Do steroids cause an increase in white blood cell (WBC) count?

Steroids Cause Leukocytosis Through Neutrophil Demargination

Yes, corticosteroids consistently cause an increase in white blood cell count, primarily through neutrophilia, which is a well-established, dose-dependent effect that can occur as early as the first day of treatment and persist throughout therapy. 1

Mechanism of Steroid-Induced Leukocytosis

Corticosteroids increase WBC count through several mechanisms:

• Neutrophil demargination: Steroids decrease the expression of neutrophil adhesion molecules (Mac-1 and L-selectin), causing neutrophils to detach from blood vessel walls and enter circulation, resulting in a 30-51% reduction in adhesion molecule expression 2
• Lymphocyte depletion: Corticosteroids are classified as lymphocyte-depleting agents, causing a decrease in lymphocyte counts while neutrophils increase 1
• The leukocytosis is predominantly neutrophilic, accompanied by monocytosis, eosinopenia, and variable lymphopenia 3

Magnitude and Timing of WBC Elevation

The degree of leukocytosis is dose-dependent and follows a predictable pattern:

• Peak timing: WBC count peaks at 24-48 hours after steroid administration 4, 5
• Low-dose steroids (prednisone <10 mg/day): Mean increase of 0.3 × 10⁹/L 4
• Medium-dose steroids (prednisone 10-20 mg/day): Mean increase of 1.7 × 10⁹/L 4
• High-dose steroids (prednisone ≥20 mg/day): Mean increase of 4.84 × 10⁹/L 4
• Individual variability: WBC counts can surpass 20,000/mm³ as early as the first day, with individual responses ranging from -600 to +8,000 cells/mm³ 3, 6

Duration of Effect

• Leukocytosis reaches maximal values within two weeks in most cases, after which the WBC count may decrease but typically does not return to pretreatment levels 3
• Even small doses of prednisone administered over prolonged periods can induce extreme and persistent leukocytosis 3
• The effect persists throughout the duration of therapy 1

Distinguishing Steroid-Induced Leukocytosis from Infection

This is a critical clinical challenge, particularly in immunocompromised patients:

Key distinguishing features:

• Left shift and toxic granulation: Investigate for infection if WBC >14,000/mm³ with left shift (>6% bands) regardless of steroid dose 1
• In steroid-induced leukocytosis, left shift and toxic granulation are rare, whereas they are commonly observed in infection 3
• Magnitude of increase: Increases larger than 4.84 × 10⁹/L after high-dose steroids, or any significant increase after low-dose steroids, suggest other causes of leukocytosis 4
• Serial monitoring: Serial WBC counts with differential are necessary if infection is suspected in patients on high-dose steroids, rather than relying on a single elevated value 1

Clinical Implications by Steroid Dose and Duration

High-risk category (moderate-to-high dose prednisone ≥20 mg/day for ≥4 weeks):

• Produces sustained leukocytosis and increases infection risk 1
• Requires Pneumocystis jirovecii prophylaxis and heightened infection surveillance 1
• Consider prophylaxis with trimethoprim/sulfamethoxazole (one single-strength tablet three times weekly) 7

Moderate-risk category (low-dose prednisone <10 mg/day for ≥4 weeks):

• Carries moderate risk for viral reactivation, indicating sustained immunologic effects 1

Low-risk category (any dose for <1 week):

• Carries low risk for significant immunosuppression but still produces measurable leukocytosis 1

Important Caveats

• Individual reproducibility: A given patient's WBC response to a given dose of steroid is reproducible when retested, but there is significant inter-patient variability 6
• Timing of blood draws: WBC and differential counts should be obtained before the morning steroid dose to avoid misinterpretation 6
• Route of administration: Even inhaled corticosteroids (budesonide, fluticasone) can increase WBC by 12.6-23.4% and neutrophil counts by 22.7-30.1% within 6 hours 2
• Blunted response in immunocompromised patients: Leukocytosis may be blunted or absent in immunocompromised patients, making infection diagnosis more challenging 1

Perioperative Considerations

Patients on corticosteroids at the time of surgery have increased risk of postoperative infectious complications:

• Risks are greater for those taking ≥40 mg prednisolone 7
• Patients should have steroids stopped or minimized prior to elective surgery wherever possible 7
• Patients on corticosteroids at the time of surgery should receive intravenous hydrocortisone in equivalent dosage until they can resume oral prednisolone (prednisolone 5 mg = hydrocortisone 20 mg) 7