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; Jonas F. Ludvigsson, MD, PhD
Grant Support: By The American-Scandinavian Foundation, Celiac Sprue Association, and grant KL2 TR000081 from the National Center for Advancing Translational Sciences of the National Institutes of Health (Dr. Lebwohl); Stockholm County Council (Dr. Ekbom); Strategic Research Program in Epidemiology's Young Scholar Award (Dr. Smedby); grants DK071003 and DK057892 from the National Institutes of Health (Dr. Murray); Örebro University Hospital, Karolinska Institutet, Swedish Society of Medicine, and grant 522-2A09-195 from the Swedish Research Council and the Swedish Celiac Society (Dr. Ludvigsson).
Potential Conflicts of Interest: Disclosures can be viewed at www.acponline.org/authors/icmje/ConflictOfInterestForms.do?msNum=M12-3067.
Reproducible Research Statement: Study protocol and statistical code: Available from Dr. Ludvigsson (e-mail, email@example.com). Data set: Not available.
Corresponding Author: Jonas F. Ludvigsson, MD, PhD, Department of Pediatrics, Örebro University Hospital, SE-70185 Örebro, Sweden; e-mail, firstname.lastname@example.org.
Current Author Addresses: Drs. Lebwohl and Green: The Celiac Disease Center at Columbia University, 180 Fort Washington Avenue, Suite 936, New York, NY 10032.
Drs. Granath, Ekbom, and Smedby: Clinical Epidemiology Unit, Karolinska Institutet, Eugeniahemmet T2, SE-171 76, Stockholm, Sweden.
Dr. Murray: 200 First Street SW Mayo East 9, Rochester, MN 55905.
Dr. Neugut: Mailman School of Public Health, Columbia University, 722 West 168th Street, Room 725, New York, NY 10032.
Dr. Ludvigsson: Department of Pediatrics, Örebro University Hospital, SE-70185 Örebro, Sweden.
Author Contributions: Conception and design: B. Lebwohl, F. Granath, A. Ekbom, P.H.R. Green, J.F. Ludvigsson.
Analysis and interpretation of the data: B. Lebwohl, F. Granath, A. Ekbom, K.E. Smedby, J.A. Murray, A.I. Neugut, J.F. Ludvigsson.
Drafting of the article: B. Lebwohl, J.F. Ludvigsson.
Critical revision of the article for important intellectual content: B. Lebwohl, F. Granath, A. Ekbom, K.E. Smedby, J.A. Murray, A.I. Neugut, P.H.R. Green, J.F. Ludvigsson.
Final approval of the article: B. Lebwohl, F. Granath, A. Ekbom, K.E. Smedby, J.A. Murray, A.I. Neugut, P.H.R. Green, J.F. Ludvigsson.
Provision of study materials or patients: J.F. Ludvigsson.
Statistical expertise: B. Lebwohl, F. Granath, J.F. Ludvigsson.
Obtaining of funding: B. Lebwohl, A. Ekbom, J.F. Ludvigsson.
Administrative, technical, or logistic support: J.F. Ludvigsson.
Collection and assembly of data: J.F. Ludvigsson.
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.
To examine the association between mucosal healing in CD and subsequent LPM.
Population-based cohort study.
28 pathology departments in Sweden.
7625 patients with CD who had follow-up biopsy after initial diagnosis.
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.
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]).
No data on dietary adherence.
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.
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.
Lebwohl B, Granath F, Ekbom A, Smedby KE, Murray JA, Neugut AI, et al. Mucosal Healing and Risk for Lymphoproliferative Malignancy in Celiac Disease: A Population-Based Cohort Study. Ann Intern Med. ;159:169–175. doi: 10.7326/0003-4819-159-3-201308060-00006
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Published: Ann Intern Med. 2013;159(3):169-175.
Celiac Disease and Malabsorption, Gastroenterology/Hepatology, Hematology/Oncology, Leukemia/Lymphoma.
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