What is the role of fecal lactoferrin testing in diagnosing the cause of chronic diarrhea?

Role of Fecal Lactoferrin Testing in Diagnosing Causes of Chronic Diarrhea

Fecal lactoferrin testing is recommended as a useful screening tool for inflammatory bowel disease in patients with chronic diarrhea, but should not be used to establish specific infectious causes of diarrhea. 1

Understanding Fecal Lactoferrin

Fecal lactoferrin is a glycoprotein expressed by activated neutrophils that serves as a surrogate marker for intestinal inflammation. Key characteristics include:

• Remains stable during stool transport and processing, unlike fecal leukocytes which degrade quickly 1, 2
• Sensitivity of approximately 83% and specificity of 75% at standard threshold (7.25 μg/g) for detecting intestinal inflammation 2
• 100% specific for ruling out irritable bowel syndrome when elevated 3

Clinical Applications in Chronic Diarrhea Evaluation

Primary Use: Screening for Inflammatory vs. Non-inflammatory Causes

1. Inflammatory Bowel Disease (IBD) Screening

   • The American Gastroenterological Association (AGA) suggests using either fecal calprotectin or fecal lactoferrin to screen for IBD in patients with chronic diarrhea (conditional recommendation, low quality evidence) 1
   • Helps distinguish inflammatory from functional disorders with high negative predictive value (99%) 4

2. Distinguishing Functional from Organic Disease

   • Sensitivity of 90% and specificity of 98% for detecting ulcerative colitis or Crohn's disease 4
   • Normal levels suggest functional disorders rather than inflammatory conditions 2

Limitations and Inappropriate Uses

1. Not Recommended for Specific Infectious Diagnosis

   • The Infectious Diseases Society of America (IDSA) strongly recommends against using fecal lactoferrin to establish the cause of acute infectious diarrhea (strong recommendation, moderate evidence) 1

2. False Positives

   • Can occur with various inflammatory conditions including:
     • Gastrointestinal infections
     • NSAID-induced enteropathy
     • Colorectal cancer
     • Microscopic colitis (in some cases) 2, 4

3. False Negatives

   • May occur in approximately 17% of patients with active IBD
   • More common in isolated small bowel Crohn's disease 2

Diagnostic Algorithm for Chronic Diarrhea

1. Initial Evaluation

   • Test for fecal lactoferrin or fecal calprotectin
   • If negative: Consider functional disorder (IBS-D, functional diarrhea)
   • If positive: Proceed to endoscopic evaluation 1, 2

2. Additional Testing Based on Lactoferrin Results

   • Negative lactoferrin + IBS-like symptoms:

     • Consider testing for celiac disease (IgA-tTG) 1
     • Consider testing for bile acid diarrhea 1
     • Consider testing for Giardia 1

   • Positive lactoferrin:

     • Proceed to colonoscopy with biopsies to evaluate for IBD, microscopic colitis
     • Consider upper endoscopy if small bowel disease suspected 2

Comparative Value with Other Tests

• Fecal Calprotectin vs. Lactoferrin

  • Both have similar diagnostic accuracy
  • Fecal calprotectin: Sensitivity 81%, specificity 87% at 50 μg/g threshold 2
  • Fecal lactoferrin: Sensitivity 83%, specificity 75% at 7.25 μg/g threshold 2

• Serum Inflammatory Markers

  • ESR and CRP are less accurate than fecal markers
  • AGA suggests against using ESR or CRP to screen for IBD (conditional recommendation, low quality evidence) 1

Cost-Effectiveness Considerations

• Screening with fecal lactoferrin before culture can increase the yield of stool cultures fivefold 5
• Can reduce the cost per positive culture result by over $800 5
• More cost-effective than performing endoscopy on all patients with chronic diarrhea 6

Practical Clinical Pearls

• Fecal lactoferrin testing is most valuable as an initial screening tool to determine which patients need endoscopic evaluation
• A negative test effectively rules out IBD in most cases due to high negative predictive value
• The test should be interpreted in clinical context, as false positives can occur with various inflammatory conditions
• In infants consuming human milk, interpretation may be difficult as lactoferrin is a normal component of human milk 1

Remember that while fecal lactoferrin is a valuable screening tool for inflammation, endoscopy with biopsy remains the gold standard for diagnosing specific causes of chronic diarrhea.