Influence of anti-rheumatic drugs on gut permeability and on the gut associated lymphoid tissue

Abstract

There is great interest in the association between intestinal inflammation and the various arthropathies. However, most studies assessing intestinal function in these diseases are confounded by the fact that non-steroidal anti-inflammatory drugs (NSAIDs) have profound effects on the small intestine. Hence NSAIDs cause quite distinct and severe biochemical damage during drug absorption (uncoupling of mitochondrial oxidative phosphorylation proving to be most important) which results in increased intestinal permeability. All commonly used NSAIDs, apart from aspirin and nabumetone, are associated with increased intestinal permeability in man. Whilst reversible in the short term, it may take months to improve following prolonged NSAID use. Increased intestinal permeability appears to be the central mechanism of converting the biochemical damage to an inflammatory tissue reaction (NSAID enteropathy). The inflammatory enteropathy is not, however, unique to NSAIDs but similar changes are found with other permeability breakers. In intestinal infections and in diseases associated with reduced mucosal defence, suggesting that the small intestinal inflammation represents a common final pathway for a number of intestinal injuries. Spondylarthropathies are associated with a high prevalence of terminal ileitis, but as most patients have been receiving NSAIDs it has been difficult to dissociate the effects of NSAIDs on intestinal function from that of the ileitis itself. Nevertheless, two studies suggest that increased intestinal permeability in spondylarthropathies occur independently of NSAID ingestion. Whilst these findings may have implications for the development of arthritis, the permeability changes in spondylarthropathy do not differ quantitatively or qualitatively from that of NSAIDs or other permeability breakers. NSAID enteropathy can be differentiated from spondylarthropathic enteropathy by differences in location of disease and lack of predilection of certain HLA types. However, as the two may coexist both enteroscopy and ileocolonoscopy may be necessary for this distinction.