Corticosteroids
Aiya Almogaber, PharmD
Corticosteroids, widely used in inpatient settings to manage inflammation, are known to elevate white blood cell counts, but the extent and timing of that effect have remained poorly defined.
A retrospective study published in the Journal of Hospital Medicine on February 11, 2025, provides much needed clarity on how steroid dose and timing influence leukocytosis in patients who are hospitalized. By isolating patients without infection, malignancy, or immunosuppression, the study findings offer practical guidance for interpreting white blood cell trends following corticosteroid initiation.
The white blood cell response followed a consistent pattern across all steroid groups: Counts peaked on day two post-initiation and then generally declined or plateaued. The magnitude of the increase, however, was dose dependent. Patients in the high-dose group (median 1,517 mg hydrocortisone equivalent) had an average white blood cell increase of 4.84 x 109/L. Medium-dose recipients (600 mg) saw a rise of 1.7 x 109/L, and low-dose patients (200 mg) experienced only a modest increase of 0.32 x 109/L.
“What surprised us was the dose effect,” said one of the study authors, Erin Sullivan, MD, a medical student at the time of the study. “The low-dose steroid group had [white blood cell] counts that did not differ from baseline. At this dosage, which a lot of patients receive, steroids don’t seem to cause leukocytosis.”
In contrast, patients who did not receive steroids exhibited a steady decline in white blood cells during the same period. Day one after steroid administration showed minimal changes across all dosing groups, suggesting clinicians should not expect significant leukocytosis in the first 24 hours. Only the high-dose group demonstrated sustained elevation through day four.
“This study adds detail to our understanding of steroid-induced leukocytosis,” said lead author Michael Rothberg, MD, director of the Center for Value-Based Care Research at Cleveland Clinic. “Because we had a large sample, we were able to study the role of the dose and timing—both of which are important clinical considerations.”
Background
“We were often attributing leukocytosis to steroids without great evidence regarding the extent to which steroids cause it,” said Rothberg. “This study was really inspired by our experience in patient care.”
The research team analyzed over 28,000 adult nonsurgical inpatients across 12 Cleveland Clinic hospitals. They focused on 1,608 patients who received systemic steroids during admission and had at least two complete blood counts drawn within a 4-day period. Patients who had taken steroids before admission or had confounding conditions were excluded to isolate the direct effect of inpatient steroid exposure.
Steroid doses, administered orally, intravenously, or via nasogastric tube, were standardized to hydrocortisone equivalents and stratified into low, medium, and high categories. White blood cell counts were monitored daily for 4 days starting at the time of the first dose. In comparison, the study also analyzed a large cohort of patients who did not receive steroids.
Implications for clinical practice
Based on the study findings, clinicians can now better interpret lab results by accounting for the expected white blood cell trajectory following steroid administration.
Increases in white blood cell of up to 4.84 x 109/L may be seen in the first 48 hours after high-dose steroids. Increases larger than this, or any significant elevation in patients on low-dose steroids, should prompt consideration of other causes such as infection or inflammation.
The authors emphasized that these findings are most applicable to noninfected inpatients, the population excluded in prior studies of leukocytosis. Rothberg noted, “This study has been well-received in the academic community. A lot of people have wondered about this.”
Future researchers focused on this topic may examine white blood cell trends in patients with concurrent infections. For now, the study findings can equip clinicians with clearer expectations and reinforce the importance of dose and timing when evaluating post-steroid leukocytosis.
“If you spend the time to create a high-quality dataset, the inquiry will flow naturally. There are many questions you can answer that are important to clinicians,” said Sullivan. ■