Rheumatoid arthritis and malignant lymphomas

Curr Opin Rheumatol. 2004 May;16(3):254-61. doi: 10.1097/00002281-200405000-00014.


Purpose of review: The reason for the increased lymphoma risk in patients with rheumatoid arthritis (RA) has remained unclear. Reports of lymphomas in patients treated with TNF-blockers have brought renewed interest in this issue. This review summarizes data on possible associations between RA and lymphomas, including different treatments and RA disease related risk factors.

Recent findings: Some recent studies reported increased lymphoma risks linked to RA disease activity. The hypothesis that disease-modifying drugs, and in particular methotrexate, would increase the lymphoma risk receives little support. Observation times for the TNF-blocking therapies are still short, but so far no clear increased risk for lymphoma has been observed. Presence of Epstein-Barr virus, as analyzed with EBER in situ hybridization, appears to be uncommon in RA related lymphomas. Hypothetically, an increased proliferative drive caused by self or non-self antigens may play a role in lymphoma development in RA patients, but this has to be further studied.

Summary: Rheumatologists need to be aware of the increased lymphoma risk in their RA patients. The reason for the increased lymphoma risk in RA patients is still unclear, but available studies rather support the hypothesis of a link between RA disease severity and the risk of lymphoma than increased risks associated with specific treatment regimens. To facilitate the future evaluation of lymphoma risks in connection with treatment, we suggest that patients treated with new drugs should be subject to structured surveillance. Collected information should include data about RA disease activity and severity.

Publication types

  • Review

MeSH terms

  • Antibodies, Monoclonal / adverse effects
  • Antirheumatic Agents / adverse effects*
  • Arthritis, Rheumatoid / complications*
  • Arthritis, Rheumatoid / drug therapy
  • Arthritis, Rheumatoid / immunology
  • Etanercept
  • Humans
  • Immunoglobulin G / adverse effects
  • Infliximab
  • Lymphoma / complications*
  • Lymphoma / immunology
  • Receptors, Tumor Necrosis Factor
  • Risk Factors
  • Tumor Necrosis Factor-alpha / antagonists & inhibitors*


  • Antibodies, Monoclonal
  • Antirheumatic Agents
  • Immunoglobulin G
  • Receptors, Tumor Necrosis Factor
  • Tumor Necrosis Factor-alpha
  • Infliximab
  • Etanercept