Rectal Bleeding with Clear Colonoscopy and Elevated CRP Requires Further Investigation for Microscopic Colitis and Small Bowel Disease
Despite the clear colonoscopy, the combination of rectal bleeding and elevated CRP in this patient indicates ongoing inflammation that cannot be attributed to IBS alone and demands additional diagnostic workup before accepting an IBS diagnosis.
Critical Diagnostic Gap
The elevated CRP is a red flag that distinguishes this presentation from typical IBS. While rectal bleeding can occur with IBS, the presence of systemic inflammation (elevated CRP) suggests an organic pathology that requires identification 1.
Essential Next Steps
Obtain colonic biopsies from the right and left colon (not rectum) to exclude microscopic colitis, which can present with chronic diarrhea, normal-appearing mucosa on colonoscopy, and elevated inflammatory markers 1. This is a critical oversight if biopsies were not obtained during the initial colonoscopy, as microscopic colitis is diagnosed histologically despite endoscopically normal mucosa.
Evaluate the small bowel with MR enterography or video capsule endoscopy to exclude Crohn's disease or other small bowel pathology that would explain both the bleeding and elevated CRP 1. The British Society of Gastroenterology guidelines emphasize that persistent symptoms with elevated inflammatory markers warrant small bowel imaging even after negative colonoscopy 1.
Additional Diagnostic Testing
Repeat fecal calprotectin measurement to quantify intestinal inflammation more specifically than CRP alone 1. While useful for initial screening, an elevated result (>250 μg/g) in this context supports ongoing investigation for inflammatory bowel disease 1.
Stool studies including culture, ova and parasites, and testing for Giardia to exclude infectious causes of chronic diarrhea with inflammation 1.
Celiac serology if not already performed, as celiac disease can present with diarrhea and elevated inflammatory markers 1.
Consider bile acid diarrhea testing with SeHCAT scan or serum 7α-hydroxy-4-cholesten-3-one if available, as bile acid diarrhea is common in functional diarrhea but would not explain the elevated CRP or bleeding 1.
Why This Is Not Simply IBS
The presence of rectal bleeding and elevated CRP represents alarm features that preclude a straightforward IBS diagnosis 1. The 2002 AGA guidelines explicitly state that rectal bleeding not attributable to hemorrhoids or anal fissures requires investigation beyond IBS criteria 1. The British Society of Gastroenterology emphasizes that elevated inflammatory markers should prompt exclusion of organic disease before attributing symptoms to IBS 1.
Normal hemoglobin does not exclude significant pathology—microscopic colitis, early Crohn's disease, and other inflammatory conditions can present with bleeding and inflammation before anemia develops 1.
Treatment Considerations Only After Diagnosis
If all investigations return negative and microscopic colitis and IBD are definitively excluded, then consider IBS-D management with:
- Rifaximin, eluxadoline, or alosetron as first-line pharmacologic options for IBS-D 1.
- Tricyclic antidepressants as gut-brain neuromodulators for persistent symptoms 1.
- Avoid SSRIs as they show no benefit and may worsen diarrhea in IBS-D 1.
However, initiating IBS treatment before completing the diagnostic workup for the elevated CRP and rectal bleeding would be premature and potentially harmful, as it could mask progressive inflammatory disease 1.
Common Pitfall
The most critical error in this scenario is accepting the "clear colonoscopy" as sufficient to exclude all organic disease. A visually normal colonoscopy does not exclude microscopic colitis, and colonoscopy does not evaluate the small bowel 1. The elevated CRP demands explanation and should not be dismissed as coincidental in a patient with daily diarrhea and bleeding.