Drug-related intestinal disease

Abstract

Drugs used for therapeutic purposes constitute an important cause of intestinal morbidity. Agents in many different categories have been incriminated but non-steroidal anti-inflammatory drugs (NSAIDs) anti-microbial agents and cytotoxic drugs account for most cases of drug-related intestinal disease. In the small intestine, NSAIDs, in particular, are thought to be capable of causing ulceration in a much higher proportion of recipients than is generally realized. Ulcerative lesions may be complicated by perforation or stricture formation, often evolving into the distinctive condition known as ‘diaphragm disease’ in which the intestinal lumen may be reduced to pinhole dimensions. Extensive mucosal erosion with serious functional consequences may also be NSAID related. Malabsorption is another well-established condition which can be drug induced. The pathological changes in the small bowel are for the most part non-specific: the presence of unexplained ulceration, erosion or chronic inflammation, especially if accompanied by eosinophils, vacuolation of enterocytes or apoptotic activity in the crypts should nonetheless raise the possibility of drug effect. Lekewise, villous atrophy lacking distinctive features should engender suspicion. In the large intestine ulceration, perforation and stricture formation may again be important consequences of drug treatment. NSAIDs are usually but not always the agents implicated. A wider range of drugs is involved in producing colitis. Antibiotics are, of course, the major cause of the best known form of this, namely pseudomembraneous colitis. Less distinctive drug related forms of colitis, both acute and chronic, are, however, by no means rare. Drug involvement in such conditions may be suspected from the presence in colo-rectal biopsies of certain histological features such as eosinophilic infiltration, an increase in intraepithelial lymphocytes with or without subepithelial collagen deposition and an increase in apoptotic bodies in the crypts of Leiberkuhn. Unexpected acute inflammatory or ischaemic changes should also be regarded with suspicion. Therefore, it should be routine practice for histopathologists to include drug exposure in the differential diagnosis of any ulcerative or inflammatory intestinal condition.