Will the white blood cell count be elevated while a patient is receiving systemic glucocorticoid (steroid) therapy?

Will WBC Be Elevated While on Steroids?

Yes, systemic glucocorticoids consistently cause leukocytosis, 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 and Pattern of Leukocytosis

Corticosteroids induce leukocytosis by decreasing neutrophil adhesion to endothelial surfaces, mediated through reduced expression of adhesion molecules (Mac-1 and L-selectin) on neutrophils, causing demargination of neutrophils from vessel walls into the circulation. 1, 2 This is not due to increased production but rather redistribution of existing cells. 3

The characteristic pattern includes:

• Neutrophilia (the predominant change, accounting for most of the WBC elevation) 1, 4
• Monocytosis 4
• Eosinopenia (eosinophil counts decrease 2- to 7-fold, appearing as early as 6 hours after administration) 1
• Variable lymphopenia 4

Magnitude and Time Course of WBC Elevation

Dose-Response Relationship

The degree of leukocytosis directly correlates with steroid dose: 1, 5

• Low-dose steroids: Mean increase of 0.3 × 10⁹/L WBCs 5
• Medium-dose steroids: Mean increase of 1.7 × 10⁹/L WBCs 5
• High-dose steroids: Mean increase of 4.84 × 10⁹/L WBCs 5

Temporal Pattern

• Peak effect: 24-48 hours after administration 1, 5
• Onset: Can occur as early as the first day of treatment 4
• Duration: Persists throughout therapy, even with prolonged use 4
• Maximum values: Typically reached within two weeks, after which WBC count may decrease slightly but remains above pretreatment levels 4

Even small doses of prednisone administered over prolonged periods can induce extreme and persistent leukocytosis, with WBC counts exceeding 20,000/mm³. 4

Clinical Implications: Distinguishing Steroid-Induced Leukocytosis from Infection

This is the critical clinical challenge, as the leukocytosis pattern mimics bacterial infection. 3

Key Distinguishing Features

Investigate for infection when: 1

• WBC >14,000/mm³ AND left shift (>6% bands) 1
• Presence of toxic granulation on peripheral smear 4
• WBC increase exceeds expected steroid effect (>4.84 × 10⁹/L after high-dose steroids, or any significant increase after low-dose steroids) 5

Steroid-induced leukocytosis characteristics: 4

• Left shift (>6% bands) is rare 4
• Toxic granulation is rare 4
• Predominantly mature neutrophils 4

Monitoring Strategy

• Check peripheral smear for left shift and toxic granulation when infection is suspected 1
• Consider the magnitude of WBC increase relative to steroid dose 1, 5
• Serial monitoring with differential is necessary if infection is suspected, rather than relying on a single elevated value 1
• Assess clinical context (fever, localizing symptoms, hemodynamic instability) 1

Special Populations and Considerations

Immunosuppressed Patients

• Maintain heightened vigilance for occult infection even without fever 1
• Consider Pneumocystis jirovecii prophylaxis for patients on chronic high-dose steroids (prednisone ≥20 mg/day for ≥4 weeks) 1
• Leukocytosis may be blunted or absent in some immunocompromised patients, making infection diagnosis more challenging 1

Monitoring During Glucocorticoid Therapy

For patients on prolonged glucocorticoid treatment, regular monitoring should include: 6

• Full blood count at 1-3 month intervals 6
• Blood glucose monitoring (as steroids cause hyperglycemia in 56-86% of patients) 6
• Blood pressure monitoring 6

Duration and Risk Stratification

• <1 week at any dose: Low risk for significant immunosuppression but still produces measurable leukocytosis 1
• ≥4 weeks at moderate-to-high dose (≥20 mg/day prednisone): Sustained leukocytosis with increased infection risk, warranting PCP prophylaxis 1

Common Pitfalls to Avoid

1. Assuming all leukocytosis in steroid-treated patients is benign: Always check for left shift and toxic granulation when WBC is significantly elevated 1, 4

2. Overlooking infection in the absence of fever: Immunosuppressed patients on chronic steroids may not mount a fever response 1

3. Failing to account for dose-response: Increases >4.84 × 10⁹/L after high-dose steroids, or any significant increase after low-dose steroids, suggest alternative causes 5

4. Not recognizing the persistent nature: Even small doses over prolonged periods can cause extreme leukocytosis (>20,000/mm³) 4

5. Ignoring the eosinophil paradox: While total WBC increases, eosinophil counts decrease with steroid therapy, which can be a useful marker of steroid effect 1