The ulcer sleuths: The search for the cause of peptic ulcers.

The search for the cause or causes of peptic ulcers has been a long one. It was recognised as early as the 19th Century that damage to the stomach or duodenal bulb was likely to result if the resistance of their mucosae to luminal acid was for some reason impaired. An early theory suggested microscopic vascular occlusion leading to local infarction could be the initiating event but evidence was lacking. Excessive acid secretion is seen in some patients but not in many so is implausible as the main factor in most ulcers. Cigarette smoking is a risk factor and chronic life difficulties has been shown to sometimes play a part, but we would now think that they play only minor roles to possibly tip the balance when a major etiologic factor is already present. The overwhelming evidence now is that the major etiologic factors in chronic peptic ulcer are ingestion of nonsteroidal anti-inflammatory drugs (NSAIDs) and infection with Helicobacter pylori. Understanding the mechanism of the first, and the discovery and demonstration of Koch's postulates for the second, have been instrumental in the award of two Nobel prizes.