What is the difference between calprotectin and lactoferrin tests in diagnosing inflammatory bowel disease (IBD)?

Differences Between Calprotectin and Lactoferrin Tests in Diagnosing IBD

Both fecal calprotectin and lactoferrin are valuable biomarkers for detecting intestinal inflammation, but they differ in their diagnostic thresholds, specificity, and clinical utilization patterns, with calprotectin being more widely used in current practice. 1

Key Differences

Diagnostic Thresholds

• Fecal Calprotectin:

  • Recommended threshold of 50 μg/g to optimize sensitivity for IBD screening 1
  • Higher thresholds (150 μg/g and 250 μg/g) provide increased specificity 1
  • Sensitivity of 81% and specificity of 87% at 50 μg/g threshold 1
  • Sensitivity decreases to 71% and specificity increases to 69% at 150 μg/g threshold 1

• Fecal Lactoferrin:

  • Recommended threshold range of 4.0-7.25 μg/g 1
  • Commercial assays typically report as positive/negative at 7.25 μg/g cutoff 1
  • Sensitivity of 83% and specificity of 75% at standard threshold 1

Clinical Performance

• Calprotectin:

  • Better established with multiple validated cutoff values (50,150,250 μg/g) 1, 2
  • More extensive evidence base with more studies evaluating its performance 1
  • Shows stronger correlation with endoscopic inflammation 1

• Lactoferrin:

  • More limited evidence base compared to calprotectin 1
  • Slightly higher sensitivity (83% vs 81%) but lower specificity than calprotectin at standard thresholds 1
  • Better correlation with histological inflammation than endoscopic findings 3

Clinical Utilization Patterns

• Calprotectin:

  • Increasingly preferred over lactoferrin (usage increased from 60% to 90% over past decade) 4
  • More commonly ordered by gastroenterologists 4
  • More frequently used in the context of abdominal pain evaluation 4
  • Better established for monitoring disease activity in confirmed IBD 1, 2

• Lactoferrin:

  • More commonly ordered by primary care providers 4
  • More frequently used in the context of acute diarrhea evaluation 4
  • May have slightly higher specificity in some clinical scenarios 3, 5

Clinical Application Algorithm

1. Initial Screening for IBD:

   • Either test is appropriate for initial screening 1
   • Calprotectin at 50 μg/g threshold provides optimal sensitivity for screening 1, 2
   • Negative test (calprotectin <50 μg/g or normal lactoferrin) effectively rules out IBD in most cases 1, 2

2. Disease Activity Monitoring:

   • For confirmed IBD patients in symptomatic remission:
     • Calprotectin <150 μg/g reliably rules out active inflammation 1
     • Normal lactoferrin also reliably rules out active inflammation 1
   • For confirmed IBD patients with mild symptoms:
     • Neither normal calprotectin nor normal lactoferrin can reliably rule out active inflammation 1

3. Treatment Decision-Making:

   • Elevated markers (calprotectin >150 μg/g or positive lactoferrin) in symptomatic patients should prompt endoscopic assessment rather than empiric treatment 1, 2
   • Serial monitoring at 3-6 month intervals is recommended for disease activity assessment 2

Common Pitfalls and Caveats

• False Positives: Both markers can be elevated in other inflammatory conditions including colorectal cancer, gastrointestinal infections, and NSAID-induced enteropathy 2

• False Negatives: Approximately 20% of patients with active CD may have normal inflammatory markers 1

• Test Selection: While guidelines suggest either test is appropriate 1, the trend is toward increased use of calprotectin due to its more extensive validation and multiple established cutoff values 4

• Interpretation: Neither test is specific for IBD type (cannot distinguish between Crohn's disease and ulcerative colitis) 6

• Confirmatory Testing: Endoscopy with biopsy remains the gold standard for diagnosis and assessment of disease activity 1, 2

In clinical practice, fecal calprotectin has become the preferred biomarker due to its more extensive validation, established cutoff values, and wider adoption by gastroenterologists, though both tests demonstrate similar overall diagnostic accuracy for detecting intestinal inflammation 4, 3, 6.