What does fecal calprotectin indicate?

Fecal Calprotectin as a Biomarker of Intestinal Inflammation

Fecal calprotectin is a sensitive and specific marker of intestinal inflammation that serves as a valuable non-invasive tool to differentiate between inflammatory bowel disease (IBD) and irritable bowel syndrome (IBS), with levels <100 μg/g strongly suggesting IBS and levels >250 μg/g indicating active intestinal inflammation requiring urgent gastroenterology referral. 1

What Fecal Calprotectin Indicates

Fecal calprotectin is:

• A neutrophil granulocyte cytosol protein released during inflammatory processes
• Released into the intestinal lumen when inflammation occurs within the intestinal tract
• Stable enough to be measured in feces, making it an excellent non-invasive biomarker 2

Diagnostic Value

Differentiating IBD from IBS

• High negative predictive value for ruling out IBD in symptomatic patients
• Patients with low calprotectin levels (<50 μg/g) are unlikely to have active inflammatory processes 2
• Significantly elevated in IBD patients compared to IBS patients and healthy controls 3

Established Thresholds

• <100 μg/g: Suggests IBS or non-inflammatory conditions
• 100-250 μg/g: Indeterminate range requiring repeat testing or routine gastroenterology referral

• 250 μg/g: Strongly suggests active inflammation, correlating well with endoscopic inflammation and requiring urgent gastroenterology referral 1

Clinical Utility

Disease Monitoring

• Correlates with clinical activity scores in Crohn's disease and ulcerative colitis 3
• Patients with clinically active disease show significantly higher calprotectin levels than those with quiescent disease 3
• Useful for predicting disease relapse with sensitivity and specificity exceeding 85% 4
• Can help determine whether symptoms in known IBD patients are due to disease flares or non-inflammatory complications 5

Limitations and Confounding Factors

• Not sensitive enough for excluding colorectal cancer 1
• Can be elevated in other conditions including:
  • Colorectal cancer
  • Infectious gastroenteritis
  • NSAID use (can cause false elevations if used within past 6 weeks)
  • Other inflammatory conditions 2, 1

Practical Considerations

When to Use

• In patients with chronic diarrhea or lower GI symptoms >4 weeks
• As an initial screening test in primary care along with other blood tests 2
• When differentiating between IBD and IBS in low-risk groups for malignancy 2

When Not to Use

• In patients with bloody diarrhea (requires flexible sigmoidoscopy regardless)
• In acute diarrhea due to infection (won't discriminate between IBD and gastroenteritis)
• In patients with suspected colorectal cancer (rectal bleeding, change in bowel habit, weight loss, or iron-deficiency anemia) 2, 1

Sample Collection and Processing

• First morning stool sample is preferred
• Sample should be stored for no more than 3 days at room temperature before analysis 1

Interpretation Pitfalls

1. Don't rely solely on calprotectin for cancer exclusion - it's not sensitive enough for colorectal cancer
2. Don't interpret in isolation - consider clinical context and pre-test probability of IBD
3. Consider confounding factors - NSAIDs, infections, and other conditions can elevate levels
4. Be aware of assay variations - different commercial tests may yield different results 1

Fecal calprotectin represents a cost-effective approach to prevent unnecessary colonoscopies in patients where IBD is unlikely, while helping to identify those who require further investigation and specialist care.