Faecal calprotectin for screening of patients with suspected inflammatory bowel disease: diagnostic meta-analysis

Patrick F van Rheenen, Els Van de Vijver, Vaclav Fidler, Patrick F van Rheenen, Els Van de Vijver, Vaclav Fidler

Abstract

Objective: To evaluate whether including a test for faecal calprotectin, a sensitive marker of intestinal inflammation, in the investigation of suspected inflammatory bowel disease reduces the number of unnecessary endoscopic procedures.

Design: Meta-analysis of diagnostic accuracy studies.

Data sources: Studies published in Medline and Embase up to October 2009. Interventions reviewed Measurement of faecal calprotectin level (index test) compared with endoscopy and histopathology of segmental biopsy samples (reference standard). Inclusion criteria Studies that had collected data prospectively in patients with suspected inflammatory bowel disease and allowed for construction of a two by two table. For each study, sensitivity and specificity of faecal calprotectin were analysed as bivariate data to account for a possible negative correlation within studies.

Results: 13 studies were included: six in adults (n=670), seven in children and teenagers (n=371). Inflammatory bowel disease was confirmed by endoscopy in 32% (n=215) of the adults and 61% (n=226) of the children and teenagers. In the studies of adults, the pooled sensitivity and pooled specificity of calprotectin was 0.93 (95% confidence interval 0.85 to 0.97) and 0.96 (0.79 to 0.99) and in the studies of children and teenagers was 0.92 (0.84 to 0.96) and 0.76 (0.62 to 0.86). The lower specificity in the studies of children and teenagers was significantly different from that in the studies of adults (P=0.048). Screening by measuring faecal calprotectin levels would result in a 67% reduction in the number of adults requiring endoscopy. Three of 33 adults who undergo endoscopy will not have inflammatory bowel disease but may have a different condition for which endoscopy is inevitable. The downside of this screening strategy is delayed diagnosis in 6% of adults because of a false negative test result. In the population of children and teenagers, 65 instead of 100 would undergo endoscopy. Nine of them will not have inflammatory bowel disease, and diagnosis will be delayed in 8% of the affected children.

Conclusion: Testing for faecal calprotectin is a useful screening tool for identifying patients who are most likely to need endoscopy for suspected inflammatory bowel disease. The discriminative power to safely exclude inflammatory bowel disease was significantly better in studies of adults than in studies of children.

Conflict of interest statement

Competing interests: All authors have completed the Unified Competing Interest form at www.icmje.org/coi_disclosure.pdf (available on request from the corresponding author) and declare that: (1) they did not receive financial support for the submitted work; (2) they have no relationships with companies that might have an interest in the submitted work in the previous 3 years; (3) their spouses, partners, or children have no financial relationships that may be relevant to the submitted work; and (4) they have no non-financial interests that may be relevant to the submitted work.

Figures

https://www.ncbi.nlm.nih.gov/pmc/articles/instance/4787947/bin/vanp744532.f1_default.jpg
Fig 1 Study selection
https://www.ncbi.nlm.nih.gov/pmc/articles/instance/4787947/bin/vanp744532.f2_default.jpg
Fig 2 Summary of methodological quality of included studies on basis of review authors’ judgments on seven best differentiating items from QUADAS checklist for each study
https://www.ncbi.nlm.nih.gov/pmc/articles/instance/4787947/bin/vanp744532.f3_default.jpg
Fig 3 Forest plots of sensitivity and 1−specificity of faecal calprotectin test in distinguishing inflammatory bowel disease from non-inflammatory bowel disease. Plots display diagnostic probabilities of included studies, corresponding 95% confidence intervals, and squares with area proportional to study weight in meta-analysis
https://www.ncbi.nlm.nih.gov/pmc/articles/instance/4787947/bin/vanp744532.f4_default.jpg
Fig 4 Receiver operating characteristic graph of faecal calprotectin test in distinguishing inflammatory bowel disease from non-inflammatory bowel disease, with 95% confidence region and 95% prediction regions for studies in adults and in children and teenagers. The confidence region consists of the most likely values of true summary sensitivity and specificity. It indicates the precision with which the summary points are estimated. The prediction region predicts the true sensitivity and specificity of a future study. The size of this region reflects the variation between studies. Individual study estimates are represented as circles, with size proportional to study weight
https://www.ncbi.nlm.nih.gov/pmc/articles/instance/4787947/bin/vanp744532.f5_default.jpg
Fig 5 Fagan’s nomogram for faecal calprotectin showing post-test probability of inflammatory bowel disease after abnormal test result (upper line) and normal test result (lower line) in adults and in children and teenagers
https://www.ncbi.nlm.nih.gov/pmc/articles/instance/4787947/bin/vanp744532.f6_default.jpg
Fig 6 Recommended position of faecal calprotectin in diagnostic pathway

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