Helicobacter pylori and nonsteroidal anti-inflammatory drugs (NSAIDs) account for the large majority of cases of peptic ulcer disease (PUD) in Europe, Asia, Australia, and some populations in the United States. (See "Association between Helicobacter pylori infection and duodenal ulcer" and "NSAIDs (including aspirin): Pathogenesis of gastroduodenal toxicity".)
However, several studies in the United States have demonstrated rates of H. pylori infection of less than 75 percent in patients with duodenal ulcer not associated with use of NSAIDs. In one study, after excluding NSAID use, 61 percent of duodenal ulcers (DU) and 63 percent of gastric ulcers (GU) were H. pylori positive . Only 52 percent of whites with DU were H. pylori positive, compared with 85 percent of nonwhites, underscoring the importance of demographics. In a retrospective study conducted over five years in a large tertiary hospital in the United Kingdom, H. pylori-negative, NSAID-negative ulcers accounted for 12 percent of all ulcers . (See "Epidemiology and etiology of peptic ulcer disease".)
Before focusing on other etiologies of PUD, it is important to carefully exclude H. pylori infection and NSAID use (table 1). False negative H. pylori testing is commonly encountered, particularly for serology and for tests that depend upon the number of organisms (rapid urease testing on gastric mucosal biopsies, urease breath testing, histology, and stool antigen) when the patient has recently taken antibiotics, proton pump inhibitors, or bismuth. Several lines of evidence indicate that H. pylori is frequently missed . For example, serology is positive in some ulcer patients when other tests are negative; although some of these results may be false positives, some are due to suppression of organisms or isolated duodenal colonization, as considered below. (See "Indications and diagnostic tests for Helicobacter pylori infection".) Furthermore, about one-half of patients with aggressive ulcer disease attributable to aspirin deny taking aspirin . Aspirin use has been detected in such patients by serum salicylate levels .
There are a number of less common, defined causes of PUD that are responsible for many of the remaining cases. In addition, some diseases, such as chronic obstructive pulmonary disease and cirrhosis, have been associated with a higher incidence of PUD than is seen in the normal population (table 2).
These causes are likely to take on increasing relative importance because of the rapid decline in H. pylori infection in developed countries , the availability of NSAIDs with lower risk of ulcer complications, and the use of concomitant therapies (such as proton pump inhibitors), which reduce the incidence of PUD in patients taking NSAIDs. The decrease in H. pylori prevalence is already translating into dramatic reductions in the prevalence of the two major associated diseases: peptic ulcer and gastric cancer.