Fecal Calprotectin in Inflammatory Bowel Disease
Fecal calprotectin is a highly valuable non-invasive biomarker that serves three critical roles: screening for IBD in patients with chronic gastrointestinal symptoms (with excellent negative predictive value to rule out disease), monitoring disease activity in established IBD patients, and guiding treatment decisions without requiring repeated endoscopy. 1, 2
Diagnostic Role: Screening for IBD
Primary Care Algorithm for New Symptoms
For patients aged 16-40 presenting with lower gastrointestinal symptoms lasting >4 weeks where IBD is suspected, fecal calprotectin provides a structured diagnostic pathway 1:
- <100 μg/g: IBS is likely; treat as IBS in primary care 1
- 100-250 μg/g: Consider repeat testing or routine referral to gastroenterology, particularly if strong clinical suspicion exists (family history, alarm features) 1
- >250 μg/g: Refer urgently to gastroenterology 1
The British Society of Gastroenterology emphasizes that calprotectin should not be used if NSAIDs have been taken in the past 6 weeks, as this can cause false elevation 1, 3. All patients should have complete blood count, urea & electrolytes, CRP, coeliac screen, and stool culture performed in primary care before referral 1.
Diagnostic Performance
Fecal calprotectin demonstrates 90.6% sensitivity for detecting endoscopically active disease at a cut-off of 50 μg/g, while levels >100 μg/g provide 78.2% specificity 2. The test has excellent negative predictive value for IBD, making it particularly useful for ruling out inflammatory disease in symptomatic patients 1, 4. However, the American Gastroenterological Association recommends higher thresholds (100-250 μg/g) to trigger colonoscopy, which improves positive predictive value with minimal reduction in negative predictive value 2.
Important Diagnostic Caveats
False negatives occur primarily in celiac disease 5. In one study, 5 of 11 false-negative results in adults were celiac disease patients, and 6 of 11 false-negative results in children had celiac disease 5. This is critical because calprotectin specifically detects neutrophilic inflammation, and celiac disease may not generate the same neutrophil-predominant response.
False positives occur with 5:
- NSAID or aspirin use
- Liver cirrhosis
- Infectious gastroenteritis 2, 6
- Hemorrhoids (due to local bleeding and inflammation) 2
- Colorectal cancer 2
The test is not sensitive enough to exclude advanced colorectal adenoma or colorectal carcinoma, so patients with alarm symptoms (rectal bleeding, abdominal pain, weight loss) require cancer pathway referral regardless of calprotectin result 2, 6.
Monitoring Disease Activity in Established IBD
Surveillance Schedule
For patients with IBD in symptomatic remission, measure fecal calprotectin every 6-12 months 2. Serial monitoring at 3-6 month intervals can facilitate early recognition and treatment of impending disease flares 2, 6.
Interpreting Results in Known IBD
Fecal calprotectin is a validated biomarker for endoscopic and histological disease activity, correlating well with endoscopic inflammation in both ulcerative colitis and Crohn's disease 1, 2:
- <50 μg/g: Generally reassuring, suggests clinical remission 6
- <150 μg/g: Suggests minimal inflammation and can reliably exclude active inflammation in asymptomatic patients 2
- >150 μg/g: Strongly suggests active inflammatory disease 2, 6
Clinically inactive disease with raised calprotectin levels predicts future relapse 2. In asymptomatic patients with known IBD and calprotectin >150 μg/g, consider endoscopic assessment, though the false positive rate is 22.4% in this scenario 6.
Guiding Treatment Decisions
Patients with Moderate to Severe Symptoms
In patients with moderate to severe symptoms suggestive of IBD flare and calprotectin >150 μg/g, you can reliably assume moderate to severe endoscopic inflammation and adjust treatment empirically without initial endoscopy 2, 6. The false positive rate is only 4.6% in this high pre-test probability scenario, meaning 95.4% of these patients truly have moderate to severe endoscopic inflammation 6.
Patients with Mild Symptoms
For patients with mild IBD symptoms and elevated calprotectin (>150 μg/g), perform endoscopic assessment rather than empiric treatment adjustment 2, 6. The false positive rate is 15.5% in this intermediate probability scenario 6.
Evidence for Biomarker-Guided Therapy
A randomized controlled trial demonstrated that treatment adjustment based on symptoms plus biomarkers versus symptoms alone increases the likelihood of achieving clinical and endoscopic remission at 12 months 2. This provides moderate-quality evidence supporting the use of calprotectin to inform decisions on treatment escalation or de-escalation 1.
Critical Limitation in Symptomatic Patients
In patients with moderate to severe symptoms, calprotectin <150 μg/g does not exclude inflammation, with a false negative rate of 24.7% 6. Therefore, if clinical suspicion remains high despite low calprotectin, proceed with endoscopic evaluation.
Practical Sampling Considerations
Use the first stool passed in the morning for sampling 1, 3. Store samples for no more than 3 days at room temperature before analysis to maintain stability 1, 3. Variation in calprotectin levels can occur related to the interval between stools being passed 1.
Role in Differentiating IBD from IBS
Fecal calprotectin consistently differentiates IBD from irritable bowel syndrome because of its excellent negative predictive value 4, 7. This is particularly useful in determining whether clinical symptoms in patients with known IBD are caused by disease flares versus non-inflammatory complications or underlying IBS 4.