title: Appropriate management of special situations in Crohn's disease (upper gastro-intestinal; extra-intestinal manifestations; drug safety during pregnancy and breastfeeding): Results of a multidisciplinary international expert panel-EPACT II.
abstract: BACKGROUND
  High-grade evidence is lacking for most therapeutic decisions in Crohn's disease. Appropriateness criteria were developed for upper gastro-intestinal, extra-intestinal manifestations and drug safety during conception, pregnancy and breastfeeding in patients with Crohn's disease, to assist the physician in clinical decision making.
  
  
  METHODS
  The European Panel on the Appropriateness of Crohn's Disease Therapy (EPACT II), a multidisciplinary international European expert panel, rated clinical scenarios based on evidence from the published literature and panelists' own clinical expertise. Median ratings (on a 9-point scale) were stratified into three categories: appropriate (7-9), uncertain (4-6 with or without disagreement) and inappropriate (1-3). Experts were also asked to rank appropriate medications by priority.
  
  
  RESULTS
  Proton pump inhibitors, steroids, azathioprine/6-mercaptopurine and infliximab are appropriate for upper gastro-duodenal Crohn's disease; for stenosis, endoscopic balloon dilation is the first-line therapy, although surgery is also appropriate. Ursodeoxycholic acid is the only appropriate treatment for primary sclerosing cholangitis. Infliximab is appropriate for Pyoderma gangrenosum, ankylosing spondylitis and uveitis, steroids for Pyoderma gangrenosum and ankylosing spondylitis, adalimumab for Pyoderma gangrenosum and ankylosing spondylitis, cyclosporine-A/tacrolimus for Pyoderma gangrenosum. Mesalamine, sulfasalazine, prednisone, azathioprine/6-mercaptopurine, ciprofloxacin, and probiotics, may be administered safely during pregnancy or for patients wishing to conceive, with the exception that male patients considering conception should avoid sulfasalazine. Metronidazol is considered safe in the 2nd and 3rd trimesters whereas infliximab is rated safe in the 1st trimester but uncertain in the 2nd and 3rd trimesters. Methotrexate is always contraindicated at conception, during pregnancy or during breastfeeding, due to its known teratogenicity. Mesalamine, prednisone, probiotics and infliximab are considered safe during breastfeeding.
  
  
  CONCLUSIONS
  EPACT II recommendations are freely available online (www.epact.ch). The validity of these criteria should now be tested by prospective evaluation.
authors.affiliation: Department of Gastroenterology and Hepatology, Centre Hospitalier Universitaire Vaudois and University of Lausanne, Lausanne, Switzerland.
authors.forename: Christian
authors.initials: C
authors.lastname: Mottet
authors.forename: John-Paul
authors.initials: JP
authors.lastname: Vader
authors.forename: Christian
authors.initials: C
authors.lastname: Felley
authors.forename: Florian
authors.initials: F
authors.lastname: Froehlich
authors.forename: Jean-Jacques
authors.initials: JJ
authors.lastname: Gonvers
authors.forename: Pascal
authors.initials: P
authors.lastname: Juillerat
authors.forename: Reinhold
authors.initials: R
authors.lastname: Stockbrügger
authors.forename: Erika
authors.initials: E
authors.lastname: Angelucci
authors.forename: Frank
authors.initials: F
authors.lastname: Seibold
authors.forename: Pierre
authors.initials: P
authors.lastname: Michetti
authors.forename: Valérie
authors.initials: V
authors.lastname: Pittet