What does elevated calprotectin (fecal calprotectin) indicate, specifically in relation to malabsorption?

Fecal Calprotectin: A Marker of Intestinal Inflammation, Not Malabsorption

Fecal calprotectin is a specific marker for intestinal inflammation, not malabsorption, with high sensitivity and specificity for detecting inflammatory bowel disease (IBD) and differentiating it from irritable bowel syndrome (IBS). 1

What Fecal Calprotectin Measures

Fecal calprotectin is:

• A neutrophil-derived protein released during intestinal inflammation
• A validated stool biomarker for detecting and monitoring intestinal inflammation
• Highly sensitive (93%) and specific (96%) for diagnosing IBD in adults 1

Interpretation of Levels

• Normal: <50 μg/g
• Borderline: 50-150 μg/g
• Elevated: >150 μg/g
• Highly elevated: >250 μg/g 1

Relationship to Intestinal Conditions

Inflammatory Bowel Disease

• Elevated in >95% of patients with IBD 2
• Correlates with clinical disease activity and endoscopic findings 3
• Can predict disease relapse with >85% sensitivity and specificity 1, 2
• Shows a topographical gradient, with higher levels detected for distal small bowel inflammation compared to proximal inflammation 4

Differentiating IBD from IBS

• Reliably differentiates between IBD and IBS with sensitivity and specificity exceeding 85% 1, 3
• A powerful tool for ruling out IBD in undiagnosed, symptomatic patients due to excellent negative predictive value 3

Other Causes of Elevated Calprotectin

• Colorectal neoplasia
• Gastrointestinal infections
• NSAID-induced enteropathy 5, 2

Calprotectin and Malabsorption

Important distinction: Fecal calprotectin does not directly measure or indicate malabsorption. Rather, it measures intestinal inflammation, which may sometimes coexist with malabsorption syndromes but is not a marker for malabsorption itself.

When evaluating diarrhea after ileocolonic resection, the British Society of Gastroenterology guidelines note that:

• Fecal calprotectin helps distinguish inflammatory from non-inflammatory causes 6
• If calprotectin is not significantly raised, other diagnoses like bile acid malabsorption should be considered 6
• A rise in calprotectin in a patient with known baseline values suggests recurrent inflammation rather than malabsorption 6

Clinical Application

When evaluating chronic diarrhea:

1. Measure fecal calprotectin
2. If normal or low (<100 μg/g): Consider non-inflammatory causes like IBS or malabsorption syndromes
3. If elevated (>250 μg/g): Refer urgently to gastroenterology for evaluation of inflammatory conditions 6
4. If borderline (100-250 μg/g): Consider repeat testing or routine referral 6

Diagnostic Algorithm for Diarrhea

• Normal calprotectin + diarrhea: Consider malabsorption syndromes (bile acid malabsorption, celiac disease), IBS, microscopic colitis
• Elevated calprotectin + diarrhea: Evaluate for IBD, infectious colitis, NSAID-induced enteropathy

Common Pitfalls

1. Misinterpreting the test: Calprotectin measures inflammation, not malabsorption
2. Sample handling issues: Calprotectin levels vary in different stool samples and degrade at room temperature after a few days 6
3. Overlooking other causes: Elevated calprotectin can occur in conditions other than IBD
4. Ignoring segmental disease: Inflammation may be patchy, particularly in Crohn's disease 1

For accurate results, the first morning stool should be used and stored for no more than 3 days at room temperature before analysis 6.