Fecal Calprotectin Elevation from Naproxen (NSAID) Use
NSAIDs including naproxen can elevate fecal calprotectin levels, but the exact magnitude of elevation is not well-quantified in the literature, making it a significant confounding factor when interpreting results for inflammatory bowel disease assessment. 1
Mechanism and Clinical Impact
NSAIDs cause intestinal inflammation through direct mucosal injury, leading to neutrophil infiltration and subsequent calprotectin release into the stool, though the precise degree of elevation varies considerably between individuals. 1, 2
The British Society of Gastroenterology identifies NSAIDs as a known cause of elevated fecal calprotectin, alongside other conditions like colorectal cancer and infectious gastroenteritis, but does not specify quantitative thresholds. 3
Calprotectin is released when inflammatory processes occur due to neutrophil degranulation, and NSAIDs trigger this process through enteropathy even in the absence of inflammatory bowel disease. 3, 4
Clinical Approach to NSAID-Related Elevation
Before ordering fecal calprotectin testing, obtain a detailed medication history specifically asking about NSAID use (including naproxen), aspirin, and proton pump inhibitors. 1
Consider discontinuing NSAIDs temporarily before testing, or interpret elevated results with extreme caution if the patient has been taking naproxen or other NSAIDs. 1
If borderline or unexpected calprotectin results occur in the context of NSAID use, repeat testing after NSAID discontinuation to account for day-to-day variation and medication effects. 1, 2
Important Caveats
No specific threshold exists in the literature defining "how much" naproxen elevates calprotectin - the effect is recognized as clinically significant but highly variable between patients. 1, 2
The standard cutoff of >150 μg/g for inflammatory bowel disease may be falsely positive in NSAID users, potentially leading to unnecessary endoscopic procedures or treatment escalation. 3, 1
Even levels >250 μg/g, which typically correlate with active endoscopic inflammation in IBD, can be confounded by NSAID use. 3