Hereditary pancreatitis is a rare genetic condition beginning in childhood that is characterized by recurrent episodes of inflammation of the pancreas, causing intense abdominal pain, nausea and vomiting. Most episodes resolve on their own, but serious complications can arise, ranging from diabetes and poor digestion, to bleeding, infection, pancreatic cancer and death. Medical treatment can help alleviate some of the symptoms, and occasionally surgery may be needed to treat some of the complications.
Description
The pancreas is an organ located in the abdomen that has several functions. First, the pancreas aids in the digestion of food through the production of digestive enzymes. Digestive enzymes are proteins that break down food components, including sugars, fats, and other proteins, so that they can be absorbed and used by the body. Normally, the digestive enzymes are stored within the pancreas in an inactive form. In response to food intake, the enzymes are released from the pancreas and travel through the pancreatic duct into the small intestine where they become activated and begin to digest food.
The second function of the pancreas is to maintain proper sugar balance in the blood. The pancreas produces several hormones, including insulin and glucagon, that are secreted into the bloodstream and act to increase or decrease sugar levels within the blood.
Pancreatitis is a condition in which the pancreas becomes irritated and inflamed. In most cases, the condition is caused by excessive alcohol use, or by the presence of gallstones, but can also be caused by medications, viral infections, injury to the abdomen, abnormal structures of the pancreas, and several metabolic disorders. In some rare instances, pancreatitis is caused by a genetic abnormality that is passed down from parent to child and is called hereditary pancreatitis.
In hereditary pancreatitis, an individual inherits a genetic abnormality in one of the digestive enzymes produced by the pancreas, called trypsin. Normally, trypsin is stored within the pancreas in an inactive state, and only becomes activated when it travels to the small intestine and encounters food to digest. However, in individuals with hereditary pancreatitis, the trypsin becomes activated while still in the pancreas and begins to digest the pancreas itself, causing irritation and inflammation. Damage to the blood vessels in the pancreas can result in bleeding or fluid leaks from the blood vessel into the abdominal cavity. The digestive enzymes also gain access to the bloodstream through the damaged blood vessels, and begin circulating throughout the body, causing further damage.
It is unclear what causes the abnormal trypsin enzyme to become activated and begin digesting the pancreas, but some studies have shown that emotional stress, alcohol, or fatty foods may trigger the process. After time, recurrent episodes of pancreatitis may leave the pancreas permanently irritated and damaged, a condition called chronic pancreatitis.
Genetic profile
Hereditary pancreatitis is a genetic disease and can be inherited or passed on in a family. The genetic abnormality for the disorder is inherited as an autosomal dominant trait, meaning that only one abnormal gene is needed to inherit the disease, and that a parent with the disease has a 50% chance of transmitting the abnormal gene and disease to a child.
Changes in the gene for the digestive enzyme trypsin (located on human chromosome 7, at 7q35) are responsible for the disease, and more than five different genetic changes in the trypsin gene have been identified. Changes in other genes may also cause hereditary pancreatitis, as recent studies have discovered families with this condition with mutations in other genes, possibly on chromosome 12.
Demographics
The annual incidence of all forms of pancreatitis is about one per 10,000 people. However, hereditary pancreatitis is a rare cause of all pancreatitis and comprises only about 2% of the total cases. While the true prevalence of the condition is difficult to measure, it is estimated that at least 1,000 individuals in the United States are affected by hereditary pancreatitis.
Approximately 100 different families with hereditary pancreatitis have been identified since the condition was first recognized in 1952. The largest concentration of hereditary pancreatitis in the United States is in the central Appalachian region, which extends from southern Ohio to eastern Kentucky and
Tennessee, western Virginia and North Carolina, and into northern Georgia.
Signs and symptoms
Hereditary pancreatitis begins with recurrent episodes of pancreatitis during childhood. The age of the first episode of pancreatitis may range from infancy to over 30 years old, but 80% of patients will show the first episode of pancreatitis before 20 years old, and the average individual shows a first episode at approximately 10 to 12 years old.
People who are experiencing an episode of pancreatitis have severe abdominal pain, nausea and vomiting that is greatly worsened by eating. The pain is often described as steady and dull pain that is centered on the navel and may extend to the back. As a result of fluids that leak from the pancreas and surrounding vessels into the abdomen, the abdomen may swell.
The severity and duration of each episode may range from only occasional abdominal discomfort to prolonged, life-threatening attacks that appear to last for weeks. The number of attacks is also quite variable. For example, severe attacks may occur three or four times in a year followed by a year without attacks.
Most episodes of pancreatitis resolve without problems. However, certain complications can arise which may worsen the condition and threaten the life of the patient. Because of the loss of large amounts of fluid into the abdomen, circulatory shock may occur. Shock occurs when fluid leaks from blood vessels, leaving an insufficient amount of blood volume to provide the body with the oxygen that it needs. Prolonged lack of appropriate levels of oxygen causes damage to many different organs of the body. If not immediately treated, shock can lead to death.
Another complication of pancreatitis is the development of a fluid collection that contains decaying products
of an inflamed pancreas and other substances. This fluid collection is called a pseudocyst. A pseudocyst can become life threatening if it becomes infected (abscess) or if the fluid collection ruptures into the abdomen.
Other dangerous and life-threatening complications of pancreatitis include severe bleeding from the pancreas (hemorrhagic pancreatitis), higher risk for the formation of blood clots, and a higher risk of serious infections in the abdomen or damaged pancreas. In addition, people with hereditary pancreatitis have a much higher risk of developing pancreatic cancer, for reasons that are not clear. Studies indicate that people with hereditary pancreatitis are at least 53 times more likely to develop pancreatic cancer than the general population and that 40-75% of people with hereditary pancreatitis will develop pancreatic cancer by the age of 70. Pancreatic cancer is very difficult to treat and is nearly always fatal.
Over time, recurrent episodes of pancreatitis may leave the pancreas permanently damaged and unable to carry out its routine functions. The absence of digestive enzymes normally secreted by the pancreas results in poor digestion, chronic diarrhea, weight loss, and malnutrition (5-45% of people), leaving a person generally weakened. The pancreas may also become unable to secrete insulin in the bloodstream normally, creating imbalances in blood sugar and causing diabetes in 10-25% of people with hereditary pancreatitis.
Diagnosis
Hereditary pancreatitis is diagnosed through a combination of medical history, physical examination, and laboratory testing. The onset of abdominal pain consistent with pancreatitis before the age of 20 in multiple family members without any other risk factor for pancreatitis (drinking large amounts of alcoholic beverages; gallstones) suggests a diagnosis of hereditary pancreatitis. The medical history and physical examination of these individuals during an episode of pancreatitis will show abdominal pain, nausea, vomiting, and abdominal swelling.
Diagnosis of pancreatitis can be made by noting high levels of pancreatic enzymes (amylase and lipase) circulating in the blood. Further abnormalities in the blood that suggest pancreatitis include: increased white blood cells, changes in the blood substances that occur with dehydration and fluid loss, and decreases in calcium levels.
Other diagnostic methods can be used to track the progress of the disease and monitor for any complications. X rays of the abdomen may show deposits of calcium that occur in 50% of cases of hereditary pancreatitis. Also, the intestines may show signs of inactivity because of the nearby inflammation. Computed tomography scans (CT scans) of the abdomen may reveal the inflammation of the pancreatitis, and are very useful in monitoring for complications such as pseudocyst, infections, and bleeding.
Genetic testing allows for the definitive diagnosis of hereditary pancreatitis by identifying abnormalities in the trypsin gene. However, these tests are currently used only for research purposes and are not generally available.
Treatment and management
There is no cure for hereditary pancreatitis. The goals for treatment consist of pain control, establishing alternate routes of feeding and fluid administration, and prevention or control of complications.
A person experiencing an episode of pancreatitis is nearly always admitted to the hospital for treatment. Since drinking or eating by mouth often worsens the patient's condition, alternative routes are needed. Large amounts of fluid are given by a small tube placed in a vein (intravenous or IV fluids) to replace the fluid that has leaked into the abdomen. This IV route can also be used to administer nutritional products and medications to relieve pain.
Fluids and acid that are produced by the stomach can worsen a patient's condition and increase pain. In order to drain these fluids, a small, flexible tube is inserted through the nose, down the throat and into the stomach (nasogastric tube). The tube is then connected to a weak vacuum to remove the contents of the stomach. Complications may arise in the setting of pancreatitis. Bleeding may require administration of donor blood products by vein, while infections are treated using antibiotics also given by vein. Abscesses, large pseudocysts or decaying portions of the pancreas may require drainage with a needle or need to be removed surgically. People with a permanently damaged pancreas may require digestive enzyme supplements by mouth to assist with digestion and insulin injections to control diabetes.
People diagnosed with hereditary pancreatitis should be seen regularly by a team of health care professionals, including a primary-care physician, gastroenterologist, and medical geneticist. Individuals with this condition should refrain from drinking alcohol and avoid fatty foods and may benefit from consultation with a licensed nutritionist.
Prognosis
Several systems have been developed to predict the outcome for people who are experiencing an episode of pancreatitis. The most widely used system utilized by health professionals is called "Ranson criteria," which utilizes a list of measurements that are determined during the first two days of the hospital stay.
In general, children who experience an episode of pancreatitis do well and are released from the hospital in three to five days. However, the development of any of the complications of pancreatitis discussed above worsens the prognosis and will likely result in a longer hospital stay. In the extreme, severe complications of pancreatitis can even lead to death.
Most people with hereditary pancreatitis will develop permanent damage to the pancreas as they grow older. Half of people will require surgery, and up to one-fourth will develop diabetes by the age of 70. Of even greater concern, a significant percentage will develop pancreatic cancer, a diagnosis that is nearly always fatal within several years.
BOOKS
Lankisch, P. G., and P. A. Banks. Pancreatitis. Garden City Park, New York: Springer Verlag, 1998.
PERIODICALS
Pietzak, M. M., and D. W. Thomas. "Pancreatitis in childhood." Pediatric Review 21 (December 2000): 406-412.
Whitcomb, D. C. "New insights into hereditary pancreatitis." Current Gastroenterology 1 (April 1999): 154-160.
