Poor Celiac Disease Control May Up Lymphoma Risk

Joe Barber Jr, PhD

August 05, 2013

In patients with celiac disease (CD), persistent villous atrophy may be associated with certain types of lymphoma, according to the findings of a population-based cohort study. One expert says the new results will change how he manages patients with CD.

Benjamin Lebwohl, MD, from Columbia University in New York City, and colleagues report their findings in an article published in the August 6 issue of the Annals of Internal Medicine.

In the study, the researchers collected data from 28 pathology departments in Sweden, analyzing biopsy reports for 7625 patients with CD who underwent a follow-up biopsy after the initial diagnosis. The researchers excluded patients who underwent biopsies originating from the ileum, those with other irregularities, those who underwent follow-up biopsy less than 6 months or more than 5 years after the initial diagnosis of CD, and those who developed lymphoproliferative malignancy (LPM) before the follow-up biopsy.

They identified 3308 patients with persistent intestinal damage.

Overall, patients with CD had a higher risk for LPM than the general population (standardized incidence ratio [SIR], 2.81; 95% confidence interval [CI], 2.10 - 3.67). Among patients with CD, those with persistent villous atrophy had a higher risk for LPM (SIR, 3.78; 95% CI, 2.71 - 5.12) compared with those with mucosal healing (SIR, 1.50; 95% CI, 0.77 - 2.62).

In multivariate analysis adjusted for age at follow-up biopsy, sex, duration of CD at the time of follow-up biopsy, year of follow-up biopsy, and education, patients with persistent villous atrophy continued to have a greater risk for LPM than those with mucosal healing (hazard ratio [HR], 2.26; 95% CI, 1.18 - 4.34). The risk was highest in the first year after follow-up biopsy (HR, 3.67; 95% CI, 0.80 - 16.86), and the association persisted after stratification by pathology department (HR, 2.10; 95% CI, 1.08 - 4.12). Conversely, the researchers found no association between LPM risk and sex, age, and year of follow-up biopsy.

In addition, persistent villous atrophy was linked to a higher risk for non-Hodgkin lymphoma (HR, 2.82; 95% CI, 1.29 - 6.17). Moreover, subtotal or total villous atrophy, but not partial villous atrophy, was associated with an elevated risk for LPM (HR, 3.96; 95% CI, 1.65 - 9.50), particularly for T-cell lymphoma (HR, 9.23; 95% CI, 1.66 - 51.34).

The limitations of the study included a lack of information on dietary adherence, missing data for lymphoma subtype for some biopsies, and the possibility that some follow-up biopsies were not true follow-up biopsies.

"We conclude that the increased risk for LPM in CD may be affected by mucosal healing," the authors write. "These findings should prompt further evaluation of mucosal healing as a goal for patients with CD to reduce their risk for LPM."

"As a clinician and practising gastroenterologist, this study will alter my practice," David S Sanders, MD, MBChB, FRCP, from the Royal Hallamshire Hospital and the University of Sheffield in the United Kingdom, told Medscape Medical News by email. "For some time, a second or follow-up duodenal biopsy has not been undertaken by many clinicians internationally. This study reasserts the importance of a second-look biopsy to ensure histological remission."

The study was supported by the National Center for Advancing Translational Sciences of the National Institutes of Health, the American-Scandinavian Foundation, the Celiac Sprue Association, Orebro University Hospital, Karolinska Institutet, the Swedish Society of Medicine, the Swedish Research Council, and the Swedish Celiac Society. Dr. Lebwohl received funding from the National Institutes of Health, The American Scandinavian Foundation, and the Celiac Sprue Association. One coauthor served as a paid advisor for ImmusanT and Alvine Pharmaceuticals, one coauthor received speaking fees from Merck & Co, one coauthor received advisory fees from Amgen, one coauthor received funding and/or personal fees from the National Institutes of Health, Alba Therapeutics, Alvine Pharmaceuticals, and 2GPharma. The remaining authors and the commentator have disclosed no relevant financial relationships.

Ann Intern Med. 2013;159:169-175. Abstract

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