Colonic toxicity from pancreatins: a contemporary safety issue

Abstract

1 ‐ 3 The disorder was subsequently termed fibrosing colonopathy. The cause of these lesions was not apparent. Most of the children came from the Liverpool area of the UK and had initially presented with symptoms of persistent gastrointestinal obstruction. Further investigation showed that the wall of the ascending and transverse colon was thickened and the lumen narrowed, although the external diameter remained normal. Initial reports described the colonic stenosis as a “stricture” rather than a primary fibrosing lesion and, because the lesion was judged to be an irreversible obstruction, a segmental or subtotal colectomy was the usual surgical procedure. The clinical recognition of fibrosing colonopathy (panel) was complicated by the fact that gastrointestinal obstruction is a regular feature in up to 15% of children with cystic fibrosis. 4 The symptoms include abdominal discomfort and distension, constipation, weight loss, and failure to thrive—known as distal intestinal obstructive syndrome (DIOS). This syndrome is secondary to the abnormal gastrointestinal secretion of cystic fibrosis and is caused by inspissation of viscid intestinal mucus, and impacted faeces. Although colonic fibrosis had not previously been reported in DIOS, some exacerbation of DIOS might induce fibrosis of the colon. A histopathological review of the resection specimens of fibrosing colonopathy showed that the pathology of the lesions was unlike that of other chronic obstructive syndromes. Externally, the colon was pale with a fusiform band of mature fibrous tissue extending over 10 cm or more in the lamina propria and submucosa (figure 1). There were occasional foci of chronic inflammatory cells in the colon wall, with areas of interruption or loss of the muscularis mucosa. The lamina propria contained variable numbers of chronic inflammatory cells, but in areas adjacent to epithelial erosion, oedema was conspicuous. In a few cases the entire colon and distal areas of the ileum were involved. The overlying mucosa was variably thinned or replaced by a cobblestone epithelium with scattered areas of ulceration, superficial haemorrhage, or r e g e n e r a t i o n . 5 , 6 The histological pattern was consistent with a lesion that had evolved over several months. In contrast to Crohn’s disease, granulomatous reactions with Langhans giant cells, or transmural inflammatory fissures and fistulae, were not a feature. During the next 3 years, more than 80 further cases of fibrosing colonopathy were reported from nine different centres in the UK, 7 D e n m a r k , 8 and the USA. 9 , 1 0 T h e disorder was not influenced by race or sex, and the age at diagnosis varied from 9 months to 13 years.