What to do with an adult patient with leukocytosis (elevated white blood cell count) to 17,000 with neutrophilic predominance while on steroid (corticosteroid) therapy?

Steroid-Induced Leukocytosis: Management Approach

Do not stop the steroid based solely on a WBC of 17,000 with neutrophilic predominance, as this elevation is an expected physiologic response to corticosteroid therapy and does not indicate infection or harm. 1, 2

Understanding Steroid-Induced Leukocytosis

Expected Magnitude of WBC Elevation

• High-dose steroids can increase WBC counts by up to 4.84 × 10⁹/L within 48 hours, with peak elevation occurring at this timeframe 1
• Medium-dose steroids typically increase WBC by approximately 1.7 × 10⁹/L, while low-dose steroids cause increases of only 0.3 × 10⁹/L 1
• Even small doses of prednisone administered over prolonged periods can induce extreme and persistent leukocytosis, with WBC counts exceeding 20,000/mm³ as early as the first day of treatment 2
• In patients with acute infections on chronic steroid therapy, the average WBC increase is approximately 5 × 10⁹/L above baseline 3

Mechanism and Cell Distribution

• Corticosteroids cause neutrophilic leukocytosis together with eosinopenia, monocytopenia, and lymphocytopenia through redistribution of cells from marginated pools into circulation 4
• The leukocytosis is predominantly due to polymorphonuclear cells and coincides with monocytosis and eosinopenia 2
• Neutrophil function remains intact despite steroid exposure, with preserved viability (98.4%), phagocytic capability (97.6%), and bactericidal activity (97.7%) 5

Distinguishing Steroid Effect from Infection

Key Diagnostic Features

The critical distinction is the presence or absence of a left shift and toxic granulation:

• A left shift (≥16% band forms or absolute band count ≥1,500 cells/mm³) and toxic granulation are rare in pure steroid-induced leukocytosis but common in bacterial infection 2, 6
• An absolute band count ≥1,500 cells/mm³ has a likelihood ratio of 14.5 for bacterial infection 6, 7
• Neutrophil percentage >90% has a likelihood ratio of 7.5 for bacterial infection 7
• Left shift ≥16% bands has a likelihood ratio of 4.7 for bacterial infection 7

Required Clinical Assessment

Order a peripheral blood smear with manual differential immediately to assess for:

• Band forms and left shift 6
• Toxic granulation 2
• Blast cells or other malignant morphology 6

Evaluate for clinical signs of infection:

• Fever, localized pain, or organ-specific symptoms 8
• Blood cultures if systemic infection suspected 8, 6
• Site-specific cultures based on clinical presentation 8
• Imaging directed at suspected infection source 6

Clinical Decision Algorithm

If WBC 17,000 with neutrophilic predominance on steroids:

1. Continue steroids if:

   • No left shift (<16% bands and absolute band count <1,500/mm³) 2
   • No toxic granulation 2
   • No fever or localizing signs of infection 8
   • Neutrophil percentage <90% 7

2. Investigate for infection if:

   • Left shift present (≥16% bands or ≥1,500 absolute band count) 6, 2
   • Toxic granulation visible 2
   • Clinical signs of infection present 8
   • WBC increase exceeds expected steroid effect (>4.84 × 10⁹/L increase with high-dose steroids) 1

3. Do not stop steroids unless:

   • Infection is confirmed and steroid continuation would compromise infection control 8
   • Patient requires immunosuppressive-dose steroids (>10 mg prednisone equivalent daily) and has uncontrolled active infection 9

Common Pitfalls to Avoid

• Do not interpret steroid-induced leukocytosis as infection without assessing for left shift and toxic granulation 2
• Do not stop necessary steroid therapy based solely on elevated WBC count, as this represents expected physiologic response 1, 2
• Do not ignore leukocytosis in the absence of fever, particularly in older adults or immunocompromised patients, as infection can occur without fever 6
• Do not overlook absolute neutrophil count elevation when total WBC is only mildly elevated, as left shift can indicate serious bacterial infection even with normal total WBC 6