Increased Risk of Lymphoma in Rheumatoid Arthritis Patients

What Causes the Increased Risk?

An increased risk of lymphoma has been associated with rheumatoid arthritis (RA). Various studies have linked the two conditions but it has never been completely clear whether disease activity or the treatments used to battle rheumatoid arthritis cause the increased risk of lymphoma. Research is ongoing but some studies have shed light on the problem.

mature doctor examining a rheumatoid arthritis patient
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Lymphoma Risk In RA Patients

Lymphoma is cancer of the lymphatic system (lymph nodes, spleen, and other organs of the immune system) that starts in white blood cells (leukocytes). The connection between an increased risk of lymphoma in rheumatoid arthritis patients concerns researchers, healthcare providers, and patients.

Here's what current research tells us:

RA patients have twice the lymphoma risk as the general population. Still, the percentage of RA patients who develop lymphoma is low. In one study of nearly 125,000 Europeans with RA, only 533 lymphoma cases were reported.

An older Swedish study had similar results, looking at 75,000 RA patients and finding 378 lymphoma cases.

Of the two main types of lymphoma, Hodgkin's and non-Hodgkin's, the latter appears to be far more common in RA patients. In the European study, 9 out of 10 lymphoma cases were non-Hodgkin's.

While the risk for developing lymphoma is higher with RA, once diagnosed, the prognosis for the cancer is no different than the general population.

Lymphoma Causes in RA Patients

Three main theories behind the lymphoma-RA connection have been studied over the years: Genetic predisposition, RA medications, and the disease itself.

For now, there appears to be no genetic cause of lymphoma in patients with RA.

There has been some connection made between certain RA medications and increased lymphoma risk, but the increase is low. One study of 12,656 RA patients found no increase in lymphoma risk from two common RA medications, methotrexate and the "biologic" tumor necrosis factor inhibitors.

The main cause of lymphoma in RA patients appears to be the RA itself.

Research has shown that the more severe the case of RA with high levels of prolonged inflammation, what healthcare providers call the "highest activity," the greater the lymphoma risk. Chronic high levels of inflammation are to blame, with two types of leukocyte (the lymphocytes B- and T-cells) causing inflammation and eventually becoming malignant in lymphoma.

Or, to quote one study, "The impact of continuing disease activity and immune stimulation appears to be the most significant in lymphomagenesis."

Early, aggressive treatment of RA is important, as lower inflammation levels mean lower lymphoma risk over time.

Lymphoma Symptoms in RA Patients

People with RA should be vigilant. Lymophoma has specific signs, though it's impossible to know at what stage the cancer may be until it is diagnosed and staged. The following lymphoma symptoms are common:

  • Swollen lymph nodes in the neck, armpits, or groin, usually not painful
  • Unexplained weight loss (10% or more of body weight over six months)
  • Swollen abdomen (with or without pain, which could be from enlarged spleen or liver, or fluid buildup)
  • Fatigue
  • Chills, fever, or night sweats
  • Early satiety (feeling full after a small amount of food)
  • Shortness of breath and/or cough (possibly from swollen lymph nodes in the chest compressing the trachea)
  • Chest pain
  • Easy bruising

Your healthcare provider will be able to advise you of your lymphoma risk based on how severe your RA is and has been over time, and what steps you can take to mitigate that risk.

6 Sources
Verywell Health uses only high-quality sources, including peer-reviewed studies, to support the facts within our articles. Read our editorial process to learn more about how we fact-check and keep our content accurate, reliable, and trustworthy.
  1. Mercer LK, Regierer AC, Mariette X, et al. Spectrum of lymphomas across different drug treatment groups in rheumatoid arthritis: a European registries collaborative project. Annals of the Rheumatic Diseases 2017;76:2025-2030. doi:10.1136/annrheumdis-2017-211623

  2. Baecklund E, Iliadou A, Askling J, et al. Association of chronic inflammation, not its treatment, with increased lymphoma risk in rheumatoid arthritisArthritis Rheum. 2006;54(3):692–701. doi:10.1002/art.21675

  3. Klein A, Polliack A, Gafter-Gvili A. Rheumatoid arthritis and lymphoma: Incidence, pathogenesis, biology, and outcomeHematol Oncol. 2018;36(5):733–739. doi:10.1002/hon.2525

  4. Hellgren K, Baecklund E, Backlin C, Sundstrom C, Smedby KE, Askling J. Rheumatoid Arthritis and Risk of Malignant Lymphoma: Is the Risk Still Increased?Arthritis Rheumatol. 2017;69(4):700–708. doi:10.1002/art.40017

  5. Arthritis Foundation. Arthritis and cancer risk.

  6. American Cancer Society. Signs and symptoms of non-hodgkins lymphoma.

Additional Reading

By Carol Eustice
Carol Eustice is a writer covering arthritis and chronic illness, who herself has been diagnosed with both rheumatoid arthritis and osteoarthritis.