Prednisone-Induced Leukocytosis: Magnitude and Patterns
Prednisone can cause significant leukocytosis with white blood cell counts potentially exceeding 20,000/mm³ within the first day of treatment, and this elevation can persist throughout therapy. The degree of leukocytosis is dose-dependent, with high-dose prednisone causing more pronounced elevations in WBC counts.
Patterns of Prednisone-Induced Leukocytosis
Magnitude of Increase
- Low-dose prednisone: Mean increase of approximately 0.3 × 10⁹/L WBCs 1
- Medium-dose prednisone: Mean increase of approximately 1.7 × 10⁹/L WBCs 1
- High-dose prednisone: Mean increase of approximately 4.84 × 10⁹/L WBCs, with individual variations ranging from -600 to +8,000/mm³ 1, 2
- Extreme cases: WBC counts can exceed 20,000/mm³ as early as the first day of treatment 3
Timeline and Duration
- Peak leukocytosis typically occurs within 48 hours after steroid administration 1
- Maximum values are generally reached within two weeks of starting therapy 3
- Leukocytosis persists for the duration of therapy, though counts may decrease somewhat after reaching peak values (but typically remain above baseline) 3
Cellular Composition
The leukocytosis is characterized by:
- Predominant increase in polymorphonuclear neutrophils (segmented granulocytes)
- Concurrent monocytosis
- Eosinopenia
- Variable degree of lymphopenia 3, 2
Clinical Implications
Differential Diagnosis
When evaluating elevated WBC counts in patients on prednisone, consider:
- Prednisone effect: Increases up to 4.84 × 10⁹/L within 48 hours after high-dose steroids are likely due to medication 1
- Other causes: Larger increases, especially after low-dose steroids, suggest other causes of leukocytosis such as infection 1
Distinguishing from Infection
- Shift to the left: More than 6% band forms is more suggestive of infection rather than steroid-induced leukocytosis 3
- Toxic granulation: Present in infection but rare in steroid-induced leukocytosis 3
Monitoring Recommendations
- WBC and differential cell counts should be obtained before the morning steroid dose to establish baseline values 2
- A given patient's WBC response to a specific dose of steroid tends to be reproducible, though it varies between individuals 2
- No correlation exists between steroid dose and magnitude of WBC response in individual patients 2
Special Considerations
Immunocompromised Patients
For patients on immunosuppressive therapy (such as transplant recipients):
- WBC responses to steroids are highly variable and unpredictable 2
- Changes in WBC count are not correlated with other factors such as azathioprine dose, initial WBC count, hematocrit value, age, or renal function 2
Inflammatory Conditions
In patients with inflammatory conditions being treated with prednisone:
- Monitoring WBC counts and LDH levels can help diagnose disease relapse, even when other inflammatory markers remain suppressed due to concurrent biologic therapy 4
Remember that even small doses of prednisone administered over a prolonged period can induce extreme and persistent leukocytosis, which is particularly important to consider when evaluating for possible infection in immunocompromised patients.