Does an elevated calprotectin level indicate colitis?

Elevated Calprotectin and Colitis: Diagnostic Implications

Elevated fecal calprotectin is a reliable indicator of intestinal inflammation but is not specific for colitis, requiring additional diagnostic evaluation to confirm the diagnosis. 1, 2

Diagnostic Value of Fecal Calprotectin

Calprotectin Thresholds and Interpretation

• Fecal calprotectin levels can be categorized as:
  • Normal: <50 μg/g
  • Borderline: 50-150 μg/g
  • Elevated: >150 μg/g
  • Highly elevated: >250 μg/g 2

Diagnostic Performance

• At a cutoff of 50 μg/g: 78% sensitivity, 57% specificity 1
• At a cutoff of 150 μg/g: 71% sensitivity, 69% specificity 1
• At a cutoff of 250 μg/g: 67% sensitivity, 73% specificity 1

Clinical Implications

• Elevated calprotectin (>150 μg/g) reliably differentiates inflammatory bowel disease (IBD) from irritable bowel syndrome (IBS) with specificity and sensitivity exceeding 85% 2
• However, elevated levels alone cannot definitively diagnose colitis without additional testing 1, 2

Relationship Between Calprotectin and Colitis

Correlation with Disease Activity

• Fecal calprotectin shows excellent correlation with endoscopic and histological activity in ulcerative colitis 3, 4
• Levels increase significantly with increasing endoscopic and histologic disease activity 3
• For ulcerative colitis, a cutoff level of 192 mg/kg identifies patients with endoscopic mucosal healing with:
  • Positive predictive value: 0.71-0.65
  • Negative predictive value: 0.90-0.93 3

Limitations and False Positives

• Elevated calprotectin is not specific to colitis and can be elevated in:
  • Other forms of IBD (Crohn's disease)
  • Infectious colitis
  • NSAID-induced enteropathy
  • Colorectal cancer
  • Diverticulitis 1, 2

Diagnostic Algorithm for Evaluating Elevated Calprotectin

1. Initial Evaluation:

   • Assess for symptoms: rectal bleeding, stool consistency/frequency, urgency, tenesmus, abdominal pain 1
   • Review medication history (especially NSAIDs, antibiotics) 1
   • Exclude infectious causes with stool testing for pathogens, particularly C. difficile 2

2. Risk Stratification Based on Calprotectin Level:

   • <50 μg/g: Low likelihood of active colitis
   • 50-150 μg/g: Borderline, consider monitoring

   • 150 μg/g: High likelihood of intestinal inflammation, warrants further investigation

   • 250 μg/g: Very high likelihood of active inflammation 1, 2

3. Further Diagnostic Steps:

   • For calprotectin >150 μg/g: Endoscopic evaluation is recommended rather than empiric treatment 2
   • Colonoscopy with biopsies remains the gold standard for diagnosing colitis 2
   • In low-risk patients with borderline calprotectin (50-150 μg/g), serial monitoring may be appropriate 1, 2

Important Caveats and Pitfalls

• False Positives: Elevated calprotectin can occur in conditions other than colitis, including infections, medications, and malignancy 2
• Segmental Disease: Patchy or segmental inflammation may be missed during routine colonoscopy, occurring in up to 10% of IBD diagnoses 2
• Gradient Effect: Calprotectin sensitivity varies by location of inflammation, with higher sensitivity for colonic inflammation than small bowel inflammation 5
• Clinical Context: Interpretation must consider clinical symptoms, as asymptomatic patients with elevated calprotectin may have subclinical inflammation 1

Monitoring and Follow-up

• Serial monitoring of fecal calprotectin every 3-6 months is recommended in confirmed IBD 2
• Rising levels in patients with previously quiescent disease can predict clinical relapse with >85% sensitivity and specificity 2
• A cutoff of 171 mg/kg identifies histologic mucosal healing with positive predictive value of 0.75 and negative predictive value of 0.90 3

In summary, while elevated fecal calprotectin strongly suggests intestinal inflammation, endoscopic evaluation with histopathology is necessary to definitively diagnose colitis and determine its specific type and extent.