title: Association of chronic inflammation, not its treatment, with increased lymphoma risk in rheumatoid arthritis.
abstract: OBJECTIVE
  Chronic inflammatory conditions such as rheumatoid arthritis (RA) have been associated with malignant lymphomas. This study was undertaken to investigate which patients are at highest risk, and whether antirheumatic treatment is hazardous or protective.
  
  
  METHODS
  We performed a matched case-control study of 378 consecutive Swedish RA patients in whom malignant lymphoma occurred between 1964 and 1995 (from a population-based RA cohort of 74,651 RA patients), and 378 controls. Information on disease characteristics and treatment from onset of RA until lymphoma diagnosis was abstracted from medical records. Lymphoma specimens were reclassified and tested for Epstein-Barr virus (EBV). Relative risks (odds ratios [ORs]) for lymphomas (by subtype) associated with deciles of cumulative disease activity were assessed, as were ORs associated with drug treatments.
  
  
  RESULTS
  The relative risks of lymphoma were only modestly elevated up to the seventh decile of cumulative disease activity. Thereafter, the relative risk increased dramatically (OR ninth decile 9.4 [95% confidence interval 3.1-28.0], OR tenth decile 61.6 [95% confidence interval 21.0-181.0]). Most lymphomas (48%) were of the diffuse large B cell type, but other lymphoma subtypes also displayed an association with cumulative disease activity. Standard nonbiologic treatments did not increase lymphoma risk. EBV was present in 12% of lymphomas.
  
  
  CONCLUSIONS
  Risk of lymphoma is substantially increased in a subset of patients with RA, those with very severe disease. High inflammatory activity, rather than its treatment, is a major risk determinant.
authors.affiliation: Department of Rheumatology, Akademiska Hospital, Uppsala, Sweden. Eva.Baecklund@swipnet.se
authors.forename: Eva
authors.initials: E
authors.lastname: Baecklund
authors.forename: Anastasia
authors.initials: A
authors.lastname: Iliadou
authors.forename: Johan
authors.initials: J
authors.lastname: Askling
authors.forename: Anders
authors.initials: A
authors.lastname: Ekbom
authors.forename: Carin
authors.initials: C
authors.lastname: Backlin
authors.forename: Fredrik
authors.initials: F
authors.lastname: Granath
authors.forename: Anca Irinel
authors.initials: AI
authors.lastname: Catrina
authors.forename: Richard
authors.initials: R
authors.lastname: Rosenquist
authors.forename: Nils
authors.initials: N
authors.lastname: Feltelius
authors.forename: Christer
authors.initials: C
authors.lastname: Sundström
authors.forename: Lars
authors.initials: L
authors.lastname: Klareskog
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D018501:Antirheumatic Agents; D001172:Arthritis, Rheumatoid / Q000150:complications* / Q000188:drug therapy; D016022:Case-Control Studies; D002908:Chronic Disease; D005260:Female; D004854:Herpesvirus 4, Human / Q000302:isolation & purification; D006801:Humans; D007249:Inflammation / Q000150:complications*; D008223:Lymphoma / Q000209:etiology* / Q000821:virology; D008297:Male; D008875:Middle Aged; D012307:Risk Factors
chemical_list: D018501:Antirheumatic Agents