Is the elevation in white blood cell (WBC) count due to infection or methylprednisone (prednisone) use in a patient with worsening leukocytosis and neutrophil-predominant pattern?

Infection is the Most Likely Cause of This WBC Elevation

In this patient, the worsening neutrophilic leukocytosis with 85.9% neutrophils (14.5 absolute) and concurrent thrombocytopenia strongly suggests an active bacterial infection rather than steroid effect alone, and warrants immediate diagnostic workup and empiric antibiotics if sepsis is suspected. 1, 2

Why This is Infection, Not Just Steroids

The Neutrophil Pattern Points to Infection

• The absolute neutrophil count of 14.5 K/μL with 85.9% neutrophils approaches the threshold (>90%) that carries a likelihood ratio of 7.5 for bacterial infection 2
• While methylprednisolone 16 mg daily (4 mg QID) is a moderate dose, steroid-induced leukocytosis typically increases WBC by only 1.7 × 10⁹/L (1,700 cells/μL) at this dose level 3
• This patient's WBC jumped from 14.4 to 16.9 (an increase of 2.5 K/μL), which exceeds the expected steroid effect 3

Critical Distinguishing Features Present

• The concurrent drop in platelets from 137 to 84 is a red flag—steroids do not cause thrombocytopenia but infection/sepsis does 1
• Manual differential is essential here to assess for left shift (≥16% bands) which has a likelihood ratio of 4.7 for bacterial infection even with normal WBC 1, 2
• Steroid-induced leukocytosis rarely produces left shift or toxic granulation, whereas infection characteristically does 4

The Clinical Context Matters

• This patient has end-stage renal disease on hemodialysis, making him immunocompromised and at high risk for infection 5
• Methylprednisolone suppresses immune function and increases infection risk, particularly with prolonged use 5
• The FDA label explicitly warns that corticosteroids can mask signs of infection while simultaneously increasing infection risk 5

Immediate Diagnostic Algorithm

Obtain Manual Differential Immediately

• Request manual differential to assess absolute band count—if ≥1,500 cells/mm³, this has the highest likelihood ratio (14.5) for bacterial infection 1, 2
• Automated analyzers cannot reliably assess band forms and immature neutrophils 1, 6

Assess for Sepsis Criteria

• Check for fever/hypothermia (>38°C or <36°C), hypotension (<90 mmHg systolic), tachycardia, tachypnea, altered mental status 1
• Obtain lactate level—if >3 mmol/L, this indicates severe sepsis 1
• Monitor urine output—oliguria (<30 ml/h) suggests sepsis 1

Identify Infection Source

• Respiratory: Obtain chest X-ray if any cough, dyspnea, or chest pain present 1, 6
• Urinary: Perform urinalysis with leukocyte esterase/nitrite and microscopic exam for WBCs—but do not treat asymptomatic bacteriuria 7, 6
• Vascular access: Examine dialysis catheter site for erythema, warmth, purulent drainage 1
• Blood cultures: Obtain if systemic infection suspected, before antibiotics 6

Management Approach

If Sepsis Suspected (Hemodynamically Unstable)

• Initiate broad-spectrum empiric antibiotics within 1 hour of recognition 1
• Aggressive fluid resuscitation for hypotension 1
• Vasopressor support if hypotension persists despite fluids 1
• Source control measures (remove infected catheters, drain abscesses) 1

If Hemodynamically Stable

• Complete diagnostic workup before antibiotics 1
• Initiate targeted antibiotic therapy based on suspected source and local resistance patterns 1
• Close monitoring for clinical deterioration 1

Critical Pitfalls to Avoid

• Do not attribute this WBC elevation solely to steroids given the magnitude of increase and concurrent thrombocytopenia 3, 4
• Do not ignore left shift when total WBC is only mildly elevated—this combination still indicates significant bacterial infection 1, 2
• Do not delay antibiotics in severe sepsis/septic shock while awaiting culture results 1
• Do not rely on automated analyzer alone—manual differential is mandatory 1, 6
• Do not treat asymptomatic bacteriuria in dialysis patients—only treat if symptomatic UTI present 7

Special Consideration for This Patient

Given this patient's immunocompromised state (ESRD, chronic steroids), consider screening for latent tuberculosis reactivation, hepatitis B reactivation, and fungal infections if fever or systemic symptoms develop 5