An in-depth report on the causes, diagnosis, treatment, and prevention of stomach and gastrointestinal (GI) ulcers.
Duodenal ulcers; Gastric ulcers; Helicobacter pylori; H. pylori
- More than 6 million people in the United States have peptic ulcer disease.
- A peptic ulcer is an open sore or raw area that tends to develop in one of two places:
- The lining of the stomach (gastric ulcer )
- The upper part of the small intestine -- the duodenum (duodenal ulcer )
- Ulcers develop when digestive juices produced in the stomach, intestines, and digestive glands damage the lining of the stomach or duodenum.
- In 1982 two Australian scientists identified the bacteria H. pylori as the main cause of peptic ulcers.
- Long-term use of nonsteroidal anti-inflammatory drugs (NSAIDs) is the second most common cause of ulcers.
- Certain drugs other than NSAIDs may aggravate ulcers.
- Peptic ulcers can have a major effect on a patient's quality of life and finances. Research finds that complications of peptic ulcer disease can cost from $1,800 to more than $25,000 per patient.
- Some NSAIDs pose greater risks than others for ulcers and bleeding. Research finds that taking a COX-2-selective NSAID (celecoxib) poses less gastrointestinal risk than a non-selective NSAID (such as diclofenac) plus a proton pump inhibitor (PPI). However, coxibs carry a higher risk for heart attack and stroke than NSAIDs.
- Endoscopy is recommended for patients over age 50 who have new symptoms of peptic ulcers, as well as for patients under age 50 who have alarm symptoms (such as unintended weight loss, gastrointestinal bleeding, or swallowing problems). Patients under age 50 who don't have alarm symptoms can be tested for H. pylori infection and treated if they are positive. Endoscopy may also be performed if peptic ulcer symptoms don't improve with treatment.
Risk Factors Include
- About 10 - 15% of people who are infected with H. pylori develop peptic ulcer disease. Other factors must also be present to trigger ulcers.
- Anyone who uses NSAIDs regularly is at risk for gastrointestinal problems.
Although stress is no longer considered to be a cause of ulcers, some studies still suggest that stress may predispose a person to ulcers or prevent existing ulcers from healing.
- Studies have found that taking PPIs with the blood thinner clopidogrel (Plavix) reduces the effectiveness of this blood thinner by nearly 50%.
- A warning added in May 2012 cautions that using certain PPIs with methotrexate, a drug commonly used to treat certain cancers and autoimmune conditions, can lead to elevated levels of methotrexate in the blood, causing toxic side effects.
More than 6 million people in the United States have a peptic ulcer -- an open sore or raw area that tends to develop in one of two places:
- The lining of the stomach (gastric ulcer )
- The upper part of the small intestine -- the duodenum (duodenal ulcer )
In the U.S. duodenal ulcers are three times more common than gastric ulcers.
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A peptic ulcer is an open sore or raw area in the lining of the stomach (gastric) or the upper part of the small intestine (duodenal).
Ulcers average between one-quarter and one-half inch in diameter. They develop when digestive juices produced in the stomach, intestines, and digestive glands damage the lining of the stomach or duodenum.
The two important components of digestive juices are hydrochloric acid and the enzyme pepsin. Both substances are critical in the breakdown and digestion of starches, fats, and proteins in food. They play different roles in ulcers:
- Hydrochloric acid. A common misperception is that excess hydrochloric acid, which is secreted in the stomach, is solely responsible for producing ulcers. Patients with duodenal ulcers do tend to have higher-than-normal levels of hydrochloric acid, but most patients with gastric ulcers have normal or lower-than-normal acid levels. Some stomach acid is actually important for protecting against H. pylori, the bacteria that cause most peptic ulcers. [Note: An exception is ulcers that occur in Zollinger-Ellison syndrome, a rare genetic condition in which tumors in the pancreas or duodenum secrete very high levels of gastrin, the hormone that stimulates the release of hydrochloric acid.]
- Pepsin. Pepsin, an enzyme that breaks down proteins in food, is also an important factor in the formation of ulcers. Because the stomach and duodenum are composed of protein, they are susceptible to the actions of pepsin.
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Fortunately, the body has a defense system to protect the stomach and intestines against these two powerful substances:
- The mucus layer, which coats the stomach and duodenum, forms the first line of defense.
- Bicarbonate. which the mucus layer secretes, neutralizes digestive acids.
- Hormone-like substances called prostaglandins help widen the blood vessels in the stomach, to ensure good blood flow and protect against injury. Prostaglandins are also believed to stimulate bicarbonate and mucus production.
Disrupting any of these defense mechanisms makes the lining of the stomach and intestine susceptible to the actions of acid and pepsin, increasing the risk for ulcers.
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 them to penetrate the mucus layer of the stomach or duodenum so that they can attach themselves 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 bacteria.
- H. pylori survive in the highly acidic environment by producing urease, an enzyme that generates ammonia to neutralize the acid.
- H. pylori stimulate the increased release of gastrin. Higher gastrin levels promote increased acid secretion. The increased acid damages the intestinal lining, leading to ulcers in certain individuals.
- H. pylori also alter certain immune factors that allow these bacteria to evade detection by the immune system and cause persistent inflammation -- even without invading the mucus membrane.
Even if ulcers do not develop, H. pylori bacteria are considered to be a major cause of active chronic inflammation in the stomach (gastritis ) and the upper part of the small intestine (duodenitis ).
H. pylori are also strongly linked to stomach cancer and possibly other non-intestinal problems.
Factors that Trigger Ulcers in H. pylori Carriers. Only around 10 - 15% of people who are infected with H. pylori develop peptic ulcer disease. H. pylori infections, particularly in older people, may not always lead to peptic ulcers. Other factors must also be present to actually trigger ulcers, including:
- Genetic Factors. Some people harbor strains of H. pylori with genes that make the bacteria more dangerous, and increase the risk for ulcers.
- Immune Abnormalities. Certain people have an abnormal intestinal immune response, which allow the bacteria to injure the lining of the intestines.
- 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 bacteria.
When H. pylori were first identified as the major cause of peptic ulcers, these bacteria were 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.
Nonsteroidal Anti-Inflammatory Drugs (NSAIDs)
Long-term use of NSAIDs such as aspirin, ibuprofen (Advil, Motrin), and naproxen (Aleve, Naprosyn) is the second most common cause of ulcers. NSAIDs also increase the risk for gastrointestinal (GI) bleeding. The risk of bleeding continues for as long as a patient takes these drugs and may last 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.
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). Famotidine (Pepcid -- an H2 blocker) may provide less effective protection.
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 ulcers in the stomach or intestine, including:
- Alcohol abuse
- Bacterial or viral infections
- Physical injury
- Radiation treatments
Zollinger-Ellison Syndrome (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.
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Another cause of peptic ulcer, although far less common than H. pylori or NSAIDs, is Zollinger-Ellison syndrome. A large amount of 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.
An estimated 1 out of every 1 million people 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.
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.
Peptic ulcers associated with ZES are typically persistent and difficult to treat. Treatment consists of removing the tumors and suppressing acid with an intravenous PPI (Protonix). In the past, removing the stomach was the only treatment option.
Dyspepsia. The most common symptoms of peptic ulcer are known collectively as dyspepsia. However, peptic ulcers can occur without dyspepsia or any other gastrointestinal symptoms, especially when they are caused by NSAIDs.
The most common peptic ulcer symptoms are abdominal pain, heartburn, and regurgitation (the sensation of acid backing up into the throat).
Other dyspepsia symptoms include:
- A feeling of fullness
- Hunger and an empty feeling in the stomach, often 1 - 3 hours after a meal
Many patients with the above symptoms do not have peptic ulcer disease or any other diagnosed condition. In that case, they have what is called functional dyspepsia .
Older patients are less likely to have symptoms than younger patients. A lack of symptoms may delay diagnosis, which may put older patients at greater risk for severe complications.
Recurrent abdominal pain and other gastrointestinal symptoms are common in children, and it is becoming the norm for pediatricians to screen for H. pylori infection in children with these symptoms. However, researchers have not been able to confirm a link between regular abdominal pain and H. pylori infection in children.
Ulcer Pain. Some symptoms are similar to those of gastric ulcers, although not everyone with these symptoms has an ulcer. The pain of ulcers can be in one place, or it can be all over the abdomen. The pain is described as a burning, gnawing, or aching in the upper abdomen, or as a stabbing pain penetrating through the gut. The symptoms may vary depending on the location of the ulcer:
- Duodenal ulcers often cause a gnawing pain in the upper stomach area several hours after a meal, and patients can often relieve the pain by eating. Many patients also have heartburn.
- Gastric ulcers may cause a dull, aching pain, often right after a meal. Eating does not relieve the pain and may even worsen it. Pain may also occur at night.
Ulcer pain may be particularly confusing or disconcerting when it radiates to the back or to the chest behind the breastbone. In such cases it can be confused with other conditions, such as a heart attack.
Because ulcers can cause hidden bleeding, patients may experience symptoms of anemia, including fatigue and shortness of breath.
Severe symptoms that begin suddenly may indicate a blockage in the intestine, perforation, or hemorrhage, all of which are emergencies. Symptoms may include:
- Tarry, black, or bloody stools
- Severe vomiting, which may include blood or a substance with the appearance of coffee grounds (a sign of a serious hemorrhage) or the entire stomach contents (a sign of intestinal obstruction)
- Severe abdominal pain, with or without vomiting or evidence of blood
Anyone who experiences any of these symptoms should go to the emergency room immediately.
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Peptic ulcers may lead to emergency situations. Severe abdominal pain, with or without evidence of bleeding, may indicate that the ulcer has perforated the stomach or duodenum. Vomiting of a substance that resembles coffee grounds or the presence of black tarry stools may indicate serious bleeding.
Most people with severe ulcers experience significant pain and sleeplessness, which can have a dramatic and adverse impact on their quality of life.
Peptic ulcers can also have a major effect on a person's finances. Research finds that the complications of peptic ulcer disease can cost from $1,800 to more than $25,000 per patient.
Bleeding and hemorrhage
Peptic ulcers caused by H. pylori or NSAIDs can be very serious if they cause hemorrhage or perforate the stomach or duodenum. Up to 15% of people with ulcers experience some degree of bleeding, which can be life-threatening. Ulcers that form where the small intestine joins the stomach can swell and scar, resulting in a narrowing or closing of the intestinal opening. In such cases, the patient will vomit the entire contents of the stomach, and emergency treatment is necessary.
Complications of peptic ulcers cause an estimated 6,500 deaths each year. These figures, however, do not reflect the high number of deaths associated with NSAID use. Ulcers caused by NSAIDs are more likely to bleed than those caused by H. pylori.
Because there are often no GI symptoms from NSAID ulcers until bleeding begins, doctors cannot predict which patients taking these drugs will develop bleeding. The risk for a poor outcome is highest in people who have had long-term bleeding from NSAIDs, blood clotting disorders, low systolic blood pressure, mental instability, or another serious and unstable medical condition. Populations at greatest risk are the elderly and those with other serious conditions, such as heart problems.
Stomach Cancer and Other Conditions Associated with H. pylori
H. pylori is strongly associated with certain cancers. Some studies have also linked it to a number of non-gastrointestinal illnesses, although the evidence is inconsistent.
Stomach Cancers. Stomach cancer, also called gastric cancer, is the second leading cause of cancer death worldwide. In developing countries, where the rate of H. pylori is very high, the risk of stomach cancer is six times higher than in the U.S. Evidence now suggests that H. pylor i may be as carcinogenic (cancer producing) to the stomach as cigarette smoke is to the lungs.
Infection with H. pylori promotes a precancerous condition called atrophic gastritis. The process most likely starts in childhood. It may lead to cancer through the following steps:
- The stomach becomes chronically inflamed and loses patches of glands that secrete protein and acid. (Acid protects against carcinogens, substances that cause cancerous changes in cells.)
- New cells replace destroyed cells, but the new cells do not produce enough acid to protect against carcinogens.
- Over time, cancer cells may develop and multiply in the stomach.
When H. pylori infection starts in adulthood it poses a lower risk for cancer, because it takes years for atrophic gastritis to develop, and an adult is likely to die of other causes first. Other factors, such as specific strains of H. pylori and diet, might also influence the risk for stomach cancer. For example, a diet high in salt and low in fresh fruits and vegetables has been associated with a greater risk. Some evidence suggests that the H. pylori strain that carries the cytotoxin-associated gene A (CagA) may be a particular risk factor for precancerous changes.
Although the evidence is mixed, some research suggests that early elimination of H. pylori may reduce the risk of stomach cancer to that of the general population. It is important to follow patients after treatment for a long period of time.
People with duodenal ulcers caused by H. pylori appear to have a lower risk of stomach cancer, although scientists do not know why. It may be that different H. pylori strains affect the duodenum and the stomach. Or, the high levels of acid found in the duodenum may help prevent the spread of the bacteria to critical areas of the stomach.
Other Diseases. H. pylori also is weakly associated with other non-intestinal disorders, including migraine headache, Raynaud's disease (which causes cold hands and feet), and skin disorders such as chronic hives.
Men with gastric ulcers may face a higher risk for pancreatic cancer, although duodenal ulcers do not seem to pose the same risk.
About 10% of people in the U.S. are expected to develop peptic ulcers at some point in their lives. Peptic ulcer disease affects all age groups, but it is rare in children. Men have twice the risk of ulcers as women. The risk of duodenal ulcers tends to rise starting at age 25, and continuing until age 75. The risk peaks between ages 55 and 65.
Peptic ulcers are less common than they once were. Research suggests that ulcer rates have even declined in areas where there is widespread H. pylori infection. The increased use of proton pump inhibitor (PPI) drugs may be responsible for this trend. Treatments have also led to a reduction in the rate of H. pylori complications that require a hospital stay. The hospitalization rate for peptic ulcer disease dropped 21% between 1998 and 2005, and hospital stays for H. pylori infection dropped 47% during that same time period.
Risk Factors for H. pylori
H. pylori bacteria are most likely transmitted directly from person to person. Yet little is known about exactly how these bacteria are transmitted.
About 50% of the world's population is infected with H. pylori. The bacteria are nearly always acquired during childhood and persist throughout life if not treated. The prevalence in children is around 0.5% in industrialized nations, where rates continue to decline. Even in industrialized countries, however, infection rates in regions with crowded, unsanitary conditions are equal to those in developing countries.
It is not entirely clear how the bacteria are transmitted. Suggested, but not clearly proven, methods of transmission include:
Intimate contact, including contact with fluids from the mouth
GI tract illness (particularly when vomiting occurs)
Contact with stool (fecal material)
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