What is the role of fecal calprotectin in diagnosing and managing inflammatory bowel disease (IBD)?

Role of Fecal Calprotectin in Diagnosing and Managing Inflammatory Bowel Disease

Fecal calprotectin is a highly effective biomarker for diagnosing, monitoring, and managing inflammatory bowel disease (IBD), with excellent sensitivity for detecting intestinal inflammation and distinguishing IBD from irritable bowel syndrome (IBS). 1, 2

Diagnostic Value

• Fecal calprotectin has a high negative predictive value for IBD, making it an excellent screening tool for patients aged 16-40 with chronic diarrhea and symptoms that may be consistent with either IBD or IBS 3
• For initial screening in primary care, the following interpretation thresholds are recommended:
  • <100 μg/g: IBS likely, treat as IBS in primary care 3
  • 100-250 μg/g: Consider repeat testing or routine referral to gastroenterology 3

  • 250 μg/g: Refer urgently to gastroenterology 3

• A calprotectin cut-off of 50 μg/g has the best sensitivity (90.6%) to detect endoscopically active disease, while levels >100 μg/g provide better specificity (78.2%) 3, 4
• Fecal calprotectin is not sensitive enough to exclude colorectal cancer, so patients with rectal bleeding, abdominal pain, change in bowel habit, weight loss, or iron-deficiency anemia should be referred via a suspected cancer pathway regardless of calprotectin result 3, 1

Monitoring Disease Activity in Known IBD

• Fecal calprotectin is a useful surrogate marker of inflammatory activity in IBD, correlating well with endoscopic inflammation in both ulcerative colitis and Crohn's disease 3, 1
• When it's unclear if new symptoms represent a relapse or other causes (particularly in Crohn's disease), calprotectin is useful to confirm active inflammation as a non-invasive alternative to endoscopy or imaging 3
• Among patients with known IBD and elevated fecal calprotectin levels, 66% required escalation of therapy within 12 months, compared to only 18% of those with normal levels 5
• For monitoring disease activity, the following thresholds are suggested:
  • <50-100 μg/g: Quiescent disease likely, continue current therapy 2, 6
  • 100-250 μg/g: Possible inflammation, further testing (e.g., colonoscopy) required 2, 6

  • 250 μg/g: Active inflammation likely, initiate strategies to control inflammation 2, 6

Practical Considerations for Sample Collection

• The first stool passed in the morning should be routinely used for sampling 3, 7
• Samples should be stored for no more than 3 days at room temperature before analysis 3, 7
• NSAID use in the past 6 weeks can affect calprotectin levels and should be considered when interpreting results 3, 1

Important Caveats and Limitations

• Fecal calprotectin can be elevated in conditions other than IBD, including:
  • Infectious gastroenteritis 1, 7
  • Colorectal cancer 3, 1
  • Hemorrhoids (due to local bleeding and inflammation) 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 1
• If relapsing disease is clinically obvious, measurement is not necessary 3

Clinical Algorithm for Using Fecal Calprotectin

• For undiagnosed patients with chronic lower GI symptoms (>4 weeks):

  • First exclude NSAID use in past 6 weeks 3
  • Check basic labs: CBC, electrolytes, CRP, celiac screen, stool culture 3
  • If rectal bleeding plus any of: abdominal pain, change in bowel habit, weight loss, or iron deficiency anemia → refer via suspected cancer pathway regardless of calprotectin 3
  • Otherwise, measure fecal calprotectin and interpret as per thresholds above 3

• For known IBD patients with new symptoms:

  • If clinically obvious relapse → treat accordingly without calprotectin testing 3
  • If unclear whether symptoms represent inflammation or other causes → measure fecal calprotectin 3
  • If calprotectin >250 μg/g → treat as active inflammation 2, 6
  • If calprotectin 100-250 μg/g → consider endoscopic assessment 1, 2
  • If calprotectin <100 μg/g → consider non-inflammatory causes of symptoms 2, 6

• For monitoring treatment response in IBD:

  • Serial calprotectin monitoring at 3-6 month intervals can facilitate early recognition and treatment of impending disease flares 1, 2
  • Declining calprotectin levels suggest response to therapy 6
  • Persistently elevated levels despite treatment suggest need for therapy adjustment 6

By incorporating fecal calprotectin testing into clinical practice, clinicians can more accurately diagnose IBD, monitor disease activity, and optimize treatment strategies while reducing the need for invasive procedures 8, 9.