What does a high fecal calprotectin level indicate and how is it treated?

High Fecal Calprotectin: Indications and Management

Elevated fecal calprotectin is a reliable biomarker of intestinal inflammation, most commonly indicating inflammatory bowel disease (IBD), but can also be present in other inflammatory conditions including infectious gastroenteritis and colorectal cancer. 1

What Does High Fecal Calprotectin Indicate?

• Fecal calprotectin is a calcium- and zinc-binding protein primarily derived from neutrophils, with concentrations directly related to the level of intestinal mucosal inflammation 1
• Values >150 μg/g strongly suggest active inflammatory disease in the gastrointestinal tract, particularly in patients with moderate to severe symptoms 2
• Elevated levels are most commonly associated with:
  • Inflammatory bowel disease (Crohn's disease or ulcerative colitis) 2, 1
  • Infectious gastroenteritis (though calprotectin cannot distinguish between IBD and infectious causes in acute presentations) 3
  • Colorectal cancer (though calprotectin is not sensitive enough to exclude cancer) 2
  • Other inflammatory conditions including peptic ulcer disease and celiac disease 4

Interpretation Based on Clinical Context

In Patients with Suspected IBD:

• Fecal calprotectin has high sensitivity (90.6%) for detecting endoscopically active disease at a cut-off of 50 μg/g 2
• Specificity improves (78.2%) at levels >100 μg/g, and further improves (82%) at levels >250 μg/g 2
• In patients with moderate to severe symptoms (frequent rectal bleeding, significantly increased stool frequency), calprotectin >150 μg/g can reliably indicate active inflammation 2

In Patients with Known IBD:

• Useful for monitoring disease activity and treatment response 2, 1
• Can help distinguish between IBD flare and functional gastrointestinal symptoms 2
• Values <50 μg/g are generally reassuring and suggest clinical remission 2
• Values between 50-250 μg/g may be challenging to interpret as they could represent mild inflammation or non-specific findings 2

Important Limitations:

• Variability exists between different assays 2
• Levels can vary in different stool samples from the same patient during one day 2
• Samples are unstable at room temperature for more than a few days 2
• NSAID use in the past 6 weeks can affect calprotectin levels 5
• The first stool passed in the morning should be used for sampling, and stored for no more than 3 days before analysis 2

Management Approach for Elevated Fecal Calprotectin

In Patients with Suspected IBD:

1. For patients with moderate to severe symptoms and calprotectin >150 μg/g:

   • Treatment adjustment can be considered without routine endoscopic assessment 2, 3
   • This approach is particularly valuable when access to endoscopy is limited 2

2. For patients with mild symptoms, even with elevated calprotectin >150 μg/g:

   • Endoscopic assessment is recommended rather than empiric treatment adjustment 2, 3
   • This is especially important when considering significant treatment adjustments such as starting immunosuppressive therapies 2

3. For patients with alarm symptoms:

   • Rectal bleeding, abdominal pain, change in bowel habit, weight loss, or iron-deficiency anemia require cancer pathway referral regardless of calprotectin result 2, 3
   • Calprotectin is not sensitive enough to exclude colorectal cancer in these cases 2

In Patients with Known IBD:

1. For monitoring disease activity:

   • Serial calprotectin monitoring at 3-6 month intervals can facilitate early recognition and treatment of impending disease flares 2
   • In patients with initially elevated calprotectin (≥100 μg/g), repeat testing after approximately 18 days showed reduction in 53% of patients 2, 3

2. For treatment decisions:

   • Values <50 μg/g suggest clinical remission 2
   • Values >250 μg/g strongly suggest active disease requiring treatment intensification 2
   • Values between 50-250 μg/g may require clinical correlation and possibly endoscopic assessment 2

In Acute Diarrheal Illness:

• Calprotectin will likely be elevated and cannot reliably distinguish between IBD and infectious gastroenteritis 3
• Stool culture and/or flexible sigmoidoscopy/colonoscopy are more appropriate diagnostic investigations in this setting 3
• For patients with bloody diarrhea, flexible sigmoidoscopy is indicated regardless of calprotectin result 3

Pitfalls and Caveats

• Calprotectin sensitivity varies by location of inflammation, with higher sensitivity for colonic inflammation than small bowel inflammation 6
• For a similar level of inflammation, calprotectin levels incrementally increase from proximal to distal small bowel segments and from distal small bowel to colon 6
• Different assays may have different optimal cut-off values despite similar manufacturer-quoted ranges 4
• A reference standard for calprotectin is lacking, which affects standardization across different testing methods 4
• False positives can occur with NSAID use, proton pump inhibitors, and in patients over 65 years of age 4