Fecal Calprotectin in Inflammatory Bowel Disease
Role and Clinical Utility
Fecal calprotectin is a highly reliable non-invasive biomarker for detecting intestinal inflammation in IBD, with excellent correlation to endoscopic disease activity and a primary role in differentiating IBD from irritable bowel syndrome, monitoring disease activity, and guiding treatment decisions without requiring repeat endoscopy. 1, 2
Diagnostic Performance
For ruling out IBD: Fecal calprotectin <50 μg/g has 90.6% sensitivity for detecting endoscopically active disease, making it excellent for excluding IBD in symptomatic patients with a negative predictive value of 87% 1, 2, 3
For confirming active inflammation: At cutoffs >100 μg/g, specificity reaches 78.2%, and at >250 μg/g, specificity improves to 73-82% 1
In ulcerative colitis specifically: A cutoff of 150 μg/g demonstrates 71% sensitivity and 69% specificity for detecting moderate-to-severe endoscopic inflammation (Mayo Endoscopic Score ≥2) 1
Interpretation Thresholds and Management Algorithm
<50 μg/g (Quiescent Disease):
- Reliably rules out active inflammation in symptomatic patients 1, 2
- Continue current therapy without escalation 4
- In patients with known IBD in clinical remission, this level predicts sustained remission 2, 5
50-100 μg/g (Low-Level Elevation):
- Gray zone requiring clinical correlation 1, 4
- Consider repeat testing in 2-3 weeks if symptoms are mild 2
- IBD is unlikely if symptoms suggest IBS 2, 3
100-250 μg/g (Intermediate Range):
- Inflammation is possible but not certain 4, 3
- For new patients with suspected IBD: Consider repeat testing or routine gastroenterology referral based on symptom severity 2
- For known IBD patients with mild symptoms: Proceed to endoscopic assessment rather than empiric treatment escalation 1
- Rule out confounding factors: NSAID use within 6 weeks, infectious gastroenteritis, hemorrhoids 2, 6
>150 μg/g (Active Inflammation Likely):
- In patients with moderate-to-severe symptoms: This threshold reliably indicates active inflammation with only 4.6% false positive rate—proceed directly to treatment adjustment without mandatory endoscopy 1, 7
- In patients with mild symptoms: Endoscopic assessment is recommended before treatment changes, as false positive rate increases to 15.5% 1, 7
- In asymptomatic patients with known IBD: Consider endoscopic evaluation, as false positive rate is 22.4% 7
>250 μg/g (Severe Active Inflammation):
- Strongly indicates active disease requiring treatment intensification 1, 2, 4
- Sensitivity of 80% and specificity of 82% for differentiating active IBD from remission 1
- Urgent gastroenterology referral warranted for new patients 2
Monitoring Disease Activity in Established IBD
Routine monitoring frequency: Measure every 6-12 months in patients with clinical remission 2
Predicting relapse: Elevated calprotectin in clinically inactive disease predicts future relapse and should prompt consideration of treatment optimization 1, 2
Assessing treatment response: Repeat measurement at 3-6 months after treatment adjustment facilitates early recognition of inadequate response or impending flares 2, 7
Mucosal healing: Calprotectin <250 μg/g corresponds with disease remission with 90% sensitivity and 76% specificity 3
Critical Caveats and Pitfalls
When NOT to use calprotectin:
- Alarm features present: In patients with rectal bleeding plus abdominal pain, change in bowel habit, weight loss, or iron-deficiency anemia, proceed directly to cancer pathway referral—calprotectin cannot exclude colorectal cancer or advanced adenomas 1, 2
Causes of false elevation (non-IBD):
- NSAID use within past 6 weeks 2, 6
- Infectious gastroenteritis (cannot be distinguished from IBD by calprotectin alone) 2, 6
- Hemorrhoids or other sources of GI bleeding 2, 6
- Colorectal cancer and advanced adenomas 2, 6
- Microscopic colitis 2
Managing suspected false positives:
- Discontinue NSAIDs and repeat testing after approximately 18 days—53% of initially elevated results will normalize 6
- Obtain stool cultures to exclude infectious causes 7
- Verify proper sample collection technique 6
Practical Collection and Testing Considerations
Optimal sample: Use the first stool passed in the morning 1, 2, 6
Storage: Samples must be analyzed within 3 days at room temperature or frozen for up to 2.5 months 1, 2, 3
Assay variability: Different commercial assays exist with variable performance—interpret results according to local laboratory reference ranges 6
Day-to-day variability: Calprotectin levels can vary between different stools from the same patient on the same day 1
Integration with Other Biomarkers
C-reactive protein (CRP): Normal CRP may rule out active inflammation in symptomatic patients, but 20% of active Crohn's disease patients have normal CRP, limiting its sensitivity 1, 2
Complete blood count: Essential for assessing anemia and thrombocytosis as markers of systemic inflammation 2
Fecal lactoferrin: At cutoff of 7.25 μg/g, provides similar diagnostic utility to calprotectin but with more limited evidence base 1