What is the diagnosis for a 7-year-old child with leukocytosis (elevated White Blood Cell (WBC) count) and intermittent fever?

Differential Diagnosis for 7-Year-Old with Leukocytosis and Intermittent Fever

The most critical diagnoses to consider in a 7-year-old with elevated WBC and on-and-off fever are serious bacterial infections (particularly pneumonia), Kawasaki disease (especially incomplete presentation), and less commonly, tickborne rickettsial diseases or emerging systemic inflammatory conditions.

Immediate Risk Stratification Based on WBC Count

If WBC >15,000/mm³ with fever, this child has significantly elevated risk for serious bacterial infection (SBI) and requires urgent evaluation. 1, 2

• WBC 15,000-25,000/mm³: 15.4% risk of SBI, primarily pneumonia 3
• WBC >25,000/mm³ (extreme leukocytosis): 39% risk of SBI, with 28% having segmental/lobar pneumonia 3
• WBC >35,000/mm³: 26% risk of serious disease and 10% risk of bacteremia 4

The peripheral smear provides critical additional information—look for toxic granulation and vacuolization of neutrophils, which have 51% and 63% positive predictive values for bacteremia respectively, and 76% when both are present 5

Primary Diagnostic Considerations

1. Serious Bacterial Infections (Most Common)

Pneumonia is the most likely SBI in this age group with leukocytosis. 3

• Obtain chest radiograph even without respiratory symptoms if WBC >15,000/mm³ and temperature >39°C 2
• Blood culture should be obtained before antibiotics 1
• Urinary tract infection remains possible but less common at age 7 than in infants 1

2. Incomplete Kawasaki Disease (Critical Not-to-Miss)

Consider Kawasaki disease in any child with prolonged unexplained fever (≥5 days) and fewer than 4 principal clinical findings, particularly with compatible laboratory findings. 1

Key laboratory findings supporting incomplete KD include: 1

• WBC ≥15,000/mm³ (one of six laboratory criteria)
• Elevated CRP ≥3.0 mg/dL and/or ESR ≥40 mm/hr
• Anemia for age
• Platelet count ≥450,000 after day 7 of fever
• Albumin <3.0 g/dL
• Elevated ALT
• Urine ≥10 WBC/hpf

This diagnosis is particularly important because delayed recognition leads to coronary artery abnormalities and affects long-term morbidity and mortality. 1

3. Tickborne Rickettsial Diseases

Rocky Mountain Spotted Fever should be considered with: 1

• Fever and leukocytosis (WBC 16,200/mm³ documented in fatal pediatric case) 1
• No tick bite history reported in up to 40% of cases 1
• Geographic distribution throughout contiguous United States, not just endemic areas 1
• Rapid progression possible—50% of deaths occur within 9 days 1

Common pitfall: Rash may be mistaken for viral exanthem or drug reaction, and initial presentation may mimic pneumonia. 1

4. Systemic Inflammatory Conditions

Based on a recent case report, persistent fever with leukocytosis and elevated inflammatory markers in a 7-year-old may represent: 6

• Systemic inflammatory disease with infectious trigger
• Conditions requiring rheumatologic evaluation if fever persists beyond 7-10 days despite antibiotics
• Consider ophthalmologic examination for uveitis if rheumatologic etiology suspected 6

Diagnostic Algorithm

Step 1: Assess fever pattern and duration 1

• Fever ≥5 days: Evaluate for Kawasaki disease criteria
• Intermittent fever with well appearance between episodes: Consider viral vs. early bacterial infection

Step 2: Obtain complete laboratory evaluation 1, 2

• Complete blood count with differential and peripheral smear examination
• Blood culture (before antibiotics)
• CRP and ESR
• Urinalysis and urine culture
• Consider chest radiograph if WBC >15,000/mm³ with temperature >39°C

Step 3: Examine peripheral smear for toxic changes 5

• Vacuolization and toxic granulation significantly increase bacteremia risk
• Left shift with bands ≥500/μL increases SBI probability

Step 4: Risk-stratify based on WBC and temperature 2, 3

• Temperature >39°C + WBC >15,000/mm³: High risk, consider empiric antibiotics and admission
• WBC >25,000/mm³: 39% SBI risk, strongly consider admission and parenteral antibiotics
• WBC >35,000/mm³: 26% serious disease risk, requires admission

Step 5: Consider specific diagnoses based on clinical context 1

• Prolonged fever (≥5 days): Evaluate for incomplete Kawasaki disease with echocardiogram
• Summer presentation or outdoor exposure: Consider tickborne illness
• Persistent fever despite antibiotics: Broaden differential to include inflammatory conditions

Critical Pitfalls to Avoid

Do not dismiss Kawasaki disease based on incomplete criteria—infants and older children/adolescents have higher rates of delayed diagnosis and coronary complications 1

Do not exclude tickborne disease based on absence of tick bite history or geographic location—40% have no reported bite and disease occurs throughout US 1

Do not rely on serology for early rickettsial disease—antibodies typically not detectable before second week of illness 1

Do not assume viral illness based solely on intermittent fever pattern—serious bacterial infections can present with fluctuating temperatures 1, 7