Sjögren’s Syndrome and Lymphoma Risk

Sjögren’s moderately increases risk for non-Hodgkin’s lymphoma.


People with Sjögren’s syndrome, an autoimmune disease that affects the moisture-producing glands in the body, have five to nine times the risk of developing non-Hodgkin’s lymphoma (NHL) than people in the general population. NHL is a cancer that develops in the lymphatic system (part of the immune system), which includes the lymph nodes and spleen. It can also strike salivary glands and other tissues often affected by Sjögren’s.

Research done in the mid-2000s and earlier suggested the risk was higher, but most of those studies were small and not statistically well-powered, says Mahdi Fallah, MD, head of the Epidemiology Research Group at the German Cancer Research Center in Heidleberg.

A number of autoimmune diseases raise the risk of NHL. Dr. Fallah’s group published a large study in 2014 in Annals of Oncology that followed 878,161 people with autoimmune diseases for an average of 9.4 years, including 14,570 people with primary Sjögren’s. (Primary Sjögren’s occurs by itself, whereas secondary Sjögren’s occurs in people with another autoimmune disease like rheumatoid arthritis [RA] or systemic lupus erythematosus.)

They found that, while people with Sjögren’s syndrome have a higher risk compared with people with most autoimmune diseases – about 5 percent for Sjögren’s versus 2 percent and 4.4 percent for RA and lupus, respectively – their lifetime risk is still relatively modest.

“The lifetime risk in the general population by age 80 years is about 1.1 percent in women and 1.6 percent in men. The lifetime risk in men with Sjögren syndrome is about 8 percent, and in women, 5.4 percent,” Dr. Fallah explains.

Other recent research has found similar rates of increased risk. A Norwegian study published in 2012 in Arthritis Care & Research found people with Sjögren’s had a nine-fold risk of NHL compared with the general population.

Like Dr. Fallah’s group, the Norwegian researchers say they found the risk of lymphoma for Sjögren’s patients lower than expected. “Study results show that the actual risk is lower than previously described, but our findings are supported by other recent studies,” says study co-author Svein Joar A. Johnsen, MD, who specializes in internal medicine at Stavanger University Hospital in Norway.

Dr. Johnsen and his colleagues looked at nearly 897,000 inhabitants living in two counties on the west coast of Norway and identified 443 patients with a diagnosis of primary Sjögren’s syndrome.

Of these patients – who were followed for an average of almost nine years – seven lymphoma cases developed. When they compared it to the risk of NHL in a person from the general population, they found the risk to be nine times greater.

“People shouldn’t panic over this. The probability is still really low,” says Eric L. Matteson, MD, chair of rheumatology at the Mayo Clinic in Rochester, Minn.

But he does caution that, because people with Sjögren’s are at increased risk, they should pay attention to any symptoms relating to NHL, including weight loss, swollen lymph nodes and fevers.

What Raises Risk?

Exactly how Sjögren’s syndrome increases risk for NHL is something scientists are still working to understand. The reason why the diseases are connected may have something to do with inflammatory cells affecting the immune system. “There may be genetic information in these cells that causes them to become cancerous,” Dr. Matteson says.

A 2015 British Journal of Haematology (BJH) review suggests that ongoing stimulation of immune complexes (clusters of antibodies and antigens that are overproduced in Sjögren’s and other autoimmune diseases) kicks off the process, most often in places where Sjögren’s is active, such as the salivary glands.

There are many types of NHL, but in people with Sjögren’s syndrome, the most commonly diagnosed type is a low-grade B-cell NHL called MALT (mucosa associated lymphoid tissue) lymphoma. In Sjögren’s, MALT lymphomas most often occur in the salivary glands, but can affect other moisture-producing tissue, including those in the eyes, lungs, stomach and lungs, according to the BJH review.

The good news is that MALT and other low-grade B-cell lymphomas are usually slow growing and respond well to treatment, which can range from watchful waiting to chemotherapy and the use of other potent drugs. For example, a 2012 study published in the journal Medicine of 53 people with NHL and Sjögren’s found that, three years after diagnosis, 78 percent hadn’t had a recurrence of the cancer (overall survival at three years was 97 percent).

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