What is the significance of a high fecal calprotectin level?

Significance of High Fecal Calprotectin (615)

A high fecal calprotectin level of 615 μg/g strongly suggests active intestinal inflammation, most likely inflammatory bowel disease (IBD), and warrants prompt endoscopic evaluation to confirm the diagnosis and assess disease severity. 1

Clinical Significance of Elevated Fecal Calprotectin

Fecal calprotectin is a calcium- and zinc-binding protein primarily derived from neutrophils that migrate into the gastrointestinal tract during inflammatory processes. The level of 615 μg/g is significantly above established thresholds:

• Normal: <50 μg/g
• Borderline: 50-150 μg/g
• Elevated: >150 μg/g
• Highly elevated: >250 μg/g (your value of 615 falls in this category)

Diagnostic Implications

• Primary indication: Strong evidence of active intestinal inflammation 1, 2
• Most likely causes:
  • Inflammatory bowel disease (Crohn's disease or ulcerative colitis)
  • Less commonly: infectious colitis, colorectal cancer, NSAID-induced enteropathy

Diagnostic Algorithm Based on Elevated Calprotectin

1. Rule out infectious causes first:

   • Stool culture and C. difficile testing should be performed 1
   • Note that infectious causes will also elevate calprotectin but typically resolve

2. Endoscopic evaluation:

   • Colonoscopy with biopsies is indicated with calprotectin >250 μg/g 1
   • This level (615) has a high positive predictive value for moderate to severe endoscopic inflammation 1

3. Consider additional testing based on clinical presentation:

   • Complete blood count, CRP, and ESR to assess systemic inflammation
   • Iron studies if anemia is suspected
   • Celiac disease testing if appropriate

Interpretation in Different Clinical Contexts

In Patients Without Known IBD:

• A value of 615 μg/g has a high positive predictive value for IBD versus IBS 1, 2
• The British Society of Gastroenterology guidelines note that values >100 μg/g warrant consideration for colonoscopy 1
• With this high value (615), the likelihood of finding endoscopic evidence of IBD is very high 1

In Patients With Known IBD:

• Indicates active disease requiring treatment adjustment 1
• Correlates well with endoscopic inflammation 1
• May predict clinical relapse in patients with quiescent disease 3

Clinical Pitfalls and Caveats

• False positives can occur with:

  • NSAID use (should be discontinued 2 weeks before testing)
  • Colorectal cancer (calprotectin is not sensitive enough to exclude malignancy) 1
  • Infectious gastroenteritis (acute diarrhea) 1
  • Recent colonoscopy or bowel preparation

• Interpretation challenges:

  • Different commercial assays may have varying thresholds and performance 4
  • Age-related variations (higher in infants, especially breastfed) 1
  • Day-to-day variations in levels can occur 4

Next Steps After Finding Elevated Calprotectin

1. If IBD is suspected:

   • Refer for colonoscopy with biopsies
   • Consider upper endoscopy if small bowel involvement is suspected (especially for Crohn's disease)

2. If known IBD patient:

   • Assess current symptoms and treatment adherence
   • Consider treatment intensification
   • Monitor response with serial calprotectin measurements at 3-6 month intervals 2

3. If infectious etiology suspected:

   • Complete stool studies and treat accordingly
   • Repeat calprotectin after resolution of infection

This markedly elevated calprotectin level of 615 μg/g requires prompt evaluation and should not be dismissed as a functional disorder without further investigation.