  • Urine ≥10 WBC/hpf 1

If CRP <3.0 mg/dL and ESR <40 mm/hr:

• Perform serial clinical and laboratory re-evaluation if fever persists
• Discharge if fever resolves 1

Echocardiography

• Perform echocardiography if:
  • ≥3 supplemental laboratory criteria are present, OR
  • Fever persists and there is ongoing evidence of inflammation 1, 2

Echocardiogram Findings

• Consider positive if any of these are present:
  • Z score of LAD or RCA ≥2.5
  • Coronary artery aneurysm
  • ≥3 other suggestive features (decreased LV function, mitral regurgitation, pericardial effusion, Z scores in LAD or RCA of 2-2.5) 1

Treatment Recommendations

If Echocardiogram is Positive or ≥3 Supplemental Laboratory Criteria Met:

• Treat with IVIG (2 g/kg as a single infusion)
• Add high-dose aspirin (80-100 mg/kg/day divided into four doses) 1, 2
• Treatment should be given within 10 days of fever onset when possible
• For patients beyond day 10, treat if there are clinical and laboratory signs of ongoing inflammation 1

After Initial Treatment:

• Continue high-dose aspirin until patient is afebrile for 48-72 hours
• Then reduce to low-dose aspirin (3-5 mg/kg/day) for antiplatelet effect
• Continue low-dose aspirin for 6-8 weeks if no coronary abnormalities develop 2

Special Considerations

High-Risk Populations

• Infants <6 months are at particularly high risk of developing coronary artery abnormalities and often present with prolonged fever as the sole clinical finding 1, 2
• These patients require a lower threshold for evaluation and treatment

Common Diagnostic Pitfalls

• Misdiagnosis as urinary tract infection when fever and pyuria are present
• Misattribution to antibiotic reaction when rash, red eyes, and red lips develop after antibiotics
• Misdiagnosis as aseptic meningitis when irritability and CSF pleocytosis are present
• Overlooking Kawasaki disease when cervical lymphadenitis or prominent gastrointestinal symptoms predominate 1

Features Suggesting Alternative Diagnoses

• Exudative conjunctivitis
• Exudative pharyngitis
• Discrete intraoral lesions
• Bullous or vesicular rash
• Generalized lymphadenopathy 1, 2

Follow-up

• For treated patients without coronary abnormalities:
  • Echocardiography at diagnosis, within 1-2 weeks, and 4-6 weeks after treatment
• For patients with coronary abnormalities:
  • More frequent echocardiography and possible additional cardiac imaging 2

By following this systematic approach, clinicians can identify and treat incomplete Kawasaki disease in patients with prolonged fever, potentially preventing serious coronary complications even when classic signs are absent.