Causes:

In 1982 two Australian scientists identified H. pylori as the main cause of stomach ulcers. They showed that inflammation of the stomach, and stomach ulcers, result from an infection of the stomach caused by H. pylori bacteria. This discovery was so important that the researchers were awarded the Nobel Prize in Medicine in 2005. The bacteria appear to trigger ulcers in the following way:

• H. pylori's corkscrew shape enables it to penetrate the mucus layer of the stomach or duodenum so that it can attach itself to the lining. The surfaces of the cells lining the stomach contain a protein, called decay-accelerating factor, which acts as a receptor for the bacterium.
• H. pylori survives in the highly acidic environment by producing urease, an enzyme that generates ammonia to neutralize the acid.
• H. pylori then produces a number of toxins and factors that can cause inflammation and damage to the stomach and intestinal lining, leading to ulcers in certain individuals.
• It also alters certain immune factors that allow it to evade detection by the immune system and cause persistent inflammation -- even without invading the mucus membrane.

Even if ulcers do not develop, the bacterium is considered to be a major cause of active chronic inflammation in the stomach (gastritis) and upper part of the small intestine (duodenitis).

H. pylori is also strongly linked to stomach cancer and possibly other non-intestinal problems.

Factors that Trigger Ulcers in H. pylori Carriers. Only around 10 to 15% of people who are infected with H. pylori develop peptic ulcer disease. H. pylori infections, particularly in older people, may not always predict whether there are peptic ulcers. Other variables must also be present to actually trigger ulcers. These may include:

• Genetic Factors. Some people harbor strains of H. pylori that contain genes that may make the bacteria more dangerous, and increase the risk for ulcers. How important these genetic factors are in the development of ulcers depends on a person's ethnicity.
• Immune Abnormalities. Some experts suggest that certain individuals have abnormalities in their intestinal immune response, which allow the bacteria to injure the lining.
• Lifestyle Factors. Although lifestyle factors such as chronic stress, drinking coffee, and smoking were long believed to be primary causes of ulcers, it is now thought that they only increase susceptibility to ulcers in some H. pylori carriers.
• Shift Work and Other Causes of Interrupted Sleep. People who work the night shift have a significantly higher incidence of ulcers than day workers. Researchers suspect that frequent interruptions of sleep may weaken the immune system's ability to protect against harmful bacterial substances.

When H. pylori was first identified as the major cause of peptic ulcers, it was found in 90% of people with duodenal ulcers and in about 80% of people with gastric ulcers. As more people are being tested and treated for the bacteria, however, the rate of H. pylori- associated ulcers has declined. Currently, H. pylori are found in about 50% of people with peptic ulcer disease.

Some researchers now believe that duodenal ulcers are not caused by H. pylori, but that the presence of the bacteria simply delays healing. This fact, they say, may explain why up to half of acute duodenal perforation cases show no evidence of H. pylori, and why duodenal ulcers can come back even after H. pylori has been eradicated.

Nonsteroidal Anti-Inflammatory Drugs (NSAIDs)

Long-term use of NSAIDs is the second most common cause of ulcers, and the rate of NSAID-caused ulcers is increasing. More than 30 million people take prescription NSAIDs regularly, and more than 30 billion tablets of over-the-counter brands are sold each year in the U.S. alone. The most common NSAIDs are aspirin, ibuprofen (Advil, Motrin), and naproxen (Aleve, Naprosyn), although many others are available.

Patients with NSAID-caused ulcers should stop taking these drugs. However, patients who require these medications on a long-term basis can reduce their risk of ulcers by taking drugs in the proton pump inhibitor (PPI) group, such as omeprazole (Prilosec). A new study shows that famotidine (Pepcid -- an H2 blocker) can also protect people who are taking low-dose aspirin for cardiovascular prevention, at least in the short-term.

There is no doubt that NSAIDs increase the risk of ulcers and gastrointestinal (GI) bleeding. The risk of bleeding continues for as long as a patient takes these drugs and may persist for about 1 year after stopping. Short courses of NSAIDs for temporary pain relief should not cause major problems, because the stomach has time to recover and repair any damage that has occurred.

Some NSAIDs pose greater risks than others for ulcers and bleeding. No NSAID, even an over-the-counter brand, should be used long-term without a doctor's supervision.

Other Causes

Certain drugs other than NSAIDs may aggravate ulcers. These include warfarin (Coumadin) -- an anticoagulant that increases the risk of bleeding, oral corticosteroids, some chemotherapy drugs, spironolactone, and niacin.

Bevacizumab, a drug used to treat colorectal cancer, may increase the risk of GI perforation. Although the benefits of bevacizumab outweigh the risks, GI perforation is very serious. If it occurs, patients must stop taking the drug.

Rarely, certain conditions may cause ulceration in the stomach or intestine, including:

• Radiation treatments
• Bacterial or viral infections
• Alcohol abuse
• Physical injury
• Burns

Zollinger-Ellison Syndrome (ZES)

What is ZES? Zollinger-Ellison syndrome (ZES) is the least common major cause of peptic ulcer disease. In this condition, tumors in the pancreas and duodenum (called gastrinomas) produce excessive amounts of gastrin, a hormone that stimulates gastric acid secretion. These tumors are usually cancerous, so proper and prompt management of the disease is essential.

Another cause of peptic ulcer, although far less common than H. pylori or NSAIDs, is Zollinger-Ellison syndrome. A large amount of excess acid is produced in response to the overproduction of the hormone gastrin, which in turn is caused by tumors on the pancreas or duodenum. These tumors are usually cancerous and must be removed. Acid production should also be suppressed to prevent ulcers from returning.

Who Gets ZES? An estimated 1 person per million per year gets ZES. The incidence is 0.1 - 1% among patients with peptic ulcers. Typically the disease starts in people ages 45 - 50, and men are affected more often than women.

How Is ZES Diagnosed? ZES should be suspected in patients with ulcers who are not infected with H. pylori and who have no history of NSAID use. Diarrhea may occur before ulcer symptoms. Ulcers occurring in the second, third, or fourth portions of the duodenum or in the jejunum (the middle section of the small intestine) are signs of ZES. Gastroesophageal reflux disease (GERD) is more common, and often more severe in patients with ZES. Complications of GERD include ulcers and narrowing (strictures) of the esophagus.

How Is ZES Treated? Peptic ulcers associated with ZES are typically persistent and difficult to treat. Treatment consists of removing the tumors and suppressing acid with an intravenous proton pump inhibitor (Protonix). In the past, removing the stomach was the only option.