Comparative and experimental pathology of fibrosing colonopathy.

Although the occurrence of fibrosing colonopathy is temporally associated with the introduction of high-strength pancreatic enzyme supplements, its pathogenesis remains uncertain. The UK case-control study showed fibrosing colonopathy to be associated with high doses of high-strength pancreatic enzyme supplements and with a group of brands which occupy only 30% of the market. Two alternative hypotheses were proposed to explain the aetiology of fibrosing colonopathy: exposure to high levels of enzymes or to as yet unidentified components of the formulation. Comparison of the anatomical pathology of fibrosing colonopathy with that of previously encountered forms of obstructive gastrointestinal pathology, such as stricturing lesions due to potassium chloride preparations and nonsteroidal anti-inflammatory drugs, confirmed it to be a previously unencountered, long-segment lesion of the colon. Thus the use of the descriptive term 'stricture' is a misnomer leading to much clinical confusion when discussing obstructive bowel pathology in cystic fibrosis patients. Gavage studies in the rat with one of the two monomers (ethyl acrylate) forming the methacrylic acid copolymer (Eudragit L30D55) used for the enteric coating of the high-strength pancreatic enzyme supplements, have shown pathology comparable to fibrosing colonopathy. These findings prompted a series of exploratory studies in adolescent pigs. After seven days caecal gavage of Eudragit L30D55 at doses of 10, 50 or 500 mg/kg/day (comparable to human intake), extensive fibrosing colonopathy-like changes, inclusive of dense submucosal fibrosis, were noted at all dose levels in seven out of nine animals. Similar studies of the monomer components of the Eudragit L30D55 copolymer, at dose levels of 0.015 to 50 mg/kg/day, representing possible residues in Eudragit L30D55, did not produce comparable changes. The conclusion is that, although the precise mechanisms have not been elucidated, the role of enteric coatings containing Eudragit L30D55 in the pathogenesis of fibrosing colonopathy requires urgent further study.