The Rheumatoid Arthritis and Lymphoma Connection

One of the biggest worries for rheumatoid arthritis sufferers, aside from the joint pain and deformity they can experience, is the heightened risk of cancer—specifically lymphoma, a blood cancer that develops in the lymphatic system. What do these two conditions have in common, and what causes the increased risk?

According to experts, what the two diseases have in common is a faulty immune system. In rheumatoid arthritis, the immune system turns against normal cells. In lymphoma, the immune system fails to turn against cancerous cells. Rheumatoid arthritis also involves cellular processes that mimic the growth of cancerous tumors. In someone with rheumatoid arthritis, the fragile lining that protects the joint becomes swollen and painful. In the course of the disease, normal cells in this lining begin to multiply, invading and destroying healthy tissue, much the same way cancer cells multiply.

But is the increased cancer risk due to the disease itself or to the drugs used to treat it? There's no one right answer, say experts. Part of the problem is that many drugs used to treat rheumatoid arthritis suppress the immune system, which could leave the body less able to fight off cancer cells. But certain drugs have shown a clearer connection to cancer than others.

Researchers first looked at the immunosuppressant drug azathioprine (Imuran). The drug had been shown to cause higher rates of lymphoma in transplant patients who took it to prevent organ rejection. When they looked at rheumatoid arthritis patients who had taken it, they found the same higher rates of lymphoma. The longer the patient had taken the drug, the higher the risk.

Next, scientists studied methotrexate, a popular drug used to treat rheumatoid arthritis. There is a very rare phenomenon known as reversible lymphoma which can occur in methotrexate users, in which lymphoma develops while the patient is taking the drug and then disappears when the drug is stopped. However, large-scale studies have not found any link between methotrexate and the rise in the number of rheumatoid arthritis patients being diagnosed with cancer.

The latest drugs to be studied are biologic drugs that inhibit tumor necrosis factor (TNF inhibitors). These newer drugs have not been available long enough for any long-term studies on cancer risk to be conducted. So far, scientists say, evidence is mixed. It might even be the case that in some patients TNF inhibitors promote cancer growth while in other patients they inhibit it.

The risk of lymphoma in rheumatoid arthritis patients is two to four times higher than in the normal population. Still, since lymphoma occurs less frequently than other cancers such as breast and prostate, experts emphasize that the overall risk remains small.



Arthritis Foundation,