NSAID–PPI Enteropathy in Humans

Abstract

The comprehensive studies by Wallace et al1Wallace J.L. et al.Gastroenterology. 2011; 141: 1314-1322Abstract Full Text Full Text PDF PubMed Scopus (364) Google Scholar strongly support a co-enhancement by nonsteroidal anti-inflammatory drugs (NSAIDs) and proton pump inhibitors (PPIs) in the development of enteropathy in rats, with the PPI contribution largely mediated through its alteration of small intestinal bacterial flora. A variety of observations support the presence of similar phenomena in human subjects, and suggest that NSAID–PPI enteropathy may be a frequent, but unappreciated, illness in clinical practice. Compare et al2Compare D. et al.Eur J Clin Invest. 2011; 41: 380-386Crossref PubMed Scopus (87) Google Scholar reported diarrhea, often associated with other prominent gastrointestinal symptoms, in 53% of 42 patients after 6 months of PPI therapy, with small intestinal bacterial overgrowth in 62% of them. Lombardo et al3Lombardo J. et al.Clin Gastroenterol Hepatol. 2010; 8: 504-508Abstract Full Text Full Text PDF PubMed Scopus (237) Google Scholar reported similar phenomena among 40%–50% of 200 adults who had consumed PPI medications for an average of 36 months, with diarrhea eliminated or improved in 94% after 2 weeks of oral rifaximin therapy. In neither study was the use of NSAIDs by their subjects analyzed. Both Goldstein et al4Goldstein J.L. et al.Clin Gastroenterol Hepatol. 2005; 3: 133-141Abstract Full Text Full Text PDF PubMed Scopus (572) Google Scholar and Hawkey et al5Hawkey C.J. et al.Clin Gastroenterol Hepatol. 2008; 6: 536-544Abstract Full Text Full Text PDF PubMed Scopus (54) Google Scholar have independently reported more frequent small intestinal injury in healthy volunteers consuming a combination of NSAID and omeprazole for 14–16 days, in comparison with those consuming a selective cyclooxygenase (COX)-2 inhibitor, supporting the presence of an independent PPI contribution to their injury, since multiple other studies have demonstrated similar small bowel damage induced by therapeutic doses of conventional NSAIDs and COX-2 inhibitors. Microscopic colitis is reported to be more common among both PPI and NSAID consumers6Wilcox G.M. et al.J Clin Gastroenterol. 2009; 43: 551-553Crossref PubMed Scopus (54) Google Scholar, 7Keszthelyi D. et al.Ailment Phamacol Ther. 2010; 32: 1124-1128Crossref PubMed Scopus (87) Google Scholar, 8Pardi D.S. et al.Gastroenterology. 2011; 140: 1155-1165Abstract Full Text Full Text PDF PubMed Scopus (165) Google Scholar with its strongest association among older adults consuming both classes of medication concurrently.8Pardi D.S. et al.Gastroenterology. 2011; 140: 1155-1165Abstract Full Text Full Text PDF PubMed Scopus (165) Google Scholar Both classes of medications are widely prescribed and also available without prescription. In my small, solo practice of general internal medicine, over a recent 2-month interval, 6 patients were identified with apparent NSAID–PPI diarrhea of 2–12 months’ duration, each of whom responded dramatically within 2 weeks to withdrawal of the offending medications without other medicinal or dietary therapy. Additional studies exploring these associations on humans should receive high priority, and patients with diarrhea, abdominal distention, flatulence, or abdominal pain while consuming medications of both classes should undergo reassessment of their diagnoses and therapy. Proton Pump Inhibitors Exacerbate NSAID-Induced Small Intestinal Injury by Inducing DysbiosisGastroenterologyVol. 141Issue 4PreviewProton pump inhibitors (PPIs) and nonsteroidal anti-inflammatory drugs (NSAIDs) are among the most commonly used classes of drugs, with the former frequently coprescribed to reduce gastroduodenal injury caused by the latter. However, suppression of gastric acid secretion by PPIs is unlikely to provide any protection against the damage caused by NSAIDs in the more distal small intestine. Full-Text PDF ReplyGastroenterologyVol. 142Issue 4PreviewWe thank Dr Daniell for his insightful remarks about our paper on the exacerbation of NSAID-induced enteropathy in rodents by proton pump inhibitors (PPIs).1 He has provided references to several studies in which data were generated that are consistent with our hypotheses that PPIs can worsen NSAID-induced small intestinal injury, and that the underlying mechanism is the PPI-induced shift in quantity and types of bacteria in the small intestine. Two additional studies are worthy of mention. Poullis et al2 reported that fecal levels of calprotectin, a marker of gut inflammation, were significantly elevated in patients taking PPIs. Full-Text PDF