title: CARD15 mutations and perianal fistulating Crohn's disease: correlation and predictive value of antibiotic response.
abstract: BACKGROUND
  CARD15 mutations alter bowel immunity and increase susceptibility to Crohn's disease (CD). However, the relation between these mutations and Crohn's perianal fistulas has not been fully clarified.
  
  
  OBJECTIVE
  To assess whether CARD15 mutations are associated with risk of developing Crohn's perianal fistulas and whether these mutations are predictors of the response of perianal fistulas to antibiotics.
  
  
  METHODS
  CARD15 mutations were investigated in 203 consecutive CD patients. Presence/absence of history of perianal fistula was recorded. Patients with history of perianal fistula were divided into two groups (with/without CARD15 mutations), and response to antibiotics was evaluated in both groups.
  
  
  RESULTS
  Of the 203 patients, 60 (29.6%) showed at least one CARD15 mutation and 55 (27.1%) had history of perianal fistula. History of perianal fistula was identified in 13 (21.7%) patients with mutations and in 42 (29.4%) patients without mutations (P = 0.260). Mean age at diagnosis of first perianal fistula was similar in patients with/without CARD15 mutations (28.7 ± 9.8 versus 29.7 ± 10.1 years, P = 0.758). Average time between disease onset and diagnosis of first perianal fistula was also similar in the two groups (4.6 ± 5.1 versus 5.0 ± 5.9 years, P = 0.816). Response of perianal fistulas to antibiotics (metronidazole alone or combined with ciprofloxacin) was significantly higher in patients without CARD15 mutations (7.7% versus 40.5%, P = 0.041).
  
  
  CONCLUSIONS
  In CD, CARD15 mutations are not associated with risk of developing perianal fistulas or with time of their outbreak. Nevertheless, patients with perianal fistulas and CARD15 mutations showed worse response to antibiotics.
authors.affiliation: Department of Gastroenterology, Coimbra University Hospital, Avenida Bissaya Barreto, 3000, Coimbra, Portugal. pauloavfreire@gmail.com
authors.forename: Paulo
authors.initials: P
authors.lastname: Freire
authors.forename: Francisco
authors.initials: F
authors.lastname: Portela
authors.forename: Maria M
authors.initials: MM
authors.lastname: Donato
authors.forename: Manuela
authors.initials: M
authors.lastname: Ferreira
authors.forename: Paulo
authors.initials: P
authors.lastname: Andrade
authors.forename: Carlos
authors.initials: C
authors.lastname: Sofia
mesh_terms: D000328:Adult; D000900:Anti-Bacterial Agents / Q000627:therapeutic use; D002939:Ciprofloxacin / Q000627:therapeutic use; D003424:Crohn Disease / Q000150:complications / Q000188:drug therapy / Q000235:genetics*; D004359:Drug Therapy, Combination; D005260:Female; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D008297:Male; D008795:Metronidazole / Q000627:therapeutic use; D008875:Middle Aged; D009154:Mutation; D053473:Nod2 Signaling Adaptor Protein / Q000235:genetics*; D012003:Rectal Fistula / Q000188:drug therapy / Q000209:etiology / Q000235:genetics*; D012189:Retrospective Studies; D016896:Treatment Outcome
chemical_list: D000900:Anti-Bacterial Agents; C429018:NOD2 protein, human; D053473:Nod2 Signaling Adaptor Protein; D008795:Metronidazole; D002939:Ciprofloxacin