Is Use of PPIs Related to Increased Intraepithelial Lymphocytes in the Colon?

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). We investigated whether PPI use is associated with increased IEL infiltration and inflammation in the lamina propria. 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. The IEL count was significantly higher in the PPI group than in controls (12.92 +/- A 6.27 vs. 8.10 +/- A 4.21 per 100 epithelial cells, p < 0.001), as was the extent of inflammation (1.74 +/- A 0.90 vs. 0.86 +/- A 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. 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.