Causes of Gastric and Duodenal Ulcers:
The most common cause of gastric and duodenal ulcers is a spiral-shaped, gram-negative bacterium -- genus: Helicobacter, species: pylori -- that lives on the gastric mucosa under the mucous layer. This organism was first observed in stomach biopsy specimens by Australian pathologist J. Robin Warren in 1979; it was first cultured by Warren and his colleague Barry Marshall in the early 1980s; it was first described in the medical literature by Warren and Marshall in 1983; and it was first covered in the Medical Sciences Bulletin in 1985. Yet today, 17 years after Warren's landmark observation, the majority of Americans have never even heard of H pylori. A recent study found that even people who have ulcers themselves are ignorant of the cause; 90% said that stress causes ulcers, 60% blamed dietary indiscretion, and a whopping 90% had never heard of H pylori.
H pylori is probably the most common infectious disease in the world. In developing nations, 60-70% of children are infected by age 10, probably because of over-crowding and poor sanitation. In some countries, almost the entire population is infected. In the US, more than half of 60-year olds are infected, but younger Americans have an infection rate of only about 20% (with the exception of African- Americans, whose infection rates are 40-50%, and immigrants; infection rates in Hispanics are more than 60%, and Eastern Europeans more than 50%). The incidence of H pylori infection in developed nations is likely to increase -- not just in older persons, but in all age groups -- as immigration increases and population density rises. Even dogs, cats and other animals have their own Helicobacter species.
In their early studies, Warren and Marshall found H pylori in 65% of patients with gastritis, 85% of gastric ulcer patients, and all of duodenal ulcer patients. The only ulcers they found that were not associated with H pylori were in patients taking nonsteroidal antiinflammatory drugs (NSAIDs). After Warren and Marshall published their results, investigators all over the world confirmed their findings. H pylori was found in association with gastritis and gastric ulcers (more than 80% of gastric ulcer patients were infected, excluding those with gastrinoma or taking NSAIDs), and duodenal ulcers (more than 95% of duodenal ulcer patients were infected). Subsequently, Marshall found that while histamine-2 (H2) blockers help ulcer symptoms, patients relapse as soon as therapy is discontinued; relapse does not occur when H pylori is eradicated; and bismuth salts easily kills H pylori, but the infection recurs unless metronidazole is added. Marshall, who still investigates H pylori, is now at the University of Virginia Health Sciences Center.
The primary disease caused by H pylori is gastritis. Not all infected persons have symptoms, but all show changes in the gastric mucosa ("chronic superficial gastritis"). H pylori are well adapted to survive in the hostile environment of the stomach. Their spiral shape allows them to corkscrew down through the mucous layer to the gastric mucosa; they attach to mucous-secreting cells that line the stomach; they break down urea to produce ammonia that helps neutralize gastric acid in their immediate vicinity; and they produce various proteins that damage mucosal cells, attracting lymphocytes (which may be their primary source of nutrients) and causing persistent inflammation. After years or even decades of chronic superficial gastritis, carriers develop lesions ("atrophic gastritis") and eventually the stomach tissue can become abnormal and precancerous.
Peptic ulcer only develops in 1% of infected adults per year, depending on the bacteria (some strains produce toxins that attract certain lymphocytes) and the host (old age or poor health reduce resistance, and smoking or NSAID therapy impair mucosal defense). H pylori infection appears to cause the acid hypersecretion seen in duodenal ulcer disease. It also causes intestinal metaplasia (replacement of gastric cells with intestine-type cells) that is associated with gastric cancer, and can cause the growth of lymph tissue that can lead to a type of lymphoma.
The determination that ulcers are an infectious disease that can be treated with antibiotics is a major medical breakthrough. Ulcers are painful at best, and life threatening in the worst case (a bleeding ulcer can result in a fatal hemorrhage, and a perforated ulcer can result in fatal shock when stomach or intestinal contents spill into the abdominal cavity). For more information, write: Helicobacter Foundation. 1500 Avon St. Ext., Charlottesville, VA 22902. Or, American Digestive Health Foundation, 1201 Connecticut Ave., NW, Suite 300, Washington DC. 20036. (Marshall BJ. JAMA. 1995;274:1064-1067. Blaser MJ. Sci Am. 1996;274:104-107. Walsh JH, Peterson WL. N Engl J Med. 1995;333:984-991.)