Can corticosteroids (steroids) cause leukocytosis (an elevated white blood cell count)?

Can Steroids Cause Leukocytosis?

Yes, corticosteroids commonly cause leukocytosis—this is a well-established, dose-dependent effect that can occur as early as the first day of treatment and persist throughout therapy. 1

Mechanism and Pattern

Corticosteroids induce leukocytosis primarily through neutrophilia, with a characteristic pattern that includes: 1, 2

• Increased polymorphonuclear leukocytes (neutrophils) as the predominant cell type 2
• Monocytosis occurring concurrently 2
• Eosinopenia (decreased eosinophils) 2
• Variable lymphopenia (decreased lymphocytes) 2, 3

The mechanism involves lymphocyte depletion and demargination of neutrophils from vessel walls into circulation. 1

Expected Magnitude of Increase

The degree of leukocytosis is dose-dependent but highly variable between patients: 4, 2

• Low-dose steroids: Mean increase of 0.3 × 10⁹/L WBCs 4
• Medium-dose steroids: Mean increase of 1.7 × 10⁹/L WBCs 4
• High-dose steroids: Mean increase of 4.84 × 10⁹/L WBCs (peak at 48 hours) 4
• Chronic steroid therapy in infected patients: Average increase of 5 × 10⁹/L 5

Critical caveat: Even small doses of prednisone administered over prolonged periods can induce extreme and persistent leukocytosis, with WBC counts exceeding 20,000/mm³ as early as the first day. 2, 1

Time Course

• Onset: Can occur within 3 hours of oral administration 3
• Peak response: Typically within 48 hours of initiation 4
• Duration: Persists throughout therapy, though maximal values usually occur within two weeks, after which counts may decrease slightly but remain above baseline 2

Distinguishing Steroid-Induced Leukocytosis from Infection

The key clinical challenge is differentiating benign steroid-induced leukocytosis from infection-related leukocytosis. 6, 1

Red Flags Suggesting Infection Rather Than Steroids Alone:

• Left shift >6% band forms (immature neutrophils) 6, 2
• Toxic granulation on peripheral smear 1, 2
• WBC increase exceeding expected range for the steroid dose administered 6
• Fever, hemodynamic instability, or localizing signs of infection 6
• Any significant WBC increase after low-dose steroids (should prompt investigation for alternative causes) 4

Specific Thresholds Requiring Investigation:

Any patient with WBC >14,000/mm³ AND left shift (>6% bands), regardless of steroid dose, should be investigated for infection. 6 This recommendation comes from the American College of Physicians and represents a critical decision point in clinical practice.

Clinical Management Algorithm

For Patients on Steroids with Leukocytosis:

1. Check peripheral smear for left shift and toxic granulation 1
2. Assess clinical context: fever, vital signs, localizing symptoms 6
3. Compare WBC increase to expected range based on steroid dose 6, 4
4. Obtain blood cultures before antibiotics if infection suspected 6

Special Considerations for Immunosuppressed Patients:

• Maintain heightened vigilance for occult infection even without fever in patients receiving immunosuppressive doses of steroids 6
• Consider PCP prophylaxis in immunosuppressed patients on chronic steroids 6
• Remember that leukocytosis may be blunted or absent in immunocompromised patients or those taking steroids, making infection diagnosis more challenging 7

Medical Emergency Threshold

Hyperleukocytosis (WBC >100,000/mm³) represents a medical emergency regardless of cause due to risk of brain infarction and hemorrhage, and requires immediate hematology consultation to exclude acute leukemia. 6, 8

Common Pitfalls

• Assuming all leukocytosis in steroid-treated patients is benign: Even on steroids, infection must be excluded when clinical suspicion exists 6, 1
• Ignoring the magnitude of increase: Increases exceeding 4.84 × 10⁹/L after high-dose steroids, or any significant increase after low-dose steroids, warrant investigation 4
• Timing of blood draws: WBC counts should ideally be obtained before the morning steroid dose to avoid acute post-dose elevations 3
• Individual variability: A given patient's WBC response to a specific steroid dose is reproducible, but varies widely between patients independent of dose 3