How is calprotectin (fecal calprotectin) used in managing inflammatory bowel disease (IBD)?

Role of Fecal Calprotectin in Managing Inflammatory Bowel Disease (IBD)

Fecal calprotectin is a valuable non-invasive biomarker for diagnosing, monitoring disease activity, and predicting relapse in inflammatory bowel disease, serving as a surrogate marker for intestinal inflammation that correlates well with endoscopic findings. 1

Diagnostic Applications

• Fecal calprotectin has high negative predictive value for IBD, making it an excellent screening tool for patients aged 16-40 presenting with chronic diarrhea and symptoms that may be consistent with either IBD or irritable bowel syndrome (IBS) 2, 1
• Normal calprotectin levels (<50 μg/g stool) have a high negative predictive value for IBD, effectively ruling out active inflammation 1, 3
• A calprotectin cut-off of 50 μg/g has the best sensitivity (90.6%) to detect endoscopically active disease, while specificity performs best (78.2%) at levels >100 μg/g 2, 4
• Higher thresholds (100-250 μg/g) are recommended to trigger colonoscopy, which improves positive predictive value with minimal reduction in negative predictive value 1, 3

Monitoring Disease Activity

• Fecal calprotectin is a useful surrogate marker of inflammatory activity in IBD, correlating well with endoscopic inflammation in both ulcerative colitis (UC) and Crohn's disease (CD) 2, 5
• When it is unclear whether new symptoms represent a relapse or have other causes (particularly in Crohn's disease), calprotectin is useful to confirm active inflammation 2
• Fecal calprotectin can serve as a non-invasive alternative to flexible sigmoidoscopy, colonoscopy, and cross-sectional imaging when monitoring disease activity 2
• If relapsing disease is clinically obvious, measurement is not necessary 2

Interpretation of Results and Clinical Algorithm

Based on available evidence, the following algorithm for interpreting fecal calprotectin results is recommended:

• <50-100 μg/g: Quiescent disease likely; continue current therapy 1, 3
• 100-250 μg/g: Inflammation possible; consider repeat testing or routine referral to gastroenterology 1, 3
• >250 μg/g: Active inflammation likely; initiate strategies to control inflammation (optimize current therapies or switch to alternative therapy) 1, 3

A threshold of 250 μg/g provides better specificity (82%) than thresholds of 100 μg/g and 50 μg/g (specificity of 66% and 60%, respectively) in differentiating active IBD from remission 2

Practical Considerations

• The first stool passed in the morning should be routinely used for sampling 2, 1
• Samples should be stored for no more than 3 days at room temperature before analysis 2, 1
• NSAID use in the past 6 weeks can affect calprotectin levels and should be considered when interpreting results 1, 6
• Fecal calprotectin is elevated in various inflammatory conditions beyond IBD, including infectious gastroenteritis and colorectal cancer 2, 1
• Fecal calprotectin is not sensitive enough for exclusion of advanced colorectal adenoma or colorectal carcinoma 2, 1

Limitations and Caveats

• There is variability between different assays, in levels from different stool samples from one patient during the same day, and in calprotectin levels related to the interval between stools being passed 2
• Fecal calprotectin performs better in ulcerative colitis than in Crohn's disease (sensitivity 87.3% vs 82.4%, specificity 77.1% vs 72.1%) 4
• In acute diarrhea due to infection, calprotectin is likely to be raised and will not discriminate between IBD and gastroenteritis 2
• Patient knowledge about fecal calprotectin testing may be limited, potentially affecting adherence to monitoring protocols 7

Emerging Technologies

• Quantitative point-of-care tests (QPOCT) for fecal calprotectin show good correlation with traditional ELISA methods and can provide more convenient assessment in clinical practice 5
• Smartphone-based home testing systems (e.g., CalproSmart) allow patients to perform the test at home and receive rapid results, which may improve monitoring efficiency 8