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Duodenal Intraepithelial Lymphocytosis With Normal Villous Architecture in Pediatric Patients: Mayo Clinic Experience, 2000–2009

Shmidt, Eugenia*; Smyrk, Thomas C.; Faubion, William A.; Oxentenko, Amy S.

Journal of Pediatric Gastroenterology & Nutrition: January 2013 - Volume 56 - Issue 1 - p 51–55
doi: 10.1097/MPG.0b013e318267c353
Original Articles: Gastroenterology

Objectives: Small bowel intraepithelial lymphocytosis (IELs) with normal villous architecture is a relatively common finding, often of uncertain significance. The aims of our study were to determine the prevalence of this finding, its clinical associations, its specificity for celiac disease (CD), and whether histologic clues exist that increase the specificity for CD in this setting, all in the pediatric population.

Methods: The Mayo Clinic electronic pathology database was searched between January 1, 2000 and December 31, 2009 for patients younger than 18 years who had the terms “normal villi” and “increased intraepithelial lymphocytes” in their small bowel biopsy reports. All of the slides were reviewed to confirm the histologic findings. Demographic, serologic, pathologic, and clinical informations were obtained.

Results: Among 1290 duodenal biopsies obtained from children during the years 2000 and 2009, 56 (4.3%) were noted to have “normal villous architecture with increased intraepithelial lymphocytes.” In the 54 patients not known to have CD before biopsy, 48 (89%) had serologic testing for CD. Of these 48 patients, 9 were labeled with CD, although only 5 of 9 met the definite criteria for the diagnosis, based on a combination of serologic markers, human leukocyte antigen haplotyping, and response to gluten-free diet. No clinical features pointed to a diagnosis of CD. There was no correlation between CD and number of IELs, but patients with newly diagnosed CD were more likely to have a tip-heavy lymphocyte distribution. Other diagnoses made during the study period and in follow-up were inflammatory bowel disease (5), Helicobacter pylori infection (3), medication-related injury (10), and systemic autoimmune disorders (2).

Conclusions: Increased IELs with normal villous architecture in small bowel biopsies are clinically important in children, and are associated with a new definite diagnosis of CD in 9% of pediatric patients. Even at this low sensitivity, clinical work-up for CD is mandated in all of the patients with this finding.

*Department of Internal Medicine

Department of Anatomic Pathology

Department of Internal Medicine, Division of Gastroenterology and Hepatology, Mayo Clinic, Rochester, MN.

Address correspondence and reprint requests to Amy S. Oxentenko, MD, Mayo Clinic, 200 First St SW, Rochester, MN 55905 (e-mail:

Received 5 January, 2012

Accepted 21 June, 2012

The authors report no conflicts of interest.

Copyright 2013 by ESPGHAN and NASPGHAN