Enterochromaffin cell hyperplasia in irritable pouch syndrome

Irritable pouch syndrome (IPS) is a functional disease in patients with ileal pouch-anal anastomosis following colectomy for ulcerative colitis (UC). The pathophysiology of IPS is characterized by the presence of visceral hypersensitivity, similar to that seen in irritable bowel syndrome. However, the exact etiology and pathogenesis of IPS are not known. We hypothesized that serotonin-containing enteroendocrine cells or enterochromaffin (EC) cell hyperplasia and alterations in the mucosal immune cells may contribute to the patients' symptoms. The aim of the study was to assess EC cell hyperplasia and alterations in the mucosal immune cells in IPS.

The Pouchitis Disease Activity Index (PDAI) was used to quantify symptoms and mucosal inflammation in 36 patients with IPS and 25 patients with normal pouches. The histology and immunohistochemistry of pouch mucosal biopsies were assessed by a blinded gastrointestinal pathologist for intraepithelial lymphocytes (IEL), CD3+ T cells, CD25- (interleukin [IL]-2 receptor), tryptase- (mast cells), and serotonin-expressing cells. The numbers of IEL and immune-stained cells were compared between the two groups.

Both groups were compatible demographically in terms of age, gender, duration of UC, stage, indication, and duration of the pouch surgery. There were no differences in the number of IEL, CD3+ T cells, CD25+ cells, and mast cells between the IPS and normal control groups. However, there were a significantly larger number of EC cells in the IPS group than that in the control group (54.8 +/- 24.9 vs 36.7 +/- 17.5 per 4 200x epithelial cells, P < 0.005). The number of EC cells appeared to be correlated with the symptom score (r = 0.276, P= 0.032). There were no significant correlations between the PDAI endoscopy and histology scores and the number of EC cells or between the PDAI scores and the number of IEL or other immune-stained cells.

A greater number of EC cells were found in the IPS group than the normal pouch group, and the number of EC cells appeared to be correlated with the clinical symptoms of IPS. EC cell hyperplasia may be a contributing mechanism of visceral hypersensitivity and symptoms in IPS.