Limitations of Fecal Calprotectin Specificity in Differential Diagnosis:
A Systematic Review and Meta-Analysis

Abstract

While fecal calprotectin has gained widespread use as a screening tool for
inflammatory bowel disease, this meta-analysis examines its diagnostic
limitations when applied to broader patient populations.

Results

Calprotectin is elevated in multiple non-IBD conditions, including NSAID
enteropathy, gastrointestinal infections, colorectal cancer, and
diverticulitis. This significantly reduces its diagnostic utility in
unselected patient populations.

Specificity of only 67% was observed when non-IBD inflammatory conditions
were included in the analysis. This contrasts sharply with the higher
specificity figures reported in studies that compared IBD exclusively
against irritable bowel syndrome.

Among patients taking regular NSAIDs, 43% had elevated calprotectin above
the standard 50 µg/g cutoff despite no evidence of IBD. Similarly, acute
gastrointestinal infections produced calprotectin elevations indistinguishable
from mild IBD flares.

Clinical Implications

Calprotectin should not be used as a standalone diagnostic tool for IBD.
Positive results must be interpreted in the clinical context, with
consideration of medication history, recent infections, and other potential
sources of intestinal inflammation.

A two-step diagnostic approach combining calprotectin with a clinical risk
score improved specificity to 84% without significantly reducing sensitivity.
