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Management of peptic ulcer disease not related to Helicobacter pylori or NSAIDs

Helicobacter pylori (H. pylori) infection is widely accepted as the most important factor in the pathogenesis of duodenal ulcer. However, in parallel with more effective eradication of H. pylori, the prevalence of H. pylori is changing, and H. pylori-negative peptic ulcer disease appears to be increasing. When making a diagnosis of H. pylori-negative peptic ulcer disease, it is essential to avoid misclassification because of inaccurate diagnosis. In addition, secondary causes may need to be excluded with appropriate investigations. In the absence of H. pylori, nonsteroidal anti-inflammatory drug usage is the most common cause of peptic ulcer; surreptitious nonsteroidal anti-inflammatory drug usage is a cause of unexplained ulcer disease in up to 60% of patients. Hypersecretory syndromes such as Zollinger-Ellison syndrome, although rare, need to be excluded. Once all known etiological factors are excluded, there remains a group of patients with so-called “idiopathic ulcers.” The interplay of etiological factors in the pathogenesis of idiopathic peptic ulcer disease is poorly defined but may include a genetic predisposition, altered acid secretion, rapid gastric emptying, defective mucosal defense mechanisms, psychological stress, and smoking. The management of idiopathic peptic ulcers is not defined; they appear to be more resistant to standard therapy, can be associated with more frequent complications, and those that relapse may require long-term maintenance therapy.