What is the best course of action for a patient with ulcerative colitis (UC) who has shown clinical and biomedical improvement but now has an abnormal white blood cell count?

Management of Ulcerative Colitis with Clinical Improvement but New Abnormal White Blood Cell Count

Endoscopic assessment is strongly recommended for a patient with ulcerative colitis who has shown clinical and biomedical improvement but now has an abnormal white blood cell count to determine the underlying cause and guide appropriate treatment decisions. 1

Evaluation of the Abnormal White Blood Cell Count

When a patient with UC presents with an abnormal white blood cell count despite clinical improvement, several potential causes should be considered:

1. Medication-related effects:

   • Immunomodulators (azathioprine, 6-mercaptopurine) commonly cause leukopenia
   • Biologics may affect white blood cell counts
   • Corticosteroid withdrawal can affect WBC counts

2. Persistent subclinical inflammation:

   • Despite clinical improvement, underlying inflammation may persist
   • Abnormal WBC may indicate ongoing disease activity not reflected in symptoms

3. Infection:

   • Opportunistic infections in immunosuppressed patients
   • C. difficile infection (more prevalent in UC patients with increased morbidity and mortality) 1

Diagnostic Approach

The following step-wise approach is recommended:

1. Repeat complete blood count to confirm the abnormality

2. Assess other inflammatory markers:

   • C-reactive protein (CRP)
   • Erythrocyte sedimentation rate (ESR)
   • Fecal calprotectin (FC)
   • Fecal lactoferrin

3. Stool studies:

   • C. difficile testing (toxin assay or PCR)
   • Stool culture and sensitivity
   • Parasitic examination

4. Endoscopic assessment:

   • The AGA recommends endoscopic assessment rather than empiric treatment adjustment for UC patients with discordance between symptoms and biomarkers 1
   • Endoscopy with biopsies can evaluate for:
     • Degree of mucosal healing
     • Presence of CMV colitis
     • Other causes of inflammation

Interpretation of Biomarkers

When evaluating the significance of the abnormal WBC in the context of other biomarkers:

• If fecal calprotectin is <150 μg/g and CRP is normal: The abnormal WBC may not indicate active inflammation 1, 2

• If fecal calprotectin is >150 μg/g or CRP is elevated: This suggests possible ongoing inflammation despite clinical improvement 1

• If WBC is low (<3000): This may be related to immunomodulator therapy and not necessarily indicate active disease 3

Treatment Recommendations

Based on the diagnostic findings, the following treatment approaches are recommended:

1. If endoscopy confirms mucosal healing (Mayo endoscopic subscore 0-1):

   • Continue current therapy with close monitoring of WBC
   • Consider dose adjustment of immunomodulators if leukopenia is present
   • Higher remission maintenance rates are observed in patients who continue immunomodulators after achieving mucosal healing 3

2. If endoscopy shows active inflammation:

   • Treatment intensification may be necessary
   • Consider biologic therapy optimization or switching classes
   • For moderate-severe inflammation, infliximab or vedolizumab have demonstrated efficacy 4, 5

3. If infection is identified:

   • Treat the specific infection
   • Consider temporary reduction of immunosuppression if appropriate

Monitoring and Follow-up

• Repeat WBC count in 2-4 weeks to monitor trends
• Serial fecal calprotectin measurements every 3-6 months 2
• Follow-up endoscopy in 6-12 months to assess mucosal healing

Important Considerations

• Do not rely solely on symptoms: Clinical remission without mucosal healing is associated with higher relapse rates

• Avoid prolonged corticosteroid exposure: This predisposes patients to increased perioperative complications if surgery becomes necessary 6

• Consider medication-specific monitoring:

  • For patients on thiopurines: Monitor complete blood count, liver function tests
  • For patients on biologics: Monitor for immunogenicity and drug levels when available

• Treatment goals: The ultimate aim is to achieve not only clinical and endoscopic remission but also histological remission to improve long-term outcomes 1

By following this algorithmic approach, the underlying cause of the abnormal white blood cell count can be identified and appropriate management instituted to optimize outcomes for the patient with ulcerative colitis.