What Elevated Fecal Calprotectin Means
Elevated fecal calprotectin indicates active intestinal inflammation, most commonly from inflammatory bowel disease (IBD), but can also result from gastrointestinal infections, colorectal cancer, NSAID use, or other inflammatory conditions affecting the gut. 1, 2
Understanding the Levels and Their Significance
The interpretation depends critically on the absolute value:
<50 μg/g: Generally reassuring and suggests clinical remission in known IBD patients, with high negative predictive value for active inflammation 1, 2
50-150 μg/g: Gray zone requiring clinical correlation; may represent mild inflammation or non-specific findings 1
>150 μg/g: Strongly suggests active inflammatory disease, particularly when accompanied by moderate to severe symptoms 1, 2
>250 μg/g: Strongly indicates active disease requiring treatment intensification or urgent gastroenterology referral 1, 2
Primary Diagnostic Implications
For New/Undiagnosed Patients
Fecal calprotectin excels at differentiating IBD from irritable bowel syndrome (IBS), with 90.6% sensitivity for detecting endoscopically active disease at a 50 μg/g cut-off 2. The specificity improves substantially at higher thresholds: 78.2% at >100 μg/g 2.
For patients aged 16-40 with new lower GI symptoms lasting >4 weeks: 2
- <100 μg/g: IBS is likely
- 100-250 μg/g: Consider repeat testing or routine gastroenterology referral
- >250 μg/g: Urgent gastroenterology referral indicated
For Known IBD Patients
The American Gastroenterological Association provides clear guidance based on symptom severity 1, 2:
Moderate to severe symptoms + calprotectin >150 μg/g:
- Reliably indicates moderate to severe endoscopic inflammation with only 4.6% false positive rate 1
- Treatment can be adjusted empirically without immediate endoscopy 1, 2
Mild symptoms + calprotectin >150 μg/g:
Asymptomatic patients + calprotectin >150 μg/g:
- Consider endoscopic evaluation, as false positive rate is 22.4% 1
Critical Caveats and Pitfalls
When Calprotectin is NOT Reliable
Do not rely on calprotectin alone in these scenarios: 1, 2, 3
Alarm symptoms present (rectal bleeding, abdominal pain, weight loss, iron-deficiency anemia): Cancer pathway referral required regardless of calprotectin result, as it is not sensitive enough to exclude colorectal cancer
Acute diarrhea/gastroenteritis: Calprotectin will be elevated and cannot discriminate between IBD and infection; stool cultures or endoscopy are needed 3, 4
Bloody diarrhea: Flexible sigmoidoscopy indicated regardless of calprotectin 3
Other Causes of Elevation
Calprotectin is not specific for IBD 1, 2, 5:
- Gastrointestinal infections (bacterial, viral, parasitic)
- Colorectal cancer and advanced adenomas
- NSAID use within past 6 weeks
- Celiac disease
- Hemorrhoids (can cause false elevation due to local bleeding) 2
False Negatives Matter Too
In patients with moderate to severe symptoms, calprotectin <150 μg/g does NOT exclude inflammation—the false negative rate is 24.7% 1. Clinical judgment must prevail when symptoms are severe despite normal calprotectin.
Monitoring and Serial Testing
For established IBD patients in remission, the American Gastroenterological Association recommends serial monitoring every 3-6 months to detect impending flares early 1, 2. Persistently elevated calprotectin in asymptomatic patients predicts future relapse 2, 6.
For initially elevated values (≥100 μg/g): Repeat testing after approximately 18 days showed reduction in 53% of patients, making repeat measurement valuable before proceeding to invasive testing 3.