What Is the Connection between Methotrexate and Lymphoma?

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  • Written By: C. K. Lanz
  • Edited By: Melissa Wiley
  • Last Modified Date: 25 October 2019
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A number of studies have linked the drug methotrexate and lymphoma by establishing that the arthritis treatment can activate the Epstein-Barr virus (EBV), which is believed to increase the likelihood of contracting the cancer. Methotrexate may also increase the risk of developing other cancers affecting the lymph glands. When those patients with lymphoma stop taking this drug, their cancer typically goes into regression, further establishing a link between methotrexate and lymphoma. Other medications used to treat rheumatoid arthritis such as cyclosporine have not been found to have any impact on EBV activity in the body.

Methotrexate is a medication used to treat rheumatoid arthritis and other illnesses caused by an aggressive immune system. It works by calming the immune system so that the damage to joints and other tissues are minimized. This reduces the pain and swelling experienced by rheumatoid arthritis patients.


A series of studies have found that exposing cells containing EBV to methotrexate causes these cells to release an infectious form of the virus. EBV is a common type of herpes virus believed to be present in more than 95 percent of young adults in the United States. It is associated with mononucleosis and chronic fatigue syndrome but is dormant for life in most people who as a result do not know they carry it. EBV is transmitted through the saliva of an infected person. Laboratory tests that can detect whether a person carries EBV exist but are not always accurate.

EBV can also increase the risk of developing Burkitt’s lymphoma, a rare form of this type of cancer. The connection between methotrexate and lymphoma is not completely understood, but it is thought that the drug’s effect on the immune system plays a role. A weakened immune system is less able to keep a latent form of EBV in check, so the virus can activate, causing infection and in rare cases contributing to the development of lymphoma. It is also possible that the drug itself actives EBV without inhibiting its replication. In other words, the drug may trigger an infectious form of the virus while weakening the immune system response.

Patients with lymphoma who participated in research studies concerning methotrexate found that their cancer often went into regression once they stopped taking the drug. The connection between methotrexate and lymphoma has not been established with other drugs that inhibit the immune system in similar ways. As a result, researchers believe that methotrexate’s effect on EBV while simultaneously inhibiting the immune system from containing the virus is unique among this type of medication.

In addition to the link between methotrexate and lymphoma, this medication is also associated with other severe side effects. Liver damage, lung damage, and gastrointestinal damage have all been reported. As the drug decreases immune system activity, the risk of contracting any number of dangerous infections increases. More common side effects include hair loss, tender gums, and drowsiness.

Only in rare instances does a patient taking this drug actually develop lymphoma. These cases usually appear in those who have taken the drug over a long period of time. As with any medication treatment, patients should weigh the potential benefits against the potential risks with their health care providers.


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