Can the white blood cell count increase after steroid therapy in a patient with asthma or an inflammatory condition?

Can White Blood Cell Count Increase After Steroid Therapy?

Yes, corticosteroids consistently cause leukocytosis through a dose-dependent mechanism that primarily increases neutrophil counts, with effects appearing as early as 6-24 hours after administration and persisting throughout therapy. 1, 2

Mechanism and Time Course

Corticosteroids are lymphocyte-depleting agents that cause a well-established increase in total white blood cell count, predominantly through neutrophilia. 1 The mechanism involves:

• Decreased neutrophil adhesion molecule expression (Mac-1 and L-selectin reduced by 39-51%), preventing neutrophils from adhering to endothelial surfaces and causing them to remain in circulation 3
• Neutrophil demargination rather than increased production, explaining the rapid onset 1

The temporal pattern follows a predictable course:

• Peak effect occurs at 48 hours after steroid administration 2
• Effects can appear as early as 6 hours after initiation 4, 1
• Leukocytosis persists throughout the duration of therapy, even with prolonged use 5

Magnitude of WBC Increase by Dose

The degree of leukocytosis is directly dose-dependent: 1, 2

• Low-dose steroids: Mean increase of 0.3 × 10⁹/L WBCs 2
• Medium-dose steroids: Mean increase of 1.7 × 10⁹/L WBCs 2
• High-dose steroids: Mean increase of 4.84 × 10⁹/L WBCs (peak at 48 hours) 2
• Even small doses of prednisone over prolonged periods can induce extreme and persistent leukocytosis, with WBC counts exceeding 20,000/mm³ as early as the first day 5

For context, white blood cell values peak 24 hours after corticosteroids for fetal lung maturity (2 SD from mean is 20.8 × 10⁶/L) and return close to baseline by 96 hours. 4

Pattern of Cell Type Changes

The leukocytosis has a characteristic differential pattern: 1, 5

• Neutrophilia: Predominant finding, with neutrophil percentage increasing (e.g., from 54.6% to 58.1%) 3
• Lymphopenia: Corticosteroids are lymphocyte-depleting agents 1
• Eosinopenia: Eosinophil counts decrease 2- to 7-fold with corticosteroid treatment 4, 6
• Monocytosis: May occur alongside neutrophilia 5

Critical Distinction: Steroid-Induced Leukocytosis vs. Infection

When WBC >14,000/mm³ with left shift (>6% bands), investigate for infection regardless of steroid dose. 1 This is the single most important clinical decision point.

Key distinguishing features: 1, 5

• Left shift (>6% band forms): Suggests infection rather than steroid effect 1, 5
• Toxic granulation on peripheral smear: Indicates infection, rare in steroid-induced leukocytosis 1, 5
• Magnitude of increase: Increases >4.84 × 10⁹/L after high-dose steroids, or any significant increase after low-dose steroids, suggest alternative causes 2
• Clinical context: Fever, localizing symptoms, or clinical deterioration warrant infection workup 1

Serial monitoring of WBC counts with differential is necessary if infection is suspected in patients on high-dose steroids, rather than relying on a single elevated value. 1

Special Considerations in Asthma and Inflammatory Conditions

Effect on Eosinophils in Asthma

While total WBC increases, eosinophil counts paradoxically decrease with corticosteroid therapy: 4, 6

• Sputum eosinophil counts decrease 2- to 7-fold with corticosteroid treatment 4
• Blood eosinophils can fall profoundly when ICS dose increases (e.g., median fall from 560 to 320 cells/µL when escalating from medium to high-dose ICS) 7
• Effect plateaus at low ICS doses (≈200 µg/day beclomethasone equivalent) 4

This creates a situation where total WBC rises due to neutrophilia while eosinophils simultaneously fall, which is important when considering biologic therapies targeting IL-5 pathways. 7

Inhaled Corticosteroids

Even inhaled corticosteroids cause measurable leukocytosis: 3

• Budesonide inhalation: 23.4% increase in WBC and 30.1% increase in absolute neutrophil count at 6 hours 3
• Fluticasone inhalation: 12.6% increase in WBC and 22.7% increase in absolute neutrophil count 3

Duration-Based Risk Stratification

The American Gastroenterological Association provides clear duration thresholds: 1

• <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; requires PCP prophylaxis and heightened infection surveillance 1
• Standard ITP treatment (prednisone 0.5-2 mg/kg/day for 2-4 weeks): Produces consistent leukocytosis throughout treatment 1

Common Pitfalls to Avoid

1. Assuming all leukocytosis in steroid-treated patients is benign: Always check for left shift and toxic granulation 1, 5

2. Overlooking infection in immunocompromised patients: Leukocytosis may be blunted or absent in some immunocompromised patients, making infection diagnosis more challenging 1

3. Failing to maintain heightened vigilance even without fever: Immunosuppressed patients on chronic steroids require ongoing infection surveillance 1

4. Not considering PCP prophylaxis: Patients on moderate-to-high dose prednisone ≥20 mg/day for ≥4 weeks require Pneumocystis jirovecii prophylaxis 1

5. Misinterpreting eosinophil counts: Remember that while total WBC increases, eosinophils decrease with steroid therapy 4, 7