What is the next step in evaluating and managing an elderly female patient with chronic diarrhea, elevated calprotectin, and no visible inflammation on CT, who is not responding to Lomotil (diphenoxylate and atropine) and takes supplements including collagen, calcium, biotin, and a multivitamin?

Colonoscopy with Biopsies is the Critical Next Step

This elderly patient with markedly elevated fecal calprotectin (>900) and chronic diarrhea unresponsive to Lomotil requires colonoscopy with biopsies from the right and left colon to exclude microscopic colitis, inflammatory bowel disease, and colorectal cancer. 1

Why Colonoscopy is Mandatory Now

• Age alone mandates colonoscopy: The British Society of Gastroenterology strongly recommends that patients over 45 years with chronic diarrhea undergo full colonoscopy due to the frequency and clinical significance of colonic neoplasia in older subjects 1

• Elevated calprotectin (>900) indicates significant colonic inflammation: This level strongly suggests organic pathology rather than functional disease, even when CT shows no visible inflammation 1, 2

• CT imaging is inadequate: CT cannot detect microscopic colitis, early inflammatory bowel disease, or subtle mucosal abnormalities that are only visible endoscopically with histology 1

Critical Biopsy Protocol

Biopsies must be obtained from both right and left colon (not rectum) even if the mucosa appears completely normal 1. This is essential because:

• Microscopic colitis has entirely normal-appearing mucosa on endoscopy but shows characteristic histologic changes 2, 3
• Missing microscopic colitis is a common pitfall when biopsies are not performed on normal-appearing mucosa 2

Most Likely Diagnoses to Consider

1. Microscopic Colitis (High Probability)

• Presents with chronic watery diarrhea in elderly patients, particularly women 3, 4
• Calprotectin is typically elevated 2
• Cannot be diagnosed without histology from colonoscopy 1, 2
• Responds to budesonide therapy once diagnosed 3

2. Inflammatory Bowel Disease

• Elevated calprotectin strongly suggests this diagnosis 1, 5, 2
• May have patchy distribution missed on CT 1

3. Bile Acid Diarrhea (Consider After Colonoscopy)

• Common in elderly patients and frequently overlooked 6
• Should be diagnosed with SeHCAT testing or serum 7α-hydroxy-4-cholesten-3-one, not empiric trial 1, 2
• Approximately 10% of patients with chronic diarrhea have bile acid malabsorption 6

Additional Testing to Complete Simultaneously

While arranging colonoscopy, ensure these tests are completed if not already done:

• Anti-tissue transglutaminase IgA with total IgA for celiac disease (mandatory screening) 1, 5, 2
• Fecal immunochemical test (FIT) to assess for occult blood loss and guide urgency of colonoscopy 1
• Complete blood count, C-reactive protein, comprehensive metabolic panel to assess for anemia, systemic inflammation, and electrolyte disturbances 1, 5, 2

Supplement Considerations

Review the patient's supplements as potential contributors:

• Calcium supplementation can paradoxically cause diarrhea in some patients, particularly with certain formulations 4
• Collagen supplements may contain additives or cause osmotic effects 4
• Consider a trial of discontinuing supplements to assess for improvement, but this should not delay colonoscopy 4

Management of Lomotil Failure

• Switch to loperamide: Initial dose 4 mg, then 2 mg after each unformed stool, with average maintenance dose of 4-8 mg daily (maximum 16 mg/day) 7, 3
• Loperamide is more effective than diphenoxylate (Lomotil) for most patients with chronic diarrhea 7, 3
• However, symptomatic treatment should not replace diagnostic evaluation in this high-risk patient 2

Common Pitfalls to Avoid

• Do not assume functional diarrhea: Rome IV criteria have only 52-74% specificity and cannot reliably exclude microscopic colitis, IBD, or bile acid diarrhea with calprotectin this elevated 1, 2

• Do not rely on CT alone: Normal CT does not exclude significant colonic pathology requiring endoscopic diagnosis 1

• Do not perform empiric treatment trials before colonoscopy: This delays diagnosis and may mask serious pathology in an elderly patient 2

• Do not skip biopsies if mucosa looks normal: This is the most common reason for missing microscopic colitis 2

After Colonoscopy Algorithm

If colonoscopy with biopsies is negative:

1. Test for bile acid diarrhea with SeHCAT or serum 7α-hydroxy-4-cholesten-3-one 1, 6, 2

2. Consider small bowel evaluation with MR enterography or video capsule endoscopy if malabsorption suspected 1, 5

3. Evaluate for small intestinal bacterial overgrowth with hydrogen breath testing or empiric antibiotic trial 1

4. Reassess medication and supplement history for diarrheogenic agents 5, 4