title: Is use of PPIs related to increased intraepithelial lymphocytes in the colon?
abstract: BACKGROUND
  The use of proton pump inhibitors (PPIs) is thought to increase the incidence of microscopic colitis (MC), although the exact mechanisms are not fully understood. Increased infiltration of intraepithelial lymphocytes (IELs) is a pathologic finding of MC (including collagenous or lymphocytic colitis).
  
  
  OBJECTIVE
  We investigated whether PPI use is associated with increased IEL infiltration and inflammation in the lamina propria.
  
  
  METHODS
  We retrospectively reviewed the medical records and histological reports of 78 patients receiving PPIs who had no symptoms of diarrhea, and their age- and gender- matched controls. The levels of IELs and inflammation in the lamina propria were assessed independently by two pathologists using H&E and immunohistochemical staining for CD3 and CD8.
  
  
  RESULTS
  The IEL count was significantly higher in the PPI group than in controls (12.92 ± 6.27 vs. 8.10 ± 4.21 per 100 epithelial cells, p < 0.001), as was the extent of inflammation (1.74 ± 0.90 vs. 0.86 ± 0.78, p < 0.001). PPI use was associated with increased IEL infiltration in a multivariate analysis (OR, 3.232; 95 % CI, 1.631-6.404, p < 0.001). Within the PPI group, however, the IEL count was not significantly associated with gender, age, type of PPI, or duration of PPI use.
  
  
  CONCLUSIONS
  The use of PPIs has a significant association with increased IEL infiltration for subjects without symptoms of diarrhea. This finding suggests that changes such histological alterations seen in the early phage seen in MC possibly represent the stage of the disease even before the onset of symptoms.
authors.affiliation: Division of Gastroenterology, Department of Internal Medicine, Hanyang University Guri Hospital, 249-1, Gyomun-dong, Guri-si, Gyunggi-do 471-701, Korea.
authors.forename: Yeon Hwa
authors.initials: YH
authors.lastname: Yu
authors.forename: Dong Soo
authors.initials: DS
authors.lastname: Han
authors.forename: Eun Young
authors.initials: EY
authors.lastname: Choi
authors.forename: Hye Sun
authors.initials: HS
authors.lastname: Park
authors.forename: Jae Yoon
authors.initials: JY
authors.lastname: Jeong
authors.forename: Chang Soo
authors.initials: CS
authors.lastname: Eun
authors.forename: Young Ha
authors.initials: YH
authors.lastname: Oh
authors.forename: Ju Yeon
authors.initials: JY
authors.lastname: Pyo
mesh_terms: D000328:Adult; D000368:Aged; D001706:Biopsy; D016022:Case-Control Studies; D003092:Colitis / Q000473:pathology*; D003106:Colon / Q000166:cytology* / Q000187:drug effects* / Q000473:pathology; D004334:Drug Administration Schedule; D005260:Female; D006801:Humans; D007413:Intestinal Mucosa / Q000166:cytology / Q000187:drug effects* / Q000473:pathology; D008214:Lymphocytes / Q000187:drug effects* / Q000502:physiology; D008297:Male; D008875:Middle Aged; D054328:Proton Pump Inhibitors / Q000009:adverse effects*; D012189:Retrospective Studies
chemical_list: D054328:Proton Pump Inhibitors