What is the approach to evaluating prolonged fever in pediatric patients?

Targeted History and Physical Examination for Prolonged Pediatric Fever

The evaluation of prolonged fever in children requires age-stratified risk assessment with focused attention to specific historical and physical examination findings that distinguish infectious, inflammatory, and neoplastic causes—prioritizing thorough, repeated evaluations over shotgun testing. 1, 2

Age-Specific Risk Stratification and Initial Assessment

Neonates (0-28 days)

• Highest risk population with 13% incidence of serious bacterial infection (SBI) requiring comprehensive evaluation including lumbar puncture for CSF analysis 1
• Document rectal temperature (≥38°C/100.4°F is fever threshold), as only 58% of infants with bacteremia or meningitis appear clinically ill 2
• Assess for hypothermia or normal temperature despite serious infection, especially if antipyretics were used in previous 4 hours 2

Young Infants (29-90 days)

• 9% incidence of SBI with potential for risk stratification using Rochester or Philadelphia criteria 1
• Urinary tract infections have 3-7% prevalence in fever without source, with higher rates in girls (8.1% ages 1-2 years) and uncircumcised boys (8-12.4% in infants) 1
• UTI with pyelonephritis carries 27-64% risk of renal scarring with potential for hypertension (10-20%) and end-stage renal disease (10%) later in life 1

Children >3 Months

• Approximately 75% will have self-limited viral infections, but the presence of one viral infection does not preclude coexisting bacterial infection 1, 2
• Approximately 50% of children with true fever of unknown origin (FUO) will have self-limited illness and never receive specific diagnosis, while other 50% will be diagnosed with infectious, inflammatory, or neoplastic conditions 1

Critical Historical Elements

Fever Characteristics

• Duration threshold: ≥5 days raises concern for Kawasaki Disease, with risk of coronary artery aneurysms increasing significantly if treatment delayed beyond 10 days of fever onset 1
• Fever >96 hours in neutropenic patients warrants chest CT for invasive fungal disease evaluation 3
• Verify accuracy of home temperature measurements and document rectal temperature in clinical setting for infants and young children 2

Infectious Exposures

• Freshwater exposure 4-6 weeks prior suggests Katayama syndrome (acute schistosomiasis) with fever, eosinophilia, and urticarial rash 1
• Epidemiologic risk factors for Q fever (Coxiella burnetii) in patients with valvular heart disease or vascular abnormalities 1
• SARS-CoV-2 exposure 2-6 weeks prior suggests Multisystem Inflammatory Syndrome in Children (MIS-C), with significantly higher temperatures and longer fever duration than routine pediatric illnesses 1

Medication History

• Drug-induced fever occurs with mean lag time of 21 days (median 8 days) after drug initiation and can take 1-7 days to resolve after discontinuation 1
• Antipsychotics (especially haloperidol in ICU settings) can cause neuroleptic malignant syndrome with muscle rigidity and elevated creatinine phosphokinase 1
• Anesthetics can cause malignant hyperthermia with delayed onset up to 24 hours 1

Focused Physical Examination Findings

Lymphadenopathy Assessment

• Lymph nodes >2 cm, hard, or matted with hepatosplenomegaly and cytopenias require immediate peripheral blood film examination to rule out acute lymphoblastic leukemia 1
• Cervical lymphadenopathy ≥1.5 cm is one of five criteria for Kawasaki Disease diagnosis 1

Kawasaki Disease Criteria (Requires Fever ≥5 Days Plus 4 of 5 Criteria)

• Bilateral conjunctival injection (non-purulent) 1
• Oral mucosal changes (erythema, cracked lips, strawberry tongue) 1
• Polymorphous rash 1
• Extremity changes (erythema, edema, desquamation) 1
• Cervical lymphadenopathy ≥1.5 cm 1
• Incomplete Kawasaki Disease occurs most commonly in infants, who may have prolonged fever as sole or primary finding with subtle or fleeting additional signs 1
• Diagnosis can be made on day 4 of fever if 4 principal criteria are present 1

Cardiac Risk Factors

• Valvular disease, prosthetic valves, or vascular grafts necessitate endocarditis evaluation and Q fever serologies 1
• Urgent echocardiography required for children with suspected Kawasaki Disease 1

Respiratory Examination

• Pneumonia prevalence is low (approximately 1-3%) in febrile infants 2
• Chest radiograph should be avoided in children with wheezing or high likelihood of bronchiolitis 2
• In neutropenic patients with prolonged fever >96 hours, chest CT should be performed if concern for occult fungal disease exists, as lungs are most commonly affected site 3

Genitourinary Assessment

• Urine collection for suspected UTI must be via catheterization, preferred over clean catch or bag specimens due to lower contamination rates 2
• Urinalysis and urine culture (catheterized specimen, NOT bag specimen) required as part of initial evaluation for prolonged fever 1

Common Pitfalls to Avoid

• Relying solely on clinical appearance, as many children with serious bacterial infections may appear well 2
• Failing to consider impact of recent antipyretic use on temperature 2
• Unnecessary radiographic studies in children with likely viral illnesses 2
• Cognitive bias of anchoring on specific diagnoses without thorough evaluation 4
• Time constraints leading to inadequate history and physical examination—thoroughness and repetition are vitally important 5
• Uncommon manifestations of common diseases are more likely than rare diseases 5, 6

Algorithmic Approach to Repeated Evaluations

Initial Evaluation (All Ages)

• Complete blood count with manual differential 1, 2, 4
• Blood culture (before antibiotics) 1, 2, 4
• Inflammatory markers (CRP, ESR, procalcitonin) to distinguish infectious from non-infectious causes 1, 2, 4
• Comprehensive metabolic panel including liver function tests 1, 2, 4
• Urinalysis and urine culture (catheterized specimen) 1, 2

Age-Specific Additional Testing

• Neonates: Lumbar puncture mandatory 1, 2
• Young infants (29-90 days): Consider lumbar puncture based on clinical assessment 1, 2
• Children >3 months: Lumbar puncture generally not required unless specific signs/symptoms suggest meningitis 2

Duration-Specific Considerations

• Fever ≥5 days: Urgent echocardiography if Kawasaki Disease criteria met 1
• Fever >96 hours in neutropenic patients: Chest CT for invasive fungal disease (sensitivity 79%, specificity 85%, PPV 76%, NPV 87% for invasive pulmonary aspergillosis) 3
• Fever >10 days: Significantly increased risk of coronary artery aneurysms if Kawasaki Disease untreated 1

Special Population Considerations

• Neutropenic patients require immediate evaluation and broad-spectrum antibiotics with risk stratification into high and low risk 2, 4
• Immunocompromised patients require broader infectious workup including opportunistic pathogens 1
• Cardiac risk factors necessitate endocarditis evaluation and Q fever serologies 1