What is the likely diagnosis and appropriate treatment for a patient with intermittent watery diarrhea, borderline elevated fecal bile acid concentration (~40 µmol/g) and markedly increased fecal lactoferrin (~11 µg/g)?

Diagnosis and Treatment of Intermittent Diarrhea with Borderline Bile Acids and Elevated Lactoferrin

Most Likely Diagnosis

This patient most likely has concurrent bile acid diarrhea (BAD) and active intestinal inflammation, requiring both endoscopic evaluation for the inflammatory component and bile acid sequestrant therapy for the malabsorption. The elevated fecal lactoferrin (11.1 µg/g, above the 7.25 µg/g threshold) indicates active mucosal inflammation with 83% sensitivity and 75% specificity for moderate to severe endoscopic disease, while the borderline elevated bile acids (~40 µmol/g) suggest bile acid malabsorption 1, 2.

Immediate Diagnostic Workup

Rule Out Infection First

• Obtain comprehensive stool studies immediately including bacterial culture (Salmonella, Shigella, Campylobacter, E. coli O157:H7) and C. difficile toxin testing, as infections can elevate lactoferrin and require specific antimicrobial therapy 1, 3.

Confirm Inflammatory Component

• Measure fecal calprotectin concurrently to provide quantitative assessment of inflammation; calprotectin >150 µg/g combined with elevated lactoferrin reduces false positive rates to only 4.6% 2, 3.
• Check serum CRP (>5 mg/L has moderate certainty for ruling in moderate to severe endoscopic inflammation) 1, 2.

Proceed to Endoscopy

• Perform colonoscopy with ileoscopy and biopsy within 7-14 days of symptom onset, even with only mild symptoms, as the elevated lactoferrin warrants endoscopic evaluation regardless of symptom severity 1, 2, 3.
• Early endoscopy (≤7 days) is associated with significantly shorter symptom duration and shorter steroid treatment duration compared to delayed endoscopy 3.
• The National Comprehensive Cancer Network specifically recommends early endoscopy for all patients with positive lactoferrin results, even those with only grade 1 symptoms 1.

Treatment Strategy

Address the Inflammatory Component

If endoscopy confirms active inflammation (Mayo Endoscopic Score ≥2):

• Initiate corticosteroid therapy based on endoscopic findings and disease severity 1, 3.
• Consider advanced therapies (biologics) if moderate to severe inflammation is documented 3.
• Monitor treatment response with repeat fecal calprotectin and lactoferrin at 2-4 months, as both markers decline significantly with successful treatment 2, 3.

Treat Bile Acid Malabsorption

Regardless of endoscopic findings, initiate bile acid sequestrant therapy for the borderline elevated bile acids:

• Start cholestyramine as first-line therapy for bile acid diarrhea, as recommended by the Canadian Association of Gastroenterology 1, 4.
• Cholestyramine adsorbs bile acids in the intestine, forming an insoluble complex excreted in feces, thereby reducing bile acid-induced diarrhea 4.
• If cholestyramine is not tolerated due to palatability issues, switch to alternative bile acid sequestrants such as colesevelam or colestipol 1.
• Use the lowest effective dose and consider intermittent, on-demand administration once symptoms are controlled 1.

Important Clinical Considerations

Risk factors that increase likelihood of bile acid diarrhea:

• History of terminal ileal resection, cholecystectomy, or abdominal radiotherapy 1.
• Crohn's disease with ileal involvement (even without active inflammation) 1.

Common pitfall to avoid:

• Do not assume the diarrhea is purely functional or purely bile acid-related based on borderline bile acid levels alone; the elevated lactoferrin (11.1 µg/g) is 100% specific for ruling out irritable bowel syndrome and indicates true mucosal inflammation requiring endoscopic evaluation 5, 6.

If bile acid sequestrants are not tolerated:

• Consider loperamide as an alternative antidiarrheal agent 1.
• The British Society of Gastroenterology suggests this approach particularly for patients with extensive ileal disease or resection 1.

Monitoring and Follow-Up

• Repeat fecal calprotectin and lactoferrin 2-4 months after initiating therapy to assess treatment response 2, 3.
• Monitor both biomarkers to determine which correlates better with the individual patient's disease activity pattern 2, 3.
• If symptoms persist despite bile acid sequestrant therapy, consider other causes including small intestinal bacterial overgrowth, functional bowel disorders, or strictures 1.
• Reinvestigate with repeat endoscopy if symptoms persist despite treatment and biomarkers remain elevated 2, 7.