What does an increase in fecal calprotectin (FC) levels indicate?

Elevated Fecal Calprotectin: Clinical Significance and Interpretation

Elevated fecal calprotectin primarily indicates intestinal inflammation, most commonly associated with inflammatory bowel disease (IBD), but can also be elevated in other inflammatory conditions including infectious gastroenteritis and colorectal cancer. 1, 2

Diagnostic Value and Interpretation

• Fecal calprotectin is a calcium- and zinc-binding protein derived from neutrophils that serves as a sensitive and specific marker of intestinal inflammation 3
• Different threshold values have specific clinical implications:
  • <50 μg/g: Normal range with high negative predictive value for ruling out IBD 1
  • 50-100 μg/g: Mild elevation suggesting possible inflammation 2
  • 100-250 μg/g: Intermediate range warranting consideration of repeat testing or routine referral to gastroenterology 1

  • 250 μg/g: Strong indication of active intestinal inflammation requiring urgent gastroenterology referral 1, 2

  • 1000 μg/g: Very high likelihood of severe active IBD requiring immediate evaluation 2

Clinical Applications

• Differentiating IBD from IBS: Fecal calprotectin has excellent negative predictive value in ruling out IBD in undiagnosed symptomatic patients, with sensitivity exceeding 90% at lower cutoffs (50 μg/g) 2, 4
• Monitoring disease activity in known IBD: Elevated levels correlate well with endoscopic and histological inflammation in both ulcerative colitis and Crohn's disease 1, 2
• Predicting disease relapse: At a given fecal calprotectin concentration in patients with quiescent IBD, the test has specificity and sensitivity exceeding 85% in predicting clinical relapse 5
• Guiding treatment decisions: In patients with moderate to severe symptoms suggestive of IBD flare, fecal calprotectin >150 μg/g reliably suggests moderate to severe endoscopic inflammation 6

Clinical Approach to Elevated Calprotectin

• For patients with mild IBD symptoms and elevated calprotectin (>150 μg/g), the American Gastroenterological Association suggests endoscopic assessment rather than empiric treatment adjustment 6
• In patients with moderate to severe symptoms suggestive of IBD flare, elevated calprotectin (>150 μg/g) can reliably indicate endoscopic inflammation without requiring immediate endoscopy 6, 2
• For patients aged 16-40 with new lower gastrointestinal symptoms (>4 weeks) where IBD is suspected:
  • <100 μg/g: IBS is likely
  • 100-250 μg/g: Consider repeat testing or routine referral

  • 250 μg/g: Urgent referral to gastroenterology 1

Important Caveats and Limitations

• Fecal calprotectin can be elevated in conditions other than IBD, including:
  • Infectious gastroenteritis
  • Colorectal cancer and advanced adenomas
  • NSAID-induced enteropathy
  • Other inflammatory conditions 1, 5, 3
• NSAID use in the past 6 weeks can affect calprotectin levels and should be considered when interpreting results 1
• Values between 50-250 μg/g may be challenging to interpret as mild calprotectin elevation may be seen with non-specific low-grade inflammation 6
• Fecal calprotectin should not be used as the sole diagnostic test for IBD but should prompt appropriate endoscopic evaluation when significantly elevated 2
• The first stool passed in the morning should be routinely used for sampling, with samples stored for no more than 3 days at room temperature before analysis 1

Monitoring and Follow-up

• In patients with mild symptoms, serial calprotectin monitoring at three to six-month intervals may facilitate early recognition and treatment of impending disease flares 6
• Normalization or decrease in fecal calprotectin concentrations in IBD patients receiving treatment indicates endoscopic healing 7
• Persistently elevated calprotectin despite clinical remission suggests ongoing subclinical inflammation that may predict future relapse 1, 7