What is the role of stool sample analysis for calprotectin or lactoferrin in diagnosing Inflammatory Bowel Disease (IBD)?

Stool Sample Analysis for IBD Diagnosis

In patients presenting with chronic diarrhea or suspected IBD, use fecal calprotectin or fecal lactoferrin as first-line screening tests to identify inflammatory bowel disease before proceeding to endoscopy. 1

Recommended Biomarkers and Thresholds

Fecal Calprotectin

• Use a threshold of 50 μg/g to optimize sensitivity for detecting IBD (pooled sensitivity 81%, specificity 87%). 1
• Higher thresholds improve specificity: 100 μg/g provides 78% specificity, while 250 μg/g provides 82% specificity, though at the cost of reduced sensitivity (80%). 1
• Calprotectin correlates well with endoscopic inflammation in both ulcerative colitis and Crohn's disease. 1

Fecal Lactoferrin

• Use threshold values of 4.0–7.25 μg/g to optimize sensitivity for IBD screening. 1
• Lactoferrin shows comparable diagnostic accuracy to calprotectin, with overall sensitivity of 80%, specificity of 85%, and diagnostic efficacy of 81%. 2
• Lactoferrin correlates particularly well with histological inflammation. 2

Clinical Algorithm for Use

For Initial IBD Screening (Chronic Diarrhea)

• Order either fecal calprotectin OR fecal lactoferrin (not both routinely, as they show 90% concordance). 3
• If calprotectin <50 μg/g or lactoferrin is negative: IBD is effectively ruled out (high negative predictive value). 4
• If calprotectin 50-250 μg/g: Consider repeat testing in 3-6 months or proceed to colonoscopy based on symptom severity. 5
• If calprotectin >250 μg/g: Urgent gastroenterology referral and colonoscopy indicated. 4

For Monitoring Known IBD

• In symptomatic remission with calprotectin <150 μg/g: Active inflammation is reliably ruled out, endoscopy not needed. 1
• In symptomatic remission with calprotectin >150 μg/g: Proceed to endoscopic assessment rather than empiric treatment escalation. 1
• With mild symptoms and normal biomarkers: Still proceed to endoscopic assessment, as normal markers cannot rule out active inflammation in symptomatic patients. 1

Practical Considerations and Pitfalls

Sample Collection

• Collect the first stool passed in the morning for optimal accuracy. 1
• Store samples for no more than 3 days at room temperature before analysis to maintain stability. 1

Factors That Affect Results

• NSAID use within the past 6 weeks can falsely elevate calprotectin levels and must be considered when interpreting results. 4
• Hemorrhoids can cause false elevations due to local bleeding and inflammation. 4
• Other conditions that elevate calprotectin include infectious gastroenteritis and colorectal cancer. 4

When NOT to Use Calprotectin

• Do not use calprotectin in patients with alarm symptoms (rectal bleeding with abdominal pain, change in bowel habit, weight loss, or iron-deficiency anemia) as it cannot exclude colorectal cancer—these patients require cancer pathway referral regardless of calprotectin result. 1
• Insufficient data exist for using calprotectin in acute infectious diarrhea. 6

Comparison to Serum Markers

Do not use ESR or CRP as primary screening tests for IBD—they are inferior to fecal markers. 1 CRP shows pooled sensitivity of only 49% and specificity of 92% for detecting endoscopic activity, significantly lower than fecal calprotectin (88% sensitivity, 73% specificity) or lactoferrin (82% sensitivity, 79% specificity). 7 However, if fecal markers are unavailable or not covered by insurance, CRP may be considered as a reasonable alternative. 1

Ordering Patterns in Practice

Gastroenterologists predominantly order calprotectin in the context of abdominal pain and IBD monitoring, while primary care providers more commonly order lactoferrin for acute diarrhea evaluation. 3 Calprotectin orders have increased from 60% to nearly 90% of all fecal inflammatory marker orders over the past decade, reflecting growing preference for this biomarker. 3