Mucosal ulceration in the pathogenesis of fibrosing colonopathy of pediatric CF patients related to the use of high-strength enzyme preparations

The pathogenesis of recently described fibrosing colonopathy (FC) recognized in a small proportion of pediatrie cystic fibrosis patients treated with novel high-strength enzyme preparations is as yet unclear. Assessment of colonie mucosa in the 14 cases classified as FC in the United Kingdom national epidemiological study revealed sharply defined limited areas of mucosal defects suggestive of (recent) reepithelialization. Although superficial, nonspecific ulcerations have been described in nonassociated chronic inflammatory bowel disease, these lesions had as yet not been systematically studied in FC patients. The aim of the study was to define the presence and extent of focal mucosal change in the terminal ileum and colon of FC patients. Six ileocecal resection specimens of FC (confirmed by independent pathologist' review) were used for the study. Patients were 2-13 years of age at diagnosis. Two-centimeter segments of terminal ileum, cecum, colon at site of stenosis, and poststenotic ascending colon were serially sliced at 2.5 mm thick and routinely processed to paraffin. Semiserial 5-jlm paraffin sections at 500-um intervals were routinely counted and stained with H&E. Using low magnification, each section was assessed for areas of mucosal change and diagrams representing the mucosa were constructed. From these images, the fraction of surface area affected by mucosal defects was calculated using point scoring and the mean area of the ulcers for each area was calculated from the individual ulcer area as measured by point scoring technique. Surface area ulceration in various states of repair was noted in all colon 3 areas of all six patients. Terminal ileum defects were found in only two out of six patients, mean area 4.5 mm , occupying less than 3% of the surface. Cecal ulcers occupied between 5 and 11% of the surface area, mean ulcer area 4.4 mm (range 2-7 mm ). The highest values were found in the most severely stenosed segments, where ulcers occupied 8-43% of the surface and had a mean size of 2.5 mm (range 1-7 mm ).The poststenotic ascending colon showed 7-19% of the area affected and ulcers had a mean size of 3.7 mm2 (3-9 mm2). Mucosal ulceration in various stages of reepithelialization is found consistently throughout the colon of FC patients. The terminal ileum is affected in only a fraction of patients and when found to a much lesser degree. The role of these mucosal defects in the pathogenesis of FC requires urgent further research. Copyright © 1997 Taylor & Francis.