Individuals with celiac disease have an 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.
Celiac disease is an autoimmune disorder of the small intestine characterized by intolerance to gluten, which is a protein found in some grains, such as wheat, rye, barley, and triticale. In individuals with celiac disease, gluten creates an immune-mediated toxic reaction that causes damage to the small intestine and interferes with the absorption of nutrients from food. 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.
Previous research has indicated that celiac disease might be associated with an increased risk of lymphoma, but the reasons for this are unclear. Some researchers speculate that it could be related to persistent villous atrophy—especially among people with celiac disease who continue to eat gluten.
This large, cohort study included 7,625 patients with biopsy-confirmed celiac disease. All of the patients in the study had a follow-up biopsy within 6 months to 5 years after their initial diagnostic biopsy. Overall, 43 percent of patients had evidence of persistent villous atrophy on the second biopsy. During a median follow-up of 9 years after the second biopsy, 53 patients were diagnosed with lymphoma.
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.
Persistent villous atrophy was associated with a higher risk of non-Hodgkin’s lymphoma (NHL), unspecified NHL, and T-cell lymphoma.
The researchers concluded that in patients with celiac disease, follow-up biopsy that indicates persistent villous atrophy may be associated with an increased risk for lymphoma. As such, follow-up biopsy could be a useful tool in identifying patients at risk for subsequent lymphoma. One limitation of the study is that there was no data regarding adherence to a gluten-free diet.
 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.
 Catassi C, Fabiani E, Corrao G, et al. Risk of non-hodgkin lymphoma in celiac disease. JAMA. 2002; 287(11):1413-9.
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