What is the recommended treatment for a patient in their late 50s with a 2-week history of diarrhea, negative stool culture for common pathogens, but elevated lactoferrin level?

Medical Advisory BoardAll articles are reviewed for accuracy by our Medical Advisory Board
Educational purpose only • Exercise caution as content is pending human review
Article Review Status
Submitted
Under Review
Approved

Last updated: November 26, 2025View editorial policy

Personalize

Help us tailor your experience

Which best describes you? Your choice helps us use language that's most understandable for you.

Endoscopic Assessment is the Priority for This Patient

This patient with 2 weeks of persistent diarrhea, negative infectious workup, and elevated fecal lactoferrin (177.44 μg/g) requires endoscopic evaluation to identify the underlying inflammatory cause before initiating treatment. 1, 2, 3

Rationale for Endoscopy

The elevated lactoferrin level indicates intestinal inflammation with high specificity:

  • Fecal lactoferrin has 90% specificity for identifying active inflammation in inflammatory bowel disease (IBD), with 90% sensitivity for detecting histologic inflammation on biopsy. 4, 5
  • In patients with chronic diarrhea and positive lactoferrin, the major underlying cause is chronic inflammatory bowel disease of the colon, with a positive predictive value of 82% for ulcerative colitis or Crohn's disease. 5
  • Early endoscopy (within 2 weeks of symptom onset) is strongly recommended for all patients with positive lactoferrin results, as it leads to shorter symptom duration (19 vs 47 days), shorter steroid treatment duration (49 vs 74 days), and reduced symptom recurrence (21.8% vs 50%). 1

Diagnostic Approach

Proceed with colonoscopy and consider upper endoscopy with biopsies:

  • The AGA recommends endoscopic assessment rather than empiric treatment when inflammatory biomarkers are elevated, even in patients with mild symptoms. 1
  • Obtain biopsies even from normal-appearing mucosa, as lactoferrin can detect microscopic inflammation before it becomes visually apparent on endoscopy. 2
  • If initial colonoscopy is unrevealing but lactoferrin remains elevated, consider capsule endoscopy to evaluate the small bowel for Crohn's disease, as standard endoscopy can miss subtle mucosal inflammation. 2

Management Based on Endoscopic Findings

If Endoscopy Confirms IBD:

  • Initiate treatment based on disease severity and distribution found on endoscopy and histology. 1
  • For ulcerative colitis with moderate to severe inflammation (Mayo Endoscopic Score 2-3), consider biologic therapy rather than mesalamine alone. 6
  • Monitor treatment response with repeat fecal lactoferrin in 2-4 months and endoscopy at 6-12 months to confirm mucosal healing. 2, 7

If Endoscopy Shows No Inflammation:

  • Consider other causes of elevated lactoferrin including NSAIDs (if used within past 6 weeks), microscopic colitis (requires biopsies), or segmental disease missed by standard endoscopy. 3
  • Repeat lactoferrin measurement in 3-6 months to confirm normalization. 2, 3
  • If lactoferrin remains elevated on repeat testing despite negative endoscopy, proceed with capsule endoscopy or consider biopsies from previously normal-appearing areas. 2

Critical Caveats

Do not initiate empiric corticosteroid or immunosuppressive therapy without endoscopic confirmation of inflammation, as this approach delays accurate diagnosis and may obscure endoscopic findings if performed later. 1

The 2-week duration of symptoms makes infectious causes less likely despite the negative stool cultures, but the elevated lactoferrin strongly suggests an inflammatory rather than functional etiology (lactoferrin is 100% specific in ruling out irritable bowel syndrome). 4, 5

References

Guideline

Guideline Directed Topic Overview

Dr.Oracle Medical Advisory Board & Editors, 2025

Guideline

Diagnostic Approach to Elevated Lactoferrin with Clear Endoscopy

Praxis Medical Insights: Practical Summaries of Clinical Guidelines, 2025

Guideline

Management of Discordant Biomarkers in Inflammatory Bowel Disease

Praxis Medical Insights: Practical Summaries of Clinical Guidelines, 2025

Guideline

Treatment of Crohn's Disease with Ileal Ulcers and Anemia

Praxis Medical Insights: Practical Summaries of Clinical Guidelines, 2025

Professional Medical Disclaimer

This information is intended for healthcare professionals. Any medical decision-making should rely on clinical judgment and independently verified information. The content provided herein does not replace professional discretion and should be considered supplementary to established clinical guidelines. Healthcare providers should verify all information against primary literature and current practice standards before application in patient care. Dr.Oracle assumes no liability for clinical decisions based on this content.

Have a follow-up question?

Our Medical A.I. is used by practicing medical doctors at top research institutions around the world. Ask any follow up question and get world-class guideline-backed answers instantly.