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Persistent intestine damage increased lymphoma risk in patients with celiac disease
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Patients with celiac disease were at increased risk for lymphoproliferative malignancy, but this risk was greater among patients with persistent intestine damage, according to results of a multicenter, population-based cohort study.
“We have known for many years that patients with celiac disease have an increased risk of lymphoma, but we did not know whether intestinal healing and its timing affect that risk,” researcher Benjamin Lebwohl, MD, MS, assistant professor of medicine, a member of the Celiac Disease Center and an assistant professor of epidemiology at the Mailman School of Public Health at Columbia University Medical Center, said in a press release. “Our study shows that celiac patients with persistent villous atrophy — as seen on follow-up biopsy — have an increased risk of lymphoma, while those with healed intestines have a risk … approaching that of the general population.”
Lebwohl and colleagues evaluated data from 7,625 patients with celiac disease who underwent follow-up biopsy between 6 months and 5 years after initial diagnosis. Median follow-up was 10.6 years from diagnosis and 8.9 years after biopsy. The cohort included 3,308 patients with persistent villous atrophy, or mucosal healing.
Lymphoproliferative malignancy occurred in 0.7% of the cohort (median onset, 4.9 years from follow-up biopsy). Investigators calculated an incidence of 67.9 cases per 100,000 person-years, which was significantly greater in the cohort compared with the general population (standardized incidence ratio=2.81; 95% CI, 2.1-3.67), particularly among those with persistent villous atrophy (SIR=3.78; 95% CI, 2.71-5.12). Patients with resolved villous atrophy remained at elevated risk compared with the general population, but less so than cohort patients without resolution (SIR=1.5; 95% CI, 0.77-2.62).
Multivariate analysis indicated a significantly increased risk for lymphoproliferative malignancy among those with persistent villous atrophy compared with mucosal healing patients (HR=2.26; 95% CI, 1.18-4.34), particularly within 1 year after biopsy (HR=3.67; 95% CI, 0.8-16.86).
This risk was significantly elevated for non-Hodgkin’s lymphoma (HR=2.82; 95% CI, 1.29-6.17) and unspecified NHL (HR=4.31; 95% CI, 1.27-14.61), and it trended toward significance for T-cell (HR=3.51; 95% CI, 0.75-16.34) lymphoma.
Associations between lymphoproliferative malignancy and villous atrophy, along with T-cell lymphoma and villous atrophy, were more pronounced with subtotal atrophy (HR=3.96; 95% CI, 1.65-9.5) or total atrophy (HR=9.23; 95% CI, 1.66-51.34) than partial atrophy.
“These findings should prompt further evaluation of mucosal healing as a goal for patients with celiac disease to reduce their risk for lymphoproliferative malignancy,” Lebwohl and colleagues wrote.
Reference:
Lebwohl B. Ann Intern Med. 2013;159:169-175.
Perspective
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Harry S. Jacob, MD, FRCPath(Hon)
It will be interesting if the recent food fad of gluten-free diets — without rigorous proof of celiac disease — might decrease incidence of intestinal lymphoma in faddists. Of course, it will be years before such an association could be demonstrated. However, if so, it might suggest that gluten proteins can cause intestinal mucosal inflammation in many patients without overt celiac symptoms or detectable antibody production.
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