What is the significance of a stool test for fecal calprotectin in diagnosing and managing inflammatory bowel disease?

Fecal Calprotectin: Clinical Significance in IBD Diagnosis and Management

Fecal calprotectin is a highly valuable non-invasive biomarker that should be used to screen for inflammatory bowel disease in patients aged 16-40 with chronic lower GI symptoms, to monitor disease activity in established IBD, and to guide treatment decisions—with specific thresholds determining clinical action. 1, 2

Diagnostic Utility in Suspected IBD

Primary Care Screening Algorithm

For patients aged 16-40 presenting with new lower GI symptoms lasting >4 weeks, fecal calprotectin serves as an excellent screening tool with high negative predictive value for ruling out IBD. 1, 2 The British Society of Gastroenterology provides clear action thresholds:

• <100 μg/g: IBS is likely; treat as IBS in primary care 1
• 100-250 μg/g: Consider repeat testing or routine gastroenterology referral 1
• >250 μg/g: Urgent gastroenterology referral required 1

Diagnostic Performance

The test demonstrates excellent sensitivity for detecting IBD. A calprotectin cut-off of 50 μg/g achieves 90.6% sensitivity for detecting endoscopically active disease, while levels >100 μg/g provide 78.2% specificity. 1, 2 The negative likelihood ratio of 0.06 makes this superior to CRP or ESR for ruling out IBD. 3

Critical Exclusions Before Testing

Do not order fecal calprotectin if the patient has used NSAIDs within the past 6 weeks, as this causes false elevation. 1, 4 Additionally, if alarm features are present (rectal bleeding with abdominal pain, weight loss, iron deficiency anemia, or palpable mass), refer directly via cancer pathway rather than ordering calprotectin, as the test cannot reliably exclude colorectal cancer. 1

Monitoring Disease Activity in Established IBD

Assessing Flares vs. Other Symptoms

In patients with known IBD where it is unclear whether new symptoms represent active inflammation or other causes (particularly in Crohn's disease), fecal calprotectin confirms active inflammation and serves as a non-invasive alternative to colonoscopy. 1 However, if relapsing disease is clinically obvious, measurement is unnecessary. 1

Correlation with Endoscopic Activity

Fecal calprotectin correlates strongly with endoscopic inflammation in both ulcerative colitis and Crohn's disease. 1, 2 Specific thresholds for endoscopic disease:

• ≤250 μg/g: Predicts endoscopic remission (CDEIS ≤3) with 94.1% sensitivity and 62.2% specificity 5
• >250 μg/g: In UC, indicates active mucosal disease (Mayo >0) with 71% sensitivity and 100% specificity 5
• >150 μg/g: In patients with moderate to severe symptoms, reliably suggests moderate to severe endoscopic inflammation 2

Predicting Relapse and Guiding Treatment

Elevated calprotectin in clinically inactive disease predicts future relapse. 2 In a prospective study, 66% of patients with known IBD and elevated calprotectin required treatment escalation within 12 months, compared to only 18% with normal levels. 6 This makes calprotectin valuable for identifying subclinical inflammation requiring intervention.

For treatment decisions: levels <50-100 μg/g suggest quiescent disease and therapy should be continued; levels >100-250 μg/g require further testing (colonoscopy) to confirm inflammation; levels >250 μg/g indicate active inflammation requiring treatment optimization or switching therapy. 7

Practical Collection and Interpretation

Optimal Sampling Technique

Collect the first stool passed in the morning and store for no more than 3 days at room temperature before analysis. 1, 2 This minimizes variability from diurnal fluctuations and sample degradation. 1

Managing Suspected False Positives

If you suspect a false positive result, repeat testing after approximately 18 days, as calprotectin levels decrease in up to 53% of patients with initially elevated results. 4 Consider alternative causes of elevation:

• Infectious gastroenteritis (cannot be distinguished from IBD by calprotectin alone—exclude with stool culture) 1, 4
• Hemorrhoids or other GI bleeding sources (local inflammation elevates levels) 2, 4
• Colorectal cancer or advanced adenomas (calprotectin is not sensitive enough to exclude these) 1, 4

Threshold Selection Nuances

While 50 μg/g maximizes sensitivity for ruling out disease, higher thresholds (100-250 μg/g) improve positive predictive value for triggering colonoscopy with minimal reduction in negative predictive value. 2 The 250 μg/g threshold provides 82% specificity for differentiating active IBD from remission, though with lower sensitivity (80%) compared to 100 μg/g (84% sensitivity). 1

Common Pitfalls to Avoid

Never interpret calprotectin in isolation from clinical context. 1 In patients with strong clinical suspicion of IBD (family history, severe symptoms), proceed to gastroenterology referral even with intermediate values (100-250 μg/g). 1 Conversely, in patients with symptoms more suggestive of IBS, repeat testing in this intermediate range provides reassurance if normal. 1

Do not use calprotectin to screen for colorectal cancer—it lacks adequate sensitivity for advanced adenomas and cannot distinguish IBD from malignancy in patients with alarm features. 1