Persistent duodenal intraepithelial lymphocytosis despite a long-term strict gluten-free diet in celiac disease

Am J Gastroenterol. 2012 Oct;107(10):1563-9. doi: 10.1038/ajg.2012.220. Epub 2012 Jul 24.


Objectives: In celiac disease, complete histological normalization of the small-intestinal mucosa occurs in only 8-20% of adult patients after commencing a gluten-free diet. Intraepithelial lymphocytosis may persist for years while villous morphology normalizes. Factors contributing to this and the clinical relevance of persistent intraepithelial lymphocytosis were here investigated.

Methods: Altogether 177 adult celiac disease patients adhering to a long-term strict gluten-free diet were enrolled. Co-morbidities, ongoing medications, and consumption of oats and wheat-starch were recorded. Small-bowel morphology and intraepithelial lymphocyte count as well as laboratory parameters of malabsorption were evaluated. Gastrointestinal symptoms and psychological well-being were measured by structured questionnaires.

Results: In all, 170 (96%) out of the 177 patients evinced normal villous architecture and 7 (4%) villous atrophy. Among patients with normal villous structure, 96 (56%) had persistent intraepithelial lymphocytosis and 74 (44%) completely normal small-intestinal mucosa. Consumption of oats was the only factor contributing to the persistent intraepithelial lymphocytosis. Co-morbidities, Helicobacter pylori gastritis, drugs, or wheat-starch in the diet had no effect. The clinical outcome of the patients with persistent intraepithelial lymphocytosis was good, since no signs of malabsorption, excess malignancies, increase in gastrointestinal symptoms, or impaired quality of life were associated with it when compared to subjects with completely normal mucosa. The only outcome found in this study was a significantly lower, although normal villous height-crypt depth ratio among the patients with persistent intraepithelial lymphocytosis as compared to those with completely normal mucosa.

Conclusions: Despite excellent villous recovery in this study, persistent intraepithelial lymphocytosis was still common among celiac disease patients on a long-term strict gluten-free diet. Consumption of oats was associated with persistent duodenal lymphocytosis and this calls for further investigations. The prognosis of patients with persistent intraepithelial lymphocytosis seems to be good while adhering to a gluten-free diet for a mean of 11 years.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Autoantibodies / blood
  • Avena / adverse effects*
  • Biopsy
  • Celiac Disease / diet therapy
  • Celiac Disease / pathology*
  • Cross-Sectional Studies
  • Diet, Gluten-Free*
  • Duodenum / pathology*
  • Endoscopy, Gastrointestinal
  • Female
  • Genotype
  • HLA-DQ Antigens / genetics
  • Humans
  • Intestinal Mucosa / pathology
  • Lymphocyte Count
  • Lymphocytosis* / pathology
  • Male
  • Middle Aged
  • Prognosis
  • Risk Factors
  • Time Factors
  • Transglutaminases / immunology


  • Autoantibodies
  • HLA-DQ Antigens
  • Transglutaminases