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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.

Personal Risk of Lymphoma Still Quite Small

Lymphoma is rare. It's estimated that fewer than 75,000 Americans were diagnosed with the disease last year. And the rarer a disease is, the lower the personal risk. 

Rheumatologist Chaim Putterman, MD, explains it this way: "Say the risk for developing a disease is 1 in 10 million. If you have a twofold increased risk, your risk is now 1 in 5 million. That would be a very small increase in your own personal risk." Putterman is chief of the division of rheumatology and professor of medicine, microbiology, and immunology at the Montefiore Medical Center and Albert Einstein College of Medicine in New York.

There are two general types of lymphoma: Hodgkin's and non-Hodgkin's lymphoma (NHL). NHL is more common. One study published in January 2009 showed that RA is associated with increased risk for a subtype of NHL called diffuse large B-cell lymphoma. That's a fast-growing form of the disease. It also found an increased risk for a rarer subtype called T-cell lymphoma.

The actual risk may be related to how long a patient is treated for RA. In other words, the longer a person's immune system is suppressed, the greater the risk of lymphoma seems to be.

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.

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