The Link between Rheumatoid Arthritis and Lymphoma

For patients with rheumatoid arthritis (RA), lowering pain and preventing the disease from worsening is top priority. However, for several years, researchers have noted a strong link between RA and lymphoma, a connection that should not go unnoticed by patients with this inflammatory joint disease. Some experts had even hypothesized that some standard treatments for rheumatoid arthritis were behind this link.

Now, a new study sheds more light on the connection between RA and lymphoma, and it highlights those patients who are at greatest risk.

"Chronic inflammatory conditions such as rheumatoid arthritis have been associated with malignant lymphomas," explained Dr. Eva Baecklund and colleagues in the study published in Arthritis and Rheumatism.

RA is a disease that occurs when a person's own immune system begins to attack cells around the joints. This causes a gradual deterioration of the tissues surrounding the joints, leading to pain and difficulty moving the affected fingers, elbows and knees.

Lymphoma, on the other hand, is a type of cancer that affects the lymph nodes. The American Cancer Society estimates that over 65,000 people will be diagnosed this year with one type of lymphoma, but those with RA seem to be about twice as likely as the general population to develop this disease, said Dr. John Patrick Whelan, pediatric rheumatologist at Massachusetts General Hospital for Children.

While RA tends to affect women more often than men, it leads to lymphoma more often in men. As a result, most people with RA will never develop lymphoma.

With the goal of determining which patients with RA are at greatest risk for developing lymphoma, Baecklund looked at a registry of almost 75,000 patients with RA. Within this population, 52 percent were classified as having a moderate level of RA, meaning that between six and 20 joints were affected by their disease, and 23 percent were classified as having severe RA, affecting more than 20 joints and seriously limiting their physical abilities. Additionally, 378 had been diagnosed with a malignant form of lymphoma between 1964 and 1995.

Comparing those RA patients who were diagnosed with malignant lymphoma to those that did not, Baecklund noted that those with a low degree RA had the lowest risk of developing lymphoma, while those with a moderate level of RA had seven times the risk. Those patients with the highest level of RA had 71 times the risk of developing this cancer.

"The risk of lymphoma is substantially increased in a subset of patients with RA: those with very severe disease," wrote Baecklund.

More importantly, the team found no connection between many standard RA treatments and the development of lymphoma. The study included such RA treatment as methotrexate, anti-malarial agents, oral steroids, non-steroidal anti-inflammatory drugs (NSAIDs) and aspirin.

Whelan, however, notes that newer treatments, such as anti-TNF alpha drugs, may still have some connection to the development of lymphoma.

"I think the evidence at this time suggests that methotrexate is very safe," Whelan said, "TNF inhibitors may marginally increase risk."

Additionally, no studies have yet been completed to determine if RA treatment can reduce the risk of developing lymphoma. "My sense is that this is a likely outcome," said Whelan.

No matter what causes the connection between RA and lymphoma, it is important for patients with moderate or severe RA to understand the link between RA and lymphoma and to speak with their doctor about options to help them lower this risk.

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