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Neuropathy and vasculopathy in colonic strictures from children with cystic fibrosis
M H Collins1, B Azzarelli, K W West
1Division of Pediatric Pathology, Indiana University School of Medicine, Riley Hospital for Children, Indianapolis, USA.
Insights
Cystic fibrosis patients taking high-dose pancreatic enzymes developed rare colonic strictures. These strictures show nerve abnormalities and increased cholinergic and adrenergic activity, suggesting a potential drug-related cause.
Area of Science:
- Gastroenterology
- Pediatric Pathology
- Pharmacology
Background:
- Colonic strictures are uncommon in cystic fibrosis (CF).
- Recent cases link strictures to delayed-release, high-dose pancreatic enzyme supplements in CF patients.
- Neural and vascular changes are implicated in gastrointestinal complications.
Purpose of the Study:
- To investigate the histological and neural characteristics of colonic strictures in pediatric CF patients treated with pancreatic enzyme supplements.
- To compare neural and vascular features in CF strictures versus controls.
- To explore potential mechanisms, including drug effects and catecholamine activity.
Main Methods:
- Histological examination of colonic strictures from eight pediatric CF patients.
- Analysis of neural abnormalities, including ganglion cell distribution and nerve fiber staining (acetylcholinesterase, tyrosine hydroxylase, vasoactive intestinal peptide).
- Assessment of vasculopathy in submucosal veins and mesenteric arteries.
Main Results:
- CF strictures exhibited ganglion cell hyperplasia/ectopia and intermyenteric plexus hyperplasia.
- Increased cholinergic (acetylcholinesterase) and adrenergic (tyrosine hydroxylase) staining in the lamina propria of CF strictures compared to controls.
- Vasculopathy (fibrointimal hyperplasia) was present in submucosal veins and mesenteric arteries of CF strictures.
- Vasoactive intestinal peptide staining did not differ significantly between groups.
Conclusions:
- Colonic strictures in CF patients on high-dose pancreatic enzymes are associated with distinct neural abnormalities and increased mucosal cholinergic/adrenergic activity.
- The observed vasculopathy may be linked to the pancreatic enzyme supplements or elevated catecholamine activity.
- These findings suggest a multifactorial etiology for these rare strictures, potentially involving drug-induced changes and altered neural regulation.
Abstract:
Colonic strictures are rare in patients who have cystic fibrosis, but recently have developed in those who have been treated with delayed-release high-dose pancreatic enzyme supplements. Colonic strictures from eight such pediatric patients showed neural abnormalities consisting of ganglion cell hyperplasia and ectopia, and intermyenteric plexus hyperplasia. Cholinergic and adrenergic stains of mucosal nerve fibers were more prominent in histological sections of the cystic fibrosis strictures than in sections from colons of children without cystic fibrosis. The mean grade of staining with acetylcholinesterase in the lamina propria of the strictured cystic fibrosis colons was 2.38 +/- 1.25, compared with .93 +/- .93 (P < .055) in bowels from children without cystic fibrosis. The mean grade for tyrosine hydroxylase staining in the lamina propria was 2 +/- .97 in the strictures and was .79 +/- .81 (P < .05) in the bowels of children who did not have cystic fibrosis. Vasoactive intestinal peptide staining in bowels from children with cystic fibrosis with and without stricture did not differ significantly from that of children without cystic fibrosis. Vasculopathy consisting of fibrointimal hyperplasia in submucosal veins and mesenteric arteries was found only in colonic strictures owing to cystic fibrosis. Colonic strictures in patients with cystic fibrosis who received high-dose pancreatic enzyme supplements contain ganglion cell abnormalities, and mucosal cholinergic and adrenergic activity may be increased in these strictures. The stricture vasculopathy may be drug-related and/or related to increased catecholamine activity.