How to manage elevated White Blood Cell (WBC) counts with high neutrophils potentially induced by steroid therapy, such as prednisone (corticosteroid)?

From the Guidelines

Managing elevated white blood cell (WBC) counts with high neutrophils due to steroid therapy primarily involves addressing the underlying steroid use rather than treating the elevated counts directly. If you're on prednisone or another corticosteroid and experiencing leukocytosis (high WBC) with neutrophilia (high neutrophils), consult your healthcare provider about potentially adjusting your steroid dosage or schedule. According to the American Society of Clinical Oncology (ASCO) guideline update 1, the lowest possible dose of steroids should be used for the shortest possible duration to minimize the harmful impact of steroids. For patients on long-term steroid therapy, consider a gradual taper to the lowest effective dose under medical supervision, as suggested by the ASCO guideline update 1. Typically, WBC counts normalize within 1-2 days after reducing or discontinuing the steroid. No specific medications are needed to treat steroid-induced leukocytosis as it's generally a benign, expected physiological response. Steroids cause this effect by demarginating neutrophils (moving them from blood vessel walls into circulation) and delaying their migration out of blood vessels, rather than by increasing production. Regular blood monitoring is recommended while on steroid therapy, but isolated elevation of neutrophils without other concerning symptoms usually doesn't require intervention beyond steroid management. This condition differs from infection-related neutrophilia and typically doesn't increase infection risk. Key considerations include:

• Evaluating the patient’s pre-existing conditions and careful monitoring of steroid-related complications, as emphasized in the ASCO guideline update 1
• Using prophylactic agents to prevent certain opportunistic infections along with preemptive measures to mitigate various toxicities for patients needing longer-term steroid use, as recommended by the ASCO guideline update 1
• Implementing a multidisciplinary approach in the management of certain steroid-related complications and considering institutional guidelines in decision making, as suggested by the ASCO guideline update 1.

From the FDA Drug Label

Corticosteroids, including prednisone tablets, suppress the immune system and increase the risk of infection with any pathogen, including viral, bacterial, fungal, protozoan, or helminthic pathogens Corticosteroids can: • Reduce resistance to new infections • Exacerbate existing infections • Increase the risk of disseminated infections • Increase the risk of reactivation or exacerbation of latent infections • Mask some signs of infection

The FDA drug label does not directly answer the question of how to manage elevated White Blood Cell (WBC) counts with high neutrophils potentially induced by steroid therapy, such as prednisone. However, it does mention that corticosteroids, including prednisone, can suppress the immune system and increase the risk of infection.

• Monitoring for the development of infection and considering prednisone tablets withdrawal or dosage reduction as needed is recommended.
• Gradual reduction of dosage is recommended when reducing or stopping prednisone therapy to minimize the risk of adrenal insufficiency.
• The label does not provide specific guidance on managing elevated WBC counts with high neutrophils, and clinical decision-making should be based on individual patient needs and medical judgment 2.

From the Research

Management of Elevated WBC Counts with High Neutrophils

Elevated White Blood Cell (WBC) counts with high neutrophils can be potentially induced by steroid therapy, such as prednisone (corticosteroid) 3, 4, 5. The following points highlight the key considerations in managing such cases:

• Steroid-Induced Leukocytosis: Glucocorticosteroids (GCS) are known to cause leukocytosis and neutrophilia, which can affect the diagnosis of sepsis and estimation of its severity 3.
• Degree of Leukocytosis: The degree of leukocytosis is related to the dosage of steroids administered, with higher doses causing greater increases in WBC count 4, 5.
• Timing of Leukocytosis: Leukocytosis can occur as early as the first day of steroid treatment and can persist for the duration of therapy 5.
• Differential Diagnosis: When interpreting WBC counts after initiating steroids, increases of up to 4.84 × 10^9/L cells may be seen within 48 hours after high-dose steroids, while larger increases or increases after low-dose steroids may suggest other causes of leukocytosis 4.
• Clinical Considerations: A shift to the left in the peripheral white blood cells, toxic granulation, and other signs of infection can help differentiate between steroid-induced leukocytosis and infection-induced leukocytosis 5, 6.
• Evaluation of Leukocytosis: A repeat complete blood count with peripheral smear, leukocyte differential, and consideration of age- and pregnancy-specific normal ranges can provide helpful information in evaluating patients with leukocytosis 6.

Key Findings from Studies

Some key findings from the studies include:

• The overall maximal leukocytes count was higher in GCS therapy groups, with an average increase of 5 × 10^9/L in patients with acute infections chronically treated with GCS 3.
• WBC response peaked at 48 hours after steroid administration, with a mean increase of 2.4 × 10^9/L WBCs 4.
• Even small doses of prednisone, administered over a prolonged period, can induce extreme and persistent leukocytosis 5.
• Glucocorticosteroids can be used as equivalent agents to endotoxin and etiocholanolone for measuring the neutrophil reserve response 7.