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Noninvasive Markers in the Assessment of Intestinal Inflammation in Inflammatory Bowel Diseases

Performance of Fecal Lactoferrin, Calprotectin, and PMN-Elastase, CRP, and Clinical Indices

Langhorst, Jost, M.D.1; Elsenbruch, Sigrid, Ph.D.2; Koelzer, Julia, M.D.1; Rueffer, Andreas, M.D.3; Michalsen, Andreas, M.D., Ph.D.1; Dobos, Gustav J., M.D., Ph.D.1

American Journal of Gastroenterology: January 2008 - Volume 103 - Issue 1 - p 162–169

OBJECTIVES The aim of this study was to compare the performance of fecal lactoferrin (Lf), calprotectin (Cal), polymorphonuclear neutrophil elastase (PMN-e), as well as serum C-reactive protein (CRP) in patients with inflammatory bowel diseases (IBD) to address (a) whether these markers can differentiate IBD patients with endoscopically assessed inflammation from IBD patients without inflammation and from irritable bowel syndrome (IBS); (b) whether they correlate with endoscopic severity of inflammation; and (c) whether a combination of fecal markers with the respective disease-specific activity indices may increase the diagnostic accuracy with reference to the endoscopic severity of inflammation.

METHODS Fecal levels of Lf, Cal, and PMN-e and serum CRP were assessed in 139 patients undergoing diagnostic ileocolonoscopy (54 IBS patients, 42 ulcerative colitis [UC], 43 Crohn's disease [CD]). Disease activity was determined for CU with the colitis activity index (CAI) and for CD with the Crohn's disease activity index (CDAI). The performance of each marker with reference to endoscopic inflammatory activity was assessed by computing correlations, and sensitivity and specificity using published as well as adjusted cutoffs. A comprehensive activity index was computed by combining results from fecal markers, serum CRP, and a clinical activity index.

RESULTS UC or CD patients with active inflammation demonstrated significantly higher levels of Lf, Cal, and PMN-e in feces as well as serum-CRP when compared to patients with inactive inflammation as well as patients with IBS (all P < 0.05). Using adjusted cutoffs enabled a marked improvement of all markers with an overall diagnostic accuracy in IBD of 80.0% for Lf, 80.0% for Cal, 74.1% for PMN-e, 64.0% for CRP, and 79.0% for the respective clinical disease scores. Cal showed the highest diagnostic accuracy in CD (81.4%), whereas Lf was superior to the other markers in UC (83.3%). The comprehensive activity index yielded a further improvement of sensitivity and specificity, with a diagnostic accuracy of 95.3% for UC patients.

CONCLUSION The fecal markers Lf, Cal, and PMN-e are able to differentiate active IBD from inactive IBD as well as from IBS. None of these three stool markers is consistently superior in its ability to reflect endoscopic inflammation, but all three are superior to CRP in their diagnostic accuracy. A combination of the stool markers with the CRP and a disease-specific activity index in a categorical comprehensive activity index can increase the diagnostic accuracy with reference to the endoscopic inflammation in UC.

1Department of Internal and Integrative Medicine, Kliniken Essen-Mitte, University of Duisburg-Essen, Germany; 2Department of Medical Psychology and Immunobiology, University Clinic of Essen, University of Duisburg-Essen, Germany; and 3Labor L+S AG, Bad Bocklet-Großenbrach, Germany

Reprint requests and correspondence: Jost Langhorst, M.D., Department of Internal Medicine, Kliniken Essen-Mitte, University of Duisburg-Essen, Am Deimelsberg 34a, D-45276 Essen, Germany.

Received January 4, 2007; accepted August 6, 2007.

[Correction added after online publication 4-Oct-2007: The spelling of UC was corrected in the abstract.]

CONFLICT OF INTERESTGuarantor of the article: Jost Langhorst, M.D.

Specific author contributions: Jost Langhorst: planning of the study, study design, writing of the article; Sigrid Elsenbruch: data analysis, writing of the article; Julia Koelzer: data collection; Andreas Rueffer: laboratory analyses, interpretation of the data; Andreas Michalsen: data interpretation, planning of the study; Gustav Dobos: planning of the study, final review of the manuscript.

Financial support: No external financial support was received. The ELISA kits for analyses of the fecal markers were supplied by Techlab and by Immundiagnostik.

Potential competing interests: None.

© The American College of Gastroenterology 2008. All Rights Reserved.
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