What is the role of fecal lactoferrin testing in differentiating between inflammatory and non-inflammatory causes of chronic diarrhea?

Role of Fecal Lactoferrin in Differentiating Inflammatory and Non-inflammatory Causes of Chronic Diarrhea

Fecal lactoferrin is a highly effective biomarker for differentiating inflammatory from non-inflammatory causes of chronic diarrhea, with a sensitivity of 79% and specificity of 93% at thresholds of 4.0-7.25 μg/g. 1, 2

Diagnostic Value of Fecal Lactoferrin

Performance Characteristics

• Fecal lactoferrin has excellent diagnostic accuracy for detecting intestinal inflammation:
  • Sensitivity: 79% (95% CI, 73-84%) 1
  • Specificity: 93% (95% CI, 63-99%) 1
  • Threshold range: 4.0-7.25 μg/g 1, 2
  • 100% specific in ruling out IBS 3

Comparison with Other Inflammatory Markers

• Fecal lactoferrin performs similarly to fecal calprotectin in identifying intestinal inflammation:

  Biomarker	Threshold	Sensitivity	Specificity
  Fecal Lactoferrin	7.25 μg/g	83%	75%
  Fecal Calprotectin	50 μg/g	81%	87%
  Fecal Calprotectin	150 μg/g	71%	69%
  2

• Serum inflammatory markers (ESR, CRP) are less sensitive and specific than fecal markers:

  • ESR: sensitivity 0.54-0.78, specificity 0.46-0.95 1
  • CRP: sensitivity 0.73, specificity 0.78 1

Clinical Application

When to Use Fecal Lactoferrin Testing

• Recommended as a screening tool for inflammatory bowel disease in patients with chronic diarrhea 2
• Particularly useful when trying to differentiate between:
  • Inflammatory bowel disease (IBD) vs. Irritable bowel syndrome (IBS)
  • Active vs. inactive IBD
  • Inflammatory vs. non-inflammatory causes of diarrhea 1, 2

Interpretation of Results

• Elevated levels (>7.25 μg/g): Strongly suggestive of inflammatory etiology, particularly IBD 2, 3
• Normal levels (<7.25 μg/g): Suggest non-inflammatory causes like IBS or functional diarrhea 2, 3

Diagnostic Algorithm

1. Perform fecal lactoferrin testing in patients with chronic diarrhea
2. If lactoferrin is elevated (>7.25 μg/g):
   • Rule out infectious causes with stool culture and C. difficile testing
   • Consider colonoscopy with biopsies to confirm IBD or other inflammatory conditions
3. If lactoferrin is normal (<7.25 μg/g):
   • Non-inflammatory causes like IBS are more likely
   • Consider other diagnostic tests for functional disorders

Advantages and Limitations

Advantages

• Non-invasive test that can reduce the need for unnecessary endoscopic procedures 3, 4
• High specificity (93%) means positive results are reliable indicators of inflammation 1
• Useful for monitoring disease activity in established IBD patients 2, 5

Limitations and Caveats

• False positives can occur with:
  • NSAID use
  • Colorectal cancer
  • Infectious gastroenteritis
  • Recent colonoscopy or bowel preparation 2
• Different commercial assays may have varying thresholds and performance 2
• Not useful for establishing specific infectious causes of diarrhea 2
• Age-related variations (higher in infants, especially breastfed) 2

Evidence-Based Recommendations

• 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) 2
• Fecal lactoferrin testing should be considered as part of the initial evaluation of patients with suspected inflammatory diarrhea 1, 2
• In patients with established IBD, normal lactoferrin levels (<7.25 μg/g) indicate likely remission or minimal inflammation 2