title: The risk of lymphoma development in autoimmune diseases: a meta-analysis.
abstract: BACKGROUND
  The risk of development of non-Hodgkin lymphoma (NHL) in autoimmune patients has been investigated in several cohort studies. These studies revealed inconclusive results. To shed some light on this controversy, we conducted a meta-analysis of all available cohort studies linking systemic lupus erythematosus (SLE), rheumatoid arthritis (RA), and primary Sjögren syndrome (pSS) to the risk of NHL development.
  
  
  METHODS
  We searched the PubMed database (1974 to April 2005) for English-language cohort studies using the key words systemic lupus erythematosus, SLE, rheumatoid arthritis, RA, Sjögren syndrome, or SS; non-Hodgkin lymphoma; and relative risk, RR, standardized incidence rate, or SIR. All cohort studies that used established diagnostic criteria for SLE, RA, and pSS; had histologic confirmation of NHL; and provided standardized incidence rates (SIRs) were included in the meta-analysis.
  
  
  RESULTS
  The 20 studies chosen for the analysis included 6 for SLE, 9 for RA, and 5 for pSS. Overall, the meta-analysis suggested extreme heterogeneity among the studies (P < .01; I2 > 70%), high risk of NHL development for pSS (random effects SIR, 18.8; 95% confidence interval [CI], 9.5-37.3); moderate risk for SLE (random effects SIR, 7.4; 95% CI, 3.3-17.0); and lower risk for RA (random effects SIR, 3.9; 95% CI, 2.5-5.9). In RA, the random effects SIRs of NHL with conventional antirheumatic treatment, cytotoxic treatment, and treatment with a biological agent were 2.5 (95% CI, 0.7-9.0), 5.1 (95% CI, 0.9-28.6), and 11.5 (95% CI, 3.7-26.9), respectively.
  
  
  CONCLUSIONS
  Rheumatic disease may present a potential risk factor for development of NHL. In this regard, we focused on the underlying pathophysiologic mechanisms related to lymphomagenesis in pSS, SLE, and RA, to justify the varying potential for and background of NHL development.
authors.affiliation: Department of Biomathematics, University of Thessaly School of Medicine, Larissa, Greece.
authors.forename: Elias
authors.initials: E
authors.lastname: Zintzaras
authors.forename: Michael
authors.initials: M
authors.lastname: Voulgarelis
authors.forename: Haralampos M
authors.initials: HM
authors.lastname: Moutsopoulos
mesh_terms: D018501:Antirheumatic Agents / Q000627:therapeutic use; D001172:Arthritis, Rheumatoid / Q000188:drug therapy / Q000453:epidemiology; D001327:Autoimmune Diseases / Q000188:drug therapy / Q000453:epidemiology*; D002170:Canada / Q000453:epidemiology; D015897:Comorbidity; D005060:Europe / Q000453:epidemiology; D005260:Female; D006801:Humans; D007166:Immunosuppressive Agents / Q000627:therapeutic use; D015994:Incidence; D008180:Lupus Erythematosus, Systemic / Q000188:drug therapy / Q000453:epidemiology; D008228:Lymphoma, Non-Hodgkin / Q000453:epidemiology*; D008297:Male; D012306:Risk; D012307:Risk Factors; D015983:Selection Bias; D017678:Sex Distribution; D012859:Sjogren's Syndrome / Q000188:drug therapy / Q000453:epidemiology; D018709:Statistics, Nonparametric; D014481:United States / Q000453:epidemiology
chemical_list: D018501:Antirheumatic Agents; D007166:Immunosuppressive Agents