Abstract
The proportion of ulcers that are not associated with Helicobacter pylori infection is increasing, especially in the United States and Australia. The alarming increase in this type of ulcer warrants an analysis of the diagnostic and treatment approaches to H. pylori‐negative ulcers, which was the aim of this study. The medical literature was reviewed to gather information about the prevalence, aetiology, and treatment of H. pylori‐negative ulcers. The reports indicated that up to 52% of duodenal ulcers and 47% of gastric ulcers are not caused by H. pylori infection. The cause of H. pylori‐negative ulceration appears to be multifactorial. Contributing factors include covert non‐steroidal anti‐inflammatory drug use, false‐negative H. pylori tests, genetic predisposition, and in rare cases, Crohn’s disease or Zollinger–Ellison syndrome. H. pylori‐negative ulcers tend to be associated with hypersecretion and can have serious clinical sequelae. H. pylori‐negative ulcers are often refractory to treatment, possibly because they lack the beneficial effect of H. pylori infection on antisecretory therapy. Proton pump inhibitors (PPIs) appear to effectively treat both H. pylori‐positive and H. pylori‐negative ulcers. We conclude that H. pylori‐negative ulcers are becoming more prevalent in the United States and Australia. These ulcers may have an aggressive clinical course and can be refractory to treatment. PPI therapy is indicated for treating and preventing H. pylori‐negative peptic ulcers.