What does a high fecal calprotectin level indicate?

High Fecal Calprotectin: Clinical Significance

High fecal calprotectin strongly suggests active intestinal inflammation, most commonly from inflammatory bowel disease (IBD), though it can also be elevated in colorectal neoplasia, gastrointestinal infections, and NSAID use. 1

What Elevated Levels Indicate

Active Intestinal Inflammation:

• Fecal calprotectin is a calcium-binding protein released by neutrophils that migrate into the intestinal lumen during inflammation 2, 3
• Values >150 μg/g strongly suggest active inflammatory disease in the gastrointestinal tract 1
• At a cut-off of 50 μg/g, calprotectin has 90.6% sensitivity for detecting endoscopically active disease 4
• Specificity improves progressively: 78.2% at >100 μg/g and further improvement at >250 μg/g 4

Interpretation by Clinical Context

In Symptomatic Patients with Suspected IBD:

• For patients with moderate to severe symptoms (frequent rectal bleeding, significantly increased stool frequency) and calprotectin >150 μg/g, there is only a 4.6% false positive rate—meaning 95.4% truly have moderate to severe endoscopic inflammation 5, 1
• In patients with mild symptoms and calprotectin >150 μg/g, the false positive rate increases to 15.5%, warranting endoscopic confirmation before treatment adjustment 5, 1

In Asymptomatic Patients with Known IBD:

• Calprotectin >150 μg/g in asymptomatic patients has a 22.4% false positive rate, suggesting endoscopic evaluation should be considered 5
• Values <50 μg/g generally indicate clinical remission and are reassuring 1

Intermediate Values (50-250 μg/g):

• These levels require clinical correlation and may necessitate repeat testing or endoscopic assessment 1
• The British Society of Gastroenterology recommends values 100-250 μg/g warrant consideration of repeat testing or routine gastroenterology referral 4

Differential Diagnosis Beyond IBD

Other Conditions Causing Elevation:

• Colorectal neoplasia (cancer and advanced adenomas) 4, 3
• Gastrointestinal infections (bacterial gastroenteritis, C. difficile) 6, 3
• NSAID use within the past 6 weeks 4
• Microscopic colitis 4
• Local bleeding from hemorrhoids can cause false elevations 4

Critical Caveat: Calprotectin is not sensitive enough to exclude colorectal cancer—patients with alarm symptoms (rectal bleeding, weight loss, iron-deficiency anemia) require cancer pathway referral regardless of calprotectin result 1, 4

Correlation with Disease Activity

In Ulcerative Colitis:

• Calprotectin correlates well with endoscopic activity, with thresholds of 112-187 μg/g predictive of active disease depending on the scoring system used 5
• Values of 75-100 μg/g correlate with histological remission 5
• CRP is less sensitive than calprotectin—patients may have normal CRP even during flares 5

In Crohn's Disease:

• At 50 μg/g cut-off: 88% sensitivity and 67% specificity for endoscopically active disease (SES-CD ≥3) 5
• At 150 μg/g cut-off: 81% sensitivity and 72% specificity 5
• At 250 μg/g cut-off: 76% sensitivity and 74% specificity 5
• Correlation may be less tight than in ulcerative colitis due to transmural inflammation patterns 3, 7

Predicting Relapse

Prognostic Value:

• Elevated calprotectin in clinically quiescent IBD patients predicts future relapse 4, 8
• Serial monitoring at 3-6 month intervals facilitates early recognition of impending flares 1, 4
• Rising trends in calprotectin may be more predictive than absolute values 8
• Low-grade elevation suggests persistent subclinical inflammation even in clinical remission 7

Important Limitations in Acute Settings

When Calprotectin Cannot Discriminate:

• In acute diarrhea, calprotectin will be elevated regardless of whether the cause is IBD or gastroenteritis—stool culture and/or endoscopy are needed for diagnosis 6
• For bloody diarrhea, flexible sigmoidoscopy is indicated regardless of calprotectin result 6
• Repeat measurement after approximately 18 days showed reduction in 53% of patients with initially elevated levels, suggesting transient inflammation in many cases 6