title: Assessment of histologic disease activity in Crohn's disease: a systematic review.
abstract: BACKGROUND
  Crohn's disease (CD) is an idiopathic, chronic, transmural inflammatory disorder of the gastrointestinal tract. Because mucosal involvement is near-universal, endoscopic healing has emerged as an important aspect in improving outcome. However, resolution of histologic disease activity has potential to convey additional benefit beyond that attained with endoscopic healing alone. Validated scoring systems of histologic disease activity are required to further assess this possibility. The aim of this study was to systematically review the existing histologic disease activity indices (HDAI) for CD and to assess their operating properties and potential use as outcome measures in clinical trials.
  
  
  METHODS
  MEDLINE (Ovid), EMBASE (Ovid), PubMed, the Cochrane Library (CENTRAL), and Digestive Disease Week (DDW) abstracts were searched from 1981 to April 2013 for applicable studies to identify relevant studies for review and analysis.
  
  
  RESULTS
  In total, 3732 citations were screened to obtain 89 articles for inclusion. Sixty-six HDAIs were characterized as either stepwise or numerical instruments. These HDAIs were used for either assessment of response to medical therapy or for comparison with biomarkers or imaging tests. None of the HDAIs identified was developed according to currently accepted methods for developing evaluative instruments, and none have been formally validated.
  
  
  CONCLUSIONS
  Measurement of histologic disease activity has potential value in CD; however, no validated measures are available. Additional research is needed to develop a methodologically rigorous instrument for use in clinical investigation and potentially for clinical practice.
authors.affiliation: *Department of Medicine, Scripps Clinic, La Jolla, California; †Robarts Clinical Trials, Robarts Research Institute, Western University, London, ON, Canada; ‡Division of Gastroenterology, University of California San Diego, La Jolla, California; §Department of Gastroenterology, Academic Medical Center, Amsterdam, the Netherlands; ‖Departments of Medicine and Epidemiology and Biostatistics, Western University, London, Ontario, Canada; ¶Department of Pathology, University of California San Diego, La Jolla, CA; and **Department of Pathology, University Hospital of KU Leuven, Leuven, Belgium.
authors.forename: Amirkaveh
authors.initials: A
authors.lastname: Mojtahed
authors.forename: Reena
authors.initials: R
authors.lastname: Khanna
authors.forename: William J
authors.initials: WJ
authors.lastname: Sandborn
authors.forename: Geert R
authors.initials: GR
authors.lastname: D'Haens
authors.forename: Brian G
authors.initials: BG
authors.lastname: Feagan
authors.forename: Lisa M
authors.initials: LM
authors.lastname: Shackelton
authors.forename: Kenneth A
authors.initials: KA
authors.lastname: Baker
authors.forename: Elena
authors.initials: E
authors.lastname: Dubcenco
authors.forename: Mark A
authors.initials: MA
authors.lastname: Valasek
authors.forename: Karel
authors.initials: K
authors.lastname: Geboes
authors.forename: Barrett G
authors.initials: BG
authors.lastname: Levesque
mesh_terms: D000818:Animals; D003424:Crohn Disease / Q000473:pathology* / Q000628:therapy*; D006801:Humans; D007150:Immunohistochemistry / Q000379:methods*; D011379:Prognosis; D012720:Severity of Illness Index