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The Link Between Rheumatoid Arthritis and Lymphoma

Having RA increases the risk of lymphoma. But for most, that risk appears quite small.

RA and Risk of Lymphoma: Is the Disease to Blame?

What is it exactly that increases the risk of lymphoma? Is it the RA disease process or the medications? "That's the $64,000 question," says Putterman.

Mounting evidence suggests that chronic activation of the immune system from the disease process is to blame for the increased lymphoma risk. But doctors are still uncertain.

"It's very hard to disentangle the disease process from the medications," says Eric Engels, MD, MPH, senior investigator at the National Cancer Institute. "That's because the people who have the most active disease are getting the strongest medications."

"In a few people," Sweetenham explains, "the immune system appears to get revved up to the point where it can no longer switch off. That eventually develops into a cancer."

"It's not a hard concept to say there are dysregulated immune system cells,” Kamen says. “If these immune system cells start growing out of control, I am going to call that a lymphoma."

RA and the Risk of Lymphoma: Could It Be the Medications?

The medicines used to treat RA suppress the immune system. They fight the inflammation and pain related to RA. But they also make your body less able to fight infections and disease.

The medication that has most often been linked to lymphoma in RA patients is methotrexate. This was one of the first drugs prescribed to Burke. It's in a class of medications known as disease modifying antirheumatic drugs or DMARDs. There have been some reports of people who developed lymphomas while taking methotrexate and whose cancer regressed once they quit taking the drug. This might indicate the drug contributes directly to the cancer's development.

However, many studies, including the Swedish study published in 2006, have shown no association between lymphoma risk and RA treatment, including treatment with methotrexate.

A newer class of medications raising concern is tumor necrosis factor (TNF) antagonists. These are also called anti-TNF drugs. This class of drugs includes Humira, Enbrel, and Remicade. They have been a lifesaver for patients with severe RA, like Burke. The Arthritis Foundation calls the medications an important addition to the disease's treatment arsenal.

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