Mucosal Healing and Risk for Lymphoproliferative Malignancy in Celiac Disease

Background: Celiac disease (CD) is associated with an increased risk for lymphoproliferative malignancy (LPM). Whether this risk is affected by the results of follow-up intestinal biopsy, performed to document mucosal healing, is unknown.

Objective: To examine the association between mucosal healing in CD and subsequent LPM.

Design: Population-based cohort study.

Setting: 28 pathology departments in Sweden.

Patients: 7625 patients with CD who had follow-up biopsy after initial diagnosis.

Measurements: The risk for LPM was compared with that of the general population by using expected rates. The rate of LPM in patients with persistent villous atrophy was compared with that of those with mucosal healing by using Cox regression.

Results: Among 7625 patients with CD and follow-up biopsy, 3308 (43%) had persistent villous atrophy. The overall risk for LPM was higher than that in the general population (standardized incidence ratio [SIR], 2.81 [95% CI, 2.10 to 3.67]) and was greater among patients with persistent villous atrophy (SIR, 3.78 [CI, 2.71 to 5.12]) than among those with mucosal healing (SIR, 1.50 [CI, 0.77 to 2.62]). Persistent villous atrophy compared with mucosal healing was associated with an increased risk for LPM (hazard ratio [HR], 2.26 [CI, 1.18 to 4.34]). The risk for T-cell lymphoma was increased (HR, 3.51 [CI, 0.75 to 16.34]) but not for B-cell lymphoma (HR, 0.97 [CI, 0.21 to 4.49]).

Limitation: No data on dietary adherence.

Conclusion: Increased risk for LPM in CD is associated with the follow-up biopsy results, with a higher risk among patients with persistent villous atrophy. Follow-up biopsy may effectively stratify patients with CD by risk for subsequent LPM.

Primary Funding Source: 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.

Authors: Benjamin Lebwohl, MD, MS; Fredrik Granath, PhD; Anders Ekbom, MD, PhD; Karin E. Smedby, MD, PhD; Joseph A. Murray, MD; Alfred I. Neugut, MD, PhD; Peter H.R. Green, MD; and Jonas F. Ludvigsson, MD, PhD