What's the next step for a patient with recurrent heavy rectal bleeding, fever, elevated calprotectin levels, and normal colonoscopy results, but no anemia?

Management of Recurrent Rectal Bleeding with Elevated Calprotectin and Normal Colonoscopy

For a patient with recurrent heavy rectal bleeding, fever, elevated calprotectin levels, and normal colonoscopy results but no anemia, the next step should be upper gastrointestinal (GI) endoscopy with biopsies to evaluate for potential small bowel inflammatory disease. 1

Diagnostic Considerations

Interpreting Elevated Calprotectin with Normal Colonoscopy

• Fecal calprotectin >150 μg/g is considered elevated and indicates ongoing intestinal inflammation despite normal colonoscopy findings 2, 1
• Elevated calprotectin with normal colonoscopy suggests:
  • Possible small bowel inflammation not visible during colonoscopy
  • Inflammation that may be patchy or located in areas not adequately visualized
  • Potential upper GI tract inflammation 1

Clinical Significance of Symptoms

• The combination of recurrent rectal bleeding, fever, and elevated calprotectin strongly suggests active inflammatory disease 3
• According to the American Gastroenterological Association (AGA), patients with mild symptoms and elevated inflammatory markers should undergo endoscopic assessment rather than empiric treatment adjustment 2
• The presence of fever indicates systemic inflammatory response that requires thorough evaluation 1

Recommended Diagnostic Algorithm

1. Upper GI Endoscopy with Biopsies

   • Essential to evaluate for small bowel inflammation not detected on colonoscopy 2, 1
   • Should include biopsies even from normal-appearing mucosa 2

2. Consider Additional Small Bowel Imaging

   • If upper endoscopy is non-diagnostic, consider:
     • Wireless capsule endoscopy to evaluate small bowel
     • Enteroscopy for direct visualization and biopsy of small bowel 2, 1

3. Rule Out Other Causes of Elevated Calprotectin

   • Check for:
     • Clostridioides difficile and other enteric pathogens 2
     • Medication effects (NSAIDs, ASA, PPIs can elevate calprotectin) 4, 5

4. Serial Monitoring of Calprotectin

   • Follow calprotectin levels every 3-6 months 1
   • Target normalization (<50 μg/g) as treatment goal 1

Important Considerations and Pitfalls

• Diagnostic Misclassification: Up to 10% of IBD diagnoses are changed within the first 5 years after symptom onset 2

• Medication Effects: Proton pump inhibitors (PPIs) can significantly increase fecal calprotectin levels (adjusted OR: 3.843) and should be considered when interpreting results 4

• Avoid Empiric Treatment: The AGA recommends establishing a definitive diagnosis through endoscopy before initiating treatment, as this leads to better outcomes and more targeted therapy 1

• Normal Colonoscopy ≠ No Disease: Despite normal colonoscopy findings, elevated calprotectin with symptoms warrants further investigation as it reliably indicates ongoing inflammation 6

• Consider Segmental Disease: Inflammatory bowel disease can present with patchy or segmental involvement that may be missed during routine colonoscopy 2

By following this approach, you can identify the source of inflammation causing the recurrent rectal bleeding and fever, even when colonoscopy appears normal, leading to appropriate targeted treatment.