From the Guidelines
A positive stool lactoferrin test indicates active intestinal inflammation, which may require further diagnostic workup, including endoscopy with biopsies, stool cultures, or imaging studies, to determine the underlying cause and guide management decisions. This finding suggests neutrophil migration into the intestinal mucosa, as lactoferrin is an iron-binding protein found in neutrophils and released during inflammation. Clinically, this result helps differentiate inflammatory from non-inflammatory causes of diarrhea or abdominal symptoms, with inflammatory conditions typically requiring different management approaches than functional disorders like irritable bowel syndrome (IBS) 1.
According to the AGA clinical practice guideline on the role of biomarkers for the management of ulcerative colitis, in patients with UC in symptomatic remission but elevated biomarkers of inflammation, repeat measurement of biomarkers (in 3–6 mo) may be a reasonable alternative to endoscopic assessment, however, if biomarkers are elevated on repeat evaluation, then endoscopic assessment may be warranted 1. The level of lactoferrin elevation may correlate with disease severity in IBD patients and can be useful for monitoring treatment response.
Some key points to consider when interpreting a positive stool lactoferrin test include:
- The test cannot distinguish between specific inflammatory conditions, so additional diagnostic workup is usually necessary 1
- False positives can occur with certain medications (NSAIDs), so clinical correlation is important 1
- The test is particularly valuable in initial patient evaluation when symptoms could represent either inflammatory or functional gastrointestinal disorders 1
- In patients with symptomatically active UC, the AGA suggests using fecal calprotectin >150 mg/g, elevated fecal lactoferrin, or elevated CRP to inform treatment decisions and avoid routine endoscopic assessment of disease 1
It is essential to consider the clinical context and correlate the test results with symptoms, medical history, and other diagnostic findings to make informed management decisions. In patients with UC in symptomatic remission but elevated stool or serum markers of inflammation (fecal calprotectin >150 mg/g, elevated fecal lactoferrin, elevated CRP), the AGA suggests endoscopic assessment of disease activity rather than empiric treatment adjustment 1.
From the Research
Clinical Implications of a Positive Stool Lactoferrin Test
A positive stool lactoferrin test has several clinical implications, including:
- Inflammatory Bowel Disease (IBD) Diagnosis: A positive test can indicate the presence of IBD, such as ulcerative colitis or Crohn's disease, with a sensitivity of 90% and specificity of 98% 2.
- Disease Activity Assessment: Fecal lactoferrin levels can reflect disease activity in patients with IBD, with higher levels indicating more severe inflammation 3, 4.
- Differentiation from Non-Inflammatory Conditions: A positive test can help differentiate IBD from non-inflammatory conditions, such as irritable bowel syndrome (IBS), with a sensitivity of 92% and specificity of 88% for ulcerative colitis and 92% and 80% for Crohn's disease 4.
- Monitoring Response to Treatment: Fecal lactoferrin levels can be used to monitor response to treatment and predict endoscopic and clinical relapse 5.
- Prediction of Postoperative Recurrence: Elevated fecal lactoferrin levels can predict postoperative recurrence in patients with IBD 5.
Potential Causes of Elevated Fecal Lactoferrin
Elevated fecal lactoferrin levels can be caused by:
- Inflammatory Bowel Disease: Ulcerative colitis, Crohn's disease, and other forms of IBD can cause elevated fecal lactoferrin levels 3, 2, 4.
- Infectious Bowel Disease: Certain infections, such as Clostridioides difficile infection, can also cause elevated fecal lactoferrin levels 6.
- Other Inflammatory Conditions: Other inflammatory conditions, such as microscopic colitis and celiac sprue, can also cause elevated fecal lactoferrin levels 2.