Calprotectin, Fecal

  • Aid in differentiation of IBD from IBS and other functional disorders of the GI system.
  • Aid in monitoring IBD and prediction of relapse.

Inflammatory bowel disease (IBD) represents a spectrum of chronic disorders that affect the gastrointestinal (GI) tract. Crohn disease (CD) and ulcerative colitis (UC) are the major IBD disorders.  Fecal calprotectin is a marker of gut inflammation with good sensitivity for detecting IBD.  Fecal lactoferrin, an iron-binding protein, is another useful marker of intestinal inflammation in IBD,  but more clinical evidence is available for fecal calprotectin. 

Disease Overview

Prevalence

IBD: 286/100,000 in United States 

Physiology

  • Calprotectin is a calcium-binding protein  and accounts for 60% of soluble protein in neutrophils 
  • Calprotectin concentration in feces is proportional to the level of inflammation in patients with UC the relationship is more variable in patients with CD 
  • Calprotectin is stable in stool samples 

Diagnostic Issues

  • IBD symptoms may be vague and similar to those of irritable bowel syndrome (IBS) (eg, diarrhea, abdominal pain)
    • IBS is much more prevalent than IBD
  • Differentiation of IBD from IBS may require invasive procedures
  • Calprotectin testing may be useful  as a screen for differentiating IBS and IBD,  reducing the necessity of invasive procedures

Monitoring Issues

  • Monitoring by endoscopy is invasive
  • Calprotectin measurement can be used to help differentiate quiescent from active IBD 
  • Mucosal healing is associated with sustained remission and is the goal of IBD treatment 
  • Calprotectin levels correlate with endoscopic scoring systems that are used to assess mucosal healing and may be useful in evaluating mucosal healing 

Test Interpretation

Clinical Validation

Screening performance for IBD

  • Sensitivity: 93% in adults; 92% in children 
  • Specificity: 96% in adults; 76% in children 
  • More sensitive and specific than serum inflammatory markers  
  • Individuals with high pretest probability of IBD (>75%) should be referred directly to endoscopy due to the risk of false-negative calprotectin results  
  • Screening for elevated fecal calprotectin in individuals with low pretest probability for IBD may result in cost savings by reducing need for unnecessary procedures 
    • Confirm positive results by endoscopy and follow negative result clinically

Results

Results Range Clinical Significance

Normal

≤50 μg/g

Likely to rule out IBD in adults with <75% prior probability

Borderline

51-120 μg/g

Reevaluation in 4-6 weeks is recommended

Abnormal

≥121 μg/g

Supports diagnosis of IBD

Limitations

  • Calprotectin is not specific for IBD and is also elevated in:
    • GI infections
    • Colorectal cancer
    • Celiac disease
    • Mild elevations may be seen with nonsteroidal anti-inflammatory drug or aspirin use
  • Calprotectin concentration alone is not diagnostic for IBD
  • Calprotectin does not distinguish celiac disease from UC
    • Results may fluctuate as disease activity fluctuates
    • GI bleeding can cause mild increases in fecal calprotectin concentrations
  • Concentrations of fecal biomarkers may vary in different stool samples from a single patient 
    References