From the Guidelines
Elevated fecal calprotectin levels primarily indicate intestinal inflammation, with the most common causes including inflammatory bowel diseases (IBD) such as Crohn's disease and ulcerative colitis, where calprotectin levels typically exceed 250 μg/g, as supported by the most recent and highest quality study 1. The causes of elevated fecal calprotectin levels can be broken down into several categories, including:
- Inflammatory bowel diseases (IBD) such as Crohn's disease and ulcerative colitis, which are characterized by chronic inflammation of the gastrointestinal tract and typically have calprotectin levels exceeding 250 μg/g 1
- Infections of the gastrointestinal tract, including bacterial, viral, or parasitic infections, which can raise calprotectin levels due to the inflammatory response to the infection
- Non-steroidal anti-inflammatory drugs (NSAIDs) like ibuprofen, naproxen, and aspirin, which may increase levels by causing intestinal irritation when used regularly
- Colorectal cancer and polyps, which can elevate calprotectin due to inflammatory responses around tumors
- Other causes, including microscopic colitis, diverticulitis, celiac disease, and food allergies
- Non-intestinal conditions, such as obesity and intense physical exercise, which can sometimes raise levels
- Age, with infants naturally having higher levels When elevated calprotectin is detected, further diagnostic testing such as endoscopy, colonoscopy, or imaging studies is typically recommended to determine the specific cause of inflammation, as suggested by the AGA clinical practice guideline on the role of biomarkers for the management of ulcerative colitis 1. The diagnostic performance of fecal calprotectin has been evaluated in several studies, with a recent meta-analysis finding that a cutoff of 50 μg/g had a sensitivity of 88% and a specificity of 67% for detecting endoscopically active disease, while a cutoff of 250 μg/g had a sensitivity of 76% and a specificity of 74% 1. Overall, the management of elevated fecal calprotectin levels should prioritize determining the underlying cause of inflammation and guiding treatment accordingly, with consideration of the patient's clinical presentation, medical history, and other diagnostic test results, as recommended by the AGA clinical practice guidelines 1.
From the Research
Causes of Elevated Fecal Calprotectin Levels
Elevated fecal calprotectin levels can be caused by several factors, including:
- Inflammatory bowel disease (IBD) such as Crohn's disease and ulcerative colitis 2, 3, 4, 5
- Intestinal inflammation 2, 3
- Gastrointestinal infections 6
- Mucosal inflammation 2, 3, 4
- Disease relapse in patients with IBD 2, 3, 4
- Subclinical mucosal inflammation in clinically quiescent IBD 2
Association with Inflammatory Bowel Disease
Fecal calprotectin levels have been shown to:
- Correlate well with histological inflammation as detected by colonoscopy with biopsies 3
- Predict relapses and detect pouchitis in patients with IBD 3
- Differentiate IBD from irritable bowel syndrome 3
- Be useful in determining whether clinical symptoms in patients with known IBD are caused by disease flares or noninflammatory complications/underlying irritable bowel syndrome 3
Non-Linear Association with GI Pathogen Detection
Fecal calprotectin levels have been found to be non-linearly associated with GI pathogen detection in patients with and without IBD, with pathogen detection being significantly associated with higher fecal calprotectin in the lower two quartiles 6