title: Persistent duodenal intraepithelial lymphocytosis despite a long-term strict gluten-free diet in celiac disease.
abstract: OBJECTIVE
  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.
authors: Department of Gastroenterology and Alimentary Tract Surgery, Tampere University Hospital, School of Medicine, University of Tampere, Tampere, Finland.
authors: Ilus
authors: I
authors: Tuire
authors: Lähdeaho
authors: L
authors: Marja-Leena
authors: Salmi
authors: S
authors: Teea
authors: Haimila
authors: H
authors: Katri
authors: Partanen
authors: P
authors: Jukka
authors: Saavalainen
authors: S
authors: Päivi
authors: Huhtala
authors: H
authors: Heini
authors: Mäki
authors: M
authors: Markku
authors: Collin
authors: C
authors: Pekka
authors: Kaukinen
authors: K
authors: Katri
mesh_terms: D000328:Adult; D000368:Aged; D001323:Autoantibodies / Q000097:blood; D018554:Avena / Q000009:adverse effects*; D001706:Biopsy; D002446:Celiac Disease / Q000178:diet therapy / Q000473:pathology*; D003430:Cross-Sectional Studies; D055050:Diet, Gluten-Free; D004386:Duodenum / Q000473:pathology*; D016099:Endoscopy, Gastrointestinal; D005260:Female; D005838:Genotype; D006683:HLA-DQ Antigens / Q000235:genetics; D006801:Humans; D007413:Intestinal Mucosa / Q000473:pathology; D018655:Lymphocyte Count; D008218:Lymphocytosis / Q000473:pathology; D008297:Male; D008875:Middle Aged; D011379:Prognosis; D012307:Risk Factors; D013997:Time Factors; D011503:Transglutaminases / Q000276:immunology
chemical_list: D001323:Autoantibodies; D006683:HLA-DQ Antigens; D011503:Transglutaminases