What are CRP (C-Reactive Protein), ESR (Erythrocyte Sedimentation Rate), and fecal calprotectin?

CRP, ESR, and Fecal Calprotectin: Inflammatory Biomarkers in Clinical Practice

CRP, ESR, and fecal calprotectin are inflammatory biomarkers used to detect, monitor, and assess the severity of inflammatory conditions, with fecal calprotectin being the most sensitive and specific marker for intestinal inflammation. 1

CRP (C-Reactive Protein)

• Definition: An acute phase protein produced by the liver in response to inflammation

• Normal value: <5 mg/L or <0.5 mg/dL 1

• Clinical applications:

  • Marker of systemic inflammation
  • Rises rapidly (within 6-8 hours) and peaks at 48 hours after inflammatory stimulus
  • More sensitive than ESR for acute inflammation
  • Used in monitoring inflammatory bowel disease (IBD), rheumatologic conditions, and infections

• Limitations:

  • Less sensitive than fecal calprotectin for intestinal inflammation
  • Pooled sensitivity for IBD detection: 73% (95% CI, 64-80%)
  • Pooled specificity for IBD detection: 78% (95% CI, 58-91%) 1

ESR (Erythrocyte Sedimentation Rate)

• Definition: Measures the rate at which red blood cells settle in a tube over one hour

• Normal values: Typically 10-15 mm/h (varies by age and gender)

• Clinical applications:

  • Marker of chronic inflammation
  • Rises slowly (24-48 hours) and remains elevated for longer periods
  • Used in rheumatologic conditions (e.g., rheumatoid arthritis, giant cell arteritis)
  • Component of disease activity scores like DAS28-ESR 2

• Limitations:

  • Less sensitive than CRP for acute inflammation
  • Affected by non-inflammatory factors (anemia, age, gender, pregnancy)
  • Lower diagnostic accuracy for IBD compared to fecal calprotectin 1

Fecal Calprotectin

• Definition: Calcium and zinc-binding protein released by neutrophils in the intestinal mucosa during inflammation

• Normal value: <50 mg/g 1

• Clinical cutoffs:

  • <50 mg/g: Normal/minimal inflammation
  • 50-150 mg/g: Mild inflammation

  • 150-250 mg/g: Moderate inflammation

  • 250 mg/g: Severe inflammation 1

• Clinical applications:

  • Gold standard non-invasive marker for intestinal inflammation
  • Differentiates IBD from functional disorders (IBS)
  • Monitors disease activity in IBD
  • Predicts relapse and response to therapy
  • Can potentially reduce the need for endoscopic procedures 1

• Diagnostic performance for IBD:

  • Pooled sensitivity: 81% (95% CI, 75-86%)
  • Pooled specificity: 87% (95% CI, 78-92%) 1
  • Superior to both CRP and ESR in detecting intestinal inflammation 3, 4

Comparative Performance

• Correlation with endoscopic disease activity:

  • Fecal calprotectin shows stronger correlation with endoscopic disease activity than CRP and ESR:
    • In Crohn's disease: r=0.847 for calprotectin vs r=0.44 for CRP and r=0.054 for ESR
    • In ulcerative colitis: r=0.798 for calprotectin vs r=0.463 for CRP and r=0.467 for ESR 3

• Area under ROC curve for detecting endoscopic inflammation:

  • Fecal calprotectin: 0.975
  • CRP: 0.740
  • ESR: 0.692 4

Clinical Algorithm for Use

1. Screening for intestinal inflammation:

   • First-line test: Fecal calprotectin (threshold 50 mg/g)
   • Alternative if fecal calprotectin unavailable: CRP (threshold 5 mg/L) 1

2. Monitoring IBD disease activity:

   • Fecal calprotectin for intestinal inflammation
   • CRP for systemic inflammation
   • Consider both markers together for comprehensive assessment 1

3. Assessing disease severity in IBD:

   • Mild: Fecal calprotectin 50-150 mg/g
   • Moderate: Fecal calprotectin 150-250 mg/g
   • Severe: Fecal calprotectin >250 mg/g 1

4. For rheumatologic conditions:

   • Both ESR and CRP should be used as components of disease activity measures 2

Common Pitfalls

• Misinterpretation of normal CRP: A normal CRP does not rule out localized intestinal inflammation; fecal calprotectin is more sensitive for this purpose 3
• Over-reliance on ESR: ESR has lower sensitivity and specificity for intestinal inflammation compared to fecal calprotectin and CRP 1
• Ignoring clinical context: Biomarkers should always be interpreted alongside clinical findings 2
• Treating the marker, not the patient: Focus treatment decisions on patient symptoms and overall clinical picture, not just biomarker levels 2

Important Considerations

• Fecal calprotectin is the preferred biomarker for intestinal inflammation due to its superior sensitivity and specificity 1
• CRP rises and falls more rapidly than ESR, making it better for monitoring acute changes in inflammation 2
• When fecal calprotectin and CRP are both elevated, this suggests active intestinal inflammation with systemic involvement 1
• A CRP ≥12 mg/L has been proposed as equivalent to an ESR >30 mm/h in assessing ulcerative colitis severity 5