The risk of lymphoma development in autoimmune diseases: a meta-analysis

Arch Intern Med. 2005 Nov 14;165(20):2337-44. doi: 10.1001/archinte.165.20.2337.


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.

Publication types

  • Meta-Analysis
  • Review

MeSH terms

  • Antirheumatic Agents / therapeutic use
  • Arthritis, Rheumatoid / drug therapy
  • Arthritis, Rheumatoid / epidemiology
  • Autoimmune Diseases / drug therapy
  • Autoimmune Diseases / epidemiology*
  • Canada / epidemiology
  • Comorbidity
  • Europe / epidemiology
  • Female
  • Humans
  • Immunosuppressive Agents / therapeutic use
  • Incidence
  • Lupus Erythematosus, Systemic / drug therapy
  • Lupus Erythematosus, Systemic / epidemiology
  • Lymphoma, Non-Hodgkin / epidemiology*
  • Male
  • Risk
  • Risk Factors
  • Selection Bias
  • Sex Distribution
  • Sjogren's Syndrome / drug therapy
  • Sjogren's Syndrome / epidemiology
  • Statistics, Nonparametric
  • United States / epidemiology


  • Antirheumatic Agents
  • Immunosuppressive Agents