Diagnostic accuracy of faecal calprotectin in patients with active perianal fistulas

Abstract

Background Faecal calprotectin (FC) is a marker of mucosal inflammation. Objective The aim of this study was to determine the diagnostic accuracy of FC to (a) differentiate between perianal fistulizing Crohn's disease (pCD) and cryptoglandular perianal fistulas; and (b) detect mucosal inflammation in pCD. Methods Patients with active perianal fistulas who had FC measured and a complete ileocolonoscopy within 10 weeks were retrospectively included. Results Fifty-six patients were included (pCD, n = 37) of whom 19 pCD patients exhibited ulcers. FC was significantly higher in pCD compared to cryptoglandular fistulas (µg/g) (708.0 (207.0–1705.0) vs 32.0 (23.0–77.0), p < 0.001). Area-under-the-curve (AUC) value for FC receiver operating characteristic (ROC) statistics was 0.900. Optimal FC cut-off was ≥ 150 µg/g. To differentiate pCD from cryptoglandular fistulas in the absence of luminal inflammation, optimal cut-off remained ≥ 150 µg/g (AUC = 0.857, sensitivity = 0.81, specificity = 0.89, positive predictive value (PPV) = 93.8% and negative predictive value (NPV) = 70.8%). In pCD, FC was significantly increased in the presence of ulcers (1672.0 vs 238.0, p = 0.004). Optimal cut-off was ≥ 250 µg/g (AUC = 0.776; sensitivity = 0.89, specificity = 0.56, PPV - 68.0% and NPV = 83.0%). Conclusion FC discriminates pCD from cryptoglandular fistulas, even in the absence of intestinal ulcers. In active pCD, an elevated FC does not accurately predict the presence of ulcers and should be interpreted with caution.

International consensus on methodological issues in standardization of fecal calprotectin measurement in inflammatory bowel diseases

“…Similarly, PPIs should be suspended 4 weeks prior to FC measurement, allowing for adequate drug wash out and preventing any measurement bias 80 . Furthermore, patients' age, including younger (<9 years) and older patients (>65 years), body mass index (obesity), physical inactivity, perianal disease, presence of an ostomy, and bowel preparation have been reported as factors associated with increased FC values 84–91 . FC is strongly correlated with disease activity in pregnant women with IBD and is frequently used for monitoring these patients 92 .…”

“…80 Furthermore, patients' age, including younger (<9 years) and older patients (>65 years), body mass index (obesity), physical inactivity, perianal disease, presence of an ostomy, and bowel preparation have been reported as factors associated with increased FC values. [84][85][86][87][88][89][90][91] FC is strongly correlated with disease activity in pregnant women with IBD and is frequently used for monitoring these patients. 92 However, a trend of progressive reduction in FC levels was found during pregnancy of IBD women suggesting that the immune changes occurring in pregnant women could be associated with a beneficial effect on disease activity.…”

Hyperbaric oxygen therapy for the treatment of perianal fistulas in 20 patients with Crohn's disease: Results of the HOT‐TOPIC trial after 1‐year follow‐up

“…A possible explanation is that the anti‐inflammatory effects of hyperbaric oxygen therapy wear off with time, while the positive effect on wound healing of the fistulas remains visible long‐term. Furthermore, current biochemical markers (in this study: C‐reactive protein and faecal calprotectin) and the patient‐reported outcomes in itself have limitations in assessing activity of perianal fistulas and mucosal inflammation 28,29 . Recently, a patient‐reported outcome measure that is designed specifically for perianal Crohn's disease was published, and the use of this scale in a future study could provide more insight into the long‐term, patient‐reported effects of hyperbaric oxygen therapy on perianal fistulas specifically 30 …”

“…Furthermore, current biochemical markers (in this study: C-reactive protein and faecal calprotectin) and the patient-reported outcomes in itself have limitations in assessing activity of perianal fistulas and mucosal inflammation. 28,29 Recently, a patient-reported outcome measure that is designed specifically for perianal Crohn's disease was published, and the use of this scale in a future study could provide more insight into the long-term, patientreported effects of hyperbaric oxygen therapy on perianal fistulas specifically. 30 Due to the design of the control group (patient-preference) as well as the small number of patients that was included a meaningful comparison between groups could not be made.…”

Crohn’s Disease-Associated and Cryptoglandular Fistulas: Differences and Similarities

“…Fecal calprotectin (FCP) is significantly increased in patients with CD-associated fistulas, with and without mucosal inflammation, when compared with cryptoglandular fistulas (FCP cut-off value ≥ 150 µg/g, AUC = 0.9000, 81% sensitivity and 89% specificity) [ 101 ]. Even in fistulizing CD patients without mucosal inflammation, FCP was still higher compared to patients with cryptoglandular fistulas (FCP cut-off value ≥ 150 µg/g, AUC = 0.857, 67% sensitivity and 90% specificity) [ 101 ]. Although above results are clear, FCP is not a 100% discriminator between non-CD and CD fistulas.…”