What is the best approach for a 13-year-old boy with leukocytosis and fatigue, and no past medical history?

Immediate Diagnostic Workup for Leukocytosis with Fatigue in an Adolescent

This 13-year-old boy requires urgent evaluation to distinguish between benign reactive leukocytosis and hematologic malignancy, with immediate peripheral blood smear examination and comprehensive metabolic assessment to guide next steps.

Initial Diagnostic Approach

Immediate Laboratory Assessment

• Obtain a peripheral blood smear immediately to evaluate white blood cell morphology, maturity, and presence of blasts or immature forms 1, 2
• Order a complete blood count with differential to assess for eosinophilia, lymphocytosis, or left shift that may indicate infection versus malignancy 1
• Check for concurrent abnormalities in red blood cell or platelet counts, as these increase suspicion for primary bone marrow disorders 2

Critical History and Physical Examination Elements

• Assess for constitutional symptoms including fever, unintentional weight loss, bruising, or bleeding that suggest hematologic malignancy 1, 2
• Examine for hepatosplenomegaly and lymphadenopathy, which are concerning for leukemia or lymphoproliferative disorders 2
• Document any recent infections, medications (particularly corticosteroids, lithium, or beta agonists), or physical/emotional stressors that could cause reactive leukocytosis 2

Risk Stratification Based on WBC Level

WBC of 20,000/mm³ Threshold

• At a WBC of 20,000/mm³, this patient exceeds the threshold that warrants heightened concern for serious underlying pathology 3
• While not meeting criteria for hyperleukocytosis (>100 × 10⁹/L), this level combined with fatigue requires aggressive workup 4

Distinguishing Malignant from Reactive Causes

• Primary bone marrow disorders should be strongly suspected given the combination of elevated WBC and persistent fatigue without obvious infection 2
• Reactive causes (infection, inflammation, stress, medications) typically present with identifiable triggers and less severe constitutional symptoms 1, 2

Management Algorithm

If Peripheral Smear Shows Blasts or Immature Cells

• Urgent hematology/oncology referral is mandatory - do not delay for additional testing 5
• Consider chronic myeloid leukemia (CML) in the differential, as pediatric CML can present with fatigue and moderate leukocytosis 4
• If CML is suspected, order BCR::ABL1 fusion gene testing and Philadelphia chromosome analysis 4

If Peripheral Smear Shows Mature Cells Only

• Evaluate for secondary causes systematically:
  • Review medication history for drugs causing leukocytosis 1, 2
  • Assess for occult infection with appropriate cultures and imaging 1
  • Consider inflammatory conditions, particularly if eosinophilia is present 1
• If no clear secondary cause is identified, hematology consultation is still warranted for persistent unexplained leukocytosis 3, 6

Specific Considerations for Fatigue

Fatigue Assessment

• Screen fatigue severity using a 0-10 numeric scale (with 7-10 indicating severe fatigue requiring immediate intervention) 4
• Evaluate for treatable contributing factors including anemia, thyroid dysfunction, and depression 4
• In the context of leukocytosis, fatigue is particularly concerning for underlying malignancy and should not be attributed to benign causes without thorough workup 4, 2

Critical Pitfalls to Avoid

Common Errors in Management

• Do not attribute leukocytosis to "stress" or "viral illness" in an adolescent with persistent fatigue without excluding malignancy first 2, 5
• Avoid empiric antibiotics based solely on WBC count in an afebrile patient, as this may delay appropriate diagnosis 3
• Do not wait for symptoms to worsen before obtaining hematology consultation - chronic leukemias often present with gradual onset symptoms and may be diagnosed incidentally 5

When to Expedite Referral

• Any patient with constitutional symptoms (fever, weight loss, bruising, fatigue) plus abnormal peripheral smear requires urgent hematology referral 1, 2, 5
• Patients with WBC >100,000/mm³ represent a medical emergency due to risk of leukostasis, though this patient's WBC of 20,000/mm³ does not meet this threshold 2, 4

Monitoring and Follow-up

• If initial workup is reassuring and a benign cause is identified, repeat CBC in 1-2 weeks to ensure resolution 6
• Persistent leukocytosis on repeat testing mandates hematology consultation regardless of other findings 3, 6
• Continue to monitor fatigue severity and reassess for development of new symptoms 4