Elevated Calprotectin Levels: Causes and Next Steps

Introduction to Calprotectin

Calprotectin is a sensitive but non-specific marker of intestinal inflammation, with 90.6% sensitivity for detecting IBD at cutoffs >50 μg/g, but lower specificity due to multiple other conditions that elevate this marker 1, 3
The British Society of Gastroenterology recommends screening with tissue transglutaminase or EMA antibodies in all patients with chronic diarrhea 1

Colorectal neoplasia is a well-established cause of elevated calprotectin and must be excluded, particularly if you have alarm symptoms like rectal bleeding or are over age 50 1, 2
Any NSAID use in the past 6 weeks can significantly elevate calprotectin levels through direct mucosal injury, including over-the-counter ibuprofen, naproxen, and aspirin at anti-inflammatory doses 1, 4, 5
Untreated celiac disease causes intestinal inflammation that elevates calprotectin 1
Local bleeding and inflammation from hemorrhoids can cause false elevations in fecal calprotectin, particularly if you have visible rectal bleeding 4

Values 50-250 μg/g represent an indeterminate range with 8% chance of developing IBD over 12 months compared to 1% with levels <50 μg/g 1
Values >250 μg/g strongly suggest active inflammation requiring endoscopic assessment, with 82% specificity for active disease 2, 3
Values >150 μg/g have 78.2% specificity for endoscopically active disease 2, 6

Review all medications, particularly NSAIDs, taken in the past 6 weeks and discontinue if possible 1, 4, 5
Ensure celiac serology (tissue transglutaminase antibodies) has been checked 1
Proceed to colonoscopy with biopsies to evaluate for microscopic colitis, colorectal neoplasia, and other mucosal abnormalities not visible on standard endoscopy 1, 2
The British Society of Gastroenterology states that endoscopic and histological assessment is necessary in most patients with chronic diarrhea and elevated inflammatory markers 1

If you have minimal or no symptoms, elevated calprotectin >150 μg/g has a false positive rate of 22.4%, meaning nearly one-quarter of asymptomatic patients with elevated levels may not have significant endoscopic inflammation 4, 6
Use the first stool passed in the morning and ensure it's analyzed within 3 days at room temperature to avoid falsely elevated or degraded results 3, 4, 5
Repeat testing in 4-6 weeks may be reasonable before proceeding to colonoscopy if your value is in the 50-250 μg/g range and you've recently stopped NSAIDs or recovered from suspected infection 1