Can high‑dose intravenous hydrocortisone (or methylprednisolone) increase the white‑blood‑cell count in a 40‑year‑old woman with systemic lupus erythematosus, severe anemia, thrombocytopenia, nephrotic‑range proteinuria, an acute peptic‑ulcer bleed, and marked leukocytosis?

Can Hydrocortisone Increase WBC?

Yes, high-dose intravenous hydrocortisone and methylprednisolone can significantly increase white blood cell counts, with peak elevations occurring approximately 48 hours after administration. 1

Magnitude and Timing of WBC Elevation

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

• High-dose corticosteroids (such as hydrocortisone 100 mg every 6 hours or methylprednisolone 30 mg every 12 hours) can increase WBC count by a mean of 4.84 × 10⁹/L within 48 hours 1
• Medium-dose regimens produce mean increases of approximately 1.7 × 10⁹/L 1
• Low-dose regimens result in minimal increases of about 0.3 × 10⁹/L 1
• The peak WBC response occurs at 48 hours after steroid administration 1

Critical Clinical Context for SLE Patients

In the specific scenario of a 40-year-old woman with systemic lupus erythematosus receiving high-dose IV corticosteroids for severe cytopenias:

Expected Steroid Effect on WBC

• The British Society of Gastroenterology recommends hydrocortisone 100 mg 6-hourly or methylprednisolone 30 mg every 12 hours for acute severe conditions requiring intensive immunosuppression 2
• At these doses, leukocytosis up to approximately 5 × 10⁹/L above baseline is attributable to the corticosteroid effect alone 1
• This steroid-induced leukocytosis can complicate the clinical picture when trying to distinguish infection from drug effect 3

Important Caveats in SLE

• Granulocytosis in SLE patients can result from three distinct mechanisms: infection, high-dose steroids, or acute disease exacerbation 3
• The presence of marked leukocytosis exceeding 5 × 10⁹/L above baseline after 48 hours should prompt investigation for infection or other causes beyond the steroid effect 1
• In SLE patients with severe neutropenia (<500 cells/mm³) at baseline, monitoring for infection risk is critical when initiating high-dose glucocorticoids 2

Distinguishing Steroid Effect from Infection

Algorithmic Approach:

1. Document baseline WBC before initiating corticosteroids
2. Expect peak increase at 48 hours: up to 4.84 × 10⁹/L for high-dose regimens 1
3. If WBC increase exceeds 5 × 10⁹/L or continues rising beyond 48 hours, investigate for:
   • Developing infection (especially with peptic ulcer bleed as portal of entry)
   • SLE disease flare
   • Other inflammatory processes 1, 3
4. After low-dose steroids, any significant WBC increase suggests causes other than the medication 1

Treatment Context for Severe SLE Cytopenias

For this patient's thrombocytopenia and severe anemia:

• High-dose parenteral glucocorticoids (methylprednisolone 30 mg/kg/day or equivalent) are appropriate first-line therapy for severe immune thrombocytopenia in SLE 2
• The EULAR/ERA-EDTA guidelines recommend three consecutive pulses of IV methylprednisolone 500-750 mg, followed by oral prednisone 0.5 mg/kg/day 2
• Corticosteroids remain the mainstay for treating immune-mediated cytopenias in SLE, though they can cause granulocytosis as a complication 3

Monitoring Strategy:

• Obtain complete blood count, CRP, and cultures before attributing leukocytosis solely to steroids 2
• In the context of acute peptic ulcer bleeding, maintain high suspicion for infection despite steroid-induced leukocytosis 2
• Screen for Clostridioides difficile and other opportunistic infections in immunosuppressed patients with GI symptoms 2

The leukocytosis from high-dose corticosteroids is a well-established phenomenon that peaks at 48 hours and can reach approximately 5 × 10⁹/L above baseline, but increases beyond this threshold or occurring with low-dose regimens warrant investigation for alternative causes, particularly infection in this high-risk clinical scenario. 1, 3