Does autoimmune disease increase the risk of developing lymphoma?

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Last updated: March 14, 2025View editorial policy

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From the Guidelines

Yes, autoimmune diseases increase the risk of developing lymphoma, with Sjögren's syndrome carrying a significant risk of around 2%–5% of patients developing lymphoma. Patients with autoimmune conditions such as rheumatoid arthritis, Sjögren's syndrome, systemic lupus erythematosus, and celiac disease have a higher likelihood of developing lymphomas, particularly non-Hodgkin lymphoma, due to chronic inflammation and immune dysregulation that characterizes autoimmune diseases, which can lead to persistent lymphocyte activation and potential malignant transformation 1. The connection between autoimmune diseases and lymphoma risk is supported by the fact that some immunosuppressive medications used to treat autoimmune conditions may slightly increase lymphoma risk in certain patients, though this relationship is complex and the benefits of treating the underlying autoimmune disease typically outweigh this risk.

Key Points to Consider

  • The risk of developing lymphoma varies by specific autoimmune condition, with Sjögren's syndrome being one of the highest risks 1.
  • Patients with autoimmune diseases should undergo regular medical follow-ups that include monitoring for lymphoma symptoms such as persistent swollen lymph nodes, unexplained weight loss, night sweats, and fatigue.
  • The management of lymphoma in patients with autoimmune diseases, such as Sjögren's syndrome, should be individualized according to the specific histological subtype and the corresponding current therapeutic guidelines, with a personalized therapeutic approach driven by the hematologist/oncologist 1.
  • Treatment options for lymphoma in patients with autoimmune diseases may include rituximab-based chemotherapy regimens, radiotherapy, or a watch-and-wait strategy, depending on the disease stage and activity 1.

Management and Treatment

  • For patients with disseminated MALT lymphoma or with concomitant high disease activity, chemotherapy may be considered on a case-by-case basis 1.
  • For patients with marginal zone lymphomas, small lymphocytic lymphoma (SLL) and lymphoplasmacytic lymphoma (LPL) in early disease stages, treatment may include radiotherapy (with or without chemotherapy), although a watch-and-wait strategy could be an alternative to spare the side effects of therapy 1.
  • Rituximab plus fludarabine or bendamustine (BR) are the recommended first-line therapy for MZL, SLL, and LPL, with a recent study showing the efficacy of the BR combination in patients with Sjögren's syndrome complicated by MZL 1.

From the Research

Association Between Autoimmune Disease and Lymphoma

  • Autoimmune diseases have been consistently associated with an increased risk of developing malignant lymphoma, as shown in studies 2, 3.
  • Certain autoimmune conditions, such as rheumatoid arthritis (RA) and primary Sjögren's syndrome (pSS), have a stronger association with lymphoma development 2, 3.
  • The exact mechanisms behind this association are not fully understood, but chronic inflammation and immune stimulation are thought to play a key role 2, 3.

Impact of Autoimmune Disease on Lymphoma Outcomes

  • Some studies suggest that autoimmune diseases may not significantly impact the outcomes of lymphoma patients, with similar progression-free survival (PFS) and overall survival (OS) rates compared to patients without autoimmune diseases 4.
  • However, other studies have found that certain autoimmune conditions, particularly those mediated by B-cell responses, may be associated with inferior outcomes, such as worse OS in patients with diffuse large B-cell lymphoma 5, 6.
  • The presence of autoimmune diseases may also increase the risk of neutropenic fever and other treatment-related complications 5.

Prevalence of Autoimmune Diseases in Lymphoma Patients

  • The prevalence of autoimmune diseases in lymphoma patients varies depending on the specific disease and population, but it is estimated to be around 10-20% 5, 6.
  • Certain autoimmune conditions, such as thyroid disease and RA, are more common in lymphoma patients, particularly those with diffuse large B-cell lymphoma 5.
  • The presence of autoimmune diseases may have implications for lymphoma treatment and management, and further research is needed to understand the relationship between these conditions 2, 6.

Professional Medical Disclaimer

This information is intended for healthcare professionals. Any medical decision-making should rely on clinical judgment and independently verified information. The content provided herein does not replace professional discretion and should be considered supplementary to established clinical guidelines. Healthcare providers should verify all information against primary literature and current practice standards before application in patient care. Dr.Oracle assumes no liability for clinical decisions based on this content.

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