title: Development of Red Flags Index for Early Referral of Adults with Symptoms and Signs Suggestive of Crohn's Disease: An IOIBD Initiative.
abstract: OBJECTIVE
  Diagnostic delay is frequent in patients with Crohn's disease (CD). We developed a tool to predict early diagnosis.
  
  
  METHODS
  A systematic literature review and 12 CD specialists identified 'Red Flags', i.e. symptoms or signs suggestive of CD. A 21-item questionnaire was administered to 36 healthy subjects, 80 patients with irritable bowel syndrome (non-CD group) and 85 patients with recently diagnosed (<18 months) CD. Patients with CD were asked to recall symptoms and signs they experienced during the 12 months before diagnosis. Multiple logistic regression analyses selected and weighted independent items to construct the Red Flags index. A receiver operating characteristic curve was used to assess the threshold that discriminated CD from non-CD. Association with the Red Flags index relative to this threshold was expressed as the odds ratios (OR).
  
  
  RESULTS
  Two hundred and one subjects, CD and non-CD, answered the questionnaire. The multivariate analysis identified eight items independently associated with a diagnosis of CD. A minimum Red Flags index value of 8 was highly predictive of CD diagnosis with sensitivity and specificity bootstrap estimates of 0.94 (95% confidence interval 0.88-0.99) and 0.94 (0.90-0.97), respectively. Positive and negative likelihood ratios were 15.1 (9.3-33.6) and 0.066 (0.013-0.125), respectively. The association between CD diagnosis and a Red Flags index value of ≥8 corresponds to an OR of 290 (p < 0.0001).
  
  
  CONCLUSIONS
  The Red Flags index using early symptoms and signs has high predictive value for the diagnosis of CD. These results need prospective validation prior to introduction into clinical practice.
authors.affiliation: IBD Center, Humanitas Research Hospital, Rozzano, Milan, Italy sdanese@hotmail.com.
authors.forename: Silvio
authors.initials: S
authors.lastname: Danese
authors.affiliation: IBD Center, Humanitas Research Hospital, Rozzano, Milan, Italy.
authors.forename: Gionata
authors.initials: G
authors.lastname: Fiorino
authors.affiliation: Inserm U1153 - SBIM Hôpital Saint-Louis, Paris, France.
authors.forename: Jean-Yves
authors.initials: JY
authors.lastname: Mary
authors.affiliation: 1st Department of Medicine, Semmelweis University, Budapest, Hungary.
authors.forename: Peter L
authors.initials: PL
authors.lastname: Lakatos
authors.affiliation: IBD Unit, Gastroenterology, Amsterdam Medical Center, Amsterdam, The Netherlands.
authors.forename: Geert
authors.initials: G
authors.lastname: D'Haens
authors.affiliation: Department of Biomedical Sciences for Health, University of Milan, Milan, Italy Unit of Clinical Epidemiology, IRCCS Galeazzi Orthopedic Institute, Milan, Italy.
authors.forename: Lorenzo
authors.initials: L
authors.lastname: Moja
authors.affiliation: Abdominal Surgery, UZ Leuven, Leuven, Belgium.
authors.forename: André
authors.initials: A
authors.lastname: D'Hoore
authors.affiliation: Gastroenterology Department, Hospital Clinic of Barcelona, IDIPABS, CIBERehd, Barcelona, Spain.
authors.forename: Julian
authors.initials: J
authors.lastname: Panes
authors.affiliation: Medizinische Universität Wien, Klinische Abt. Gastroenterologie & Hepatologie, AKH Wien, Austria.
authors.forename: Walter
authors.initials: W
authors.lastname: Reinisch
authors.affiliation: Division of Gastroenterology, UC San Diego Health System, La Jolla, CA, USA.
authors.forename: William J
authors.initials: WJ
authors.lastname: Sandborn
authors.affiliation: Translational Gastroenterology Unit, John Radcliffe Hospital, Oxford, UK.
authors.forename: Simon P
authors.initials: SP
authors.lastname: Travis
authors.affiliation: Department of Gastroenterology, University Hospitals Leuven, Leuven, Belgium.
authors.forename: Séverine
authors.initials: S
authors.lastname: Vermeire
authors.affiliation: Department of Hepato-Gastroenterology and Inserm U954, Nancy University Hospital, Lorraine University, Vandoeuvre-lès-Nancy, France.
authors.forename: Laurent
authors.initials: L
authors.lastname: Peyrin-Biroulet
authors.affiliation: Department of Gastroenterology, Icahn Medical School at Mount Sinai, New York, NY, USA.
authors.forename: Jean-Fréderic
authors.initials: JF
authors.lastname: Colombel
mesh_terms: D000328:Adult; D003424:Crohn Disease / Q000175:diagnosis*; D003430:Cross-Sectional Studies; D003661:Decision Support Techniques; D057210:Delayed Diagnosis / Q000517:prevention & control; D042241:Early Diagnosis; D006305:Health Status Indicators; D006801:Humans; D012017:Referral and Consultation; D018570:Risk Assessment; D012680:Sensitivity and Specificity; D011795:Surveys and Questionnaires
keywords: Crohn’s disease; Red Flags; diagnostic delay