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Risk for Lymphoma Increases in Celiac Patients With Persistent Villous Atrophy

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Key Points

  • Patients with celiac disease who have persistent villous atrophy are at a significantly higher risk for all types of lymphoma compared with patients whose intestines have healed.
  • Routine follow-up biopsies to monitor the effects of dietary changes and treatment on mucosal healing may effectively risk-stratify patients with celiac disease for subsequent lymphoma.
  • Dieticians can help patients with celiac disease with persistent villous atrophy determine whether their diet is completely gluten-free.

Although celiac disease is associated with an increased risk of lymphoma, including enteropathy-associated T-cell lymphoma, it was not known whether persistent atrophy of the villi, the fingerlike projections that normally absorb nutrients, contributed to that risk. In a large population-based cohort study of 7,625 Swedish patients with celiac disease who had a follow-up biopsy after initial diagnosis, researchers found that 3,308 (43%) of the patients had persistent villous atrophy and that their overall risk for lymphoproliferative malignancy was higher than in the general population. The study results were published in Annals of Internal Medicine.

In the study, researchers collected data from reports on biopsies of the small intestine of the patients diagnosed with celiac disease. The data included morphologic characteristics and topographic information, but not dietary adherence. The median duration between the celiac disease diagnosis and follow-up biopsy was 1.3 years. The patients were then followed for an average of 8.9 years after their follow-up biopsy.

The researchers found that overall, patients with celiac disease had an annual lymphoma risk of 67.9 per 100,000, a 2.81-fold increase compared with the general population risk of 24.2 per 100,000. The patients with celiac disease with persistent villous atrophy had a greater annual risk of 102.4 per 100,000, compared with patients with healed intestines, whose risk was 31.5 per 100,000.

“The significance of persistent villous atrophy has been largely unknown. And what is really not known is whether the follow-up biopsy result is linked to any important outcomes,” said Benjamin Lebwohl, MD, MS, Assistant Professor of Medicine and Epidemiology at the Mailman School of Public Health at Columbia University Medical Center, and lead author of the study. “What we have found is that the patients who underwent follow-up biopsy and had persistent villous atrophy had a significantly greater risk of a subsequent diagnosis of lymphoma compared to patients with a healed intestine. Among those patients who had healing, the increased risk of lymphoma was actually quite small, it didn’t meet statistical significance.”

Importance of Follow-up Biopsies

Although intestinal healing is more likely to occur among patients with celiac disease who adhere to a strict gluten-free diet as compared to those who do not completely eliminate wheat, barley, and rye from their diet, some diet-adherent patients fail to heal. “There are patients who despite their best efforts have persistent abnormalities even if they feel much better,” said Dr. Lebwohl.

Although currently there are no guidelines for when routine follow-up biopsies should be performed on patients with celiac disease, “this study suggests that the results of the follow-up biopsy are useful in that they serve a risk-stratifying function on lymphoma risk. If a patient undergoes a follow-up biopsy and is found to have persistent abnormalities, it may prompt additional consultation with a dietician to help sort out whether there is ongoing inadvertent gluten exposure,” said Dr. Lebwohl.

According to the National Institutes of Health, celiac disease affects about 1 in 100 people worldwide.

Primary funding sources for this study include the National Institutes of Health, The American-Scandinavian Foundation, Celiac Sprue Association, Örebro University Hospital, Karolinska Institutet, Swedish Society of Medicine, Swedish Research Council, and Swedish Celiac Society.

None of the authors reported any financial or other conflict of interest.

The content in this post has not been reviewed by the American Society of Clinical Oncology, Inc. (ASCO®) and does not necessarily reflect the ideas and opinions of ASCO®.


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