Elevated Fecal Calprotectin in Diarrheal Illness: Interpretation and Clinical Significance
Elevated fecal calprotectin in diarrheal illness indicates active intestinal inflammation, with levels >150 μg/g strongly suggesting inflammatory bowel disease (IBD) or infectious enteritis, particularly bacterial infections rather than viral causes. 1, 2
Diagnostic Value of Fecal Calprotectin
- Fecal calprotectin is a calcium- and zinc-binding protein released from neutrophils during intestinal inflammation, serving as a reliable biomarker for distinguishing inflammatory from non-inflammatory causes of diarrhea 1, 3
- Values >150 μg/g have high sensitivity (90.6%) for detecting endoscopically active inflammatory disease, with specificity improving at levels >250 μg/g 2
- Significantly higher levels are seen in bacterial infections (Salmonella: median 765 μg/g; Campylobacter: median 689 μg/g) compared to viral infections (rotavirus: median 89 μg/g; norovirus: median 93 μg/g) 4
Clinical Interpretation Based on Calprotectin Levels
- <50 μg/g: Generally indicates absence of significant intestinal inflammation; low likelihood of IBD 1, 2
- 50-150 μg/g: Indeterminate range requiring clinical correlation; 8% chance of developing IBD within 12 months compared to 1% with levels <50 μg/g 1
150 μg/g: Strongly suggests active inflammatory disease, particularly IBD in appropriate clinical context 1, 2
250 μg/g: High specificity for moderate to severe endoscopic inflammation; strongly suggests active disease requiring treatment intensification 1, 2
Disease-Specific Considerations
Inflammatory Bowel Disease
- Better reflects disease activity in ulcerative colitis than Crohn's disease 5
- Correlates with endoscopic findings of inflammation and can predict disease relapse 6
- In patients with moderate to severe symptoms and calprotectin >150 μg/g, treatment adjustment can be made without requiring endoscopic assessment 7
- For patients with mild symptoms and elevated calprotectin, endoscopic assessment is recommended before treatment adjustment 7
Infectious Diarrhea
- Significantly higher levels in bacterial infections compared to viral causes 4
- Correlates with clinical severity of infectious diarrhea (severe: 843 μg/g; moderate: 402 μg/g; mild: 87 μg/g) 4
- Levels decrease as infection resolves, making it useful for monitoring disease course 4
Clinical Pitfalls and Limitations
- Not specific for IBD; elevated levels also occur in colorectal cancer, infectious enteritis, and with use of non-steroidal anti-inflammatory drugs 1, 8
- False negative results (normal calprotectin despite inflammation) may occur in patients with typical symptoms of IBD flare, with up to 14.5% false negative rate 1
- Not sensitive enough to exclude colorectal cancer; patients with alarm symptoms require cancer pathway referral regardless of calprotectin result 2
- Interpretation must always consider clinical history and symptoms specific to each patient 8
Monitoring and Follow-up
- Repeat measurement 2-4 months after initiating or adjusting therapy to monitor response 7
- Serial monitoring at 3-6 month intervals can facilitate early recognition of impending disease flares in patients with known IBD 2
- Consider endoscopic assessment 6-12 months after treatment initiation to confirm mucosal healing in IBD patients 7