NONSTEROIDAL ANTIINFLAMMATORY DRUGS AND INFLAMMATORY BOWEL-DISEASE

Nonsteroidal anti-inflammatory drugs (NSAIDs)adversely affect the entire gastrointestinal tract. The small intestinal side effects of NSAIDs are well-characterized and are a source of bleeding and protein loss which contributes to iron deficiency and hypoalbuminemia, respectively. NSAIDs rarely cause strictures, but these may be pathognomic when they occur. There are only isolated reports of small intestinal perforations and massive bleeding. The pathogenesis of NSAID enteropathy can be divided into two stages. The first stage is characterized by specific biochemical damage, principally to enterocyte mitochondria, followed by inhibition of generation of reparative prostaglandins. Collectively this causes a breach in mucosal integrity with increased intestinal permeability, which leads to the second, nonspecific tissue stage, representing an interplay between luminal aggressive factors and mucosal defences. This results in inflammation and macroscopic damage. The large intestine is not subjected to the same type of damage, presumably because of the completeness of drug absorption from the small intestine. However, NSAIDs have been implicated in colonic perforations and bleeding, diverticulitis and occasionally colitis. NSAIDs are recognized as one of four main causes of relapse in inflammatory bowel disease (IBD), all of which may have the potential to increase intestinal permeability. Extensive studies in patients with Crohn's disease - including sequential changes in intestinal inflammation, intestinal permeability and T cell activation in response to treatment with elemental diets, along with comparative studies on the site of neutrophil chemoattractants in IBD and NSAID enteropathy - suggest that the clinical spectrum of Crohn's disease can be viewed as two separate events. It is suggested that the relapse of Crohn's disease (with its unchecked inflammation) involves mechanisms identical to the nonspecific second stage of NSAID enteropathy, fundamentally unrelated to the cause of Crohn's disease. The basic cause may be found by exploring the mechanism for the inappropriate severity of the acute inflammatory response to luminal aggressive factors.