Does steroid use cause an elevated white blood cell (WBC) count?

Does Steroid Use Cause Elevated WBC?

Yes, corticosteroid use consistently causes leukocytosis, primarily through neutrophilia, with the magnitude and timing dependent on dose and route of administration.

Mechanism and Magnitude of Steroid-Induced Leukocytosis

Corticosteroids cause leukocytosis through redistribution of neutrophils from the marginated pool to the circulating pool, mediated by decreased expression of adhesion molecules (Mac-1 and L-selectin) on neutrophil surfaces, preventing their adherence to endothelial walls 1, 2.

Expected WBC Increases by Dose:

• Low-dose steroids: Mean increase of 0.3 × 10⁹/L WBCs 1
• Medium-dose steroids: Mean increase of 1.7 × 10⁹/L WBCs 1
• High-dose steroids: Mean increase of 4.84 × 10⁹/L WBCs 1
• Peak effect occurs at 48 hours after steroid administration 1

Timing Patterns:

• WBC elevation can occur as early as 3 hours after oral glucocorticoid administration, with mean increases of +2,400 cells/mm³ (range -600 to +8,000/mm³) 3
• Maximal leukocytosis typically develops within 2 weeks of starting therapy, though the WBC count may remain elevated above baseline for the duration of treatment 4
• Even small doses administered over prolonged periods can induce extreme and persistent leukocytosis, with counts exceeding 20,000/mm³ 4

Differential Count Characteristics

The leukocytosis is characterized by:

• Predominant neutrophilia (polymorphonuclear cell increase) 1, 4
• Concurrent monocytosis 4
• Eosinopenia 4
• Variable lymphopenia (due to lymphocyte redistribution to bone marrow) 4, 5
• Absence of left shift (typically <6% band forms) 4
• Absence of toxic granulation 4

Clinical Implications for Distinguishing Infection from Steroid Effect

When to Suspect Infection Rather Than Steroid Effect:

Any WBC increase exceeding the expected dose-related response suggests alternative pathology 1. Specifically:

• WBC increases >4.84 × 10⁹/L after high-dose steroids 1
• Any increase after low-dose steroids (beyond 0.3 × 10⁹/L) 1
• Presence of >6% band forms (left shift) 4
• Presence of toxic granulation 4

Important Caveats:

• Individual patient responses to steroids are highly variable but reproducible in the same patient with the same dose 3
• The WBC response does not correlate with steroid dose in a linear fashion across different patients 3
• In immunotherapy contexts, elevated WBC in CSF may occur with immune-related neurologic adverse events, showing reactive lymphocytes, neutrophils, or histiocytes with normal glucose and negative cultures 6

Route-Specific Considerations

Even inhaled corticosteroids cause measurable leukocytosis 2:

• Budesonide inhalation: 23.4% increase in WBC and 30.1% increase in absolute neutrophil count at 6 hours 2
• Fluticasone inhalation: 12.6% increase in WBC and 22.7% increase in absolute neutrophil count 2

Practical Monitoring Recommendations

• Obtain WBC counts before morning steroid doses in patients requiring serial monitoring, as timing significantly affects interpretation 3
• In patients on chronic steroids, establish individual baseline WBC patterns to better identify deviations suggesting infection 3
• When infection is suspected in steroid-treated patients, prioritize clinical assessment and left shift/toxic granulation over absolute WBC count alone 4