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by Dr. C.H. Weaver M.D. Medical Editor: updated 6/2020

Individuals with autoimmune or celiac disease appear to be at increased risk of lymphoma, particularly if they have a condition known as persistent villous atrophy, according to the results of a large cohort study published in the Annals of Internal Medicine. (1,2)

​​According to a study published in the Journal of the National Cancer Institute, the risk of diffuse large B-cell lymphoma (a subtype of non-Hodgkin’s lymphoma) is elevated among patients with rheumatoid arthritis, Sjögren syndrome, systemic lupus erythematosus, or celiac disease. Some of these conditions were also linked with marginal zone lymphoma, lymphoplasmacytic lymphoma, and T-cell lymphoma.

Non-Hodgkin’s lymphoma (NHL) is a form of cancer that begins in the cells of the lymph system. The lymph system includes the spleen, thymus, tonsils, bone marrow, lymph nodes, and circulating immune cells. The main cells in the lymph system are lymphocytes, which exist in two forms: B-cells and T-cells. Each of these cells has a very specific function in fighting infection.NHL is characterized by the excessive accumulation of atypical (cancerous) lymphocytes. These lymphocytes can crowd the lymph system and suppress the formation and function of other immune and blood cells. NHL is categorized by the type of lymphocyte it involves and by the rate at which the cancer grows-both are determined by the cells’ appearance under a microscope.

Autoimmune disorders are diseases in which the patient’s immune system attacks the body’s own tissues. Previous studies have suggested a link between certain autoimmune diseases and the risk of NHL, but there is less information about how risk varies by subtype of NHL.

To evaluate the relationship between autoimmune conditions and specific subtypes of NHL, researchers in Sweden and Denmark conducted a study among 3055 patients with NHL (cases) and 3187 age- and sex-matched patients without NHL (controls). Four autoimmune diseases were linked with an increased risk of NHL overall, as well as with an increased risk of at least one subtype of NHL:

  • Rheumatoid arthritis was linked with a 50% increase in risk of all NHL, an 80% increased in risk of diffuse large B-cell lymphoma, and a two and a half-fold increase in lymphoplasmacytic lymphoma.
  • Primary Sjögren syndrome was linked with a six-fold increase in all NHL, an 11-fold increase in diffuse large B-cell lymphoma, and a 28-fold increase in marginal zone lymphoma.
  • Systemic lupus erythematosus was linked with a 4.6-fold increase in all NHL, and a 6-fold increase in diffuse large B-cell lymphoma.
  • Celiac disease was linked with a two-fold increase in all NHL, a 2.8-fold increase in diffuse large B-cell lymphoma, and a 17-fold increase in T-cell lymphoma.
  • There was no link between any type of NHL and Crohn’s disease, ulcerative colitis, sarcoidosis, or psoriasis.
  • Type 1 diabetes was linked with a three-fold increase in chronic lymphocytic leukemia/small lymphocytic lymphoma, but was not linked with NHL overall.

Although there is a link between specific autoimmune diseases and NHL, autoimmune diseases appear to explain only a small proportion of all NHL cases. The researchers estimate that rheumatoid arthritis, Sjögren syndrome, systemic lupus erythematosus, and celiac disease account for roughly 2.3% of NHL cases. The researchers conclude that these results confirm that a link exists between certain autoimmune conditions and risk of NHL. The links may apply only to specific subtypes of NHL. Individuals with autoimmune diseases may wish to speak with their physician about their individual risks of developing NHL.

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NHL and Celiac Disease

Celiac disease is considered a disease of the digestive system as well as an autoimmune disease. Celiac disease is characterized by intolerance to gluten, which is a protein found in some grains, such as wheat, rye, barley, and triticale. It causes damage to the small intestine, which interferes with the absorption of nutrients from food and triggers an abnormal immune response to foods containing gluten. Celiac disease affects the villi, which are tiny, fingerlike protrusions that line the small intestine and are supposed to allow nutrients from food to be absorbed into the bloodstream. In celiac disease, the villi are damaged—and ultimately this damage can result in a condition called villous atrophy, which refers to the erosion of the villi.

The disease affects people worldwide, including more than 2 million people in the United States and it's important to know that gluten may also be present in products such as medicines, vitamins, lip balms, and many processed foods. Because people who have celiac disease cannot tolerate gluten, it’s very important that they learn to carefully read labels and identify foods that may contain gluten. Learn all about celiac disease here

Previous research has indicated that celiac disease might be associated with an increased risk of lymphoma, but the reasons for this association are unclear. (2) Some researchers speculate that it could be related to persistent villous atrophy—especially among people with celiac disease who continue to eat gluten.

In one large study of 7,625 patients with biopsy-confirmed celiac disease 43 percent of patients had evidence of persistent villous atrophy on a second biopsy and 53 patients were ultimately diagnosed with a lymphoma. (3)

The incidence rate of lymphoma was higher among patients with persistent villous atrophy—67.9 per 100,000 patient years in the overall group, compared with 102.4 per 100,000 in those with persistent villous atrophy. Even after adjusting for age, sex, education, and duration of disease, the risk of lymphoma was higher among those with ongoing villous atrophy compared with those who had healing of the intestinal mucosa.

Among patients with persistent villous atrophy, the higher risk was most pronounced during the first 12 months after the follow-up biopsy and continued to decline over time. The researchers speculated that these patients may experience a gradual healing process and future biopsies could indicate mucosal healing.


  1. Lebwohl B, Granath F, Ekbom A, et al. Mucosal healing and risk for lymphoproliferative malignancy in celiac disease: A population-based cohort study. Annals of Internal Medicine. 2013;159(3):169-175.
  2. Catassi C, Fabiani E, Corrao G, et al. Risk of non-hodgkin lymphoma in celiac disease. JAMA. 2002; 287(11):1413-9.
  3. Ekström Smedby KE, Hjalgrim H, Askling J et al. Autoimmune and Chronic Inflammatory Disorders and Risk of Non-Hodgkin Lymphoma by Subtype. Journal of the National Cancer Institute. 2006;98:51-60.