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

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Last updated: June 10, 2025View editorial policy

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From the Guidelines

Fecal lactoferrin (FL) testing is a recommended diagnostic tool for differentiating between inflammatory and non-inflammatory causes of chronic diarrhea, with a threshold value of 7.25 mg/g optimizing sensitivity for inflammatory bowel disease (IBD) 1. When evaluating patients with chronic diarrhea, a positive FL test suggests inflammatory conditions such as IBD, including Crohn's disease and ulcerative colitis, or infectious colitis. Conversely, a negative FL test points toward non-inflammatory causes like irritable bowel syndrome (IBS), microscopic colitis, or malabsorption disorders. The test works because during active intestinal inflammation, neutrophils migrate to the intestinal mucosa and release lactoferrin, which can then be detected in stool samples. FL testing offers several advantages: it's non-invasive, relatively inexpensive, and provides quick results compared to more invasive procedures like colonoscopy. However, it should be interpreted alongside clinical presentation and other diagnostic findings, as false positives can occur with certain medications or conditions. The American Gastroenterological Association (AGA) suggests the use of either fecal calprotectin or fecal lactoferrin to screen for IBD in patients presenting with chronic diarrhea, with a conditional recommendation based on low-quality evidence 1. In a high pretest probability scenario, approximately 3.7% of patients with elevated fecal lactoferrin (>7.25 mg/g) may be misclassified as having moderate to severe endoscopic activity, while normal fecal lactoferrin (<7.25 mg/g) had significantly high rates of being false negative (14.5%) 1. Key points to consider when using FL testing include:

  • Threshold value: 7.25 mg/g for optimizing sensitivity for IBD
  • Sensitivity and specificity: around 80-90% and 85-95%, respectively, for detecting inflammatory bowel conditions
  • Interpretation: alongside clinical presentation and other diagnostic findings
  • Advantages: non-invasive, relatively inexpensive, and quick results
  • Limitations: potential for false positives with certain medications or conditions, and false negatives in some cases.

From the Research

Fecal Lactoferrin Testing

  • Fecal lactoferrin (FL) is a sensitive and specific marker for identifying intestinal inflammation 2, 3, 4.
  • The test can help differentiate between inflammatory and non-inflammatory causes of chronic diarrhea 2, 5, 3, 4.

Sensitivity and Specificity

  • The sensitivity and specificity of fecal lactoferrin for inflammatory bowel disease (IBD) are 90% and 88%, respectively, for ulcerative colitis (UC), and 92% and 80%, respectively, for Crohn's disease (CD) 3.
  • The test has a high positive predictive value for inflammatory conditions, such as UC and CD 2, 4.
  • Fecal lactoferrin is 100% specific in ruling out irritable bowel syndrome (IBS) 2.

Clinical Applications

  • FL testing can be used to evaluate patients with chronic diarrhea and help determine the need for further testing or empiric therapy 5, 6.
  • The test can aid in the diagnosis of inflammatory causes of chronic diarrhea, such as IBD, and help exclude non-inflammatory causes, such as IBS 2, 3, 4.
  • Fecal lactoferrin levels can also be used to monitor disease activity in patients with IBD 3.

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.

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