title: Excess primary intestinal lymphoproliferative disorders in patients with inflammatory bowel disease.
abstract: BACKGROUND
  It remains to be shown whether inflammatory bowel disease (IBD) is associated with an increased risk of primary intestinal lymphoproliferative disorders (PILD). We assessed this risk in the CESAME French nationwide prospective observational cohort.
  
  
  METHODS
  In all, 680 gastroenterologists enrolled 19,486 patients with IBD (Crohn's disease in 60.3%) from May 2004 to June 2005. Follow-up ended on 31 December 2007. Available biopsy samples and surgical specimens from patients with PILD (n = 14) were centralized for review. The reference incidence of PILD in the general population was obtained from the Côte d'Or registry and was used as a comparator to assess the standardized incidence ratio (SIR). The influence of thiopurine exposure was explored in a nested case-control study.
  
  
  RESULTS
  In the CESAME population the crude incidence of PILD was 0.12/1000 patient-years, with a corresponding SIR of 17.51 (95% confidence interval [CI], 6.43-38.11; P < 0.0001). The risk was highest in patients exposed to thiopurines (SIR 49.52, 95% CI 13.49-126.8; P < 0.0001), while it did not reach statistical significance in patients naïve to thiopurines (SIR 4.83, 95% CI, 0.12-26.91; P = 0.37). The odds ratio associated with ongoing thiopurine exposure (vs. naïve) was 2.97 (95% CI, 0.30-infinity; P = 0.38). All 14 cases of PILD were non-Hodgkin's B-cell LD, 78.6% occurred in males, 85.7% arose in IBD lesions, and 45.5% were Epstein-Barr virus-positive. Eleven cases occurred in patients with Crohn's disease. Mean (SD) age at PILD diagnosis was 55.1 (5.6) years and the median time since IBD onset was 8.0 years (interquartile range, 3.0-15.8).
  
  
  CONCLUSIONS
  Patients with IBD have an increased risk of developing PILD.
authors.affiliation: Department of Gastroenterology, AP-HP, Hôpital Saint-Antoine and UPMC University of Paris, Paris, France.
authors.forename: Harry
authors.initials: H
authors.lastname: Sokol
authors.forename: Laurent
authors.initials: L
authors.lastname: Beaugerie
authors.forename: Marc
authors.initials: M
authors.lastname: Maynadié
authors.forename: David
authors.initials: D
authors.lastname: Laharie
authors.forename: Jean-Louis
authors.initials: JL
authors.lastname: Dupas
authors.forename: Bernard
authors.initials: B
authors.lastname: Flourié
authors.forename: Eric
authors.initials: E
authors.lastname: Lerebours
authors.forename: Laurent
authors.initials: L
authors.lastname: Peyrin-Biroulet
authors.forename: Matthieu
authors.initials: M
authors.lastname: Allez
authors.forename: Tabassome
authors.initials: T
authors.lastname: Simon
authors.forename: Fabrice
authors.initials: F
authors.lastname: Carrat
authors.forename: Nicole
authors.initials: N
authors.lastname: Brousse
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001379:Azathioprine / Q000627:therapeutic use*; D016022:Case-Control Studies; D002648:Child; D003093:Colitis, Ulcerative / Q000150:complications*; D003424:Crohn Disease / Q000150:complications*; D005260:Female; D005500:Follow-Up Studies; D005602:France / Q000453:epidemiology; D006801:Humans; D007166:Immunosuppressive Agents / Q000627:therapeutic use*; D015994:Incidence; D008232:Lymphoproliferative Disorders / Q000188:drug therapy / Q000453:epidemiology* / Q000209:etiology; D008297:Male; D015122:Mercaptopurine / Q000627:therapeutic use*; D008875:Middle Aged; D011446:Prospective Studies; D016896:Treatment Outcome; D055815:Young Adult
chemical_list: D007166:Immunosuppressive Agents; D015122:Mercaptopurine; D001379:Azathioprine