Can fecal calprotectin be positive in patients with collagenous colitis?

Fecal Calprotectin in Collagenous Colitis

Yes, fecal calprotectin can be positive in patients with collagenous colitis, but elevated levels are not a universal finding, limiting its use as a reliable inflammatory marker for this condition. 1

Relationship Between Fecal Calprotectin and Collagenous Colitis

Fecal calprotectin (FC) serves as a marker of intestinal inflammation, primarily reflecting neutrophil activity in the intestinal mucosa. In collagenous colitis (CC), the evidence shows:

• Studies have found increased FC levels in patients with active collagenous colitis compared to those in remission and healthy controls 1
• However, approximately 38% of patients with active collagenous colitis have normal FC levels, making it an inconsistent marker 1
• The inflammatory pattern in collagenous colitis differs from other inflammatory bowel diseases (IBD), with eosinophil activation playing a more significant role than neutrophil activity 2

Alternative Fecal Markers for Collagenous Colitis

Given the limitations of FC in collagenous colitis, other fecal markers may be more useful:

• Fecal eosinophil cationic protein (F-ECP) and eosinophil protein X (F-EPX) have shown better discriminating capacity in detecting active collagenous colitis 2, 3
• In one study, 92% of patients with active collagenous colitis had elevated F-ECP levels compared to 75% with elevated FC 2
• F-ECP and F-EPX decrease rapidly during budesonide treatment, correlating with clinical improvement 2

Clinical Implications and Diagnostic Approach

When evaluating patients with chronic non-bloody diarrhea:

• FC levels >150 μg/g are considered elevated and indicate ongoing intestinal inflammation 4
• For patients with mild symptoms and elevated inflammatory markers, the American Gastroenterological Association (AGA) recommends endoscopic assessment rather than empiric treatment 5, 4
• Colonoscopy with biopsies remains necessary to establish a diagnosis of collagenous colitis, as FC has limited diagnostic value 4

Interpretation of Fecal Calprotectin Results

When interpreting FC results in suspected collagenous colitis:

• Normal: <50 μg/g
• Borderline: 50-150 μg/g
• Elevated: >150 μg/g
• Highly elevated: >250 μg/g 4

However, these thresholds were primarily established for IBD rather than microscopic colitis.

Pitfalls and Caveats

Important considerations when using FC in the evaluation of collagenous colitis:

• FC has lower sensitivity for detecting inflammation in collagenous colitis compared to ulcerative colitis or Crohn's disease 6, 1
• FC may be less accurate in detecting inflammation in limited segmental disease or proctitis 5
• There can be substantial within-stool and within-day variations of FC measurements from a single patient 5
• Different FC assays may not be interchangeable, so the same assay should be used for a given patient to compare results over time 5

Diagnostic Algorithm for Suspected Collagenous Colitis

1. For patients with chronic non-bloody diarrhea:

   • Consider measuring FC along with F-ECP and F-EPX if available
   • Normal levels of all fecal markers suggest a low probability (8%) of microscopic colitis 3

2. If FC is elevated (>150 μg/g):

   • Proceed with colonoscopy with biopsies, even from normal-appearing mucosa 4
   • Check for other causes of elevated FC (infections, other IBDs)

3. If FC is normal but clinical suspicion remains high:

   • Still consider colonoscopy with biopsies, as up to 38% of active collagenous colitis cases have normal FC 1

In summary, while FC can be elevated in collagenous colitis, its inconsistent elevation limits its diagnostic utility. Eosinophil-derived markers (F-ECP and F-EPX) appear to be more sensitive and specific for collagenous colitis and may be better biomarkers for this condition.