FitSugar

DrSugar Answers: IBS Treatment With No Health Insurance?

DrSugar — Thu, 24 Jul 2008 05:30:00 -0700

DrSugar is in the house and answering your questions.

Dear DrSugar,
I'm pretty positive I have Irritable Bowl Syndrome. Are there any things you can do to treat it without going to see a doctor? I don't have insurance and would like to avoid a costly office visit. Any advice you could give would be helpful.
Thanks,
– IBS Betty

To see what DrSugar has to say, read more.

Irritable Bowel Syndrome (IBS) is characterized by uncomfortable abdominal symptoms such as chronic pain, constipation, and diarrhea. The pain is often crampy in nature and is classically relieved by a bowel movement. Either diarrhea or constipation can predominate or the symptoms can alternate between the two. It is a chronic condition that usually waxes and wanes in severity and is often worsened by emotional stress or stressful life events. Mild cases are often self-diagnosed and treated, but moderate to severe cases always require physician evaluation because other diseases can present with similar symptoms. Diseases with similar symptoms to IBS include celiac disease, inflammatory bowel disease, and endometriosis.

Although there are some prescription medications for IBS, the most important initial treatment options are simple and do not require special medications. The most important initial consideration in treating IBS involves evaluating potential dietary causes of the IBS symptoms. A good place to start is eliminating dairy products because lactose intolerance is very common and often under recognized. Other foods to avoid include coffee, alcohol, highly fatty foods, and gas producing foods such as beans and broccoli. Increasing dietary fiber and water consumption can help with symptoms of constipation. Simple over the counter medications are also commonly used to treat IBS. Imodium is frequently used if chronic diarrhea is the main symptom. Colace and sennakot are common medications used to treat chronic constipation. It is also important to seek help in the treatment of depression or anxiety, which are commonly associated with IBS. Treating underlying depression with antidepressant medications often greatly improve IBS symptoms.

It is very important to consult a doctor if any concerning symptoms are present. Concerning symptoms include: weight loss, rectal bleeding, bloody stools, fevers, moderate to severe abdominal pain, profuse watery diarrhea, and chronic constipation. If you are reluctant to see a doctor due to lack of insurance, then you have a number of options. These options include applying for Medicaid, locating a local free clinic, buying health insurance out of pocket if you find the problem might require many visits to a physician.

If you have a question for DrSugar, send me a private message here and I will forward it to the good doctor.

DrSugar's posts are for informational purposes only and should not be considered medical advice, diagnosis, or treatment recommendations. Click here for more details.

Many Probiotics Short on Bacteria

FitSugar — Fri, 20 Nov 2009 03:00:09 -0800

With claims that they improve digestion, bolster immunity, and fight acne, it's no wonder that probiotic supplements are big business. Newsweek reports that sales of these supplements have more than quadrupled in the last 10 years. I will admit, I'm a fan these friendly bacteria found in yogurt and miso, but it's the quality of the supplements that's raising eyebrows.

Many popular probiotic supplements were tested by Consumer Lab, an independent agency that monitors vitamins, herbal remedies, and supplements not regularly tested by the government. The lab's findings are a bit startling. Some of the products contain as little as 13 percent of the amount of "viable bacteria" claimed on the products' labels, although most products do contain one billion organisms - the amount needed to register some health benefits.

When it comes to misleading marketing with these supplements, much of the problem stems from the fact that the term probiotics has no legal definition and can be used loosely by manufactures. Of the supplements tested, ConsumerLab ranked Advocare Probiotic Restore, GNC Nature Brand Best Super Acidophilus, and Jarrow Formulas Jarro-Dophilus as having the highest quality. You can buy a full review from Consumer Lab for $12.

Organ Lessons: The Pancreas

FitSugar — Tue, 10 Nov 2009 03:47:02 -0800

It's time to take some organ lessons, but not the musical kind. I'm going to teach you about your internal organs, starting with the pancreas.

November is National Pancreatic Cancer Awareness Month, devoted to educating people about the disease that took the life of Patrick Swayze earlier this year. If you're like most people, you probably don't know exactly what the pancreas does, so read on to learn more.

Product Review: Greens First

FitSugar — Thu, 22 Oct 2009 12:00:53 -0700

I try my absolute best to eat five to nine servings of fruit and veggies a day but sometimes I fall short. I also find that sometimes it's hard for me to digest all that roughage. I talked to my nutritionist about this problem and she recommended Greens First - a megablend powder that contains super foods, organic fruits and vegetables, probiotics, fiber, enzymes, and more.

It's lightly sweetened with stevia and has a slight minty flavor, it definitely tastes better than any of the other "green" drinks I've tried. I mix the powder with a glass of cold water in the morning and I'd say that within 30 minutes I feel a boost in my energy level. The website says that one serving of Greens First fulfills your fruit and veggie quota for the day but I still eat as much fresh stuff as I can.

Gastroesophageal reflux disease and heartburn

FitSugar — Wed, 08 Oct 2008 17:35:29 -0700

HEALTH GUIDE REFERENCE FROM A.D.A.M

Highlights

New Research

Obesity and GERD. Increased weight in women is linked to more frequent GERD symptoms, according to the Nurses' Health Study, which included 10,545 female participants. Overweight and obese women were two to three times more likely to have frequent symptoms than women of normal weight. GERD symptoms decreased nearly 40% in women whose body mass index (BMI) dropped by more than 3.5, compared to women whose BMI remained the same.
Proton-Pump Inhibitors and Bone Fracture. Long-term use of PPIs may increase the risk of hip fractures in older adults, according to a study in the Journal of the American Medical Association. People taking high doses of PPIs for more than a year were 2.6 times as likely to fracture a hip as those who were not taking the drug. The authors suggested that the stomach acids blocked by PPIs may be needed to absorb calcium, or the drugs may interfere with the body's natural process of breaking down and rebuilding bones.
PPIs and H2 Blockers in Children. Otherwise healthy children who take PPI inhibitors or H2 blockers may be at increased risk for intestinal and respiratory infections, according to a study of 186 children with GERD. The rate of gastroenteritis and community-acquired pneumonia significantly increased in children who were taking these medications when researchers compared the 4 months before and after enrollment in the study.

New Approval

Proton-Pump Inhibitor Approved for Adolescents. Esomeprazole (Nexium) delayed-release capsules have been approved for use in children ages 12 - 17 for the short-term treatment of GERD. Research shows that this medication reduces heartburn symptoms in adolescents.

Introduction

Gastroesophageal reflux disease (GERD) is a condition in which acids from the stomach move backward into the esophagus (an action called reflux). Reflux occurs if the muscular actions in the esophagus or other protective mechanisms fail.

Click the icon to see an animation about heartburn.

The hallmark symptoms of GERD are:

Heartburn: a burning sensation in the chest and throat.
Regurgitation: a sensation of acid backed up in the esophagus.

Although acid is a primary factor in damage caused by GERD, other products of the digestive tract, including pepsin and bile, can also be harmful.

Heartburn is a condition in which the acidic stomach contents back up into the esophagus, causing pain in the chest area. This reflux usually occurs because the sphincter muscle between the esophagus and stomach is weakened. Standing or sitting after a meal can help reduce the reflux that causes heartburn. Continuous irritation of the esophagus lining as in gastroesophageal reflux disease is a risk factor for the development of adenocarcinoma.

The esophagus, commonly called the food pipe, is a narrow muscular tube about nine-and-a-half inches long. It begins below the tongue and ends at the stomach. The esophagus is narrowest at the top and bottom; it also narrows slightly in the middle. The esophagus consists of three basic layers:

An outer layer of fibrous tissue.
A middle layer containing smoother muscle.
An inner membrane, which contains numerous tiny glands.

Click the icon to see an image of the esophagus.

When a person swallows food, the esophagus moves it into the stomach through the action of peristalsis, wave-like muscle contractions. In the stomach, the starch, fat, and protein in food are broken down by acid and various enzymes, notably hydrochloric acid and pepsin. The lining of the stomach has a thin layer of mucous that protects it from these fluids.

If acid and enzymes back up into the esophagus, however, its lining offers only a weak defense. The esophagus is protected using specific muscles and other factors.

The most important structure protecting the esophagus may be the lower esophageal sphincter (LES). The LES is a band of muscle around the bottom of the esophagus where it meets the stomach.

The LES opens after a person swallows to let food enter the stomach and then immediately closes to prevent regurgitation of the stomach contents, including gastric acid.
The LES maintains this pressure barrier until food is swallowed again.

Click the icon to see an image of the stomach.

If the pressure barrier is not sufficient to prevent regurgitation and acid backs-up (reflux), then peristaltic action of the esophagus serves as an additional defense mechanism and pushes the contents back down into the stomach.

Esophagitis. In most people, GERD symptoms are short-lived and occur infrequently. In about 20% of cases, however, the condition becomes chronic. When the acid causes irritation or inflammation, the condition is called esophagitis. If the damage becomes extensive and injures the esophagus, the disorder is known as erosive esophagitis.

Non-Erosive Esophageal Reflux Disease. Symptoms of gastroesophageal reflux disease can occur without any signs of inflammation or injury to the esophagus. This condition is also referred to as non-erosive esophageal reflux disease (NERD). NERD rarely progresses to full-blown GERD. Patients with NERD have no signs of inflammation or erosion in the esophagus, but they experience certain symptoms of GERD, such as burning sensations behind the breastbone for at least 3 months. Researchers suggest that nerves lying near the surface of the lining become exposed to acid that has penetrated the layers. The nerves then trigger prolonged and painful symptoms in response.

Barrett's Esophagus. A small percentage of patients with GERD may eventually develop Barrett's esophagus, a serious complication of GERD that results in precancerous changes in the tissue lining the esophagus.

Eosinophilic Esophagitis. This is a distinct disorder characterized by difficult or painful swallowing. It can occur along with GERD. The lining of the esophagus develops furrows and rings. This condition can be treated with swallowed fluticasone propionate, the active ingredient in some asthma medications.

Causes

Anyone who eats a large amount of acidic foods can have mild and temporary heartburn. This is especially true when lifting, bending over, or taking a nap after eating a large meal high in fatty, acidic foods. Persistent GERD, however, may be due to various conditions, including abnormal biologic or structural factors.

The band of muscle tissue called the LES is responsible for closing and opening the lower end of the esophagus and is essential for maintaining a pressure barrier against contents from the stomach. It is a complex area of smooth muscles and various hormones. If it weakens and loses tone, the LES cannot close up completely after food empties into the stomach. In such cases, acid from the stomach backs up into the esophagus. Dietary substances, drugs, and nervous system factors can weaken the LES and impair its function.

A study showed that more than half of GERD patients had abnormal nerve or muscle function in the stomach. These abnormalities cause impaired motility, which is the inability of muscles to act spontaneously. The stomach muscles do not contract normally, which causes delays in stomach emptying, increasing the risk for acid back-up.

Some studies suggest that most people with atypical GERD symptoms (such as hoarseness, chronic cough, or the feeling of having a lump in the throat) may have specific abnormalities in the esophagus. (In one study, such abnormalities appeared in 73% of patients who had atypical symptoms.)

Motility Abnormalities. Problems in spontaneous muscle action (peristalsis) in the esophagus commonly occur in GERD, although it is not clear if such occurrences are a cause or result of long-term effects of GERD.

Adult-Ringed Esophagus. This condition is characterized by an esophagus with multiple rings and persistent trouble with swallowing (including getting food stuck in the esophagus). It occurs mostly in men.

The hiatus is a small hole in the diaphragm through which the esophagus passes into the stomach. It normally fits very snugly, but it may weaken and enlarge. When this happens, part of the stomach muscles may protrude into it, producing a condition called hiatal hernia. It is very common, occurring in over half of people over 60 years old, and is rarely serious. Until recent years, it was believed that most cases of persistent heartburn were caused by a hiatal hernia. Hiatal hernia may impair LES muscle function. Studies have failed to confirm evidence, however, that it is a common cause of GERD, although its presence may increase GERD symptoms in patients with both conditions.

A hiatal hernia occurs when part of the stomach protrudes up into the chest through the sheet of muscle called the diaphragm. This may result from a weakening of the surrounding tissues and may be aggravated by obesity or smoking.

Studies indicate that 31 - 43% of reflux may be hereditary. An inherited risk exists in many cases of GERD, possibly because of inherited muscular or structural problems in the stomach or esophagus. Genetic factors may play an especially strong role in susceptibility to Barrett's esophagus, a precancerous condition caused by very severe GERD.

At least half of people with asthma also have GERD. Some experts speculate that the coughing and sneezing accompanying asthmatic attacks cause changes in pressure in the chest that can trigger reflux. Certain asthma drugs that dilate the airways may relax the LES and contribute to GERD. On the other hand, GERD has been associated with a number of other upper respiratory problems and may be a cause of asthma, rather than a result.

Crohn's disease is a chronic ailment that causes inflammation and injury in the colon and other parts of the gastrointestinal tract, including the esophagus. Other disorders that may affect areas that can contribute to GERD include diabetes, any gastrointestinal disorder, peptic ulcers, lymphomas, and cancer.

Click the icon to see an image of inflammatory bowel disease.

Helicobacter Pylori, also called H. pylori, is a bacterium found in the mucous membranes and is now known to be a major cause of peptic ulcers. Antibiotics used to eradicate H. pylori are now accepted treatment for curing ulcers. Of some concern, however, are studies indicating that H. Pylori may actually protect against GERD by reducing stomach acid. Furthermore, curing ulcers by eliminating the bacteria might actually trigger GERD in some people. Studies are mixed, however, on whether patients with cured H. Pylori infections are at risk for GERD. An analysis of 8 studies reported no higher risk for GERD after antibiotic treatments, nor was GERD any worse in patients who already had it. Seven of the 8 studies, however, were conducted only 2 months after antibiotic treatment. Longer follow-up studies are needed to determine long-term consequences, if any.

In any case, the bacteria should be eradicated in infected patients with existing GERD who are taking ongoing acid suppressing agents. There is some evidence that the combination of H. pylori and chronic acid suppression in these patients can lead to atrophic gastritis, a precancerous condition in the stomach.

In some cases, the esophagus appears normal, but GERD symptoms are present. This may indicate an over-reaction of the immune system to irritants that are introduced into the esophagus. In such cases, the immune system reacts with an exaggerated (or hyper-reactive) response, triggering the release of certain factors that end up causing inflammation and possibly injury. (This event is similar to the asthmatic response in the airways.)

NSAIDs. Nonsteroidal anti-inflammatory drugs (NSAIDs), common causes of peptic ulcers, may also cause GERD and increase severity in people who already have GERD. In a 3-year study of 25,000 people, NSAID users were twice as likely to have GERD symptoms as non-users. Symptoms did not become evident until after about 6 months of regular use. There are dozens of NSAIDs, including over-the-counter aspirin, ibuprofen (Motrin, Advil, Nuprin), and naproxen (Aleve), as well as prescription anti-inflammatory medicines. A person with GERD who takes the occasional aspirin or other NSAID will not necessarily experience adverse effects. This is especially true if there are no risk factors or indications of ulcers. Acetaminophen (Tylenol), which is NOT an NSAID, is a good alternative for those who want to relieve mild pain. It does not, however, relieve inflammation.

Other Drugs. Many other drugs can cause GERD, including but not limited to the following: calcium channel blockers (used to treat high blood pressure and angina), anticholinergics (used in drugs that treat urinary tract disorders, allergies, and glaucoma), beta adrenergic agonists (used for asthma and obstructive lung diseases), dopamine (used in Parkinson's disease), bisphosphonates (used to treat osteoporosis), sedatives, antibiotics, potassium, or iron pills.

Weakened peristaltic movement in the esophagus may contribute to GERD. If the mucous membrane is impaired, even a normal amount of acid can harm the esophagus. Pressure on the abdomen caused by obesity and also wearing tight clothing can contribute to acid backing up into the esophagus.

Click the icon to see an image of peristalsis.

Risk Factors

GERD occurs monthly in about half of American adults. People of all ages are susceptible to GERD. Elderly people with GERD tend to have a more serious condition than younger people.

Eating Pattern. Anyone who eats a heavy meal and subsequently lies on the back or bends over from the waist is at risk for an attack of heartburn. Anyone who snacks at bedtime is at high risk for heartburn.

Pregnancy. Pregnant women are particularly vulnerable to heartburn in their third trimester as the growing uterus puts increasing pressure on the stomach. Heartburn in such cases is often resistant to dietary interventions and even antacids.

Obesity. A number of studies suggest that obesity contributes to GERD and may increase the risk for erosive esophagitis in GERD patients. The Nurses' Health Study found that being overweight or obese significantly increased GERD symptoms in women. The higher a woman's body mass index (BMI), the study found, the more frequent were her symptoms. Women who lost weight in the study saw a decrease in their symptoms. Research suggests that the prevalence of GERD symptoms among obese patients has been underreported. Other researchers have reported that increased BMI is associated with a higher risk for cancer of the esophagus (esophageal adenocarcinoma).

Respiratory Diseases. People with asthma are at very high risk for GERD. One study indicated that patients with chronic obstructive pulmonary diseases (e.g., emphysema or chronic bronchitis) were more likely to have GERD.

Chronic obstructive pulmonary disease (COPD) refers to chronic lung disorders that result in blocked air flow in the lungs. The two main COPD disorders are emphysema and chronic bronchitis, the most common causes of respiratory failure. Emphysema occurs when the walls between the lung's air sacs become weakened and the sacs get enlarged and filled with too much air. Damage from COPD is usually permanent and irreversible.

Smoking. Increasing evidence indicates that smoking raises the risk for GERD. Studies suggest that smoking reduces LES muscle function, increases acid secretion, impairs muscle reflexes in the throat, and damages protective mucous membranes. Smoking reduces salivation, which helps neutralize acid. Whether it is the smoke, nicotine, or both that triggers GERD is unknown. Some people who use nicotine patches to quit smoking, for example, experience heartburn, but it is not clear if it's the nicotine or stress that produces acid back-up.

Alcohol Use. Alcohol has mixed effects on GERD. It relaxes the LES muscles and, in high amounts, may irritate the mucous membrane of the esophagus. All alcoholic beverages increase stomach acid levels. A combination of heavy alcohol use and smoking increases the risk for esophageal cancer. (Small amounts of alcohol, however, may actually protect the mucosal layer.)

In general, overweight Caucasian males over 40 are at highest risk for complications, notably Barrett's esophagus. Others at high risk for severe symptoms, inflammation, or both include:

People who use nonsteroidal anti-inflammatory drugs (NSAIDs). Studies suggest that certain NSAID users are at higher risk for GERD, including older adults, women, alcohol and tobacco users, and patients with asthma, hiatal hernia, or obesity. One study reported that NSAIDs put people at risk for ulcers but not for erosive esophagitis or strictures. Interestingly, NSAIDs are being studied for protection against Barrett's esophagus.
People with hiatal hernia

GERD is very common in children of all ages, but it is usually mild. Heartburn has been reported in 1.8% of 3-year-olds and in 5.2% of young people 10 - 17 years old. Children with the following conditions are at higher risk for severe GERD:

Neurologic impairments
Food allergies
Scoliosis
Cyclic vomiting
Cystic fibrosis
Problems in the lungs, ear, nose, or throat
Any medical condition affecting the digestive tract

Symptoms in Children. A physician should examine any child who has the following symptoms as soon as possible, because they may indicate complications such as anemia, failure to gain weight, or respiratory problems. Symptoms of severe GERD in infants and small children may include:

Chronic coughing
Frequent infections
Wheezing
Gasping or frequent cessation in breathing while asleep (called sleep apnea). However, one study found no association between GERD and apneas in premature infants.
Frequent vomiting in infants. About half of all infants up to 3 months old regurgitate milk at least once a day. Some simply spit up; others vomit large amounts after feedings. Vomiting in infants and older children is rarely a sign of GERD. In infants it usually resolves by age one. Severe vomiting -- particularly if it is bilious (green colored) -- always requires a doctor's visit, since it could be a symptom of severe obstruction.
Having to burp babies very frequently during and after feeding.

Babies and children may experience these symptoms without having GERD. An Australian study suggested that many infants who have normal irritability may be treated inappropriately for reflux disorders.

Feeding Problems. Feeding problems may be more severe than previously thought in children with GERD. In one study, children who had GERD and problems swallowing tended to refuse food and were late in eating solids. They also cried more and reacted more negatively in general than non-GERD babies. Such behaviors negatively affected the mothers as well. These findings were supported in an earlier study which reported that children at 1 year who had GERD in infancy were no longer spitting up, but still tended to have negative dining experiences ("too slow," "upsetting"). However, these children were at no greater risk for respiratory illnesses than other 1-year-old children.

Associations with Asthma and Infections in the Upper Airways. In addition to asthma, GERD is associated with other upper airway problems, including ear infections and sinusitis. Some experts argue that the association with common childhood infections and asthma is unfounded, since GERD is normal in most children.

Dental Erosion. GERD can cause irreversible loss of tooth enamel. Based on a 2002 study, some experts suggest checking for GERD in children with dental erosions. In the study, no child without GERD experienced loss of tooth enamel.

Rare Complications in Infants. Although GERD is very common, the following complications are very rare and only occur in certain cases:

Failure to thrive
Feeding problems and severe vomiting may cause anemia
Acid back-up may be inhaled into the airways and cause pneumonia

The infant's life may be in danger if acid reflux causes spasms in the larynx severe enough to block the airways. In fact, some experts believe this action may contribute to sudden infant death syndrome (SIDS). More research is needed to determine whether this association is valid.

Managing GERD in Infancy. Here are some hints on managing GERD in infants:

During and after feeding, infants should be positioned vertically and burped frequently.
If a baby with GERD is fed formula, the mother should ask the doctor how to thicken it in order to prevent splashing up from the stomach.
Parents of infants with GERD should discuss the baby's sleeping position with their pediatrician. Experts strongly recommend that all healthy infants sleep on their backs to help prevent sudden infant death syndrome (SIDS). For babies with GERD, however, lying on the back may obstruct the airways. In one study, infants with gastroesophageal reflux who spent prolonged periods of time in infant seats, including car seats, had more reflux than those who spent waking time on their stomachs. If the physician recommends that babies with GERD sleep on their stomachs, parents should be sure that their infant's mattress is very firm, possibly tilted up at the head, and that there are no pillows. The baby's head should be turned so that the mouth and nose are completely unobstructed.
Because food allergies may trigger GERD in children, parents may want to discuss a dietary plan with their physician that starts the child on formulas using non-allergenic proteins, and then incrementally adds other foods until symptoms are triggered.

Managing GERD in Children. The same drugs used in adults may be tried in children with chronic GERD. While some drugs are available over the counter, they should not be given to children without physician supervision.

Milder medications, such as antacids, are used first.
H2 blockers may be tried next. They are available over the counter and include famotidine (Pepcid AC), cimetidine (Tagamet HB), ranitidine (Zantac 75), and nizatidine (Axid AR). The FDA has issued a warning on Pepcid AC for adults with kidney problems.
Proton-pump inhibitors (PPIs), such as omeprazole (Prilosec) and lansoprazole (Prevacid), are even more powerful agents that suppress the production of stomach acid. Delayed-release esomeprazole (Nexium) capsules have been approved for use in children ages 12 - 17 for the short-term treatment of GERD. One study found that esomeprazole (Nexium) in either a 20 or 40 mg dose once a day significantly reduced heartburn symptoms in adolescents. PPIs appear to be safe and effective even for children as young as 1 year old who fail the less intensive therapies. However, a 2006 study found that otherwise healthy children who were treated with H2 blockers and PPIs had an increased risk of developing respiratory and intestinal infections.

Surgical fundoplication involves wrapping the upper curve of the stomach (fundus) around the esophagus. The goal of this surgical technique is to strengthen the LES. Until recently, surgery was the primary treatment for children with severe complications from GERD because older drug therapies had severe side effects, were ineffective, or had not been designed for children. However, with the introduction of proton-pump inhibitor drugs, some children may be able to avoid surgery. Surgical fundoplication can be performed laparoscopically through small incisions. In one study, of 238 children from 5 months to 16 years of age who underwent laparoscopic fundoplication, all but 9 were symptom free at least 5 years after the surgery. A 2006 study found that children who underwent antireflux surgery before age 4 were less likely to be hospitalized again, or to have reflux-related events such as pneumonia and esophagitis after the surgery.

Symptoms

Heartburn. Heartburn is the primary symptom of GERD. It is a burning sensation that radiates up from the stomach to the chest and throat. Heartburn is most likely to occur in connection with the following activities:

After a heavy meal
Bending over
Lifting
Lying down, particularly on the back

According to one study, nearly three-quarters of patients with frequent GERD symptoms experience them at night. Patients with nighttime GERD also tend to experience more severe pain than those whose symptoms occur at other times. One study found that patients with nighttime pain reported levels of severity that were similar to those reported in angina and heart failure.

The severity of heartburn does not necessarily indicate actual injury in the esophagus. For example, Barrett's esophagus, which causes precancerous changes in the esophagus, may trigger few symptoms, especially in elderly people. On the other hand, people can suffer severe heartburn without the presence of damage to the esophagus.

Dyspepsia. Up to half of GERD patients have dyspepsia, a syndrome consisting of the following:

Pain and discomfort in the upper abdomen
Fullness in the stomach
Nausea after eating

People can have dyspepsia without having GERD.

Regurgitation. Regurgitation is the feeling of acid backing up in the throat. Sometimes acid regurgitates as far as the mouth and can be experienced as a "wet burp." Uncommonly, it may come out forcefully as vomit.

Many patients with GERD do not experience heartburn or regurgitation. Elderly patients with GERD often have less typical symptoms than do younger people. Instead symptoms may appear in other locations.

Chest Sensations or Pain. Patients may have the sensation that food is trapped behind the breastbone. Chest pain is a common symptom of GERD. It is very important to differentiate it from chest pain caused by heart conditions, such as angina and heart attack.

Symptoms in the Throat. Less commonly, GERD may produce symptoms that occur in the throat:

Acid laryngitis. A condition that includes hoarseness, dry cough, the sensation of having a lump in the throat, and the need to repeatedly clear the throat.
Trouble swallowing (dysphagia). In severe cases, patients may even choke or food may become trapped in the esophagus, causing severe chest pain. This may indicate a temporary spasm that narrows the tube, or it could also be an indication of serious esophageal damage or abnormalities.
Chronic sore throat
Persistent hiccups

Coughing and Respiratory Symptoms. Asthmatic symptoms, such as coughing and wheezing, may occur. In fact, in one study, GERD alone accounted for 41.1% of cases of chronic cough in nonsmoking patients. The incidence was even higher when GERD and asthma were combined.

Chronic Nausea and Vomiting. Nausea that persists for weeks or even months and is not attributable to a common cause of stomach upset may be a symptom of acid reflux. In rare cases, vomiting can occur as often as once a day. All other causes of chronic nausea and vomiting should be ruled out, including ulcers, stomach cancer, obstruction, and pancreas or gallbladder disorders.

Complications

Nearly everyone has an attack of heartburn at some point in their lives. In the vast majority of cases the condition is temporary and mild, causing only transient discomfort. If patients develop persistent gastroesophageal reflux disease with frequent relapses, however, and it remains untreated, serious complications may develop over time. They can include the following:

Erosive esophagitis (severe inflammation in the esophagus)
Severe narrowing (stricture) of the esophagus
Barrett's esophagus
Problems in other areas, including the teeth, throat, and airways leading to the lungs

Older people are at higher risk for complications from persistent GERD. The following conditions also put individuals at risk for recurrent and serious GERD:

The esophagus is very inflamed.
Initial symptoms are severe.
Symptoms persist in spite of treatments that successfully heal the esophagus.
There are severe underlying muscular abnormalities.

Erosive esophagitis develops in chronic GERD patients when acid causes enough irritation and inflammation to produce extensive injuries in the esophagus. Some studies have suggested that overweight Caucasian males with GERD are at highest risk for this condition. In anyone, however, the longer and more severe the GERD condition, the higher the risk for erosive esophagitis.

Bleeding. In one study, bleeding occurred in more than 8% of patients with erosive esophagitis (severe inflammation of the esophagus), which is associated with GERD. In very severe cases, the patient may detect dark-colored, tarry stools (indicating the presence of blood) or may vomit blood, particularly if ulcers have developed in the esophagus. This is a sign of severe damage and requires immediate attention.

Sometimes long-term bleeding can result in iron-deficiency anemia and may even require emergency transfusions. This condition can occur without heartburn or other warning symptoms, or even obvious blood in the stools.

Barrett's Esophagus (BE) and Esophageal Cancer. In some cases, BE develops as an advanced stage of erosive esophagitis. BE results in abnormal cellular changes in the esophagus that, in turn, put a patient at risk for esophageal cancer. There are many issues involved with BE, however, including its prevalence and true severity, that are unresolved.

Of note, GERD itself poses no significant risk for esophageal cancer. One study reported an annual incidence of 6.5 cancer cases per 10,000 people with regular GERD symptoms.

If the esophagus becomes severely injured over time, narrowed regions called strictures can develop, which may impair swallowing (dysphagia). Food may even become blocked in some cases. Stretching procedures or surgery may be required to restore normal swallowing. Paradoxically, strictures may actually prevent other GERD symptoms by helping to keep acid from traveling up the esophagus.

Asthma. Asthma and GERD often occur together. Studies report that reflux disorder coincides with 32 - 80% of asthma cases. Some theories for the causal connection between GERD and asthma are as follows:

Acid leaking from the lower esophagus in GERD stimulates the vagus nerves, which run through the gastrointestinal tract. These stimulated nerves trigger the nearby airways in the lung to constrict, which causes asthma symptoms.
Acid back-up that reaches the mouth may be inhaled into the airways (aspirated). Here, the acid triggers a reaction in the airways that causes asthma symptoms.

There is some evidence that asthma causes GERD. In contrast, some evidence suggests that GERD causes asthma. Some clinical trials report that treating GERD in patients who also have asthma reduces symptoms of both conditions. Not all such patients report improved asthma symptoms with GERD treatments, and these treatments do not appear to have much effect on actual lung function. One study suggested that this approach works in asthmatic individuals who tended to be overweight and to have severe GERD in the lower part of the esophagus.

Other Respiratory and Airway Conditions. Current studies indicate an association between GERD and various upper respiratory problems that occur in the sinuses, ear and nasal passages, and airways of the lung. People with GERD appear to have an above-average risk for chronic bronchitis, chronic sinusitis, emphysema, pulmonary fibrosis (lung scarring), and recurrent pneumonia. If a person inhales fluid from the esophagus (aspirates) into the lungs, serious pneumonia can occur. It is not yet known whether treatment of GERD would also reduce the risk for these respiratory conditions.

Dental erosion (the loss of the tooth's enamel coating) is a very common problem among GERD patients, including children. It results from the acid backing up into the mouth and eroding the enamel.

An estimated 20 - 60% of patients with GERD have atypical symptoms in the throat (hoarseness, sore throat) without any significant heartburn. A failure to diagnose and treat GERD may lead to persistent throat conditions such as chronic laryngitis, hoarseness, difficulty in speaking, sore throat, cough, constant throat clearing, and granulomas (soft, pink bumps) on the vocal cords.

GERD commonly occurs with obstructive sleep apnea, a condition in which breathing stops temporarily but repeatedly during sleep. It is not clear which condition is responsible for the other, but GERD is particularly severe when both conditions occur together. One study reported that spasms in the vocal cords caused by acid reflux may block the flow of air and cause sleep apnea in adults. On the other hand, other research suggests that the disordered breathing in sleep apnea alters pressure in the chest area and causes GERD. Both conditions may also have risk factors in common, such as sleeping on the back. Studies suggest that in such patients GERD can be markedly improved with a continuous positive airway pressure (CPAP) device, which opens the airways and is the standard treatment for severe sleep apnea.

Barrett's Esophagus

Barrett's esophagus (BE) is a serious condition in which changes occur in the cells that line the lower esophagus and cause the cells to become abnormal and precancerous. Barrett's esophagus is categorized as either long-segment or short-segment disease:

Long-segment BE occurs when abnormal cells affect 3 cm or more of the esophagus. This condition occurs in about 3 - 7% of GERD patients. It is associated with a more severe condition.
Short-segment BE affects less than 3 cm of the esophagus and is found in about 10 - 17% of GERD patients.

About 10% of patients with symptomatic GERD have BE. In some cases, BE develops as an advanced stage of erosive esophagitis. Some studies suggest that individuals at highest risk for BE are obese white males over the age of 50 with persistent GERD who drink alcohol. However, a number of studies have reported no relationship between alcohol use or being male and overweight with BE. Such studies have also reported no higher risk in smokers or relatives of BE patients. Only the persistence of symptoms suggested a higher risk. Nevertheless, not all patients with BE have either esophagitis or symptoms of GERD.

The true prevalence of BE, in fact, is not entirely clear, since studies suggest that significantly more than half of people with BE have no GERD symptoms at all. BE, then, is likely to be much more prevalent and probably less harmful than is currently believed. (BE that occurs without symptoms can only be identified in clinical trials or in autopsies, so it is difficult to determine the true extent.) Some evidence suggests that the presence of specific immune factors may be involved in determining the development of BE.

The rate of esophageal cancer has been rising steadily at about 2% a year in white men. The American Cancer Society estimates that there will be 15,560 new cases of esophageal cancer and 13,940 deaths from the disease in 2007. Esophageal cancer is also very difficult to cure. The 5-year survival rate for all stages of esophageal cancer is 17% in white patients, and 12% in African-American patients. Most cases of esophageal cancer start with BE, with less than half of the cases developing with any symptoms. Of note, only a minority of BE patients develop cancer. Some evidence suggests that acid reflux may contribute to the development of cancer in BE. Researchers have speculated that exposure to extra acid in people with Barrett's esophagus produces more of an enzyme called NOX5-S, which may put stress on cells, leading to DNA damage.

Evidence suggests that asymptomatic BE is quite common in the general population, and if true, BE would pose far less of a threat than is now believed. (GERD itself poses no significant risk for esophageal cancer. One study reported an annual incidence of 6.5 cancer cases per 10,000 people with regular GERD symptoms.)

Barrett's esophagus is diagnosed using endoscopy, a procedure that involves inserting a tube down the throat so that the physician can view the esophagus.

Monitoring High-Risk GERD Patients. Some experts recommend a one-time screening test for BE using endoscopy in high-risk patients (such as Caucasian overweight men) with chronic GERD.

Monitoring Patients with Barrett's Esophagus for Cancer. Periodic endoscopy is recommended for detecting early cancer in patients who have been diagnosed with Barrett's esophagus. In an important 2002 study, 5-year survival was 73% in BE patients whose cancer was detected with endoscopy screening and was 0% in patients who were not regularly screened.

To date, no treatments can reverse the cellular damage done after Barrett's esophagus has developed, although some procedures are showing promise.

Medications. Some evidence suggests that a combination of proton-pump inhibitors to suppress acid, coupled with anti-inflammatory COX-2 inhibitors, might be a promising approach.

Proton-Pump Inhibitors. Some experts recommend very aggressive treatments to reduce acid reflux using high-dose proton-pump inhibitors. The standard agent has been omeprazole (Prilosec). Newer oral PPIs include lansoprazole (Prevacid), esomeprazole (Nexium), and rabeprazole (Aciphex). Even when drugs relieve symptoms completely, the condition usually recurs within months after the drugs are discontinued. In chronic cases, drugs may need to be taken throughout a patient's life. These agents provide no protection against Barrett's esophagus. Still, there is some evidence that acid reflux may contribute to the development of cancer in BE, although it is not yet known if acid blockers have any protective effects against cancer in these patients.
COX-2 (cyclooxygenase-2) inhibitors reduce inflammation and pain, as do well-known agents such as aspirin and ibuprofen, but COX-2 inhibitors may pose less of a risk for peptic ulcers and bleeding. Some early evidence suggests they may be protective against cancerous changes in patients with Barrett's esophagus. However, Vioxx and Bextra have been withdrawn from the market due to their association with an increased risk of heart attack. Celebrex remains available, but must be used with caution, especially by patients with cardiovascular risk factors. Also, research is mixed on the benefits of NSAIDs for esophageal cancer. Some studies have found that they may decrease the risk of developing or dying from esophageal cancer. However, a 2007 study indicated that a small dose of Celebrex did not prevent the progression of cancer in Barrett's esophagus patients.

Peptic ulcers may lead to emergency situations. Severe abdominal pain with or without evidence of bleeding may indicate a perforation of the ulcer through the stomach or duodenum. Vomiting of a substance that resembles coffee grounds, or the presence of black tarry stools, may indicate serious bleeding.

Procedures to Remove the Mucous Lining. Various techniques or devices have been developed to remove (ablate) the mucous lining of the esophagus. The intention is to remove early cancerous or precancerous tissue and allow regrowth of new and hopefully healthy tissue in the esophagus. Such techniques include photodynamic therapy (PDT) or laser, electrical, or heat probes.

Studies on the use of these ablation techniques combined with aggressive use of proton-pump inhibitors or surgical treatments are very encouraging. Some of these techniques may eventually even offer potential cures. At this time, they can be very effective in removing harmful tissue, although the benefits do not last in all patients. In one study, an average of 5.6 years after anti-GERD surgery and laser treatment, only a third of patients showed no evidence of renewed precancerous cell growth. These procedures also have complications, such as possible problems swallowing, that patients should discuss with their physician.

Esophagectomy. Esophagectomy is the surgical removal of all or part of the esophagus. Patients with Barrett's esophagus, who are otherwise healthy, are candidates for this procedure if endoscopy shows developing cancer. After esophageal removal, in total or in part, a new conduit for foods and fluids must be established to replace the absent esophagus. Alternatives include the stomach, colon, and part of the small intestine called the jejunum. The stomach is the optimal choice.

Diagnosis

If a patient suffers from chronic heartburn, chances are good the patient also has GERD. (Occasional heartburn does not necessarily indicate the presence of GERD.) The following is the general diagnostic approach:

A physician can usually make an easy diagnosis of GERD if the patient finds relief from persistent heartburn and acid regurgitation after taking antacids for short periods.
If the diagnosis is uncertain but the physician still suspects GERD, a drug trial using a proton-pump inhibitor medication, such as omeprazole (Prilosec) identifies 80 - 90% of people with the conditions. This class of medication blocks stomach acid secretion.

Laboratory or more invasive tests, including endoscopy, may be required if the diagnosis is still uncertain, if atypical symptoms are present, if Barrett's esophagus is suspected, or if complications, such as signs of bleeding or difficulty in swallowing, are present. Some of these tests are described below.

A barium swallow radiograph (x-ray) is useful for identifying structural abnormalities and erosive esophagitis (severe inflammation). When taking this test, the patient drinks a solution containing barium, then x-rays are taken. This test can show stricture, active ulcer craters, hiatal hernia, erosion, or other abnormalities. The test cannot reveal mild irritation.

Upper endoscopy, also called esophagogastroduodenoscopy or panendoscopy, is more accurate than a barium-swallow radiograph. It is also more invasive and expensive. It is widely used in GERD, including for identifying and grading severe esophagitis, for periodic monitoring of patients with Barrett's esophagus or for screening people at high risk, or when other complications are suspected. It is also now employed as part of various surgical techniques.

Endoscopy to Diagnose GERD. Endoscopy may be performed either in a hospital or in a doctor's office:

First, the patient should eat nothing for at least 6 hours before the procedure.
The doctor administers a local anesthetic using an oral spray and an intravenous sedative to suppress the gag reflex and to relax the patient.
Next, the physician places an endoscope (a thin flexible plastic tube containing a tiny camera) into the patient's mouth and down the esophagus. The procedure does not interfere with breathing. It may be slightly uncomfortable for some patients; others are able to sleep through it.
Once the endoscope is in place, the tiny camera allows the physician to see the surface of the esophagus and to search for abnormalities, including hiatal hernia and damage to the mucous lining.
The physician performs a biopsy (the removal and microscopic examination of small tissue sections). The biopsy may detect tissue injury indicative of GERD. It may also be used to detect cancer or other conditions, such as yeast (Candida albicans) or viral infections (e.g., herpes simplex and cytomegalovirus). Such infections are more likely to occur in people with impaired immune systems.
Complications from the procedure are uncommon. If they occur, complications are almost always mild and typically include minor bleeding from the biopsy site or irritation where medications were injected.

If a patient has moderate-to-severe GERD symptoms and the procedure reveals injury in the esophagus, usually no further tests are needed to confirm a diagnosis. The test is not foolproof, however. A visual view misses about half of esophageal abnormalities.

Capsule Endoscopy. Capsule endoscopy was first approved for use in 2001. A new version of this pill-sized camera, renamed PillCam, was approved by the FDA in 2004. PillCam reduces the imaging time previously required by the original capsule endoscopy technique. The PillCam capsule contains tiny video cameras on both ends. After the patient swallows the capsule, a series of 2600 color pictures are transmitted to a recording device where they can be downloaded and interpreted by a doctor. A newer version of the PillCam takes 14 frames per second as opposed to the 4 frames per second of the original device. The newer PillCam is superior in visualizing the entire esophagus and in identifying GERD. The entire procedure takes 20 minutes. The capsule is naturally passed through the digestive system within 24 hours. Capsule endoscopy may provide a more attractive and less invasive alternative for patients than traditional endoscopy. However, while capsule endoscopy is useful as a screening device for diagnosing esophageal conditions such as GERD and Barrett's esophagus, traditional endoscopy is still required for gathering tissue samples or removing polyps.

The (ambulatory) pH monitor examination may be employed to determine acid back-up. It is useful when endoscopy has not detected damage to the mucous lining in the esophagus, but GERD symptoms are present. pH monitoring may be used when patients have not found relief from medicine or surgery. The traditional trans-nasal catheter diagnostic procedure involved inserting a tubular probe through the nose and down to the esophagus. The tube was left in place for 24 hours. This test was irritating to the throat, and uncomfortable and awkward for most patients.

A new method, known as the Bravo pH test, uses a small capsule-sized data transmitter that is temporarily attached to the wall of the esophagus during endoscopy. The capsule records pH levels and transmits these data to a pager-sized receiver worn by the patient. Patients can continue their usual diet and activity schedule during the 24 - 48-hour monitoring period. After a few days, the capsule detaches from the esophagus, passes through the digestive tract, and is eliminated through a bowel movement.

Manometry is a technique that measures muscular pressure. It employs a tube containing various openings, which is placed through the esophagus. As the muscular action of the esophagus exerts pressure on the tube in various locations, a computer connected to the tube measures it. It is useful for the following situations:

To determine if a GERD patient would benefit from surgery by measuring pressure exerted by the lower esophageal sphincter muscles (LES).
To detect impaired stomach motility (an inability of the muscles to contract normally), which cannot be surgically corrected with standard procedures.
To determine if impaired peristalsis or other motor abnormalities are causing chest pain in people with GERD who have these symptoms.

Blood and Stool Tests. Stool tests may show traces of blood that are not visible. Blood tests for anemia should be performed if bleeding is suspected.

Bernstein Test. For patients with chest pain in which the diagnosis is uncertain, a procedure called the Bernstein test may be useful, although it is rarely used. A tube is inserted through the patient's nasal passage. Then solutions of hydrochloric acid and saline are administered separately into the esophagus. If the acid infusion causes symptoms and the saline solution does not, then a diagnosis of GERD is established.

Because many illnesses share similar symptoms, careful analysis and consideration of the patient's history is key to an accurate diagnosis. The following are only a few of the conditions that could accompany or resemble GERD.

Dyspepsia. The most common disorder confused with GERD is dyspepsia, which is defined as pain or discomfort in the upper abdomen without heartburn. Specific symptoms may include a feeling of fullness (particularly early in the meal), bloating, and nausea. Dyspepsia can be a symptom of GERD, but does not always occur with GERD. The drug metoclopramide (Reglan) helps stomach emptying and may be helpful for this condition.

Angina and Chest Pain. About 600,000 people come to emergency rooms each year with chest pains. More than 100,000 of these people are believed to actually have GERD. Chest pain from both GERD and from severe angina can occur after a heavy meal. In general, a heart problem is probably not responsible for the pain if it is worse at night and does not occur after exercise. It should be noted that the two conditions often coexist. In fact, there is some theory that in patients with coronary artery disease, acid reflux may actually trigger angina. In such cases, experts believe that acid in the esophagus may activate nerves that temporarily impair blood flow to the heart.

Asthma. Because asthma and GERD commonly occur together, physicians must be sure that each disorder is diagnosed accurately.

Other Diseases. Many gastrointestinal diseases (e.g., inflammatory bowel disease, ulcers, intestinal cancers) can cause GERD, but they are often easily identified, since they have other symptoms and affect other areas of the intestinal tract.

Treatment

Acid suppression continues to be the mainstay for treating GERD. The aim of drug therapy is to reduce the amount of acid present and improve any abnormalities in muscle function of the lower esophageal sphincter (LES), the esophagus, or the stomach.

Most cases of gastroesophageal reflux are mild and can be managed with lifestyle changes and over-the-counter medications and antacids.

Patients with moderate-to-severe symptoms that do not respond to lifestyle measures, or who are diagnosed at a late stage may be started on more or less potent agents depending on their complications at diagnosis. Experts argue, however, about the best way to initiate drug treatment for GERD in most of these patients. The two major treatment options are known as the step-up and step-down approaches:

Step-up. With a step-up drug approach the patient first tries an H2 blocker drug, which is available over the counter. These drugs include famotidine (Pepcid AC), cimetidine (Tagamet HB), ranitidine (Zantac 75), and nizatidine (Axid AR). If the condition fails to improve, therapy is "stepped up" to the more powerful proton-pump inhibitors, usually omeprazole (Prilosec).
Step-down. A step-down approach first uses a more potent agent, most often a proton-pump inhibitor (PPI), such as omeprazole (Prilosec). When patients have been symptom-free for 2 months or longer, they are then "stepped down" to a half-dose. If symptoms do not recur, the drug is withdrawn. If symptoms recur, the patient is put on high-dose H2 blockers. In one study using this step-down approach, 58% of patients remained symptom-free after a year, with 27% not using any medications at all. Some physicians argue that the step-down approach should be used for most patients with moderate-to-severe GERD.

Recent guidelines indicate that PPIs should be the first drug treatment, and that these drugs should be given once a day for approximately 8 weeks. Even when symptoms are completely relieved by medication, they usually return within a few months after drug treatment has stopped. Long-term maintenance may be necessary.

If neither approach relieves symptoms, the physician should look for other conditions. Endoscopy and other tests might be used to confirm GERD and rule out other disorders. In some cases, bile, not acid, may be responsible for symptoms, so that acid-reducing or blocking agents would not be helpful. (Bile is a fluid that is present in the small intestine and gallbladder.)

Surgery may be indicated under certain circumstances:

If lifestyle changes and drug treatments have failed
In patients with other medical complications
In younger people with chronic GERD, who face a lifetime of expense and inconvenience with maintenance drug treatment

Some physicians are recommending surgery as the treatment of choice for many more patients with chronic GERD, particularly since minimally invasive surgical procedures are becoming more widely available, and since only surgery improves regurgitation. Furthermore, persistent GERD appears to be much more serious than was previously believed, and the long-term safety of acid suppression using medication is still uncertain.

Nevertheless, anti-GERD procedures have many complications and high failure rates (ranging from 30% at 5 years to 63% at 10 years) and, as with medications, current surgical procedures cannot cure GERD. About 15% of patients still require anti-GERD medications after surgery. Furthermore, about 40% of surgical patients are at risk for new symptoms after surgery (e.g., gas, bloating, trouble swallowing), with most occurring more than a year after surgery. Finally, evidence -- notably an important 2002 Swedish study -- now strongly suggests that the procedure does not reduce the risk for esophageal cancer in high-risk patients, such as those with Barrett's esophagus. New procedures may improve current results, but at this time patients should consider surgical options very carefully with both a surgeon and their primary doctor.

Prevention

People with heartburn should first try lifestyle and dietary changes. In one study, 44% of patients who experienced symptoms of gastroesophageal reflux disease (GERD) reported improvement after changing their diet. Some suggestions are the following:

Avoid or reduce consumption of foods and beverages that contain caffeine, chocolate, peppermint, spearmint, and alcohol. Both caffeinated and decaffeinated coffees increase acid secretion.
Avoid all carbonated drinks, because they increase the risk for GERD.
Although physicians often advise patients with GERD to cut down on fatty foods, many studies have found no evidence that a low-fat or high-fat meal makes any difference in symptom exacerbation. One small study, however, found that the frequency of GERD symptoms increased with a high-fat compared to a low-fat diet. Better studies are needed to confirm this. In any case, as a rule, it is always wise to avoid saturated fats (which are from animal products), and cut down on all fats if one is overweight.
Choose low-fat or skim dairy products, poultry, or fish. Increasing protein may help strengthen muscles in the muscle valve.
Consume whole-grain products rich in selenium, which may have some protective role against dangerous cell changes in Barrett's esophagus.
Eat a diet rich in fruits and vegetables, although it's best to avoid acidic vegetables and fruits (e.g., oranges, lemons, grapefruit, pineapple, tomatoes).

Patients who have trouble swallowing should avoid tough meats, vegetables with skins, doughy bread, and pasta.

Nearly three-quarters of patients with frequent GERD symptoms have them at night. Patients with nighttime GERD also tend to experience severe pain. It is very important to take preventive measures before going to sleep. Some suggestions for preventing acid reflux at night are as follows:

After meals, take a walk or, at the very least, remain upright.
Avoid bedtime snacks. In general, avoid eating for at least 2 hours prior to bedtime.
When going to bed, try lying on the left side rather than on the right. The stomach is located higher than the esophagus when a person sleeps on the right side, which can put pressure on the lower esophageal sphincter (LES), increasing the risk for fluid back-up.
Sleep in a tilted position to help keep acid in the stomach at night. To do this, raise the bed at an angle using 4- to 6-inch blocks at the head of the bed and use a wedge-support to elevate the top half of the body. (Extra pillows that only raise the head actually increase the risk for reflux.)

A reflux board is prescribed for use in children who have gastroesophageal reflux. A board tilts the child upward while he is lying in bed to prevent the stomach contents from going back into the esophagus and mouth, and possibly into the lungs.

Quitting smoking is essential.
People who are overweight should try to reduce food intake and exercise to lose weight.
People with GERD should avoid tight clothing, particularly around the abdomen.
If possible, GERD patients should avoid nonsteroidal anti-inflammatory drugs (NSAIDs), such as aspirin, ibuprofen (Motrin, Advil), or naproxen (Aleve), among others. Tylenol (acetaminophen) is a good alternative pain reliever.

Although gum chewing is commonly believed to increase the risk for GERD symptoms, one study reported it might be helpful. Because saliva helps neutralize acid and contains a number of other factors that protect the esophagus, chewing gum 30 minutes after a meal has been found to help relieve heartburn and even protect against damage caused by GERD. Chewing on anything at all can help since it stimulates saliva production.

Medications

Antacids neutralize digestive acids and are the primary drugs for mild symptoms. They are best used alone for relief of occasional and unpredictable episodes of heartburn. They all work by neutralizing the acid in the stomach. They may also stimulate the defensive systems in the stomach by increasing bicarbonate and mucous secretion. Many antacids are available without a prescription and are the first drugs recommended to relieve heartburn and mild symptoms. Despite the many brands, they all rely on various combinations of three basic ingredients: magnesium, calcium, or aluminum.

Magnesium. Magnesium salts are available in the form of magnesium carbonate, magnesium trisilicate, and most commonly, magnesium hydroxide (Milk of Magnesia). The major side effect of magnesium salts is diarrhea. Magnesium salts offered in combination products with aluminum (Mylanta and Maalox) balance the side effects of diarrhea and constipation.

Calcium. Calcium carbonate (Tums, Titralac, and Alka-2) is a potent and rapid acting antacid that can cause constipation. These antacids are actually sources of calcium. There have been rare cases of hypercalcemia (elevated levels of calcium in the blood) in people taking calcium carbonate for long periods of time. This can lead to kidney failure and is very dangerous. None of the other antacids has this side effect.

Aluminum. Aluminum salts (Amphogel, Alternagel) are also available. The most common side effect of antacids containing aluminum salts is constipation. People who take large amounts of antacids that contain aluminum may also be at risk for calcium loss, which can lead to osteoporosis.

Osteoporosis is a condition characterized by progressive loss of bone density, thinning of bone tissue, and increased vulnerability to fractures. Osteoporosis may result from disease, dietary or hormonal deficiency, or advanced age. Regular exercise and vitamin and mineral supplements can reduce and even reverse loss of bone density.

It is generally believed that liquid antacids work faster and are more potent than tablets, although evidence suggests that they all work equally well. Antacids can interact with a number of drugs in the intestines by reducing their absorption. These drugs include tetracycline, ciprofloxacin (Cipro), propranolol (Inderal), captopril (Capoten), and H2 blockers. Interactions can be avoided by taking the drugs 1 hour before or 3 hours after taking the antacid. Long-term use of nearly any antacid increases the risk for kidney stones.

H2 blockers impede acid production by blocking or antagonizing the actions of histamine, a chemical found in the body that encourages acid secretion in the stomach. They are available over the counter and provide symptom relief in about half of GERD patients. It takes 30 - 90 minutes for them to work, but the benefits last for hours. The drugs are usually taken at bedtime. Some people may need to take them twice a day.

H2 blockers inhibit acid secretion for 6 - 24 hours and are very useful for people who need persistent acid suppression. They may also prevent heartburn episodes in people who are able to predict its occurrence. In some studies, H2 blockers improved asthmatic symptoms in people who have both conditions. A 2001 study suggested, however, that they rarely provide complete symptom relief for chronic heartburn and dyspepsia and they have done little to reduce office visits to physicians for GERD.

Brands. Four H2 blockers are currently available in the U.S.:

Famotidine (Pepcid AC). Famotidine (Pepcid AC, Pepcid Oral) is the most potent H2 blocker. The most common side effect of famotidine is headache, which occurs in 4.7% of people who take it. Famotidine is virtually free of drug interactions, but the FDA has issued a warning on its use in patients with kidney problems.
Cimetidine (Tagamet, Tagamet HB). Cimetidine (Tagamet) is the oldest H2 blocker. It has few side effects; approximately 1% of people taking it will experience mild temporary diarrhea, dizziness, rash, or headache. Cimetidine interacts with a number of commonly used medications, such as phenytoin, theophylline, and warfarin. Long-term use of excessive doses (more than 3 grams a day) may cause impotence or breast enlargement in men. These problems resolve after the drug is discontinued.
Ranitidine (Zantac, Zantac 75, Zantac Efferdose, Zantac injection, Zantac Syrup). Ranitidine (Zantac) interacts with very few drugs. In a recent study, ranitidine provided more pain relief and healed ulcers more quickly than cimetidine in people less than 60 years old, but there was no difference in older patients. A common side effect associated with ranitidine is headache, which occurs in about 3% of the people who take it.
Nizatidine Capsules (Axid AR, Axid Capsules, Nizatidine Capsules). Nizatidine (Axid) is nearly free of side effects and drug interactions. A controlled-release form is proving to help alleviate nighttime GERD symptoms.

Famotidine is excreted primarily by the kidney. This can pose a danger to people with kidney problems. Physicians are now being advised by the U.S. Food and Drug Administration (FDA) and Health Canada to reduce the dose and increase the time between doses in patients with kidney failure. Use of the drug in those with impaired kidney function can affect the central nervous system and may result in anxiety, depression, insomnia or drowsiness, and mental disturbances.

Drug Combinations.

Over-the-counter antacids and H2 blockers: This combination may be the best approach for many people who experience heartburn after eating. Both classes of drugs are effective in relieving GERD, but have different timing. Antacids work within a few minutes but are short-acting, while H2 blockers take longer but have long-lasting benefits. Pepcid AC combined with an antacid (calcium carbonate and magnesium) is now available as Pepcid Complete.
Proton-pump inhibitors and H2 blockers: Physicians sometimes recommend a nighttime dose of an H2 blocker for people who are taking proton-pump inhibitors twice a day. This is based on the belief that adding the H2 blocker will prevent a rise in acid reflux at night. An important 2002 study, however, reported no additional benefits from the nighttime H2 blocker. Some experts recommended an H2 blocker in patients who are on proton-pump inhibitors only to prevent breakthrough symptoms, such as before a heavy meal.

Long Term Complications. In most cases, these agents have good safety profiles and few side effects. H2 blockers can interact with other drugs, although some less so than others. In all cases, however, the physician should be made aware of any other drugs a patient is taking. More research is needed. Anyone with kidney problems should use famotidine only under the direction of a physician.

Concerns and Limitations. Some experts are concerned that the use of acid-blocking drugs in people with peptic ulcers may mask ulcer symptoms and increase the risk for serious complications.

These agents provide no protection against Barrett's esophagus. In fact, of concern are reports that long-term acid suppression with these drugs may cause cancerous changes in the stomach in patients who are infected with H. pylori. Research on this question is still ongoing.

Proton-pump inhibitors (PPIs) suppress the production of stomach acid and work by inhibiting the molecule in the stomach glands that is responsible for acid secretion, which is called the gastric acid pump. According to recent guidelines, initial drug treatment should be with PPIs once daily for about 8 weeks.

The standard agent has been omeprazole (Prilosec), which is now available over the counter without a prescription. Newer prescription oral PPIs include esomeprazole (Nexium), lansoprazole (Prevacid), rabeprazole (Aciphex), and pantoprazole (Protonix).

Studies report significant relief from PPIs in most patients with heartburn. PPIs are effective for healing erosive esophagitis and may also be helpful in patients with chronic laryngitis that is suspected to be caused by GERD. The newer agents provide quicker symptom relief compared to omeprazole. However, a comparison study suggested that, to date, esomeprazole (Nexium) is the only newer oral PPI to show any significant advantage over omeprazole (Prilosec). All PPIs are more effective than the H2 blockers.

In addition to relieving most common symptoms, including heartburn, proton-pump inhibitors also have the following advantages:

They are effective in relieving chest pain and laryngitis caused by GERD.
They may also reduce acid reflux that typically occurs during strenuous exercise.

Patients with impaired esophageal muscular action are still likely to experience acid breakthrough and reflux at night. Proton-pump inhibitors also may have little or no effect on regurgitation or asthmatic symptoms. Some experts believe, however, that they should be the first drugs of choice, even for patients with milder symptoms. At this time, these drugs are recommended for the following patients:

Those with moderate symptoms that do not respond to H2 blockers
Those with severe symptoms
Those who have respiratory complications
Those who have persistent nausea
Those who have esophageal injury

These agents have no affect against non-acid reflux, such as bile back-up.

Adverse Effects. Proton-pump inhibitors may pose the following concerns:

Side effects are uncommon but may include headache, diarrhea, constipation, nausea, and itching.
Proton-pump inhibitors should be avoided by pregnant women and nursing mothers, although recent studies suggest that they do not pose an increased risk of birth defects.
They may interact with certain drugs, such as anti-seizure agents (such as phenytoin), anti-anxiety drugs (such as diazepam), and blood thinners (such as warfarin).
Long-term use of high-dose PPIs may produce vitamin B12 deficiencies, but studies are needed to confirm whether there is any significant risk. High-dose PPIs used over the long-term also may increase the risk of hip fracture in older adults, according to one study.

There is some evidence that acid reflux may contribute to the higher risk of cancer in BE, but it is not yet confirmed whether acid-blockers have any protective effects against cancer in these patients. In fact, the long-term use of proton-pump inhibitors by people with H. pylori may, in theory at least, reduce acid secretion enough to cause atrophic gastritis (chronic inflammation of the stomach). This condition is a risk factor for stomach cancer. To compound concerns, long-term use of PPIs may mask symptoms of stomach cancer and so delay a diagnosis. To date, however, there have been no reports of an increased risk of stomach cancer with the long-term use of these drugs.

Sucralfate (Carafate) protects the mucous lining in the gastrointestinal tract. It seems to work by sticking to an ulcer crater and protecting it from damage due to stomach acid and pepsin. It may be helpful for maintenance therapy in people with mild-to-moderate GERD. Other than constipation, which occurs in 2.2% of patients, the drug has few side effects. Sucralfate interacts with a wide variety of drugs, however, including warfarin, phenytoin, and tetracycline.

Most drugs used for GERD have no effect on non-acid reflux, such as back-up of bile. Baclofen, known as a gamma-amino butyric acid agonist, is commonly used to reduce muscle spasms. Investigators are now showing that it can reduce both acid and non-acid reflux episodes (as much as 70% in one study) and increase LES pressure, an important factor for preventing back-up.

Surgery

The standard surgical treatment for GERD is fundoplication. The goal of this procedure is twofold:

To increase LES pressure and, therefore, prevent acid back-up (reflux)
To repair any present hiatal hernia

There are two primary approaches:

Open Nissen fundoplication (the more invasive technique)
Laparoscopic fundoplication

In general, the overall long-term benefits of these procedures are similar. Some studies report that more than 90% of patients are free of heartburn after the operation and satisfied with their choice, even after 5 years. Fundoplication relieves GERD-induced coughs and some other respiratory symptoms in up to 85% of patients. (Its effect on asthma associated with GERD, however, is unclear.) It may enhance stomach emptying and improve peristalsis in about half of patients. (It may actually cause abnormal peristalsis in about 14% of patients, although in such cases the problem does not appear to be very significant.)

Still, it has other significant limitations and postoperative problems. For example, the results of one 2003 survey suggested that 18% of surgical patients still required anti-GERD medications and 38% had new symptoms (e.g., gas, bloating, trouble swallowing), with most occurring more than a year after surgery. Other studies have reported similar results. Also, fundoplication does not cure GERD. Finally, evidence from a 2002 Swedish study strongly suggests that the procedure does not reduce the risk for esophageal cancer in high-risk patients, such as those with Barrett's esophagus.

Candidates. Fundoplication is recommended for patients whose condition includes one or more of the following:

Esophagitis (inflamed esophagus)
Symptoms that persist or are recurrent in spite of anti-reflux drug treatment
Strictures
Failure to gain or maintain weight (children)

Fundoplication has little benefit for patients with impaired stomach motility (an inability of the muscles to move spontaneously).

The Open Nissen Fundoplication Procedure. Until recently, most fundoplication procedures for GERD have been the 360° Nissen fundoplication. This is called an open procedure because it requires wide surgical incisions.

With this procedure, the physician wraps the upper part of the stomach (fundus) completely around the esophagus to form a collar-like structure.
The collar places pressure on the LES and prevents stomach fluids from backing up into the esophagus.
Open fundoplication requires a 6- to 10-day hospital stay.

Click the icon to see an illustrated series detailing gastroesophageal reflux surgery.

Laparoscopic Fundoplication. The standard invasive fundoplication procedure has been replaced in many cases by a less invasive fundoplication procedure that uses laparoscopy. In the operation:

Tiny incisions are made in the abdomen.
Small instruments and a tiny camera are inserted into tubes, through which the surgeon can view the region.
The surgeon creates a collar using the fundus, although the area is smaller to work with.

When performed by experienced surgeons, the procedure shows results that are equal to those of standard open fundoplication, but with faster recovery time.

Overall, laparoscopic fundoplication appears to be safe and effective in people of all ages, even babies. Laparoscopy is more difficult to perform in certain patients, including those who are obese, who have a short esophagus, or who have a history of previous surgery in the upper abdominal area. It may also be less successful in relieving atypical symptoms of GERD, including cough, abnormal chest pain, and choking. In about 8% of laparoscopies, it is necessary to convert to open surgery during the procedure because of unforeseen complications.

Other Variations. There are now a number of variants of fundoplication procedures. Examples include the following:

Toupet fundoplication employs only a partial wrap, as does a Thal fundoplication. Partial fundoplication procedures may be more effective in patients with poor or no esophageal motility (spontaneous muscle contraction). Those with normal motility may do better with the full-circle wrap.
Others use a very short and "floppy" Nissen full wrap.

Many surgeons report that such limited fundoplications result in earlier feeding and discharge from the hospital and a lower incidence of complications (trouble swallowing, gas bloating, gagging) than the full Nissan fundoplication. A British study, however, reported no significant differences in swallowing problems.

Postoperative Problems and Complications after Fundoplication. Postoperative problems can include a delay in intestinal functioning causing bloating, gagging, and vomiting. These side effects usually resolve in a few weeks. A 2003 study suggested, however, that 38% of patients develop such symptoms, and most occur more than a year after the procedures. If symptoms persist or if they start weeks or months after surgery, particularly if vomiting is present, then surgical complications are likely. Complications include the following:

An excessively wrapped fundus. This is fairly common and can cause difficulty swallowing (dysphagia), as well as gagging, gas, bloating, or an inability to burp. (A follow-up procedure that dilates the esophagus using an inflated balloon may help correct dysphagia, although it cannot treat other symptoms.)
Bowel obstruction
Wound infection
Injury to nearby organs
Respiratory complications, such as a collapsed lung. These are uncommon, particularly with laparoscopic fundoplication.
Muscle spasms after swallowing food. This can cause intense pain, and patients may require a liquid diet, sometimes for weeks. This is a rare complication in most patients, but it can be very high in children with neurologic abnormalities. Such children are already at very high risk for GERD.

Reasons for Treatment Failure. Long-term failure rates after fundoplication are 30% after 5 years and 63% after 10 years. Hiatal herniation is the most common reason for surgical failure and the need for a repeat fundoplication. Other common reasons for reoperation include breakdown, slippage, and excessive tightness of the wrap. Surgeon experience can lessen complication risks. Some studies have reported that repeat operations after open procedures occur in 9 - 30% of cases and 13% after laparoscopy. (Repeat surgery usually has good results.)

A number of treatments that make use of endoscopy are being used or investigated for increasing LES pressure and preventing reflux, as well as for treating severe GERD and its complications.

Transoral Flexible Endoscopic Suturing. Transoral flexible endoscopic suturing (sometimes referred to as Bard's procedure) uses a tiny device at the end of the endoscope that acts like a miniature sewing machine. It places stitches in two locations near the LES, which are then tied to tighten the valve and increase pressure. There is no incision and no need for general anesthesia.

Radiofrequency. Radiofrequency energy generated from the tip of a needle (sometimes called the Stretta procedure) heats and destroys tissue in the problem spots in the LES. Either the resulting scar tissue strengthens the muscle, or the heat kills the nerves that caused the malfunction. Patients may experience some chest or stomach pain afterwards. Few serious side effects have been reported, although there have been reports of perforation, hemorrhage, and even death. A recent study reported that 81% of patients remained symptom-free for up to 3 years following the Stretta procedure.

Implants. In 2003, the FDA approved the Enteryx procedure as a treatment option for people who have persistent symptoms of GERD and who regularly take and respond to PPIs. In 2005, however, the manufacturer of Enteryx (Boston Scientific), voluntarily removed Enteryx from clinical use due to problems related to the difficult injection technique.

Techniques to Stop Bleeding. Endoscopic ablation treatment of bleeding involves using a probe passed through the endoscopic tube, which applies electricity or heat to coagulate blood and stop the bleeding.

Dilation Procedures. Strictures (abnormally narrowed regions) may need to be dilated (opened) with endoscopy. Dilation may be performed by inflating a balloon in the passageway. About 30% of patients who need this procedure require a series of dilation treatments over a long duration in order to fully open the passageway. Long-term use of proton-pump inhibitors may reduce the duration of treatments.

One study also suggested that dilation may help correct swallowing problems that can occur after fundoplication. In the study dilation improved dysphagia in 67% of the surgical patients who had experienced it.

A recent advance is the development of small-caliber upper endoscopy, which does not require sedation and can be performed in the physician's office.

Resources

http://digestive.niddk.nih.gov -- National Digestive Diseases Information Clearinghouse
www.gastro.org -- American Gastroenterological Association
www.acg.gi.org -- American College of Gastroenterology
www.asge.org -- American Society for Gastrointestinal Endoscopy
www.ssat.com -- Society for Surgery of the Alimentary Tract
www.naspgn.org -- North American Society for Pediatric Gastroenterology, Hepatology, and Nutrition
www.reflux.org -- Pediatric/Adolescent Gastroesophageal Reflux Association
www.iffgd.org -- International Foundation for Functional Gastrointestinal Disorders

References

DeVault KR, Castell DO. Updated guidelines for the diagnosis and treatment of gastroesophageal reflux disease. Am J Gastroenterol. 2005;100(1):190-200.

Deviere J, Costamagna G, Neuhause H, Voderholzer W, Louis H, Tringali A, et al. Nonresorbable copolymer implantation for gastroesophageal reflux disease: a randomized sham-controlled multicenter trial. Gastroenterology. 2005;128(3):532-540.

Esposito C, Montupet P, van Der Zee D, Settimi A, Paye-Jaouen A, Centonze A, Bax NK. Long-term outcome of laparoscopic Nissen, Toupet, and Thal antireflux procedures for neurologically normal children with gastroesophageal reflux disease. Surg Endosc. 2006 Jun;20(6):855-8. Epub 2006 May 12. Accessed June 2, 2006.

Gilger MA, Yeh C, Chiang J, Dietrich C, Brandt ML, El-Serag HB. Outcomes of surgical fundoplication in children. Clin Gastroenterol Hepatol. 2004;2(11):978-984.

Gold BD, Schelman JM, Sabesin SM, Vitat P. Updates on the management of upper gastrointestinal disorders in primary care setting:NSAID-related gastropathies and pediatric reflux disease. The Journal of Family Practice. March 2007;56(3):S1-S11.

Hirano I, Richter JE, and the Practice Parameters Committee of the American College of Gastroenterology. ACG practice guidelines: esophageal reflux testing. American Journal of Gastroenterology. 2007;102:668-685.

Kim CY, O'Rourke RW, Chang EY, Jobe BA. Unsedated small-caliber upper endoscopy: an emerging diagnostic and therapeutic technology. Surg Innov. 2006 Mar;13(1):31-9.

Koslowsky B, Jacob H, Eliakim R, Adler SN. PillCam ESO in esophageal studies: improved diagnostic yield of 14 frames per second (fps) compared with 4 fps. Endoscopy. 2006 Jan;38(1):27-30.

Remedios M, Campbell C, Jones DM, Kerlin P. Eosinophilic esophagitis in adults: clinical, endoscopic, histologic findings,and response to treatment with fluticasone propionate. Gastrointest Endosc. 2006 Jan;63(1):3-12.

Rudolph CD, Mazur LJ, Liptak GS, Baker RD, Boyle JT, Colletti RB, et al. Guidelines for evaluation and treatment of gastroesophageal reflux in infants and children: recommendations of the North American Society for Pediatric Gastroenterology and Nutrition. J Pediatr Gastroenterol Nutr. 2001;32 Suppl 2: S1-S31.

Review Date:
5/22/2007
Reviewed By:
Harvey Simon, MD, Associate Professor of Medicine, Harvard Medical School; Physician, Massachusetts General Hospital.

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adam.com

Crohn's disease

FitSugar — Wed, 08 Oct 2008 17:35:29 -0700

In This Report

Highlights

Introduction

Causes

Symptoms

Complications

Risk Factors

Diagnosis

Dietary Factors

Symptom Management

Medications

Surgery

Resources

References

HEALTH GUIDE REFERENCE FROM A.D.A.M

Highlights

Biologic Drugs

In February 2007, the FDA approved adalimumab (Humira) for treatment of adult patients with moderate-to-severe Crohn’s disease. Adalimumab and infliximab (Remicade) are now the two biologic drugs approved for Crohn’s disease. Infliximab is approved for treating both adults and children.

As of August 2007, the FDA was considering approving natalizumab (Tysabri) for moderate-to-severe Crohn’s disease in patients who have not responded to, or cannot tolerate, other therapies. However, natalizumab has serious risks -- in 2007, the European medicine agency rejected natalizumab for Crohn’s disease treatment.

Certolizumab (Cimzia) is another biologic drug that is showing promise for Crohn’s disease, according to several 2007 studies in the New England Journal of Medicine.

The risks of biologic drugs need to be weighed against their potential benefits, according to a 2007 consensus statement from the American Gastroenterological Association. These drugs may be appropriate as initial treatments for select patients who have fistulas or for patients who have not been helped by corticosteroid drugs.

Genetic Research

In 2006 and 2007, scientists achieved major breakthroughs in identifying specific genes associated with Crohn’s disease. Among these recent discoveries:

The interleukin-23 receptor (IL23R) gene is associated with variations that can either increase or decrease the risk for Crohn’s disease and ulcerative colitis.

The ATG16L1 gene regulates a process called autophagy, which involves how a cell digests itself. Scientists think that waste build-up from improperly regulated autophagy may play a role in the inflammatory response associated with Crohn’s disease.

Other recently identified genes that may be linked with Crohn’s disease include PHOX2B and NCF4.

Pregnancy Complications

According to a 2007 review in Gut, inflammatory bowel disease significantly increases the risk for pregnancy complications, such as premature birth, low birth weight, and birth defects. Women who experience disease flares during pregnancy are especially at risk.

Introduction

Inflammatory bowel disease (IBD) is a general term that covers two disorders:

Ulcerative colitis (UC)

Crohn's disease (CD)

Some evidence suggests that these two diseases are part of a biologic continuum. At this time, however, they are considered distinct disorders with somewhat different treatment options. The basic distinctions between UC and CD are location and severity. However, as many as 10% of patients with IBD have features and symptoms that match the criteria for both disorders, at least in the early stages. (This is called indeterminate colitis.)

Crohn's disease, also called regional enteritis, is a chronic inflammation of the intestines which is usually confined to the terminal portion of the small intestine, the ileum. Ulcerative colitis is a similar inflammation of the colon, or large intestine. These and other IBDs (inflammatory bowel disease) have been linked with an increased risk of colorectal cancer.

Crohn's Disease. Crohn's disease is an inflammation that extends into the deeper layers of the intestinal wall. It is found most often in the area bridging the small and large intestines, specifically in the ileum and the cecum, sometimes referred to as the ileocecal region. Crohn's disease occurs less frequently in other parts of the gastrointestinal tract, including the anus, stomach, esophagus, and even the mouth. It may affect the entire colon or form a string of contiguous ulcers in one part of the colon. It may also develop as multiple scattered clusters of ulcers throughout the gastrointestinal tract, skipping healthy tissue in between.

Click the icon to see an image of Crohn's disease.

Ulcerative Colitis. Ulcerative colitis is an inflammatory disease of the large intestine. Ulcers form in the inner lining, or mucosa, of the colon or rectum, often resulting in diarrhea, blood, and pus. The inflammation is usually most severe in the sigmoid and rectum and typically diminishes higher in the colon. The disease develops uniformly and consistently until, in some people, the colon becomes rigid and foreshortened. [See In-Depth Report #69: Ulcerative colitis.]

Click the icon to see an image of the structure of the colon.

The gastrointestinal tract (the digestive system) is a tube that extends from the mouth to the anus. It is a complex organ system that first carries food from the mouth down the esophagus to the stomach and then through the small and large intestine to be excreted out through the rectum and anus.

Esophagus. The esophagus, commonly called the food pipe, is a narrow muscular tube, about 9 1/2 inches long, that begins below the tongue and ends at the stomach.

Stomach. In the stomach, acids and stomach motion break food down into particles small enough so that nutrients can be absorbed by the small intestine.

Small Intestine. The small intestine, despite its name, is the longest part of the gastrointestinal tract and is about 20 feet long. Food that passes from the stomach into the small intestine first passes through three parts:

First it enters the duodenum

Then the jejunum, and

Finally the ileum

Most of the digestive process occurs in the small intestine.

Large Intestine. Undigested material, such as plant fiber, is passed to the large intestine, mostly in liquid form. The large intestine is approximately 6 feet long and is the final portion of the digestive tract. It follows the small intestine and includes the cecum, the appendix, the colon, and the rectum, which extends to the anus.

Cecum and Appendix. The cecum and the appendix are located in the lower-right quadrant of the abdomen.

Colon. The colon absorbs excess water and salts into the blood. The remaining waste matter is converted to feces through bacterial action. The colon is divided into four major sections.

The first section, the ascending colon, extends upward from the cecum on the right side of the abdomen.

The second section, the transverse colon, crosses the upper abdomen to the left side.

The third section extends downward on the left side of the abdomen toward the pelvis and is called the descending colon.

The final section is the sigmoid colon.

Rectum and Anus. Feces are stored in the descending and sigmoid colon until they are passed through the rectum and anus. The rectum extends through the pelvis from the end of the sigmoid colon to the anus.

Click the icon to see an image of the digestive system.

Click the icon to see an image of the stomach.

Click the icon to see an image of the structure of the small intestine.

Click the icon to see an image of the structure of the colon.

Causes

Inflammatory bowel disease has many different causes. It is due in many cases to a genetic susceptibility that enables an organism such as a virus or bacteria to trigger an abnormal immune reaction, which in turn, causes an inflammatory response in the intestines. Although Crohn's disease has features that resemble an autoimmune disease (in which the body's immune system attacks its own cells), some researchers think that it may be due to initial immune deficiencies.

The Immune System's Infection Fighters. The primary infection-fighting units are two types of white blood cells: lymphocytes and leukocytes.

Lymphocytes include two subtypes known as T cells and B cells. Both types of cells are designed to recognize foreign invaders (antigens) and to launch an offensive or defensive action against them:

B cells produce antibodies, which are separate substances that can either ride along with a B cell or travel on their own to attack the antigen.

T cells have special receptors attached to their surface that recognize the specific antigen.

T cells are further categorized as killer T cells or helper T cells.

Killer T cells directly attack antigens that occur in any cells that contain a nucleus.

Helper T cells also recognize antigens, but their role is two fold. They stimulate B cells and other white cells to attack the antigen. They also produce cytokines, powerful immune factors that have an important role in the inflammatory process.

Helper T cells and Inflammatory Bowel Disease. The actions of the helper T cells (TH cells) are of special interest in inflammatory bowel disease:

TH cells stimulate other white blood cells called B cells to produce antibodies. In this case, however, they appear to direct the B cells to produce autoantibodies, which are directed against the body's own cells.

TH cells also secrete or stimulate the production of powerful immune factors called cytokines. In small amounts, cytokines are indispensable for healing. If overproduced, however, they can cause serious damage, including inflammation and cellular injury. Cytokines, particularly specific ones known as tumor necrosis factor, interferon-gamma, and interleukins, cause intestinal inflammation and damage, which, in a vicious cycle, attract even more helper T cells.

Helper T cells are further categorized as TH1 and TH2. An imbalance in these two types appear to occur in IBD, although each disorder has a different balance:

Ulcerative colitis patients favor a TH2 response, which activates the interleukins IL-5, IL-6, and IL-10. These mostly affect mucosal areas in the intestine.

Research indicates that patients with Crohn's disease have increased activity in TH1 cells, activating interleukin-2 (IL-2) and interferon-gamma, which affect intestinal cells. Tumor necrosis factor (TNF) may be a particularly potent immune factor in Crohn's disease. It is important in properties that regulate inflammation and cell proliferation. If genetic or other factors increase production of this immune compound, it can lead to great harm.

Interleukin 6 appears to play a part in both IBDs, by inhibiting a natural process called apoptosis, in which cells self-destruct. As a result, cells proliferate faster than they die, causing an excessively strong immune response.

Adhesion Molecules. Increased levels of certain molecules called E-selectin and intercellular adhesion molecule-1 (ICAM-1) also appear to play a major role in the inflammatory process by causing damaging immune factors to build up on intestinal cells.

Matrix Metalloproteinase. Greater activity of enzymes called matrix metalloproteinase has been detected in the colons of patients with IBD. These increased levels tend to break down the extracellular matrix, a barrier composed of structural proteins and elastic fibers that surrounds and supports cells, in this case in the colon. Researchers suggest that this activity may cause persistent damage once the inflammatory process has triggered IBD.

Although the causes of inflammatory bowel disease are not yet known, genetic factors certainly play some role. Between 10 - 20% of people with ulcerative colitis have family members with the disease. Several identified genes and chromosome locations play a role in the development of ulcerative colitis, Crohn's disease, or both. Genetic factors appear to be more important in Crohn's disease, although there is evidence that both forms of inflammatory bowel disease have common genetic defects.

Specific Genes Involved. The first important genetic discovery for Crohn’s disease was the identification of the genetic variant CARD15 (also called NOD2), which alters the immune system so that it launches an over-reaction in response to bacteria, causing inflammation. However, this genetic factor only affects a small percentage of Crohn’s disease cases and is not involved with ulcerative colitis.

In 2006, scientists made a significant genetic research breakthrough by identifying the interleukin-23 receptor (IL23R) as a major link to the development of both Crohn’s disease and ulcerative colitis. Interleukin 23 is a cytokine that plays an important part in the inflammatory response and inflammatory diseases. Interestingly, scientists found that certain variations in the IL23 receptor gene can either increase or decrease the risk for inflammatory bowel disease. Further research in 2007 indicated that IL23R gene variants may also increase or decrease the risk for Crohn’s disease in children.

Also in 2007, scientists identified several other genetic risk factors for Crohn’s disease, including the genes PHOX2B, NCF4, and ATG16L1. Scientists are particularly interested in the ATG16L1 gene. This gene regulates autophagy, the process in which a cell digests its own cytoplasm, including cellular waste products such as bacteria. Problems with autophagy may lead to a build-up of unprocessed waste products within the cell. This build-up may then provoke the inflammatory response associated with Crohn’s disease. Mutations of the ATG16L1 gene have been linked to increased susceptibility to Crohn’s disease in both adults and children.

Future genetic research may help develop targeted drug therapy for treatment of inflammatory bowel disease.

One theory suggests that viruses or bacteria within the intestine may alter properties in the lining and intestinal tract. Over time, these changes may trigger the processes that lead to inflammatory bowel disease.

Measles. Some studies report that children with IBD may have had more and earlier childhood infections. The measles virus has been of particular interest. According to the U.S. Centers for Disease Control, and many studies, the measles virus does not cause Crohn’s or IBD.

Much publicity has centered on whether the vaccine for measles, mumps, and rubella (the MMR vaccine) causes conditions such as autism and Crohn’s disease. This theory has been rigorously reviewed and refuted in many well-conducted studies, including several published in 2006. The evidence clearly indicates that the MMR vaccine does not increase the risk of Crohn’s disease, other inflammatory bowel disease, or autism.

Mycobacteria. A type of bacterium associated with tuberculosis is another possible candidate for an infectious cause of Crohn’s disease.

Escherichia coli. The intestine normally harbors E. coli bacteria. In most cases, the bacteria are harmless and even protective. Some E. coli strains, however, can bind to the intestinal walls and penetrate the lining. These damaging strains may be associated with Crohn’s disease.

Cytomegalovirus. Cytomegalovirus (CMV) is a common virus that is also under suspicion as a contributor to severe cases of IBD.

Inflammatory bowel disease is much more prevalent in industrialized nations and in higher-income groups. Diet may play some role, although studies have been conflicting over its importance.

Symptoms

The two major inflammatory bowel diseases (IBDs), ulcerative colitis and Crohn's disease, share certain characteristics:

Symptoms usually appear in young adults.

Symptoms can develop gradually or have a sudden onset.

Both are chronic. In either disease, symptoms may flare up (relapse) after symptom-free periods (remission) or symptoms may be continuous without treatment.

Symptoms can be mild or very severe and disabling.

The severity of symptoms and relapse rates of both IBDs vary with seasons, with the highest risk in the winter and autumn and lowest in summer.

The two disorders, however, have different symptom profiles and is it important to differentiate between them, since they require different treatments.

Symptoms

Ulcerative Colitis

Crohn's Disease

Diarrhea

Recurrent diarrhea is very common, but onset may be very gradual and mild or it may not be present. Feces may also contain mucus.

Recurrent diarrhea is fairly common.

Rectal Bleeding

Blood is almost always present in stools. It may be readily visible or visible only using a microscope (called occult blood).

Bleeding not as common as in UC, but can occur.

Constipation

Constipation can be a symptom of UC, but not as common as diarrhea. Can occur during flare-ups. May occur when the inflamed rectum triggers a reflex response in the colon that causes it to retain the stool.

Constipation in Crohn's disease is usually a symptom of obstruction in the small intestine.

Abdominal Symptoms

Pain is not prominent symptom, but can vary. May cause vague discomfort in the lower abdomen, an ache around the top of the hipbone, or cramps in the middle of the abdomen. Severe pain can occur during flare-ups. Vomiting and nausea.

Main symptom is recurrent episodes of pain in the lower right part of the abdomen or above the pubic bone. Often preceded by and relieved by defecation. Bloating, nausea, and vomiting may also occur. Intestinal pain may also be an indication of a serious condition, such as an abscess, or a perforation of the intestinal wall.

Fever

May occur with severe attacks.

Usually low-grade. Spiking fever and chills indicates complications.

Loss of appetite, weight loss, and impaired growth in children

Often not evident in mild or even moderately severe UC. Occasionally impairs growth in children and teenagers.

Common. Typical weight loss is 10 - 20% of normal. Commonly impairs growth in children and teenagers.

Abnormal defecation: Increased frequency, a feeling of incomplete evacuation, and tenesmus (a painful urge for a bowel movement even if the rectum is empty). Fecal incontinence.

Symptoms may be mild or severe.

Can occur in active stages.

Anal ulcers and fistulas: (channels that can burrow between organs, loops of the intestine, or between the intestines and skin).

Almost never a symptom.

Fistulas and ulcers around the anus may be early symptoms.

Neurologic or psychiatric symptoms

No.

May be early signs of Crohn's disease when accompanied by gastrointestinal problems.

There are three body views (front, back and side) that may be helpful if you are uncertain of a body area. Many areas are referred to by both descriptive and technical names. For example, the back of the knee is called the popliteal fossa. However, areas like the "flank" may not have both names, so the location may be unclear.

Click the icon to see a depiction of an anorectal fistula.

Complications

The outlook for Crohn's disease varies widely. Crohn's disease can range from being benign (such as when limited Crohn's disease occurs only around the anus in older people) or it can be very severe. At the extreme end, some patients may experience only one episode and others suffer continuously. Although recurrences tend to be the norm, disease-free periods can last for years or decades in some patients. Although Crohn's disease cannot be cured even with surgery, treatments are now available that can offer significant help to most patients. Crohn's disease is rarely a direct cause of death, and most people can live a normal lifespan with this condition.

Mild Crohn's Disease. The fewer bowel movements, the milder the disease. In mild disease, abdominal pain is absent or minimal. The patient has a sense of well-being that is normal or close to normal. There are few, if any, complications outside the intestinal tract. The doctor does not detect any mass when pressing the abdomen. The red blood cell count is normal or close to normal, and the patient is not underweight.

Severe Crohn's Disease. In severe Crohn's disease, the patient has bowel movements frequent enough to require opiates or other potent anti-diarrhea medication. Abdominal pain is severe and usually located in the lower right quadrant of the abdomen. (The location of the pain might not indicate the site of the actual problem, a phenomenon known as referred pain.) The red blood cell count is low. The patient has a poor sense of well-being and experiences complications that may include weight loss, joint pain, inflammation in the eyes, reddened or ulcerated skin, fistulas, abscesses, and fever. The surgical and medical treatments of Crohn's disease, as with ulcerative colitis, have complications of their own that can be severe.

Malabsorption and malnutrition. Malabsorption is the inability of the intestines to absorb nutrients. In IBD, this occurs as a result of bleeding and diarrhea, as a side effect from some of the medications, and as a result of surgery. Malnutrition usually develops slowly and tends to become severe, with multiple nutritional deficiencies. It is very common, ranging from 25 - 80% of patients with Crohn's disease.

Ulcer, Fistulas, and Abscesses. Between 30 - 40% of patients with Crohn's disease experience complications around the anal area from inflammation. Fistulas (channels beneath the skin) frequently develop from the deep ulcers that can form with Crohn's. If fistulas develop between the loops of the small and large intestines, they can interfere with absorption of nutrients. They often form pockets of infection or abscesses, which may become life threatening without treatment.

Bleeding. Massive bleeding can occur in 1 - 2% of cases and may be recurrent. Bleeding is usually from a localized area in the intestine. Surgery may be performed to remove the bleeding sites.

Colorectal Cancers. Patients with inflammatory bowel disease have a slightly higher risk for colorectal cancer. The risk is greater for patients with severe ulcerative colitis than for those with Crohn’s disease. Patients with Crohn’s disease do have a 40-fold increased risk for small bowel cancer. (However, small bowel cancer is a very rare type of cancer.) The risk increases with the severity of the condition and the length of time the patient has had Crohn’s. [See In-Depth Report #55: Colon and rectal cancers.]

Intestinal Blockage. Inflammation from Crohn's disease produces scar tissue known as strictures that can constrict the intestines, causing bowel obstruction with severe cramps and vomiting. Strictures usually occur in the small intestine but can also occur in the large intestine.

Intestinal Infections. Inflammatory bowel disease can increase patients’ susceptibility to Clostridium difficile, a species of intestinal bacteria that causes severe diarrhea. As its name implies, C. difficile is difficult to treat and is resistant to many types of antibiotics. It is usually acquired in a hospital. However, several 2007 studies indicated that C. difficile is increasing among patients with inflammatory bowel disease and that many patients acquire this infection outside of the hospital setting. Patients with ulcerative colitis are at particularly high risk.

People with inflammatory bowel disease have a higher risk of developing other inflammatory diseases that affect the lungs and central nervous system.

Asthma. According to a 2005 study, people with IBD are 1.5 times more likely to have asthma than people without IBD. Of all the conditions that can accompany IBD, asthma is the most common. People with IBD are also at increased risk for bronchitis and other lung inflammations

Eyes. Inflammation in the eyes may sometimes be an early sign of Crohn’s disease. Retinal disease, including detachment, can occur but is rare. People with accompanying arthritic complications may be at higher risk for eye problems.

Joints. Inflammation causes arthritis and stiffness in the joints. The back is commonly affected. Patients with Crohn’s disease are also at risk for clubbing (abnormal thickening and widening at the ends of fingers and toes).

Click the icon to see an image of nail clubbing.

Bones. Crohn’s disease, and the corticosteroid drugs used to treat it, can cause osteopenia (low bone density) and osteoporosis (bone loss).

Anemia. Internal blood loss from ulcers in the intestine is a particular problem in Crohn's disease because of the impaired ability to absorb vitamins and minerals necessary for blood production.

Liver and Gallbladder Disorders. Patients have a higher than average risk for mild but not severe liver problems. They have double the normal risk for gallstones.

Click the icon to see an image of gallstones.

Mouth Sores. Canker sores are common, and when they occur they persist. Those at higher risk are males and younger people. Mouth yeast infections also common in people with Crohn's disease.

Skin Disorders. Patients with Crohn’s disease are likely to develop red knot-like swellings. Such swellings or other skin lesions, such as ulcers, may spread to sites far removed from the colon, (including the arms and legs). People with Crohn's disease have an increased risk for psoriasis.

Thromboembolism (Blood Clots). Clots may occur, most likely in the legs and pelvic area.

Click the icon to see an image of a thrombus.

Urinary Tract and Kidney Disorders. Urinary tract infections are common. Patients have an increased risk for kidney stones. Amyloidosis (deposits of a protein called amyloid in the kidney or other organs) is a rare but very serious kidney condition.

Click the icon to see an image of kidney stones.

Delayed Growth and Development in Children. Up to half of children with Crohn’s disease have impaired physical growth, and nearly all are underweight. About 30% reach puberty late, but once it occurs, hormonal cycles tend to be normal.

Infertility. Infertility rates are only slightly lower than average. Active disease at conception increases risk for miscarriage or prematurity. Men may have lower sperm count during active disease or because of impaired nutrition, but in general fertility is normal.

Pregnancy. Inflammatory bowel disease doubles the risk of pregnancy complications. According to a 2007 review, women with inflammatory bowel disease are nearly twice as likely to give birth prematurely. Children born to mothers with this disease are more than twice as likely to be below normal weight and to have birth defects. If a woman experiences active bouts of disease during the course of her pregnancy, her risk for complications increases.

Menstrual Problems. Menstrual problems in women are common, including premenstrual disorder, abnormal bleeding, and pain. Pain with intercourse occurs in about half of patients. Sexual function may be impaired, not only because of the emotional impact, but also by treatment side effects and complications of the disease, such as fistulas.

Neurologic Factors. Inflammatory bowel disease has been associated with neurologic complications, including a higher risk for dementia, movement disorder, and stroke. People with IBD have a higher risk for developing multiple sclerosis and inflammation of the optic nerve (optic neuritis).

Emotional Factors. The emotional consequences of UC cannot be overestimated, particularly in children. Eating becomes associated with fear of abdominal pain before the end of the meal. Frequent attacks of diarrhea can cause such a strong sense of humiliation that social isolation and low self-esteem may result. Adolescents with IBD may have added problems that increase emotional distress, including weight gain from steroid treatments and delayed puberty.

Risk Factors

About 1 - 2 million Americans suffer from inflammatory bowel disease (IBD), and about 400,000 of these patients have Crohn's disease. (This wide variation is due to the difficulty in diagnosing these disorders and because people in remission may not be identified.) The number of people with Crohn's disease may be increasing, and Crohn's disease is now considered to be the second most common chronic inflammatory disorder (after rheumatoid arthritis).

IBD often runs in families. The incidence may vary depending on gender, age, and geography:

Women may be slightly more at risk for Crohn's disease than men. Both genders are equally at risk for ulcerative colitis.

IBDs in general are diagnosed most often in young people age 10 - 19, but they can occur at any age. Another lesser peak onset occurs in people ages 50 - 80. About 2% of IBD cases appear in children below age 10. Between 10 - 15% of patients with Crohn's are children, and the childhood prevalence appears to be increasing.

IBD occurs four times more often in Americans of Northern European descent than in African-Americans. Scandinavia has the highest rate of Crohn's disease in the world. Studies in Britain suggest, however, that Asians may have a higher rate of IBD than people of European descent. Ashkenazi Jewish people have an even higher risk, five times that of the general population.

IBD seems to be more common among city than country dwellers and occurs more frequently in developed than in less developed nations, indicating that both genetic factors and environmental conditions, such as diet, may be involved in its development.

People who are left-handed have a significantly higher risk for both IBDs as well as certain other diseases associated with problems in the immune system.

Diagnosis

The doctor will take a history and perform a thorough physical examination. The disease is particularly difficult to diagnose in children. In children, IBD may be mistaken for an infection or even depression if other characteristic symptoms, such as bloody diarrhea and weight loss, are not present. Slow growth may be a key feature in making a diagnosis, particularly of Crohn's disease, in children.

Several laboratory tests may be performed:

Blood tests are used for various purposes. An increased number of white blood cells may indicate the presence of inflammation. Blood tests are used to determine the presence of anemia and to measure liver enzymes. (They are abnormal in about 3% of ulcerative colitis patients.) New blood tests that measure certain antibodies may make it easier to differentiate Crohn's disease from ulcerative colitis in children.

A stool sample is taken and examined for blood, infectious organisms, or both.

Standard Endoscopic Procedures. Flexible sigmoidoscopy and colonoscopy are procedures that involve snaking a fiberoptic tube called an endoscope through the rectum to view the lining of the colon. The doctor can also insert instruments through it to remove tissue samples.

Sigmoidoscopy, which is used to examine only the rectum and left (sigmoid) colon, lasts about 10 minutes and is done without sedation. It may be mildly uncomfortable, but it is not painful.

Colonoscopy allows a view of the entire colon and requires a sedative, but it is still performed on an outpatient basis. It is important in differentiating between Crohn's disease and ulcerative colitis and in screening for colon cancer.

There are three basic tests for colon cancer: a stool test (to check for blood); sigmoidoscopy (inspection of the lower colon); and colonoscopy (inspection of the entire colon). All three are effective in catching cancers in the early stages, when treatment is most beneficial.

The procedures may help the doctor to distinguish between ulcerative colitis and Crohn's disease, as well as other diseases. A variation called chromoendoscopy uses a blue stain during the process to reveal fine details on the intestinal lining. It might prove to be useful for identifying areas that may be precancerous and need to be biopsied.

Wireless Capsule Endoscopy. Wireless capsule endoscopy (WCE) is a newer imaging approach that is very useful for diagnosing Crohn's disease. With WCE, the patient swallows a capsule containing a tiny camera that records and transmits images as it passes through the gastrointestinal tract. Some studies have found it to be much more accurate for evaluating small bowel disease than barium x-rays or CT scans. Patients also find it easier to tolerate than standard endoscopy.

Ultrasound. Intestinal wall ultrasound is proving to be useful for identifying the extent and severity of Crohn's disease. It is uncertain if ultrasound is useful for an initial diagnosis.

Upper and Lower Gastrointestinal Barium X-Rays. An upper gastrointestinal barium x-ray may be used if Crohn's disease is suspected in the small intestine. Swallowed barium passes into the small intestine and shows up on an x-ray image, which may reveal inflammation, ulcers, and other abnormalities.

Click the icon to see an image of the barium enema procedure.

Positron Emission Tomography (PET) and Computed Tomography (CT) Scans. PET/CT scans are proving to be extremely useful in evaluating active IBD. With Crohn's disease, CT scans may show thickened walls and complications, such as fistulas, which occur outside the intestine.

Magnetic Resonance Imaging (MRI). Magnetic resonance imaging is another advanced imaging technique that may be useful for detecting abscesses and other injuries related to Crohn's disease in the pelvis. A variant called magnetic resonance spectroscopy (MRS) may prove to be useful for differentiating between Crohn's disease and ulcerative colitis.

Endoscopy

Ulcerative colitis almost always involves the lower left colon and rectum and can be diagnosed using sigmoidoscopy. Crohn's disease may require colonoscopy as well. Endoscopy often reveals ulcers, diseased regions that have a cobblestone-like appearance in Crohn's disease, but not in ulcerative colitis.

X-Rays (Barium Enema) or Computed Tomography Scans

In ulcerative colitis, inflammation is usually evenly distributed on the surface lining of the intestine, and the bowel wall bleeds easily when touched with a swab. The pattern observed in Crohn's disease is usually one of scattered patches of ulcers that are deep, thick, and large.

Crohn's disease produces pockets (fissures) or channels (fistulas). They do not occur with UC.

In ulcerative colitis the ileum (the lower part of the small intestine) is often dilated while it is narrowed in Crohn's disease.

Laboratory Tests

Tissue samples obtained from a patient with Crohn's disease may reveal granulomas, small collections of inflammatory cells. Granulomas may also be present in other conditions, however. Tissue samples should also be examined for the presence of cancerous cells.

About 70% of antibody tests for patients with UC will show immune factors called perinuclear-staining antineutrophil cytoplasmic antibodies, and over 50% of Crohn's patients have anti-Saccharomyces cerevisiae antibodies. Each antibody group shows up only occasionally in the other disorder. Researchers are also investigating other antibodies, such as antilaminaribioside and antichitobioside, which may serve as new markers for Crohn’s disease.

Irritable Bowel Syndrome. Irritable bowel syndrome (IBS), also known as spastic colon, functional bowel disease, and spastic colitis cause many of the same symptoms as inflammatory bowel disease (IBD). (However, it is NOT the same as inflammatory bowel disease.) Bloating, diarrhea, constipation, and abdominal cramps are all symptoms of IBS. Irritable bowel syndrome is not caused by inflammation, however, and no fever or bleeding occurs. Behavioral therapy may be helpful in treating IBS. (Psychological therapy does not improve inflammatory bowel disease.)

Microscopic Colitis. Microscopic colitis causes chronic watery diarrhea, but the colon lining shows little or no signs of inflammation. It may be genetically linked to celiac sprue. Most patients can expect to improve.

Celiac Sprue. Celiac sprue, or celiac disease, is an intolerance to gluten (found in wheat) that triggers inflammation in the small intestine and causes diarrhea, vitamin deficiencies, and stool abnormalities. It occurs in a significant number of people with inflammatory bowel disease and is usually first noticed in children.

Click the icon to see foods to avoid if you have celiac sprue.

Interstitial Cystitis. Interstitial cystitis (IC) is an inflammation of the bladder wall that occurs almost exclusively in women. Some evidence suggests that the risk for IBD in these patients is 100 times above that in the general population and that there may be some common factor to both conditions. The average age of patients with interstitial cystitis is 40, but 25% of cases occur in women under age 30. Symptoms are very similar to urinary tract infections, but no bacteria are present. Pain during sex is a very common complaint in these patients, and stress may intensify symptoms.

Infections. If endoscopy reveals inflammation, a doctor must always rule out possible infections before confirming a diagnosis of inflammatory bowel disease.

Acute Appendicitis. Crohn's disease may cause tenderness in the right lower part of the abdomen, where the appendix is located, that resembles an appendicitis.

Click the icon to see an image of the appendix.

Cancer. Colon or rectal cancers must always be ruled out when symptoms of IBD occur.

Intestinal Ischemia. Symptoms similar to IBD can be caused by blockage of blood flow in the intestine. This is more likely to occur in elderly people.

Dietary Factors

The role of diet and nutrition is very important in Crohn's disease and should be considered for four separate situations:

As important add-on treatment to medical therapies for maintaining nutrition and correcting any nutritional deficiencies

As primary treatment for reducing disease activity

As maintenance therapy on a long-term basis in the case of severe intestinal failure or short-bowel syndrome

For reversing growth-failure in children

Malnutrition is very common in Crohn's disease. In fact, patients with Crohn's appear to burn fat calories at a higher rate than the general population and most patients are underweight. Some experts recommend that children with inflammatory bowel disease increase their calorie and protein intake by 150% of the daily recommended allowance for their specific ages and heights. Studies indicate that nutritional support in children is as important as medications for achieving remission. People whose weights are normal or no less than 90% of normal do not need to add extra calories.

Fluids (non-caffeinated). Drinking plenty of water is extremely important. Vegetable juice and sports drinks may be helpful for restoring important minerals. People with inflammatory bowel disease (IBD) should avoid caffeinated beverages in general, although green tea may have some benefits for Crohn's disease.

Protein. Proteins are very important for growth in children and for repair of cells. Diarrhea can cause protein deficiency, and patients with inflammatory bowel disease may need more protein than the general population. Oily fish, such as salmon and tuna, may be particularly beneficial in Crohn's disease. Other options are poultry and lean meats. Dried beans and legumes also provide protein.

Complex Carbohydrates. Complex carbohydrates, found in whole grains, fruits, and vegetables, should make up half of a patient's calories. Fresh fruit (such as apples, grapefruit, oranges, plums, blueberries, raspberries, and strawberries) may actually be specifically protective for IBD and may possibly reduce the risk for colon cancer. (Simple sugars can increase inflammation, however, so patients should avoid dried fruits and high-sugar fruits, such as grapes, pineapple, and watermelon.)

Foods made up of complex carbohydrates are also often a good source of fiber, which may help reduce damage in the intestinal tract caused by inflammation. However, high-fiber foods can cause gas, bloating, and pain, particularly in IBD patients. Commercial products (such as Beano) are available that can reduce gas. Eating small, frequent meals can also help.

Liquid Supplements. Over-the-counter liquid diets that meet full nutritional needs and are absorbed in the upper intestine, such as Ensure, Sustacal, and other products, may be helpful for some patients with Crohn's. However, it is important to note that no studies have determined this.

Potassium-rich Foods. Examples are potatoes, avocados, and bananas.

Exclusion Diets. Exclusion diets are those that eliminate certain foods that may cause allergies or irritate the intestine. To determine these foods, patients use an "elimination/challenge" approach. First, they remove all suspect foods from their diet for 2 weeks and then reintroduce one food every 3 days. Patients then watch for any symptoms that might indicate an allergic or irritant response, including gastrointestinal problems, headaches, and flushing. This approach, however, may be very difficult, and studies are weak in confirming its value for maintaining remission.

Typical foods people with inflammatory bowel disease (IBD) may avoid include:

Fats. Fats appear to worsen intestinal inflammation in Crohn's disease. Patients should limit fats, particularly saturated fats, found in meat and dairy products. However, certain fatty acids, such as those found in fish oil, may be helpful. The optimal balance between a low-fat diet with addition of these fatty acids is under investigation.

Milk products. Some people with IBD are lactose intolerant (unable to digest the sugar lactose, found in milk products). However, milk, along with the calcium it contains, has been associated with a lower risk for colon cancer. Taking lactase tablets or specially prepared dairy products may help. (Many lactose-intolerant patients are still able to eat yogurt with active cultures, which could be helpful for IBD.)

Foods associated with inflammation (alcohol, simple sugars, and caffeine).

Fruits may be protective, but patients should avoid dried fruits or high-sugar fruits, such as grapes, watermelon, or pineapple.

Products containing corn or gluten (those made from wheat, oats, barley, or triticale).

Common allergenic foods, such as soy, eggs, peanuts, tomatoes.

Foods that may irritate the intestine, particularly so-called Brassica vegetables (cabbage, Brussels sprouts, broccoli, cauliflower, kale).

Kidney stones are painful and common complications in inflammatory bowel disease (IBD), particularly in patients who have had intestinal surgery. IBD patients are at risk for the most common types of kidney stones -- those composed of either calcium oxalate or uric acid crystals. The following are some considerations in reducing the risk for stones:

The most important dietary recommendation is to increase fluid and restrict sodium intake.

Limiting protein is recommended for reducing kidney stones. However, people with IBD who have frequent diarrhea are protein deficient. Having enough protein in the diet, particularly in children with IBD, is very important. Patients should weigh the importance of protien against any risk for kidney stones.

Patients should eat more potassium-rich foods (bananas, watermelon, cantaloupe, oranges, tomatoes, beans).

Patients should try to correct any dietary habits that cause acidic or alkaline imbalances in the urine that promote stone formation.

Many kidney stones are formed from calcium-oxalate stones. Patients should avoid or limit intake of oxalate-rich foods, such as beets, beet tops, black tea, chenopodium, chocolate, cocoa, dried figs, ground pepper, lamb quarters, lime peel, nuts, parsley, poppy seeds, purslane, rhubarb, sorrel, spinach, and Swiss chard. A high calcium diet does not appear to increase the risk for kidney stones as long as it also contains plenty of fluids, dietary potassium, and phosphate. Importantly, calcium is associated with protection against colon cancer and osteoporosis -- two conditions that are associated with IBD.

Patients who have stones associated with short-bowel syndrome should eat less fat and foods that contain oxalates. In these people, calcium may bind to unabsorbed fat instead of to oxalates, which increase oxalate levels.

The general recommendations for avoiding kidney stones need to be tailored to the dietary requirements of IBD. Patients should work with their doctors to develop a plan.

Researchers are currently investigating bacteria (called probiotics) and specific foods (called prebiotics) that are metabolized by these bacteria, and the compounds they produce (called synbiotics). Some evidence suggests that alone or in combination, they may have significant benefits in the intestine.

Probiotics are bacterial strains that by themselves may provide a barrier against harmful bacteria, possibly through various mechanisms such as excreting certain acids (lactate, acetate) that inhibit harmful bacteria or compete with them for nutrients. It has been suggested that probiotics may help maintain remission in patients with inflammatory bowel disease (IBD). The specific bacterial strains that might be beneficial, however, are not fully known. The most well-known probiotics are the lactobacilli strains, such as acidophilus, which are found in yogurt and other fermented milk products. Others, however, may prove to be more important, such as bifidobacteria and GG lactobacilli. Other probiotics that may be beneficial for patients with IBD include lactobacilli rhamnosus, casel, plantarium, bulgaricus, and salivarius, and also Enterococcus faecium and Streptococcus thermophilus.

Prebiotics are specific non-digestible molecules called fructo-oligosaccharides, which stimulate the growth of probiotics. These molecules are found in many foods, including Jerusalem artichokes, onions, salsify, bananas, honey, garlic, and leeks. (However, some of these foods can irritate the intestine in patients with IBD.)

Researchers are investigating probiotics, prebiotics, or both for intestinal protection, including benefits for patients with IBD. Foods and supplements containing these substances are available in the U.S. and are heavily marketed in Europe, Japan, and Australia. To date, however, no studies have determined any clear benefits of any specific organism or formulation.

Crohn's disease and surgical procedures that remove parts of the small intestine can inhibit absorption of vitamins, fats, and other important supplements. Taking certain supplements -- such as fish oil, antioxidants, and mineral supplements -- may be beneficial for patients with Crohn's disease.

Vitamins. Deficiencies of vitamins A, C, D, E, B12, and folate (a B vitamin) may result from malabsorption. In general, vitamin supplements may be recommended for everyone with inflammatory bowel disease (IBD), particularly for children to avoid growth retardation. Vitamins A, C, and E are antioxidants, which are scavengers of damaging particles in the body. Folic acid supplements are particularly important for patients who must restrict fresh fruits and vegetables and for those taking sulfasalazine. Folate deficiencies may contribute to the increased risk for colon cancer. Monthly injections of vitamin B-12 may be necessary. Vitamin D is necessary for bone protection. Because some vitamins, such as A and D, can be toxic at high doses, patients should discuss specific dosages with their doctors.

Omega-3 Fatty Acids. The role of fats in inflammatory bowel disease is complex and not fully known. Some evidence suggests that patients with Crohn's burn fat calories at a higher rate than the general population. Patients with IBD may be deficient in essential fatty acids, particularly omega-3 fatty acids (polyunsaturated fats found in oily fish and certain vegetable products such as flaxseed and canola oils). Such fatty acids are also available in supplements as docosahexaenoic (DHA) and eicosapentaneoic (EPA) acids, which are specific compounds found in fish oil.

Omega-3 fatty acids, found plentifully in oily fish and flaxseed and canola oils, are beneficial to people afflicted with inflammatory bowel disease.

Mineral Supplements. Supplements of calcium, magnesium, zinc, selenium, and iron may be needed to offset deficiencies in patients with severe IBD.

Calcium and magnesium are critical for health and strong bones. Many patients with IBD suffer from calcium and vitamin D deficiencies, which cause low bone density. Studies indicate that calcium and vitamin D supplements may be adequate to increase bone density without drugs.

Selenium is a potent antioxidant.

Zinc is important for wound healing, and deficiencies may promote fistulas in Crohn's disease.

Iron supplements may be required for anemia. However, iron overdose is very dangerous. As few as three adult iron tablets can poison children, even fatally. No one, even adults, should take a double dose of iron if one is missed. A doctor should advise patients on correct dosage.

Enteral Nutrition. Enteral nutrition uses a feeding tube that is inserted either through the nose and down through the throat or directly through the abdominal wall into the gastrointestinal tract. It is the preferred method for feeding patients with malnutrition who cannot tolerate eating by mouth. The nutritional formulas used in enteral administration include:

Polymeric diets (containing a balance of standard nutrients).

Elemental diets (predigested nutrients that are absorbed in the first meter of the small intestine). These diets are used less commonly than polymeric diets.

In children, enteral nutrition is given for 6 - 8 weeks. Simple foods are then introduced (chicken, potato, rice), and more complex foods (milk, fiber, wheat-based foods) are then added gradually. However, relapse is still common.

Total Parenteral Nutrition. Total parenteral nutrition (TPN), or hyperalimentation, is the intravenous administration of nutrients through an indwelling catheter (tube). It is used for very severe IBD when patients cannot tolerate any nutrition by mouth or with a feeding tube, and may even be useful as a primary therapy for patients with Crohn's (although not for those with fistulas). It is usually given in the hospital, although increasingly people are giving it to themselves at home. The procedure carries a risk for complications, some serious, including infection, blood clots, and liver failure.

Symptom Management

The following are some ways of managing diarrhea, constipation, or both:

Mild-to-moderate diarrhea may be reduced by taking 1 teaspoon of psyllium hydrophilic colloid (Metamucil) twice a day in a glass of water.

Antidiarrheal drugs include loperamide (Imodium) and a combination of atropine and diphenoxylate (Lomotil). In very ill patients, large doses of some antidiarrheal drugs, such as Lomotil, can trigger the onset of toxic megacolon. Toxic megacolon is a life-threatening complication of other intestinal conditions. It is characterized by a very inflated colon, abdominal distention, and sometimes fever, abdominal pain, or shock.

Opiates or drugs used to relax muscle spasms may help relieve mild-to-moderate diarrhea and abdominal cramps, but they should be used for very short periods and not for severe cases.

Cholestyramine (Questran) has been found to be useful for reducing diarrhea in patients who have had ileal resections.

Bulk-type laxatives can help constipation.

Iron supplements may be required for anemia. Intravenous iron with or without erythropoietin (a hormone that acts in the bone marrow to increase the production of red blood cells) is effective for severe anemia in IBD that does not respond to iron alone. Patients with Crohn's disease benefit most from the combination.

Antidepressants may help relieve emotional problems. However, inflammatory bowel disease is not a psychological disorder, and these drugs will not affect the basic illness.

Acetaminophen (Tylenol) and nonsteroidal anti-inflammatory drugs (NSAIDs) are used for relieving mild pain. NSAIDs include aspirin, ibuprofen (Advil, Motrin), naproxen (Aleve), and celecoxib (Celebrex), the only COX-2 inhibitor left on the market. NSAIDs have been thought to cause symptom flare-ups in patients with inflammatory bowel disease (IBD). However, a comprehensive 2006 study concluded that these drugs are as safe for patients with IBD as for other people, and that they can help prevent relapse as well as provide short-term pain relief. Still, long-term use of NSAIDs can cause stomach bleeding and, with the exception of aspirin, may increase the risks for heart attack and stroke. Acetaminophen can cause liver damage if taken in high doses or combined with alcoholic drinks. Discuss with your doctor whether acetaminophen, NSAIDs, or other pain relievers are appropriate for you.

Although stress is not a cause of inflammatory bowel disease, there are reports of an association between stress and symptom flare-ups. Although no evidence exists to confirm that stress reduction techniques such as relaxation methods, meditation, or cognitive therapy, manage the disease, they might be helpful.

The effects of exercise in Crohn's disease are uncertain. Some research indicates that moderate exercise may trigger excess production of chemicals that could cause flare-up. One small study, however, reported significant improvement in patients who had been sedentary but then embarked on a 12-week exercise program. They walked a little over 2 miles three times a week. During that period there were no flare-ups, and they felt physically and emotionally better than before.

Medications

The primary goal of drug therapy is to reduce inflammation in the intestine. Drugs are effective in reducing the inflammation and accompanying symptoms in up to 80% of patients. Unfortunately, relapses are still frequent, and researchers continue to look for the optimal treatments that will both control symptoms and prevent relapse.

Drugs Used for Crohn's Disease. Drug therapies for Crohn’s disease aim to resolve symptoms (induce remission) and prevent flare-ups (maintain remission). The drugs used depend on the severity of the condition:

Mild-to-moderate Crohn's disease is generally treated with antibiotics and an oral aminosalicylate, such as mesalamine or sulfasalazine. (Some researchers suggest, however, that corticosteroids may be more effective than these drugs in patients with disease in the small intestine and ascending colon. Furthermore, new forms of oral corticosteroids, such as budesonide, may have a lower risk for adverse effects.)

Moderate-to-severe Crohn's disease is treated with corticosteroids, immunosuppressants, or biologic drugs such as infliximab or adalimumab. These drugs may be used alone or in combinations. Some patients with severe Crohn's may be candidates for surgery.

Determining Success. Therapy is considered successful if it can push the disease into remission (and keep it there) without causing significant side effects. The patient's condition is generally considered in remission when the intestinal lining has healed, and symptoms, such as diarrhea, abdominal cramps, and tenesmus (painful defecation), are normal or close to normal. It is sometimes difficult to define remission in Crohn's disease because diagnostic test results do not always correlate with a patient's symptoms or complications outside the intestine.

Aminosalicylates contain the compound 5-aminosalicylic acid, or 5-ASA, which helps reduce inflammation. These drugs are used to prevent relapses and maintain remission in mild-to-moderate Crohn’s disease.

The standard aminosalicylate drug is sulfazine (Azulfidine). This drug combines the 5-ASA drug mesalamine with sulfapyridine, a sulfa antibiotic. While sulfazine is cheap and effective, the sulfa component of the drug can cause unpleasant side effects, including headache, nausea, and rash.

Patients who cannot tolerate sulfazine, or who are allergic to sulfa drugs, have other options for aminosalicylate drugs, including mesalamine (Asacol, Pentasa), olsalazine (Dipentum), and balsalazide (Colazal). These drugs, like sulfazine, are available as pills. Mesalamine is also available in enema (Rowasa) and suppository (Canasa) forms.

Mesalamine can cause kidney problems and should be used with caution by patients with kidney disease. Common side effects of aminosalicylate drugs include:

Abdominal pain and cramps (mesalamine, balsalazide)

Diarrhea (mesalamine, olsalazine)· Gas (mesalamine)

Nausea (mesalamine)

Hair loss (mesalamine)

Headache (mesalamine, balsalazide)

Dizziness (mesalamine)

All mesalamine preparations, including sulfasalazine, appear to be safe for children, and for women who are pregnant or nursing.

General Guidelines. Corticosteroids (commonly called steroids) are powerful anti-inflammatory drugs used for treating Crohn's disease in adults. Because of their severe side effects, steroids should be reserved for those with moderate-to-severe disease or those who relapse after other therapies. Steroids appear to be safe for pregnant women and can be used if necessary during pregnancy.

Corticosteroids are frequently combined with other drugs, such as 5-aminosalicylic acid (or 5-ASA) drugs, to produce more rapid symptom relief and to allow quicker withdrawal, although such combinations do not improve remission time.

In general, corticosteroids are recommended only for short-term use for achieving remission in active Crohn's disease. The lowest possible dose should be used for the shortest amount of time. Long-term treatments cause significant side effects, and alternative drugs exist. Corticosteroids do not prevent flare-ups and are rarely used for maintenance treatment.

Patients who are malnourished are less likely to respond to steroids, and those who had an initial inadequate response to steroids are also less likely to do well with repeat therapy. Some patients who have had Crohn's disease for a long time may have partial or complete resistance to corticosteroids.

Corticosteroid Types. Prednisone (Deltasone), methylprednisolone (Medrol), and hydrocortisone (Cortef, Cortisol) are the most common corticosteroids. Newer steroids, such as budesonide (Entocort), affect only local areas in the intestine and do not circulate throughout the body. Such drugs may avoid the widespread side effects that are a serious problem with long-term treatment using older conventional steroids. Recent studies suggest that budesonide can help prolong and maintain remission periods in patients with Crohn’s disease.

Administering Corticosteroids. Most corticosteroids can be taken as a pill. For patients who cannot take oral forms, methylprednisolone and hydrocortisone may also be given intravenously or rectally as a suppository, enema, or foam. The severity or location of the condition often determines the form.

Side Effects of Corticosteroids. Standard steroids can have distressing and sometimes serious long-term side effects, including:

Susceptibility to infection

Weight gain (particularly increased fatty tissue on the face and upper trunk and back)

Acne

Excess hair growth

High blood pressure (hypertension)

Weakened bones (osteoporosis)

Cataracts and glaucoma

Diabetes

Muscle wasting

Menstrual irregularities

Upper gastrointestinal ulcers

Personality change, including irritability, insomnia, psychosis, and depression; such emotional changes are sometimes severe enough to produce suicidal thoughts

Withdrawing from Corticosteroids. Once the intestinal inflammation has subsided, steroids must be withdrawn very gradually in order to give the body time to recover its own ability to produce natural steroids. Withdrawal symptoms, including fever, malaise, and joint pain, may occur if the dosage is lowered too rapidly. If this happens, the dosage is increased slightly and maintained until symptoms are gone. More gradual withdrawal is then resumed.

For very active inflammatory bowel disease that does not respond to standard treatments, immunosuppressant drugs are used for long-term therapy. Such drugs suppress or limit actions of the immune system and therefore its inflammatory response, which causes Crohn's disease. Immunosuppressants may help maintain remission in Crohn's disease and heal fistulas and intestinal ulcers caused by this disease. These drugs are sometimes combined with a corticosteroid drug for treating active disease flares.

Azathioprine (Imuran, Azasan) and 6-mercaptopurine (6-MP, Purinethol) are the standard oral immunosuppressant drugs. However, it can take 3 - 6 months for these drugs to have an effect. To speed up the response, they are sometimes prescribed along with a corticosteroid drug. Lower steroid doses are then needed, resulting in fewer side effects. Corticosteroids may also be withdrawn more quickly. For this reason, immunosuppressants are sometimes referred to as steroid-sparing drugs.

Other pill forms of immunosuppressants include cyclosporine A (Sandimmune, Neoral) and tracrolimus (Prograf). These drugs are quicker-acting than azathiopine and 6-mercaptopurine. Cyclosporine A generally takes 1 - 2 weeks to take effect. For patients who have Crohn’s disease accompanied by fistulas, Cyclosporine A may be given intravenously. For patients whose condition affects the mouth or area around the anus, tracrolimus is available as a topical ointment.

Methotrexate (MTX, Rheumatrex, Mexate) is another fast-acting type of immunosuppressant. It is given by weekly injections and may be an option for patients with severe Crohn’s disease who have not been helped by other immunosuppressant drugs. However, methotrexate can cause miscarriages and birth defects. Because of these pregnancy complications, both men and women who take methotrexate should use birth control.

General side effects of immunosuppressants may include nausea, vomiting, and liver or pancreatic inflammation. Patients should receive frequent blood tests to monitor bone marrow, liver, and kidneys. Patients who take cyclosporine A or tacrolimus need to have their blood pressure and kidney function checked regularly.

Antibiotics are often used to induce remission in mild-to-moderate Crohn's disease. They are also important for treating fistulas, bacterial overgrowth, abdominal abscesses, and any infections around the anus and genital areas. Stopping antibiotics brings on relapse, so long-term therapy is required, carrying a risk for side effects.

The standard antibiotics used for inducing remission in Crohn's disease are ciprofloxacin (Cipro) and metronidazole (Flagyl). Ciprofloxacin is the antibiotic of choice. Over time, metronidazole can cause peripheral neuropathy, a nerve disorder that can cause numbness and tingling in the hands and feet. Other side effects associated with netronidazole include nausea, vomiting, diarrhea, loss of appetite, dizziness, and headaches.

Although ciprofloxacin causes fewer side effects than metrondizaole, it can interact with antacids (Rolaids, Tums) and vitamin and mineral supplements that contain calcium, iron, or zinc. Do not take antacids or vitamin supplements at the same time as the ciprofloxacin dose.

Biologic response modifiers are genetically engineered drugs that target specific proteins involved with the body’s inflammatory response. Of special interest for patients with Crohn's disease are drugs such as infliximab and adalimumab, which target the inflammatory immune factor known as tumor necrosis factor (TNF).

According to a 2007 consensus statement from the American Gastroenterological Association, biologic drugs are generally not used as first-line treatment for most patients with Crohn’s disease. However, some patients -- especially those who have not responded to corticosteroids or who suffer from fistulas -- may benefit from initial treatment with infliximab or other biologic drugs. In all cases, the benefits of biologic drugs need to be weighed against their potential risks, which can include increased risk for infections, lymphoma, and drug-related side effects.

Infliximab (Remicade) acts against TNF and was the first biologic drug approved for treating adults with Crohn's disease. It is made from a genetically designed antibody called a monoclonal antibody (MAb) that blocks the activity of tumor necrosis factor-alpha (TNF-a). In 2006, the FDA approved infliximab for children with active Crohn’s disease.

Infliximab cannot cure Crohn’s disease, but it can help control symptoms and, possibly, keep the disease in remission. Studies suggest that up to 80% of patients respond initially, and about a third of all patients remain in remission after a single infusion. Remissions last a few weeks to several months. A 6-week course of infliximab helps close and heal fistulas in half of patients and reduces drainage in 70%. The drug is also being studied for maintenance therapy, although given some significant side effects, it will most likely be reserved for active disease that does not respond to other treatments.

Infliximab’s severe side effects may include tuberculosis, pneumonia, and other infections; lymphoma (a type of cancer); liver failure; and aplastic anemia.

Adalimumab (Humira) was approved early in 2007 for treating adult patients with moderate-to-severe Crohn's disease. Like infliximab, adalimumab blocks TNF. Also approved for treating symptoms of rheumatoid arthritis, adalimumab requires injections to initiate treatment, followed by a maintenance shot every other week.

Adalimumab's label includes a boxed warning. The medicine has been associated with serious, sometimes fatal, infections, including tuberculosis and sepsis. Other severe side effects may include lymphoma, upper respiratory infections, sinusitis, and nausea.

Several other TNF modifiers are being investigated. Among the most promising, according to several 2007 studies in the New England Journal of Medicine, is certolizumab (Cimzia).

Selective adhesion molecule inhibitors block the genetic expression of cell adhesion molecules (CAMs). CAMs play an important role in the accumulation of immune factors that cause the inflammatory response. Natalizumab (Tysabri) is a monoclonal antibody that blocks alpha4 integrin, a protein that binds to CAMs. This drug is approved to treat multiple sclerosis and is also being studied for Crohn’s disease. Studies have suggested that natalizumab can help patients with Crohn’s disease achieve and maintain remission.

However, natalizumab is associated with severe side effects, including a rare neurological condition called progressive multifocal leukoencephalopathy (PML). A 2006 study found that patients who take natalizumab have a very low risk for PML. Still, the potential benefits of natalizumab need to be weighed against its risks for serious side effects. As of summer 2007, the FDA was considering approving natalizumab for treatment of moderate-to-severe Crohn’s disease in patients who have failed or cannot tolerate other therapies

Other Biologic Therapies. Investigators are researching other biologic therapies that target other types of immune factors that play a role in the inflammatory response. These factors include interferons, anti-interferon antibodies, anti-interleukin antibodies, p65 anti-sense oligonucleotides, growth factors, and others. Several 2006 studies indicated that fontolizumab (HuZaf), an anti-interferon gamma monoclonal antibody, shows promise as a treatment for Crohn’s disease. Sargramostim (Leukine), a granulocyte-macrophage colony stimulating factor, is another biologic drug that may help improve symptoms and quality of life for patients with active Crohn’s disease. Visilizumab (Nuvion), which targets the CD3 receptor on T cells, is another biologic drug being investigated. More research in each of these areas is needed.

Parasites. Inflammatory bowel disease is rare in countries where intestinal infection with parasites called helminthes is common. Small studies have reported significant remission rates in patients with Crohn's disease or ulcerative colitis who have swallowed the eggs of a specific parasitic worm. The parasite does not invade tissue or spread other diseases. The parasite induces production of specific T cells, called TH-2, which are immune factors that may be protective against overactivity of cytokines that trigger Crohn's. More research is needed.

Growth Factors. Growth factor hormones increase immune factors, so one would think they might be harmful for patients with Crohn's disease. However, some research suggests that growth factors may be helpful for speeding healing in certain patients, including children. More research, however, is needed.

Surgery

Between two-thirds to three-quarters of patients with Crohn's eventually need surgery when medication cannot control symptoms. Among children with Crohn's, half require surgery within 5 years of diagnosis.

In general, surgery is used to remove damaged areas of the colon:

The entire colon (proctocolectomy) or a section of it (subtotal colectomy) may need to be removed in cases of extensive disease in the large intestine.

Resection or strictureplasty, which removes limited sections of the colon, may be appropriate for many patients.

Surgery is useful only for reducing symptoms. It cannot cure Crohn's disease because new disease can appear in other areas of the intestine. Surgery may be helpful for relieving symptoms and to correct blockage, perforation, fistulas, or bleeding.

Surgery has reportedly improved the quality of life in most patients, except for those who continued to have active disease. Many children with Crohn's who have suffered growth problems catch up to near-normal growth levels after surgery. Some experts urge, in fact, that many patients should consider surgery in the early stages of the disease.

Some patients may be candidates for a procedure called strictureplasty, which involves cutting and stitching only the areas obstructing the intestine, so that it widens the intestine without removing sections of it. It involves the following:

A balloon attached to a catheter (a thin tube) is passed along the intestine.

If it becomes blocked, then a stricture (an obstruction) is indicated.

The surgeon widens the intestine at the point, but does not remove sections of it.

The procedure is by no means foolproof. Nearly half of patients require re-operation, but strictureplasty in the jejunum and ileum of the small intestine is safe and generally effective over the long term. It may not be useful for Crohn's disease in duodenum (the first section of the small intestine).

The invasiveness of the surgical procedure to remove damaged portions of the colon depends on the severity of the disease.

Resection of the Colon. In most cases of Crohn's disease, only a part of the colon needs to be removed, a procedure called resection.

Click the icon to see an illustrated series depicting large bowel resection surgery.

Subtotal Colectomy. Subtotal colectomy is more extensive than resection and removes more of the colon. Disease in the upper parts of the small intestine tends to require more extensive surgery than in the lower small intestine.

In general, either procedure requires a general anesthetic and involves the following:

An incision is made in the abdomen.

The diseased portion of the colon is identified and removed. (Strictureplasty is sometimes used alone with resection.)

Once a diseased segment of the colon is removed, the two ends are reconnected, and this connection is called an anastomosis.

Open Surgery or Laparoscopy. Resection or subtotal colectomy may be performed using one of two surgical approaches:

Open surgery, which requires a wide abdominal incision.

Laparoscopy, which uses a few small incisions through which a tube is inserted containing a tiny camera for viewing the area. To date, however, this procedure is best suited for patients with short-segment disease in the ileum who also have no other complications, such as fistulas and abscesses.

Click the icon to see an image of a laparoscopy procedure.

Short-bowel syndrome. If large segments of the small intestine are removed, the patient is at higher risk for short-bowel syndrome, a complication in which there is a problem absorbing nutrients. The risk is far lower with strictureplasty. The condition used to be fatal, but patients now can live normal and productive lives using total parenteral nutrition (the intravenous administration of nutrients), which can be self-administered at home in many cases.

Leakage or obstruction in the areas where the colon has been reconnected (the anastomosis).

Infections. In a 2003 study, the use of drugs that modify the immune system (azathioprine, 6-MP, methotrexate, and infliximab) was effective in reducing the risk for serious infection in the abdomen.

Proctocolectomy with ileostomy is removal of the entire colon and creation of an ileostomy. It involves the following:

To perform proctocolectomy, the surgeon removes the entire colon, including the lower part of the rectum and the sphincter muscles that control bowel movements.

To perform ileostomy, the surgeon makes a small opening in the lower right corner of the abdomen called a stoma. The surgeon then connects cut ends of the small intestine to this opening. A bag is placed over the opening and accumulates waste matter. It requires emptying several times a day.

Recurrence of Crohn's disease is very common after any procedure. The risk may be 7 - 25% for each year after resection, with an average risk of 50% at 5 years after resection. (Even if the entire colon is removed, there is still a high chance of recurrence in the rectum and a somewhat lower risk for recurrence in the small intestine.)

Patients at highest risk for recurrence include:

Smokers

Those whose disease occurred in the ileum (the lowest part of the small intestine) and colon

Those with abscesses or fistulas

Those have had previous surgeries

Various drugs are used to prevent recurrence. They include the antibiotic metronidazole (Flagyl), mesalamine, infliximab, and mercaptopurine. These drugs can have severe side effects. And, it is not clear if these or any other drugs are effective in preventing recurrence. Even if medications can help prevent recurrence in some patients, it is not yet known how to identify this subset of patients. (In any case, steroids do not appear to help prevent recurrence.)

In some cases, surgery is needed for emergency conditions that can occur with Crohn's disease. Emergency surgery is used to:

Stop severe intestinal bleeding

Clear small bowel obstruction

Drain and heal abscesses or fistulas

Repair perforation

Procedures for transplanting the small intestine in patients with intestinal failure are under investigation. These are still experimental and are being tested in patients who have lost so much of their small intestine that they must rely on total parenteral nutrition (intravenous administration of nutrition). Small-bowel transplantation is a more difficult procedure than some other transplants, because of the high rate of potential complications, including infection and organ rejection. Patients who have transplants must take immunosuppressant drugs for the rest of their lives. Furthermore, there is some evidence that Crohn's disease recurs in the transplanted bowel.

Resources

www.ccfa.org -- Crohn's & Colitis Foundation of America

www.gastro.org -- American Gastroenterological Association

www.acg.gi.org -- American College of Gastroenterology

www2.niddk.nih.gov -- National Digestive Diseases Information Clearinghouse

References

Baldassano RN, Bradfield JP, Monos DS, Kim CE, Glessner JT, Casalunovo T, et al. Association of the T300A non-synonymous variant of the ATG16L1 gene with susceptibility to paediatric Crohn's disease. Gut. 2007 Aug;56(:1171-1173.

Baldassano RN, Bradfield JP, Monos DS, Kim CE, Glessner JT, Casalunovo T, et al. Association of variants of the interleukin-23 receptor gene with susceptibility to pediatric Crohn's disease. Clin Gastroenterol Hepatol. 2007 Jul 5; [Epub ahead of print]

Clark M, Colombel JF, Feagan BC, Fedorak RN, Hanauer SB, Kamm MA, et al. American gastroenterological association consensus development conference on the use of biologics in the treatment of inflammatory bowel disease, June 21-23,2006. Gastroenterology. 2007 Jul;133(1):312-39.

Cornish J, Tan E, Teare J, Teoh TG, Rai R, Clark SK, et al. A meta-analysis on the influence of inflammatory bowel disease on pregnancy. Gut. 2007 Jun;56(6):830-7. Epub 2006 Dec 21.

Cummings JR, Cooney R, Pathan S, Anderson CA, Barrett JC, Beckly J, et al. Confirmation of the role of ATG16l1 as a Crohn's disease susceptibility gene. Inflamm Bowel Dis. 2007 Aug;13(:941-6.

Dotan I, Fishman S, Dgani Y, Schwartz M, Karban A, Lerner A, et al. Antibodies against laminaribioside and chitobioside are novel serologic markers in Crohn's disease. Gastroenterology. 2006 Aug;131(2):366-78.

Dubinsky MC, Wang D, Picornell Y, Wrobel I, Katzir L, Quiros A, et al. IL-23 receptor (IL-23R) gene protects against pediatric Crohn's disease. Inflamm Bowel Dis. 2007 May;13(5):511-5.

Duerr RH, Taylor KD, Brant SR, Rioux JD, Silverberg MS, Daly MJ, et al. A genome-wide association study identifies IL23R as an inflammatory bowel disease gene. Science. 2006 Dec 1;314(5804):1461-3. Epub 2006 Oct 26.

Issa M, Vijayapal A, Graham MB, Beaulieu DB, Otterson MF, Lundeen S, et al. Impact of Clostridium difficile on inflammatory bowel disease. Clin Gastroenterol Hepatol. 2007 Mar;5(3):345-51.

Rioux JD, Xavier RJ, Taylor KD, Silverberg MS, Goyette P, Huett A, et al. Genome-wide association study identifies new susceptibility loci for Crohn disease and implicates autophagy in disease pathogenesis. Nat Genet. 2007 May;39(5):596-604. Epub 2007 Apr 15.

Rodemann JF, Dubberke ER, Reske KA, Seo da H, Stone CD. Incidence of Clostridium difficile infection in inflammatory bowel disease. Clin Gastroenterol Hepatol. 2007 Mar;5(3):339-44.

Sandborn WJ, Feagan BG, Stoinov S, Honiball PJ, Rutgeerts P, Mason D, et al. Certolizumab pegol for the treatment of Crohn's disease. N Engl J Med. 2007 Jul 19;357(3):228-238.

Schreiber S, Khaliq-Kareemi M, Lawrance IC, Thomsen OO, Hanauer SB, McColm J, et al. Maintenance therapy with certolizumab pegol for Crohn's disease. N Engl J Med. 2007 Jul 19;357(3):239-250.

Tremaine WJ. Inflammatory bowel disease and Clostridium difficile-associated diarrhea: a growing problem. Clin Gastroenterol Hepatol. 2007 Mar;5(3):310-1.

Tremelling M, Cummings F, Fisher SA, Mansfield J, Gwilliam R, Keniry A, et al. IL23R variation determines susceptibility but not disease phenotype in inflammatory bowel disease. Gastroenterology. 2007 May;132(5):1657-64. Epub 2007 Feb 24.

Review Date:
8/30/2007
Reviewed By:
Harvey Simon, MD, Associate Professor of Medicine, Harvard Medical School; Physician, Massachusetts General Hospital.

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adam.com

Gallstones and gallbladder disease

FitSugar — Wed, 08 Oct 2008 17:35:38 -0700

In This Report

Highlights

Introduction

Symptoms

Prognosis

Risk Factors

Prevention

Diagnosis

Treatment

Surgery

Lithotripsy and Dissolution...

Managing Common Bile Duct S...

Resources

References

HEALTH GUIDE REFERENCE FROM A.D.A.M

Highlights

Connection to endometrial cancer

Excess estrogen appears to play a role in the development of both gallstones and endometrial cancer. One study found that women who had undergone cholecystectomy (surgery to remove the gallbladder) had a 50% increased risk of developing endometrial cancer. The connection was weaker in women who developed asymptomatic gallstones.

Diet

Men who consume a diet high in foods containing heme iron, such as meat and seafood, are at increased risk for developing gallstones. Gallstones are not associated with diets high in non-heme iron sources, such as beans, lentils, and enriched grains.

Fruits and vegetables appear to substantially reduce the risk of symptomatic gallstone formation. The effect holds true regardless of which fruits or vegetables are consumed. Risk drops in proportion to the percentage of fruits and vegetables in the diet.

Genetics

Studies of twins and families indicate a genetic connection to gallstone formation, but until recently, the mechanism has eluded researchers. Defects in proteins involved in biliary lipid secretion have been identified as a factor predisposing men and women to gallstone disease. But not everyone with these genes develops gallstones. The disease appears to result from the interaction between genetic and environmental factors, with immune and inflammatory mediators possibly playing key roles.

Bariatric Surgery

Patients who undergo bariatric surgery are at increased risk for gallstones and are often required to have their gallbladders removed (cholecystectomy) before their bariatric surgery is performed. Recent studies indicate this practice may not be necessary. In one study, only 8% of patients who did not undergo cholecystectomy before a Roux-en-Y procedure developed symptomatic gallstones. In another study, only 3% of those who underwent lap banding developed symptomatic gallstones.

Prolonged Intravenous Feeding

People who must rely on intravenous nutrition (home parenteral nutrition or total parenteral nutrition) are at greatly increased risk of developing gallstones, possibly due to lack of intestinal stimulation that decreases the flow of bile. However, gallstones in these patients are easily treated and have a low risk of complications.

Introduction

Gallstones are small, hard pellets that can form in the gallbladder, a sac-like organ that lies under the liver on the right side of the abdomen. Most people with gallstones don't even know they have them. But in some cases a stone may cause the gallbladder to become inflamed, resulting in pain, infection, or other serious complication.

The formation of gallstones is a complex process that starts with bile, a fluid composed mostly of water, bile salts, lecithin (a fat known as a phospholipid), and cholesterol. Most gallstones are formed from cholesterol.

Bile is important for the digestion of fat. It is first produced by the liver and then secreted through tiny channels that eventually lead into a larger tube called the common bile duct, which leads to the small intestine.

Only a small amount of bile drains directly into the small intestine, however. Most flows into the gallbladder through the cystic duct, which is a side extension off the common bile duct. This system of ducts through which bile flows is called the biliary tree.

Click the icon to see an image of the biliary tree.

The gallbladder is a 4-inch sac with a muscular wall that is located under the liver. Here, most of the bile fluid (about 2 - 5 cups a day) is removed, leaving a few tablespoons of concentrated bile.

The gallbladder serves as a reservoir until bile is needed in the small intestine to digest fats. This need is triggered by a hormone called cholecystokinin, which is released when food enters the small intestine.

Cholecystokinin signals the gallbladder to contract and deliver bile into the intestine. The force of the contraction propels the bile down the common bile duct and into the small intestine, where it emulsifies (breaks down) fatty molecules.

This part of the digestive process enables the emulsified fat along with important fat-absorbable nutrients (e.g., vitamins A, D, E, and K) to pass through the intestinal lining and enter the blood stream.

Gallstones can range from a few millimeters to several centimeters in diameter. Most are formed from cholesterol. Pigment stones are the second most common type of gallstones (approximately 15% of stones are pigment stones). Patients can also have a mixture of the two. Pigment stones are formed from a brown-colored substance called calcium bilirubinate.

Cholesterol Stones. Although cholesterol makes up only 5% of bile, about three-fourths of the gallstones found in the US population are formed from cholesterol. Cholesterol gallstones typically form in the following way:

Cholesterol is not very soluble, so in order to remain suspended in fluid it must be transported within clusters of bile salts called micelles. If there is an imbalance between these bile salts and cholesterol, then the bile fluid turns to sludge. This thickened fluid consists of a mucus gel containing cholesterol and calcium bilirubinate.

If the imbalance worsens, cholesterol crystals form (a condition called supersaturation), which can eventually form gallstones.

This process of gallstone formation is referred to as cholelithiasis. It is very slow and most often painless.

Click the icon to see an image of gallstones.

Supersaturation and cholelithiasis can occur as a result of various abnormalities, although the cause is not entirely clear. There are many events that may promote cholelithiasis:

The liver secretes too much cholesterol into the bile.

The gallbladder may not be able to empty normally, so bile becomes stagnant.

The cells lining the gallbladder may not be able to efficiently absorb cholesterol and fat from bile.

High levels of bilirubin have been observed in patients with gallstones. Bilirubin is a substance normally formed by the breakdown of hemoglobin in the blood and is excreted in bile. Some experts believe it may play an important role in the formation of cholesterol gallstones.

Pigment Stones. Pigment stones are composed of calcium bilirubinate, or calcified bilirubin. Pigment stones can be black or brown.

Black stones form in the gallbladder and are the more common type. They represent 20% of all gallstones in the US. They are more likely to develop in people with hemolytic anemia (a relatively rare anemia where red blood cells are destroyed) or cirrhosis (scarred liver).

Brown pigment stones are more common in Asian populations. They contain more cholesterol and calcium than black pigment stones and are more likely to occur in the bile ducts. Infection plays a role in the development of these stones. One report suggested that bacteria or other microorganisms may trigger oxidation (a damaging chemical process in the body) which, in this case, can cause changes that lead to pigment stone formation.

Gallstones can also be present in the common bile duct. This is called choledocholithiasis.

Click the icon to see an image of gallstone obstruction.

Secondary Common Bile Duct Stones. In most cases, common bile duct stones originally form in the gallbladder and pass into the common duct (called secondary stones). Choledocholithiasis occurs in about 10% of patients with gallstones.

Primary Common Bile Duct Stones. In less common cases, the stones form in the common duct itself (called primary stones). Primary common duct stones are usually of the brown pigment type and are more likely to cause infection than secondary common duct stones.

Gallbladder disease can occur without stones, a condition called acalculous gallbladder disease. It can be acute (arising suddenly) or chronic (persistent).

Acute acalculous gallbladder disease usually occurs in patients who are very ill from other disorders. In such cases, inflammation occurs in the gallbladder, usually from a diminished blood supply or an impaired ability to contract and empty its bile.

Chronic acalculous gallbladder disease (also called biliary dyskinesia) appears to be caused by muscle defects or other problems in the gallbladder that cause impaired motility.

Diagnosing Acute Acalculous Gallbladder Disease. Symptoms are similar to those of acute cholecystitis with gallstones, but they may be obscured by other medical conditions, since patients with this condition are often critically ill with other illnesses.

Diagnosing Chronic Acalculous Gallbladder Disease. Chronic acalculous gallbladder disease is usually diagnosed when a patient complains of gallbladder symptoms, but no evidence of stones is seen using standard imaging techniques. More than half of patients initially diagnosed with this disease, however, are eventually shown to have small stones or gallbladder sludge. The patient is given the hormone cholecystokinin octapeptide (CCK), which induces gallbladder contraction, followed by a radioisotope scan to determine whether the gallbladder is emptying correctly. If the gallbladder demonstrates difficulty releasing bile, doctors usually consider the diagnosis confirmed.

Treatment for Acute Acalculous Gallbladder Disease. Acute acalculous gallbladder disease has a very high rate of serious complications (gangrene, perforation, and pus in the gallbladder), so emergency removal of the gallbladder is warranted.

Treatment for Chronic Acalculous Gallbladder Disease. Most patients (75 - 90%) diagnosed with chronic acalculous gallbladder disease are relieved of their symptoms by cholecystectomy (removal of the gallbladder). Between 10 - 23%, however, still experience pain. Surgery is most warranted in these patients when the symptoms are caused by impaired emptying of the gallbladder.

Symptoms

About 90% of gallstones provoke no symptoms at all. If problems do develop, the chance of developing pain is about 2% per year for the first 10 years after stone formation. After this, the chance for developing symptoms declines. On average, symptoms take about 8 years to develop. The reason for the decline in incidence after 10 years is not known, although some doctors suggest that "younger," smaller stones may be more likely to cause symptoms than larger, older ones.

The mildest and most common symptom of gallbladder disease is intermittent pain called biliary colic, which occurs either in the mid- or the right portion of the upper abdomen. A typical attack has several features:

The primary symptom is typically a steady gripping or gnawing pain in the upper right abdomen near the rib cage, which can be quite severe and can radiate to the upper back. Some patients with biliary colic experience the pain behind the breast bone.

Nausea or vomiting may occur.

Changes in position, over-the-counter pain relievers, and passage of gas do not relieve the symptoms.

Biliary colic typically disappears after 1 to several hours. If it persists beyond this point, acute cholecystitis or more serious conditions may be present.

The episodes typically occur at the same time of day, but less frequently than once a week. Large or fatty meals can precipitate the pain, but it usually occurs several hours after eating and often awakens the patient during the night.

Recurrence is common, but attacks can be years apart. In one study, for example, 30% of people who had had 1- 2 attacks experienced no further biliary pain over the next 10 years.

Digestive complaints such as belching, feeling unduly full after meals, bloating, heartburn (burning feeling behind the breast bone), or regurgitation (acid back-up in the food pipe) are not likely to be caused by gallbladder disease. Conditions that may cause these symptoms include peptic ulcer, gastroesophageal reflux disease, or indigestion of unknown cause. [See In-Depth Report #19 Peptic Ulcers and In-Depth Report #85 Gastroesophageal Reflux Disease.]

Between 1 - 3% of people with symptomatic gallstones develop inflammation in the gallbladder (acute cholecystitis), which occurs when stones or sludge obstruct the duct. The symptoms are similar to those of biliary colic but are more persistent and severe. They include the following:

Pain in the upper right abdomen is severe and constant and can last for days. Pain frequently increases when drawing a breath.

Pain also may radiate to the back or occur under the shoulder blades, behind the breast bone, or on the left side.

About a third of patients have fever and chills.

Nausea and vomiting may occur.

Anyone who experiences such symptoms should seek medical attention. Infection develops in about 20% of these cases, which increases the danger. Acute cholecystitis can progress to gangrene or perforation of the gallbladder if left untreated. People with diabetes are at particular risk for serious complications.

Chronic gallbladder disease (chronic cholecystitis) is marked by gallstones and low-grade inflammation. In such cases the gallbladder may become scarred and stiff. Symptoms of chronic gallbladder disease include the following:

Complaints of gas, nausea, and abdominal discomfort after meals are the most common, but they may be vague and indistinguishable from similar complaints in people without gallbladder disease.

Chronic diarrhea (4 - 10 bowel movements every day for at least 3 months) may be a common symptom of gallbladder dysfunction.

Stones lodged in the common bile duct (choledocholithiasis) can cause symptoms that are similar to those produced by stones that lodge in the gallbladder, but they may also cause the following symptoms:

Jaundice (yellowish skin)

Dark urine, lighter stools, or both

Heartbeat may become rapid and blood pressure may drop abruptly

Fever, chills, nausea and vomiting, and severe pain in the upper right abdomen. These symptoms suggest an infection in the bile duct (called cholangitis).

As in acute cholecystitis, patients who have these symptoms should seek medical help immediately. They may require emergency treatment.

Prognosis

Asymptomatic gallstones seldom lead to problems. Death, even from symptomatic gallstones, is very rare, accounting for only 0.2% of annual deaths in the United States. Serious complications are rare. If they do occur, complications usually develop from stones in the bile duct or after surgery.

Gallstones, however, can cause obstruction at any point along the ducts that carry bile and, in such cases, symptoms can develop.

In most cases of obstruction, the stones block the cystic duct, which leads from the gallbladder to the common bile duct. This can cause pain (biliary colic), infection and inflammation (acute cholecystitis), or both.

About 10% of patients with symptomatic gallstones also have stones that pass into and obstruct the common bile duct (called choledocholithiasis).

The most serious complication of acute cholecystitis is infection, which develops in about 20% of cases. It is extremely dangerous and life-threatening if it spreads to other parts of the body (septicemia), and surgery is often required. Symptoms include fever, rapid heartbeat, fast breathing, and mental confusion. Among the conditions that can lead to septicemia are the following:

Gangrene or Abscesses. If acute cholecystitis is untreated and becomes very severe, inflammation can cause abscesses or destroy enough tissue in the gallbladder ( necrosis) to lead to gangrene. Studies have reported this complication in between 2 - 30% of cases. The highest risk is in men over 50 with a history of heart disease who have high levels of infection.

Perforated Gallbladder. An estimated 10% of acute cholecystitis cases result in a perforated gallbladder, which is a life-threatening condition. In general, this occurs in people who wait too long to seek help or who do not respond to treatment. This condition is most common in people with diabetes. The risk for perforation increases with a condition called emphysematous cholecystitis, in which gas forms in the gallbladder. Once the gallbladder has been perforated, pain may temporarily decrease. This is a dangerous and misleading event, however, since peritonitis (widespread abdominal infection) develops afterward.

Empyema. Pus in the gallbladder (empyema) occurs in 2 - 3% of patients with acute cholecystitis. Patients usually experience severe abdominal pain for more than 7 days. The physical exam often fails to reveal the underlying cause. The condition can be life-threatening, particularly if infection spreads to other parts of the body.

Fistula. In some cases, the inflamed gallbladder adheres to and perforates nearby organs, such as the small intestine. In such cases a fistula (channel) between the organs develops. Sometimes, in these cases, gallstones can actually pass into the small intestine, which can be very serious and requires immediate surgery.

Gallstone Ileus. A gallstone blocking the intestine is known as gallstone ileus. It primarily occurs in patients over age 65, and can sometimes be fatal. Depending on where the stone is located, surgery to remove the stone may be required.

When gallstones lodge in the common bile duct (choledocholithiasis) instead of the gallbladder, serious complications can occur.

Infection in the Common Bile Duct (Cholangitis). Infection in the common bile duct (cholangitis) from obstruction is common and serious. Those at highest risk for a poor outlook also have one or more of the following conditions:

Kidney failure

Liver abscess

Cirrhosis

Being over 50 years

If antibiotics are administered immediately, the infection clears up in 75% of patients. If cholangitis does not improve, the infection may spread and become life-threatening. Either surgery or a procedure known as endoscopic sphincterotomy is required to open and drain the ducts.

Pancreatitis. Choledocholithiasis is responsible for most cases of pancreatitis (inflammation of the pancreas), a condition that can be life threatening. The pancreatic duct, which carries digestive enzymes, joins the common bile duct right before it enters the intestine. It is therefore not unusual for stones that pass through or lodge in the lower portion of the common bile duct to obstruct the pancreatic duct.

Gallstones are present in about 80% of people with gallbladder cancer. Symptoms of gallbladder cancer usually do not appear until the disease has reached an advanced stage and may include weight loss, anemia, recurrent vomiting, and a lump in the abdomen. When the cancer is caught at an early stage and has not spread beyond the mucosa (the inner lining), removal of the gallbladder results in a 5-year survival rate of 68%. If cancer has spread to deeper layers, more extensive surgery or other treatments may be required.

This cancer is very rare, however, even among people with gallstones. Certain conditions in the gallbladder, however, pose a higher than average risk for cancer.

Gallbladder Polyps and Primary Sclerosing Cholangitis. Polyps (growths) are sometimes detected during diagnostic tests for gallbladder disease. Small gallbladder polyps (up to 10 mm) pose little or no risk, but large ones (greater than 15 mm) pose some risk for cancer, so the gallbladder should be removed. Patients with polyps 10 - 15 mm have a lower risk, but they should still discuss removal of their gallbladder with their doctor.

Primary Sclerosing Cholangitis. Primary sclerosing cholangitis is a rare disease that causes inflammation and scarring in the bile duct. It is associated with a lifetime risk of 7 - 12% for gallbladder cancer. The cause is unknown although it tends to strike younger men with ulcerative colitis. Polyps are often detected in this condition and have a very high likelihood of malignancy.

Anomalous Junction of the Pancreatic and Biliary Ducts. With this rare congenital condition, the junction of the common bile duct and main pancreatic duct is located outside the wall of the small intestine and forms a long channel between them. This problem poses a very high risk of cancer in the biliary tract.

Porcelain Gallbladders. Gallbladders are referred to as porcelain when their walls have become so calcified that they look like porcelain on an x-ray. Porcelain gallbladders have been associated with a very high risk of cancer, although recent evidence suggests that the risk is lower than previously thought. The incidence appears to depend on the presence of specific factors, such as partial calcification involving the mucosal lining. This condition may develop from a chronic inflammatory reaction that may actually be responsible for the cancer risk. Studies are reporting no higher risk with "true" porcelain gallbladders, in which the gallbladder walls are entirely calcified.

Risk Factors

About 20 million Americans harbor gallstones. Only 1 - 3% of the population, however, complains of symptoms during the course of a year, and less than half of these people will experience recurrent symptoms.

Women are much more likely than men to develop gallstones. Gallstones occur in nearly 25% of women in the U.S. by age 60 and as many as 50% by age 75. In most cases, they are asymptomatic. In general, women are probably at increased risk because estrogen stimulates the liver to remove more cholesterol from blood and divert it into the bile.

Pregnancy. Pregnancy increases the risk for gallstones, and pregnant women with stones are more likely to have symptoms than nonpregnant women. Surgery should be delayed until after delivery if possible. In fact, gallstones may disappear after delivery. If surgery is necessary, laparoscopy is the safer approach.

Hormone Replacement Therapy. Several large studies have shown that use of hormone replacement therapy (HRT) doubles or triples the risk for gallstones or gallbladder surgery. A 2005 Journal of the American Medical Association study found that while all types of HRT raise the risks, estrogen alone has higher risks than combined estrogen and progesterone therapy. Estrogen has an effect on the liver and raises triglycerides, a fatty acid that increases the risk for cholesterol stones. Recent studies on HRT reporting negative effects on the heart and increased risks for breast cancer are also making this treatment a less attractive option for most postmenopausal women.

About 20% of men have gallstones by the time they reach age 75. Because most cases are asymptomatic, however, the rates may be underestimated in elderly men. One study of nursing home residents reported that 66% of the women and 51% of the men had gallstones. Men who have their gallbladders removed, moreover, are more likely to have severe disease and operative complications than women.

Gallstone disease is relatively rare in children. When gallstones occur in this age group they are more likely to be pigment stones. Girls do not seem to be more at risk than boys are. The following conditions may put children at higher risk:

Spinal injury

History of abdominal surgery

Sickle-cell anemia

Impaired immune system

Intravenous nutrition

Because gallstones are related to diet, particularly fat intake, the incidence of gallstones varies widely among nations and regions. For example, Hispanics and Northern Europeans have a higher risk for gallstones than people of Asian and African descent do. People of Asian descent who develop gallstones are most likely to have the brown pigment type.

Native North and South Americans, such as Pima Indians in the U.S. and native populations in Chile and Peru, are especially prone to developing gallstones. Pima women have an 80% chance of developing gallstones during their lives, and virtually all native Indian females in Chile and Peru develop gallstones. Such cases are most likely due to a combination of genetic and dietary factors.

Having a family member or close relative with gallstones may increase the risk of gallstones. Up to one-third of cases of painful gallstones may be related to genetic factors.

Defects in transport proteins involved in biliary lipid secretion appear to predispose certain people to gallstone disease, but this alone many not be sufficient to create gallstones. Studies indicate that the disease is complex and may result from the interaction between genetics and environment. Some studies suggest immune and inflammatory mediators may play key roles.

People with diabetes are at higher risk for gallstones and have a higher-than-average risk for acalculous gallbladder disease (without stones). Gallbladder disease may progress more rapidly in patients with diabetes, who tend to suffer worse infections.

In theory, drugs designed to improve insulin resistance should reduce the incidence of gallstones. However, this may not always occur. Researchers were surprised when animal studies showed that the type 2 diabetes drug pioglitazone (Actos) caused gallbladder volume to increase, indicating that its function may be compromised. This may raise the risk of gallstone formation.

Obesity. Being overweight is a significant risk factor for gallstones. In such cases, the liver over-produces cholesterol, which is delivered into the bile and causes it to become supersaturated. Some evidence suggests that specific dietary factors (saturated fats and refined sugars) are the primary culprit in these cases, although studies are conflicting. Animal studies, however, suggest that obesity itself, not any particular foods, triggers the process leading to cholesterol supersaturation and the formation of stones.

Weight Cycling. Rapid weight loss or cycling (dieting and then putting weight back on) further increases cholesterol production in the liver, with resulting supersaturation and risk for gallstones. A 2000 study suggested the following rates for gallstones related to extreme and rapid weight loss:

The risk for gallstones is as high as 12% after 8 -16 weeks of restricted-calorie diets.

The risk is more than 30% within 12 -18 months after gastric bypass surgery.

About one-third of gallstone cases in these situations are symptomatic. The risk for gallstones is highest in the following dieters:

Those who lose more than 24% of their body weight.

Those who lose more than 1.5 kg (3.3. lb.) a week.

Those on very low-fat, low-calorie diets.

Weight cycling also puts people at risk for gallstones. For example, a 16-year study found that the risk for gallstone surgery was 68% higher for women who lost and then regained more than 20 pounds at least once, as compared with women whose weight remained stable.

Men are also at increased risk for developing gallstones when their weight fluctuates. The risk increases proportionately with dramatic weight changes as well as with frequent weight cycling.

Bariatric Surgery. Patients who have either Roux-en-Y or laparoscopic banding bariatric surgery are at increased risk for gallstones. For this reason, many centers request the patient undergo cholecystectomy before their bariatric procedure. Doctors are now questioning this practice. A study of nearly 1,000 patients who did not have gallbladder surgery before their Roux-en-Y found that only 8% developed symptomatic gallstones requiring cholecystectomy, and that all cases occurred within 29 months of the bariatric procedure. In another study of 261 patients who underwent lap banding, only 3 developed symptomatic gallstones after the procedure.

Metabolic syndrome is a cluster of conditions that includes obesity (especially belly fat), low HDL (good) cholesterol, high triglycerides, high blood pressure, and high blood sugar. Research suggests that metabolic syndrome is a risk factor for gallstones.

Although gallstones are formed from supersaturation of cholesterol in the bile, high total cholesterol levels themselves are not necessarily associated with gallstones. Gallstone formation, however, is associated with low levels of "good" HDL cholesterol and high triglyceride levels. Some evidence suggests that high triglycerides may impair the emptying actions of the gallbladder.

Unfortunately, some fibrates (drugs used to correct these conditions) actually increase the risk for gallstones by increasing the amount of cholesterol secreted into the bile. They include gemfibrozil (Lopid), fenofibrate (Tricor), and bezafibrate (Bezalip). Other cholesterol-lowering agents do not have this effect. [See In-Depth Report #23: Cholesterol.]

Prolonged Intravenous Feeding. Prolonged intravenous feeding reduces the flow of bile and increases the risk for gallstones. Up to 40% of patients on home parenteral nutrition develop gallstones, and the risk may be higher in patients on total parenteral nutrition. It is suspected that the cause is lack of stimulation in the gut, since patients who also take some food by mouth have less risk of developing gallstones. However, treatment for gallstones in this population is associated with a low risk of complications.

Crohn's Disease. Crohn's disease, an inflammatory bowel disorder, leads to poor reabsorption of bile salts from the digestive tract and substantially increases the risk of gallbladder disease. Patients over age 60 and those who have had numerous bowel operations (particularly in the region where the small and large bowel meet) are at especially high risk.

Cirrhosis. Cirrhosis poses a major risk for gallstones, particularly pigment gallstones.

Organ Transplantation. Bone marrow or solid organ transplantation increases the risk. The complications can be so severe that some organ transplant centers require the patient's gallbladder be removed before the transplant is performed.

Medications. Octreotide (Sandostatin) poses a risk for gallstones. In addition, the cholesterol-lowering drugs known as fibrates and thiazide diuretics may slightly increase the risk for gallstones.

Blood Disorders. Chronic hemolytic anemia, including sickle cell anemia, increases the risk for pigment gallstones.

Heme Iron. High consumption of heme iron, the type of iron found in meat and seafood, has been shown to lead to gallstone formation in men. Gallstones are not associated with diets high in non-heme iron foods such as beans, lentils, and enriched grains.

Prevention

Diet plays a role in gallstones. The following discussions are some observations on specific dietary factors.

Fats. Although fats (particularly saturated fats found in meats, butter, and other animal products) have been associated with gallstone attacks, some studies have found a lower risk for gallstones in people who consume foods containing monounsaturated fats (found in olive and canola oils) or omega-3 fatty acids (found in canola, flaxseed, and fish oil). Fish oil may be of particular benefit in patients with high triglyceride levels by improving the emptying actions of the gallbladder.

Fiber. High intake of fiber has been associated with a lower risk for gallstones.

Nuts. Studies suggest that people may be able to reduce their risk of gallstones by eating more nuts (peanuts and tree nuts such as walnuts and almonds).

Fruits and Vegetables. Researchers who followed more than 77,000 healthy women for 16 years in the Nurses' Health Study found that those who ate the most fruits and vegetables had the lowest risk of developing symptomatic gallstones requiring removal of the gallbladder. The effect was consistent regardless of which fruits or vegetables they ate.

Vegetable Protein. A 2004 epidemiologic study found evidence that consumption of vegetable protein (such as soybean products) can help to prevent symptomatic gallstones.

Lecithin. Lecithin is a key component of bile. It contains choline and inositol, two compounds that are important for the breakdown of fat and cholesterol. Low levels of lecithin may precipitate the formation of cholesterol gallstones. Animal studies have suggested that lecithin-rich soy and buckwheat protein may protect against gallstones. (Buckwheat may be more protective than soy.) Dietary lecithin is available in health food stores and is found in eggs, soybeans, liver, wheat germ, and peanuts. There is no evidence, however, that lecithin supplements or foods containing it can prevent gallstones in humans.

Sugar. High-intake of sugar has been associated with an increased risk for gallstones. Diets that are high in carbohydrates such as pasta and bread can also increase risk, since carbohydrates are converted to sugar in the body.

Alcohol. A few studies have reported a lower risk for gallstones with alcohol consumption. Even small amounts (1 ounce per day) have been found to reduce the risk of gallstones in women by 20%. Moderate intake (defined as 1 - 2 drinks a day) also appears to have heart protection benefits. It should be noted, however, that even moderate intake increases the risk for breast cancer in women. Pregnant women, people who can't drink moderately, and people with liver disease should not drink at all.

Vitamin C. Ascorbic acid (vitamin C) appears to help break cholesterol down in bile. Vitamin C deficiencies have been associated with a higher risk for gallstones.

Coffee. In one study, men who drank 2 or more cups of regular coffee daily (either instant, filtered, or espresso) had a 40% lower risk of developing gallbladder disease over 10 years than men who did not drink coffee regularly. Those who drank more than 4 cups had the lowest risk. A more recent study in 2000 did not find any general protective effect, although women with gallstones who drank coffee reported fewer symptoms than those who didn't.

Maintaining a normal weight and avoiding rapid weight loss are the keys to reducing the risk of gallstones. Taking the medication ursodiol (also called ursodeoxycholic acid, or Actigall) during weight loss may reduce the risk for people who are very overweight and need to lose weight quickly. This medication is ordinarily used to dissolve existing gallstones. A promising 2001 study suggested that orlistat (Xenical), a drug for treating obesity, may protect against gallstone formation during weight loss. The drug appeared to reduce bile acids and other components involved in gallstone production.

Exercising regularly and vigorously may reduce the risk of gallstones and gallbladder disease, even in people who are overweight. Studies are reporting a lower risk for gallstones in both men and women who exercise. Active sports exercise appears to be most protective for both men and women. A 1999 study of women reported that exercise reduced gallstone risk regardless of whether the women lost weight or not. Some evidence suggests that, in addition to controlling weight, exercise helps reduce cholesterol levels in the biliary tract, which could help prevent gallstones.

Some data have indicated that taking nonsteroidal anti-inflammatory drugs (NSAIDs) such as aspirin or ibuprofen protects against the development of gallstones. Recent studies have been mixed, although a 2001 study reported significant protection against gallstone recurrence in people who took NSAIDs after being treated with lithotripsy.

NOTE: Long-term use of NSAIDS can cause stomach problems, such as ulcers and bleeding, and possible heart problems. In April 2005, the FDA asked drug manufacturers of NSAIDs to include a warning label on their product that alerts users of an increased risk for cardiovascular events and gastrointestinal bleeding. Talk to your doctor before taking these drugs.

Although it would be reasonable to believe that agents used to lower cholesterol would protect against gallstones, they either have little effect or, in the case of fibrates, actually increase the risk. One study reported a weak association between statins and a lower risk for gallstones. These are the most effective drugs for treating high cholesterol and include lovastatin (Mevacor), pravastatin (Pravachol), simvastatin (Zocor), fluvastatin (Lescol), atorvastatin (Lipitor), and rosuvastatin (Crestor). Most evidence, however, has found no protection even from these agents. Reducing cholesterol itself, then, does not have any effect on cholesterol gallstones.

Diagnosis

The diagnostic challenge posed by gallstones is to verify that abdominal pain is caused by stones and not by some other condition. Ultrasound or other imaging techniques can usually detect gallstones. Nevertheless, because gallstones are common and most cause no symptoms, simply finding stones does not necessarily explain a patient's pain, which may be caused by any number of ailments.

In patients with abdominal pain, causes other than gallstones are usually responsible if the pain lasts less than 15 minutes, frequently comes and goes, or is not severe enough to limit activities.

Irritable Bowel Syndrome. Irritable bowel syndrome (IBS) has some of the same symptoms as gallbladder disease, including difficulty digesting fatty foods. However, the pain of IBS usually occurs in the lower abdomen.

Pancreatitis. It is sometimes difficult to differentiate between pancreatitis and acute cholecystitis, but a correct diagnosis is critical, since treatment is very different. About 40% of pancreatitis cases are associated with gallstones. The risk for gallstone-associated pancreatitis is highest in older Caucasian and Hispanic women. About 25% of pancreatitis cases are severe, and the rate is much higher in people who are obese.

Blood tests showing high levels of pancreatic enzymes (amylase and lipase) usually indicate a diagnosis of pancreatitis. Elevated levels of the liver enzyme alanine aminotransferase (ALT) are very specific in identifying gallstone pancreatitis.

Imaging techniques are useful in confirming a diagnosis. Ultrasound is often used. A computed tomography (CT) scan, along with a number of laboratory tests, can determine the severity of the condition.

Pancreatic Cancer. Symptoms of pancreatic cancer may be very similar to those of gallbladder disease. It should be suspected if such symptoms are accompanied by weight loss or suspicious results from imaging tests of the pancreas.

Other Conditions with Similar Symptoms. Acute appendicitis, inflammatory bowel disease (Crohn's disease or ulcerative colitis), pneumonia, stomach ulcers, gastroesophageal reflux and hiatal hernia, viral hepatitis, kidney stones, urinary tract infections, diverticulosis or diverticulitis, pregnancy complications, and even a heart attack may mimic a gallbladder attack.

In patients with known gallstones, the doctor can often diagnose acute cholecystitis (gallbladder inflammation) based on classic symptoms (constant and severe pain in the upper right quadrant of the abdomen). Imaging techniques are necessary to confirm the diagnosis. There is usually no tenderness in chronic cholecystitis.

Blood tests are usually normal in people with simple biliary colic or chronic cholecystitis. The following abnormalities may indicate gallstones or complications:

The enzyme alkaline phosphatase and bilirubin are usually elevated in acute cholecystitis, and especially choledocholithiasis (common bile duct stones). Bilirubin is the orange-yellow pigment found in bile. High levels cause jaundice, which gives the skin a yellowish tone.

Liver enzymes known as aspartate aminotransferase (AST) and alanine aminotransferase (ALT) are elevated when common bile duct stones are present. A threefold or more increase in ALT strongly suggests pancreatitis.

A high white blood cell count is a common finding in many (but not all) patients with cholecystitis.

General Guidelines. Common duct stones (choledocholithiasis) may be detected at one of several points:

When the patient complains of gallbladder symptoms.

At the same time that gallstones are diagnosed. (Common duct stones often accompany gallstones.)

During or after performing surgery to remove the gallbladder for gallstones (cholecystectomy).

If the doctor only suspects common duct stones, however, identifying them is problematic. It requires blood tests, imaging tests, invasive procedures, or some combination that serve both for detection and possibly removal.

Laboratory Tests. Evidence that may suggest common bile duct stones includes dark urine, jaundice, or pancreatitis. In such cases, the doctor may perform certain blood tests. Elevated levels of the following suggest the presence of common duct stones:

Alkaline phosphatase (ALP). Elevated levels of this enzyme are typically the first signs of common bile duct stones.

Bilirubin (the orange-yellow pigment found in bile). Bilirubin levels increase after alkaline phosphatase rises.

Liver enzymes known as aspartate aminotransferase (AST) and alanine aminotransferase (ALT). These enzymes may temporarily spike if the stone passes into the small intestine.

A number of techniques, particularly endoscopic retrograde cholangiopancreatography (ERCP), endoscopic ultrasound (EUS) and magnetic resonance cholangiography (MRC), are proving to be equally effective for detecting common bile duct stones. Only ERCP, however, allows removal of the stones, but it is invasive. A National Institutes of Health expert panel has endorsed the use of ERCP as a diagnostic technique for patients who are clearly ill with symptoms of gallstones. For patients who are not as sick, the panel recommended noninvasive imaging techniques.

Ultrasound. Ultrasound is a simple, rapid, and noninvasive imaging technique. It is the diagnostic method most frequently used to detect gallstones and is the method of choice for detecting acute cholecystitis. The patient must not eat for 6 or more hours before the test, which takes only about 15 minutes. During the procedure, the doctor can check the liver, bile ducts, and pancreas, and quickly scan the gallbladder wall for thickening (characteristic of cholecystitis).

Ultrasound detects gallstones as small as 2 mm in diameter with an accuracy of 90 - 95%. Some experts recommend that if an ultrasound does not detect stones, but gallstones are still strongly suspected, the test should be repeated.

Air in the gallbladder wall may indicate gangrene.

Ultrasound does not appear to be very useful for identifying cholecystitis in symptomatic patients who do not have gallstones. In one study, ultrasound detected some gallbladder abnormalities, no matter what the cause of the abdominal pain. In only a few cases, however, were the symptoms actually caused by cholecystitis.

Ultrasound is also not as useful for common bile duct stones and cannot image the cystic duct. Nevertheless, normal ultrasound results along with normal bilirubin and liver enzyme tests are very accurate indications that there are no stones in the common bile duct.

An ultrasound variation called endoscopic ultrasound (EUS) is accurate and useful for patients with an intermediate risk for common bile ducts stones. Its accuracy is comparable to endoscopic retrograde cholangiopancreatography (ERCP), the standard for diagnosing stones in the common bile duct. However, if common duct stones are detected, they cannot be removed. It is useful, then, when common bile duct stones are suspected, but the patient is not clearly ill.

X-Rays. Standard x-rays of the abdomen may detect calcified gallstones and gas. Variations include oral cholecystography or cholangiography.

In oral cholecystography the patient takes a tablet containing a dye the night before the test. The dye fills the gallbladder, and x-ray images are taken the next day. The test has largely been replaced by ultrasound. It is more sensitive than standard x-rays, however, and may be useful in some cases for determining the structural and functional status of the gallbladder, often before nonsurgical procedures.

Cholangiography uses a dye injected into the bile duct and x-ray to view the common bile duct. It is typically used during operations to provide a clear image of the biliary tract.

Cholescintigraphy (Also Called Gallbladder Radionuclide Scan). Cholescintigraphy, a nuclear imaging technique, is more sensitive than ultrasound for diagnosing acute cholecystitis. It is noninvasive but can take 1 - 2 hours or longer. The procedure involves the following steps:

A tiny amount of a radioactive dye is injected intravenously. This material is excreted into bile.

The patient lies on a table under a scanning camera, which detects gamma rays emitted by the dye as it passes from the liver into the gallbladder.

The test can take up to 2 hours, since each image takes about a minute, and they are taken every 5 -15 minutes.

If the dye does not enter the gallbladder, the cystic duct is obstructed, indicating acute cholecystitis. The scan cannot identify individual gallstones or chronic cholecystitis. Occasionally, the scan gives false positive results (detecting acute cholecystitis in people who do not have the condition). Such results are most common in alcoholic patients with liver disease or patients who are fasting or receiving all nutrition intravenously.

Endoscopic Retrograde Cholangiopancreatography (ERCP). Endoscopic retrograde cholangiopancreatography (ERCP) has been the gold standard for detecting common bile duct stones, particularly because they can be removed during the procedure. However, it is invasive and carries a risk for complications. With the advent of noninvasive imaging techniques, ERCP is now generally limited to patients who have a high likelihood of common bile ducts stones, which would need to be removed.

Computed Tomography. Computed tomographic (CT) scans may be a valuable additional imaging technique if the doctor suspects complicating features, such as perforation, common duct stones, or other problems such as cancer in the pancreas or gallbladder. Helical (spiral) CT scanning is advanced technique that shortens the time and obtains clearer images. With this process, the patient lies on a table while a donut-like, low-radiation x-ray tube rotates around the patient.

Magnetic Resonance Imaging (MRI). MRIs may be very useful for detecting common bile duct stones, particularly a specific MRI technique called magnetic resonance cholangiography (MRC). It employs MRI and cholangiography, in which a dye is injected into the bile duct and x-rays are used to view the duct. MRC is extremely sensitive in detecting biliary tract cancer. This imaging procedure is very expensive, however, and may not detect very small stones or chronic infections in the pancreas or bile duct. As with EUS, it is most likely to be useful in a small subset of patients and would not eliminate the need for ERCP in most patients.

Click the icon to see an image of a cholangiogram.

Virtual Endoscopy. Virtual endoscopy is an investigative technique that uses data from CT and MRI scans to generate a 3-dimensional view of various body structures. The images resemble those used in endoscopy, but the procedure is noninvasive. It one study it was able to detect smaller stones in the common bile duct than MRI. At this time it is still experimental.

Treatment

Acute pain from gallstones and gallbladder disease is usually treated in the hospital, where diagnostic procedures are performed to rule out other conditions and complications. There are 3 approaches to gallstone treatment:

Expectant management ("wait and see")

Nonsurgical removal of the stones

Surgical removal of the gallbladder

Guidelines from the American College of Physicians state that when a person has no symptoms, the risks of both surgical and nonsurgical treatment for gallstones outweigh the benefits. Experts suggest a wait-and-see approach for such patients, which they have termed expectant management. Exceptions to this policy are those at risk for complications from gallstones, including the following:

People at risk for gallbladder cancer

Pima Native Americans

Patients with stones larger than 3 cm

One study reported that very small gallstones increase the risk for acute pancreatitis, a serious condition. Some experts therefore believe that gallstones smaller than 5 mm warrant immediate surgery.

There are some minor risks with expectant management for asymptomatic or low-risk individuals. Gallstones almost never spontaneously disappear, except sometimes when they are formed under special circumstances, such as pregnancy or sudden weight loss. At some point, then, the stones may cause pain, complications, or both, and require treatment. Some studies suggest the patient's age at diagnosis may be a factor in the possibility of future surgery. The probabilities are as follows:

15% likelihood of future surgery at age 70

20% at age 50

30% at age 30

The slight risk of developing gallbladder cancer might encourage young adults who are asymptomatic to have their gallbladders removed.

Gallstones are the most common cause for hospital admissions of patients with severe abdominal pain. Diagnostic tests are performed and, depending on results, the approach may be as follows:

Normal Test Results and No Severe Pain or Complications. If the patient has no fever or underlying serious medical problems and shows no signs of severe pain or complications, and if laboratory tests are normal, then the patients may be discharged with oral antibiotics and pain relievers.

Gallstones and Presence of Pain (Biliary Colic) but No Infection. Patients with pain and tests that indicate gallstones but who do not show signs of inflammation or infection have the following options:

Intravenous painkillers are administered for severe pain. Such drugs include meperidine (Demerol) or the potent NSAID ketorolac (Acular, Toradol). Ketorolac should not be used for patients who are likely to need surgery. These drugs can cause nausea, vomiting, and drowsiness. Opioids such as morphine may have fewer adverse effects, but some doctors avoid them for gallbladder disease.

They may electively choose to have the gallbladder removed (called cholecystectomy) at their convenience.

A minority of such patients may be candidates for a stone-breaking technique called lithotripsy. The treatment works best on solitary stones that are less than 2 cm in diameter.

Drug therapy for gallstones is available for some patients who are unwilling to undergo surgery or who have serious medical problems that increase the risks of surgery. Recurrence rates are high with nonsurgical options. The introduction of laparoscopic cholecystectomy has greatly reduced the use of nonsurgical therapies. Note: Drug treatments are generally inappropriate for patients who have acute gallbladder inflammation or common bile duct stones, since delaying or avoiding surgery could be hazardous.

Acute Cholecystitis (Gallbladder Inflammation). The first step if there are signs of acute cholecystitis is to "rest" the gallbladder in order to reduce inflammation. This involves the following treatments:

Fasting

Intravenous fluids and oxygen therapy

Intravenous painkillers, usually meperidine (Demerol). Potent NSAIDs, usually indomethacin, may be particularly useful. Indomethacin, for example, can reduce pain and inflammation and improve emptying actions of the gallbladder. Some doctors believe morphine should be avoided for gallbladder disease.

Intravenous antibiotics. These are administered if the patient shows signs of infection, including fever or an elevated white blood cell count, or in patients without such signs who do not improve after 12 - 24 hours.

Surgery to remove the gallbladder (called cholecystectomy) is nearly always indicated in people with acute cholecystitis. The most common procedure is now laparoscopy, a less invasive technique than open cholecystectomy (which involves a wide abdominal incision). Timing can be within hours to weeks after the acute episode, depending on the severity of the condition.

Click the icon to see an illustrated series detailing a gallbladder removal.

Gallstone-Associated Pancreatitis. Patients who have developed gallstone-associated pancreatitis almost always require surgery with either laparoscopic or open cholecystectomy.

Common Duct Stones. If noninvasive diagnostic tests suggest obstruction from common duct stones, the doctor will perform a procedure called endoscopic retrograde cholangiopancreatography (ERCP) to confirm the diagnosis and remove stones. This technique is used urgently along with antibiotics if infection is present in the common duct (cholangitis). In most cases, common duct stones are discovered during or after gallbladder removal.

Surgery

The gallbladder is not an essential organ, and even today, only surgical removal of the gallbladder (cholecystectomy ) guarantees that the patient will not suffer a recurrence of gallstones. This is one of the most common surgical procedures performed on women, and it can even be performed on pregnant women with low risk to the baby and the mother. The primary advantages of surgical removal of the gallbladder over nonsurgical treatment are elimination of gallstones and prevention of gallbladder cancer.

Open Procedures versus Laparoscopy. Until the early 1990s, open cholecystectomy (the removal of the gallbladder through a wide abdominal incision) was the standard treatment. Now, laparoscopic cholecystectomy (commonly called lap choly), which uses small incisions, is the most commonly used surgical approach. First performed in 1987, lap choly is now used in most cholecystectomies in the United States. In fact, about 700,000 people now have their gallbladders removed each year -- 200,000 more than before the introduction of laparoscopy. Of concern, then, is a significant increase in its use in patients who have inflammation in the gallbladder but no infection or gallstones and in those who have gallstones but no symptoms.

Laparoscopy has largely replaced open cholecystectomy because of some significant advantages:

The patient can leave the hospital and resume normal activities earlier than with open surgery.

The incisions are small, and there is less postoperative pain and disability than with the open procedure.

Laparoscopy has fewer complications.

It is less expensive than open cholecystectomy in the long term. The immediate treatment cost of laparoscopy may be higher than the open procedure, but the more rapid recovery with lap choly and fewer complications translate into shorter hospital stays and fewer sick days, and so a greater reduction in overall costs.

Some experts believe, however, that the open procedure still has a number of advantages compared to laparoscopy:

It is faster to perform.

It poses less of a risk for bile duct injury, which occurs in only 0.1 - 0.5% of open procedures, compared to about 0.3 - 2% with laparoscopy. Open surgry has more overall complications than laparoscopy, however, and bile-duct injury rates with laparoscopy are declining.

The type of surgery performed on specific patients may vary depending on different factors.

Appropriate Surgical Candidates. Candidates for gallbladder removal often have, or have had, one of the following conditions:

A very severe gallstone attack

Several less severe gallstone attacks

Endoscopic sphincterotomy for common bile duct stones i(n patients with residual gallbladder stones)

Cholecystitis (gallbladder inflammation).

Pncreatitis (inflammation of the pancreas)

High risk for gallbladder cancer (e.g., patients with anomalous junction of the pancreatic and biliary ducts or patients with certain forms of porcelain gallbladder)

Acalculous biliary pain (gallbladder disease symptoms without the presence of gallstones). The best candidates are those with evidence of impaired gallbladder emptying.

Timing of Surgery. Cholecystectomy may be performed within days to weeks after hospitalization for an acute gallbladder attack, depending on the severity of the condition.

Emergency gallbladder removal within 24 - 48 hours is warranted in about 20% of patients with acute cholecystitis. Indications for surgery include deterioration of the patient's condition, or signs of perforation or widespread infection.

The timing and type of surgery in patients with acute cholecystitis whose condition improves and have no signs of severe complications are under debate. Previously, the standard was open cholecystectomy between 6 - 12 weeks after the acute episode. Some evidence now suggests that early surgery performed between 72 - 96 hours after symptoms have lower complications than surgery performed after that.

General Outlook. Although cholecystectomy is very safe, as with any operation, there are risks of complications depending on whether the procedure is done on an elective or emergency basis.

When cholecystectomy is performed as elective surgery, the mortality rates are very low. (Even in the elderly, mortality rates are only 0.7 - 2%.)

Emergency cholecystectomy carries a much higher mortality rate (as high 19% in ill elderly patients).

Long-Term Effects of Gallbladder Removal. Although removal of the gallbladder has not been known to cause any long-term adverse effects aside from occasional diarrhea, some researchers have been concerned about its long-term impact on the body's cholesterol levels.

One study found that within 3 days of the operation, levels of total cholesterol and LDL returned to their preoperative levels. After 3 years, however, some types of cholesterol not ordinarily associated with coronary artery disease had risen significantly. These results did not necessarily indicate any increased risk for coronary artery disease, but they did show that the metabolism of cholesterol by the liver had been altered. People who have had their gallbladders removed should have their cholesterol levels checked periodically, as should every adult. Short-term treatment with the cholesterol-lowering known as statins, such as pravastatin (Pravachol), appears to lower cholesterol levels in surgical patients.

Laparoscopy

Open Cholecystectomy

Treatment of choice for most adult gallstone patients with or without symptoms, who have electively chosen to have their gallbladders removed.

Patients who have had extensive previous abdominal surgery.

Most patients with acute cholecystitis not accompanied by infection or perforation. (Up to 30% will need to convert to open surgery, depending on the severity of the condition.)

Patients with complications of acute cholecystitis (empyema, gangrene, perforation of the gallbladder).

Patients with acalculous gallbladder disease (without stones) who choose to have surgery. (if the patients have inflammation, however, the procedure of choice is percutaneous cholecystostomy to drain the gallbladder.

Very elderly patients. (Those over 80 are likely to have lower complication rates from open cholecystectomy than laparoscopy, although laparoscopy may even be appropriate in these patients.)

Patients with residual gallbladder stones after endoscopic sphincterotomy for common bile duct stones.

Candidates when experienced surgeons are available:

Patients with acute gallstone pancreatitis that has subsided.

Severely obese patients

Patients with prior surgery in the upper abdomen.

Patients with severely infected gallbladders.

Pregnant women with symptomatic gallstones.

Seriously ill patients with acute cholecystitis who do not respond to fluid aspiration (percutaneous cholecystostomy).

The Procedure. With laparoscopy, removal of the gallbladder is typically performed as follows:

Laparoscopic cholecystectomy requires general anesthesia, although it is now mostly done as outpatient surgery.

The surgeon inserts a needle through the navel and pumps carbon dioxide gas through it to create space in the abdomen. This step may raise blood pressure. The antihypertensive drug clonidine may be helpful during surgery to protect patients with high blood pressure or heart or kidney disease. Of note, a 2000 study recommended that elderly patients not receive gas. Such patients are more likely to require a longer operating time, and the on-going pressure from the carbon dioxide increases the risk for problems that require conversion to an open procedure.

One or two 10 - 12 mm (about one-half inch) and three 5 mm (.20 inches), are made in the abdomen.

The surgeon inserts a laparoscope (a thin telescope) which contains a small surgical instrument and a tiny camera that relays an image to a video monitor.

The surgeon separates the gallbladder from the liver and other areas and removes it through one of the incisions.

Evidence suggests that the use of cholangiography during the operation helps prevent injury in the bile ducts, a serious complication of cholecystectomy. With this procedure, dye is injected into the bile duct, and moving x-rays are used to view the duct.

In general, the patient can go home the same day. In a 2001 study, however, some patients were found to be at higher risk for readmission later on, including those operation took longer than 1 hour or who had thicker gallbladder walls

Risk Factors for Conversion from Laparoscopy to an Open Procedure. In about 5 - 10% of laparoscopies, conversion to open cholecystectomy is required during the procedure. The rate of conversion to open surgery is higher in men than in women. This may be due to the higher rate of inflammation and fibrosis in men with symptomatic gallstones. Other reasons for conversion from laparoscopic to open surgery include:

Possible or known injury to major blood vessels

Internal structures not clearly visible

Unexpected problems that cannot be corrected with laparoscopy

Common bile duct stones that cannot be removed with laparoscopy or subsequent ERCP.

Previous endoscopic sphincterotomy

A thickened gallbladder wall

Complications and Side Effects of Surgery

Pain and fatigue are common side effects of any abdominal surgery. Patients should abstain from light recreational activities for about 2 days and from work and more strenuous activities for about a week.

There is a relatively high incidence of nausea and vomiting after laparoscopic cholecystectomy, which can be treated with injections of metoclopramide. Preoperative anti-nausea agents such as granisteron may prevent these effects. One study reported that patients who received a local anesthesia at the incision sites (in addition to general anesthesia) before surgery had less pain and nausea afterwards.

Injury to the bile duct. Bile duct injury is the most serious complication of laparoscopy. It can include leakage, tears, and the development of narrowing (strictures) that can lead to liver damage. In order to minimize such injuries, some experts recommend that surgeons perform laparoscopy with a procedure called cholangiography, in which a dye is injected into the bile duct and x-rays are used to view the duct. Bile duct injury has been a more common problem than with the open procedure but increasing surgical experience and the use of cholangiography is reducing this complication and studies are now reporting more comparable rates between the two procedures.

In about 6% of procedures, the surgeon misses some gallstones, or they are spilled and remain in the abdominal cavity. In a small percentage of these cases, the stones cause obstruction, abscesses, or fistulas (small channels) that require open surgery.

As with all surgeries, there is a risk for infection, but it is very low.

Patients should not be shy about inquiring into the number of laparoscopies the surgeon has performed (the minimum should be 40). Obese patients were originally thought to be poor candidates for laparoscopic cholecystectomy, but recent research indicates that this surgery is safe for them.

Before the development of laparoscopy, the standard surgical treatment for gallstones was open cholecystectomy (surgical removal of the gallbladder through an abdominal incision), which requires a wide incision and leaves a large surgical scar. In this procedure, the patient usually stays in the hospital for 5 - 7 days and may not return to work for a month. Complications include bleeding, infections, and injury to the common bile duct. The risks of this procedure increase with other factors, such as the age of the patient or if the surgeon needs to explore the common bile duct for stones at the same time.

Whether or not to insert a drain in the wound after surgery is under debate. Many surgeons implant drains primarily to prevent abscess or peritonitis. That practice may change. A recent analysis of all randomized clinical trains comparing drains versus no drains or type of drain used found that patients who received drains had a dramatically increased risk of wound and chest infection. The type of drain used made no difference.

Percutaneous Cholecystostomy. Percutaneous cholecystostomy is a procedure that may be used in seriously ill patients with severe gallbladder infection who cannot tolerate immediate surgery. It is also the standard treatment for patients with acalculous cholecystitis (gallbladder inflammation without stones). This procedure uses a needle to withdraw fluid (aspirate) from the gallbladder. A drainage catheter is inserted through the skin and into the gallbladder while the fluid drains out. In some cases, it may be left in place for up to 8 weeks. After that time, if possible, laparoscopy or an open cholecystectomy may be performed. Without a laparoscopy, recurrence rates with this procedure are high.

Gallbladder Aspiration. With this procedure, fluid is aspirated in one procedure while the gallbladder is viewed using ultrasound. It does not require an indwelling catheter afterward and may have fewer complications than percutaneous cholecystostomy.

Mini-Laparotomy Cholecystectomy. Mini-laparotomy cholecystectomy uses small abdominal incisions but, unlike laparoscopy, it is an "open" procedure, and the surgeon does not operate through a scope. The surgical instruments used are very small (2 - 3 mm in diameter, or about a tenth of an inch). Eventually, this technique may reduce operative time and enable surgeons to obtain better results than with laparoscopy.

Needlescopic Cholecystectomy. Procedures that use even fewer and smaller incisions than laparoscopy are being developed. There are many variations, including those referred to as twin-port, mini-site, or mini- or micro-laparoscopic surgeries. These procedures make even fewer incisions (2 - 3) and smaller ones (1.2 - 3 mm, or less than one-tenth of an inch). It should be noted, however, that these procedures still require one larger incision (10 - 12 mm, or about one-half inch). They are still investigative and have some disadvantages:

Fiberoptics, used to view the surgical areas, do not provide light that is as bright as the light used in conventional laparoscopy.

The instruments are very fragile.

The field of vision is very limited.

Although experience is very limited, studies are showing promise for reducing postoperative pain and improving recovery time beyond that of standard laparoscopy.

Telerobotic Surgery. In one high-tech experiment, surgeons in New York removed the gallbladder of a woman in France in a laparoscopic procedure using tools controlled by a remote robotic device. The procedure took 54 minutes and was free of complications.

Lithotripsy and Dissolution Therapies

Oral agents used to dissolve gallstones, and lithotripsy alone or in combination with other drugs had gained some popularity in the 1990s. But these oral agents have lost favor with the increase in laparoscopy. They still may have some value in specific circumstances.

Oral Dissolution Therapy. Oral dissolution therapy uses bile acids in pill form to dissolve gallstones and may be used in conjunction with lithotripsy, although both techniques are rarely used at present. Ursodiol (ursodeoxycholic acid, Actigall) and chenodiol (Chenix) are the standard oral bile acid dissolution drugs. Most doctors prefer ursodeoxycholic acid, which is considered to be among the safest of common drugs and without significant side effects. Long-term treatment appears to notably reduce the risk of biliary pain and acute cholecystitis. The treatment is only moderately effective, however, since gallstones recur in the majority of patients.

Patients most likely to benefit from oral dissolution therapy are those with small stones (less than 1.5 cm in diameter) that have a high cholesterol content.

Patients who probably will not benefit from this treatment include obese patients and those with gallstones that are calcified or composed of bile pigments

Only about 30% of patients are candidates for oral dissolution therapy; the number actually may be much lower, since compliance is often a problem. The treatment can take up to 2 years and can cost thousands of dollars per year.

Contact Dissolution Therapy. Contact dissolution therapy requires the injection of the organic solvent methyl tert-butyl ether (MTBE) into the gallbladder to dissolve gallstones. This is a somewhat technically difficult and hazardous procedure and performed only by experienced doctors in hospitals where research on this treatment is being done. Preliminary studies indicate that MTBE rapidly dissolves stones. The ether remains liquid at body temperature and dissolves gallstones within 5 - 12 hours. Serious side effects include severe burning pain.

Investigative Agents. Fatty acid bile acid conjugates (FABACs) are experimental agents that are being investigated for dissolving gallstones and for preventing gallstone formation.

Gallstone fragmentation by extracorporeal shock wave lithotripsy (ESWL) may be an appropriate therapy for some patients who cannot undergo surgery, but it is no longer widely used. The treatment works best on solitary stones that are less than two centimeters in diameter. Less than 15% of patients are good candidates for lithotripsy. The typical procedure is as follows:

The patient typically sits in a tub of water.

High-energy, ultrasound shock waves are directed through the abdominal wall toward the stones.

The shock waves travel through the soft tissues of the body and break up the stones.

The stone fragments are then usually small enough to be passed through the bile duct and into the intestines.

Lithotripsy is generally combined with oral dissolution (bile acid) treatment to help dissolve the fragmented pieces of the original gallstone.

Complications. Complications include pain in the gallbladder area and pancreatitis, usually occurring within a month of treatment. In addition, not all of the fragments may clear the bile duct. Adding erythromycin to the treatment regimen may help remove these fragments. About 35% of patients who are left with fragments are at risk for further problems, which can be severe. The chance of recurrence is high with this procedure, and in one study, 45% of patients eventually required surgery. Elderly people may have a lower risk for recurrence than younger adults, which may make this a good choice for some.

Managing Common Bile Duct Stones

Common duct stones (choledocholithiasis) pose a high risk for complications and nearly always warrant treatment. There are various options available. It is not clear yet which one is optimal.

In the past, when common bile duct stones were suspected, the approach was open surgery (open cholecystectomy) and surgical exploration of the common bile duct. This required a wide abdominal incision.

Endoscopic retrograde cholangiopancreatography (ERCP) with endoscopic sphincterotomy (ES) is now the most frequently used procedure for detecting and managing common duct stones. The procedure involves the use of an endoscope (a flexible telescope containing a miniature camera and other instruments), which is passed down the throat to the bile duct entrance.

Laparoscopic cholecystectomy also is increasingly being used for detection and removal of common duct stones. This is an approach through the abdomen but uses small incisions. In such cases, it is used in combination with ultrasound or a cholangiogram (an imaging technique in which a dye is injected into the bile duct and moving x-rays are used to view any stones).

Experts are currently debating the choice between laparoscopy (an abdominal approach) and ERCP (approaching through a tube down the throat). Many surgeons believe that laparoscopy is becoming safe and effective and should be the first choice. Still, laparoscopy for common duct stones should be performed only by surgeons experienced in this technique.

Endoscopic Retrograde Cholangiopancreatography (ERCP)

Laparoscopic Common Bile Duct Exploration

Open Common Bile Duct Exploration (Choledocholithotomy)

Before gallbladder surgeries when there is strong suspicion that common bile duct stones are present.

After gallbladder surgeries in which the surgeon detects stones in the common bile duct (only if there are experts in ERCP and equipment is available).

For patients with gallstone cholangitis (serious infection in the common bile duct). In such cases urgent ERCP plus antibiotics is required.

When acute pancreatitis is caused by gallstones. In such cases urgent ERCP plus antibiotics is required. (The use of ERCP compared to conservative treatment has been controversial. One study reported that only patients who had infection and persistent obstruction in the ducts benefited from urgent ERCP intervention. In a 2000 analysis of four studies, however, ERCP significantly improved survival rates and reduced complications.)

As an alternative to ERCP before gallbladder surgeries when there is high suspicion of common bile duct stones. (Should be performed only in centers with expertise in this procedure, where it may actually be preferable to ERCP.)

During gallbladder surgeries when common duct stones are detected or highly suspected. (Only for centers with expertise in this procedure.)

During or after some gallbladder operations when stones are detected. If procedure is laparoscopy, surgeon may convert to open procedure. Less often used now.

When ERCP or laparoscopic procedures are not available.

The ERCP and ES Procedure. A typical ERCP and endoscopy sphincterotomy (ES) procedure includes the following steps:

The patient is given a sedative and asked to lie on his or her left side.

An endoscope (a tube containing fiber optics connected to a camera) is passed through the mouth and stomach and into the duodenum (top part of the small intestine) until it reaches the point where the common bile duct enters. This does not interfere with breathing, but the patient may have a sensation of bloating.

A thin catheter (tubing) is then passed through the endoscope.

Contrast material (a dye) is injected through the catheter into the opening of the duct. The dye allows x-ray visualization of the biliary tree (the system of ducts through which bile flows, including the common bile duct) and any stones contained in the area.

Instruments may also be passed through the endoscope to remove any stones that are detected.

The next phase of the procedure is known as endoscopic sphincterotomy (ES). (It is also sometimes referred to as papillotomy, although this is a slightly different variation.) It serves to widen the junction between the common bile duct and intestine (called the ampulla of Vater) so that the stones can be extracted more easily. With ES a tiny incision is usually made in the orifice of the common bile duct and through the muscles that enclose the lower common bile duct (called the sphincter of Oddi).

One recent alternative to ES is the use of a small inflatable balloon (called endoscopic balloon dilation) that opens up the ampulla of Vater to allow stones to pass and so avoid cutting the muscles. According to 2003 studies, it is equal in effectiveness to ES but offers no advantage at this time.

Once the junction has been opened, the stones may pass out on their own or they may be extracted with the use of tiny baskets or balloons.

Complications. Complications of ERCP and ES occur in 5 - 8% of cases, and some can be serious, with mortality rates of 0.2 - 0.5%. They include the following:

Pancreatitis (inflammation of the pancreas) occurs in 3 - 9% of cases and can be very serious. Younger adults are at higher risk than the elderly. The risk is also higher with more complex procedures. The drugs somatostatin or gabexate are sometimes used to reduce the risk, although evidence suggests somatostatin may not reduce this risk. Gabexate appears to be more effective, although studies are mixed on whether its benefits are significant, particularly with short-term administration.

Postoperative infection. Antibiotics may be given before the procedure to prevent infection, although one study reported that they had little benefit.

Bleeding occurs in 2% of cases. There is an increased risk in patients taking anti-clotting drugs and those who have cholangitis. This complication is treated by flushing the area with epinephrine.

Perforations (rare).

Long-term complications include stone recurrence and abscesses.

ERCP and ES are difficult procedures, and patients must be certain their doctor and the medical center have experience with them. The surgeon should have performed at least 180 ERCPs. Under such circumstances, ERCP can usually be performed successfully even in critically ill patients on mechanical ventilators.

ERCP and Gallbladder Removal (Cholecystectomy). ERCP is often performed after gallstones in the common duct are discovered during cholecystectomy (removal of the gallbladder).

In some cases, stones in the gallbladder are detected during ERCP. In such cases laparoscopic cholecystectomy is usually warranted. There is some debate about whether the gallbladder should be removed in such cases at the same time as ERCP or if patients should wait. A 2002 study suggested that immediate gallbladder removal is preferred, since the risk for recurring symptoms is very high.

Surgeons are now increasingly using laparoscopy plus an imaging technique called cholangiography instead of ERCP when common duct stones are suspected. The laparoscopic procedure for common duct stones should be performed only in centers where there is expertise. It generally proceeds as follows:

The initial approach is the same as with laparoscopic cholecystectomy. Small incisions, one or two 10 - 12 mm (around half an inch) and three 5 mm (.20 inches), are made in the abdomen.

A tiny opening is made in the cystic duct that connects the gallbladder to the bile duct, and a thin tube is introduced to perform a cholangiogram. (In this procedure, a dye is administered to reveal the stone's location on x-rays.)

The procedure is typically used in combination with cholangiography, an imaging technique in which a dye is injected into the bile duct and x-rays are used to view any stones. Cholangiography reduces the risk for injury in the common duct.

If stones are identified, the surgeon inserts a tube with an inflatable balloon that is used to widen the duct.

Stones are usually retrieved or withdrawn from the duct either with the use of a balloon or with a tiny basket.

If laparoscopy is unsuccessful, then ERCP or open surgery is performed.

Experts are debating whether the use of this procedure is better than ERCP. Many surgeons believe that laparoscopy is becoming safe and effective and should be the first choice. Still, laparoscopy for common duct stones should be performed only by surgeons experienced in this new and demanding technique.

Choledocholithotomy, or common bile duct exploration, is used to remove large stones or in cases when the duct anatomy is complex. In this procedure, the doctor carries out open abdominal surgery and extracts gallstones through an incision in the common bile duct. Routinely, a so-called "T-tube" is temporarily left in the common bile duct after surgery and the doctor x-rays the bile duct through the tube 7 - 10 days postoperatively to determine if any stones remain in the duct.

Shock wave lithotripsy is an option in certain cases for bile duct stones that cannot be extracted.

Mechanical Endoscopic Lithotripsy. Endoscopy with mechanical lithotripsy employs a tiny steel crushing basket, which is inserted through the endoscope and into the common bile duct. The basket opens to trap and then crush the stone. It is capable of crushing and removing very large stones. The overall success rate is 80 - 90%, although 20 - 30% of patients require more than one treatment.

Extracorporeal Shock Wave Lithotripsy. Extracorporeal shock wave lithotripsy is an option in certain cases of bile duct stones as it is for stones in the gallbladder.

Resources

http://digestive.niddk.nih.gov -- National Digestive Diseases Information Clearinghouse

www.gastro.org -- American Gastroenterological Association

www.acg.gi.org -- American College of Gastroenterology

www.liverfoundation.org -- American Liver Foundation

References

Al-Azzawi HH, Mathur A, Lu D, Swartz-Basile DA, Nakeeb A, Pitt HA. Pioglitazone increases gallbladder volume in insulin-resistant obese mice. J Surg Res. 2003;136(2):192-197.

Dray X, Joy F, Reijasse D, et al. Incidence, risk factors, and complications of cholelithiasis in patients with home parenteral nutrition. J Am Coll Surg. 2007;204(1):13-21.

Grunhage F, Lammert F. Gallstone disease. Pathogenesis of gallstones: A genetic perspective. Best Pract Res Clin Gastroenterol. 2006;20(6):997-1011.

Gurusamy K, Samraj K. Routine abdominal drainage for uncomplicated open cholecystectomy. Cochrane Database Syst Rev. 2007;18;(2):CD006003.

Lyons MA, Wittenburg H. Susceptibility to cholesterol gallstone formation: evidence that LITH genes also encode immune-related factors. Biochim Biophys Acta. 2006;1761(10):1133-1147.

Masannat Y, Masannat Y, Shatnawei A. Gallstone ileus: a review. Mt Sinai J Med. 2006;73(:1132-1134.

Morimoto LM, Newcomb PA, Hampton JM, Trentham-Dietz A. Cholecsytectomy and endometrial cancer: a marker of long-term elevated estrogen exposure? Int J Gynecol Cancer. 2006;16(3):1348-1353.

Myers JA, Fischer GA, Sarker S, Shayani V. Gallbladder disease in patients undergoing laparoscopic adjustable gastric banding. Surg Obes Relat Dis. 2005;1(6)561-563.

Portenier DD, Grant JP, Blackwood HS, Pryor A, McMahon RL, Demaria E. Expectant management of the asymptomatic gallbladder at Roux-en-Y gastric bypass. Surg Obes Relat Dis. 2007. Epub Apr 17 ahead of print.

Sarkio S, Salmela K, Kyllonen L. Rosliakova M, Honkanen E, Halme L. Complications of gallstone disease in kidney transplantation patients. Nephrol Dial Transplant. 2007;22(3):886-890.

Tsai CJ, Leitzmann MF, Willett WC, Giovannucci EL. Fruit and vegetable consumption and risk of cholecystectomy in women. Am J Med. 2006;119(9):760-767.

Tsai CJ, Leitzmann MF, Willett WC, Giovannucci EL. Heme and non-heme iron consumption and risk of gallstone disease in men. Am J Clin Nutr. 2007;85(2):518-522.

Tsai CJ, Leitzmann MF, Willett WC, Giovannucci EL. Weight cycling and risk of gallstone disease in men. Arch Intern Med. 2006;166(21):2369-2374.

Wittenburg H, Lammert F. Genetic predisposition to gallbladder stones. Semin Liver Dis. 2007;237(1):109-121.

Yol S, Kartal A, Vatansev C, Aksoy F, Toy H. Sex as a factor in conversion from laparoscopic cholecystectomy to open surgery. JSLS. 2006;10(3):359-363.

Review Date:
5/15/2007
Reviewed By:
Harvey Simon, MD, Associate Professor of Medicine, Harvard Medical School; Physician, Massachusetts General Hospital.

A.D.A.M., Inc. is accredited by URAC, also known as the American Accreditation HealthCare Commission (www.urac.org). URAC's accreditation program is an independent audit to verify that A.D.A.M. follows rigorous standards of quality and accountability. A.D.A.M. is among the first to achieve this important distinction for online health information and services. Learn more about A.D.A.M.'s editorial policy, editorial process and privacy policy. A.D.A.M. is also a founding member of Hi-Ethics and subscribes to the principles of the Health on the Net Foundation (www.hon.ch).

A.D.A.M. Copyright

The information provided herein should not be used during any medical emergency or for the diagnosis or treatment of any medical condition. A licensed medical professional should be consulted for diagnosis and treatment of any and all medical conditions. Call 911 for all medical emergencies. Links to other sites are provided for information only -- they do not constitute endorsements of those other sites. © 1997-2009 A.D.A.M., Inc. Any duplication or distribution of the information contained herein is strictly prohibited.

adam.com

Restless legs syndrome and related disorders

FitSugar — Wed, 08 Oct 2008 17:35:14 -0700

In This Report

Highlights

Introduction

Causes

Risk Factors

Complications

Diagnosis

Treatment

Medications

Resources

References

HEALTH GUIDE REFERENCE FROM A.D.A.M

Highlights

Treatment

The American Academy of Sleep Medicine recommends medications for restless legs syndrome (RLS) or periodic limb movement disorder (PLMD) only for persons who fulfill strict diagnostic criteria and experience too much daytime sleepiness as a result of these conditions. (Excessive daytime sleepiness results from nighttime sleeplessness due to RLS or PLMD symptoms).

The U.S. Food and Drug Administration (FDA) announced in March 2007 that the dopamine agonist drug pergolide (Permax) has been voluntarily withdrawn from the market. This drug can cause serious damage to the heart valves of patients who take it.

The FDA approved pramipexole (Mirapex) for use in moderate-to-severe restless legs syndrome (RLS) in November 2006.

Bupropion (Wellbutrin), a newer antidepressant, may also be helpful for RLS. Bupropion, a weak dopamine reuptake inhibitor, causes a slight increase in the availability of dopamine in the brain. It is not addictive and does not have the severe side effects of other RLS drugs, but more research is needed to determine its usefulness. It is not FDA approved for RLS.

Research

Results from a large study show that RLS is more common in children and teens than epilepsy and diabetes. The study also found that more than 70% of affected children had at least one biological parent with RLS.

Two recently-published studies found an abnormal gene on chromosome 6 makes some people susceptible to RLS and PLMD.

People with type 2 diabetes have higher rates of secondary RLS. Nerve pain (neuropathy) related to their diabetes cannot fully explain this increased rate in RLS.

Introduction

Restless legs syndrome (RLS) is an unsettling and poorly understood movement disorder affecting 3 - 15% of the general population. RLS can affect both children and adults. Although effective treatments are available, the condition often remains undiagnosed.

Symptoms of RLS. The core symptom of RLS is an irresistible urge to move the legs (medically known as akathisia). Some people describe this symptom as a sense of unease and weariness in the lower leg, which is aggravated by rest and relieved by movement. Specific characteristics of RLS include:

"Pulling, searing, drawing, tingling, bubbling, or crawling" beneath the skin, usually in the calf area, causing an irresistible urge to move the legs. These sensations can occur not only in the lower legs, but they can also affect the thighs, feet, and even the upper body. RLS-type symptoms may also occur in the arms. This may be the first symptom of RLS in some people.

About 80% of patients with RLS also experience semi-rhythmic movements called periodic limb movement disorder (PLMD).

Itching and pain, particularly aching pain, may be present.

Patients experience symptoms when they feel most relaxed and their legs are at rest. (Movement, however, brings relief.) Symptoms usually occur at night when lying down, or sometimes during the day while sitting.

Episodes of RLS usually develop between 10 p.m. and 4 a.m. Symptoms are often most severe shortly after midnight. They typically occur for 30 - 60 seconds, and they usually resolve by morning. If the condition becomes more severe, people may begin to have symptoms during the day. These symptoms are always worse at night, however.

At night, the unpleasant sensations and the resulting uncontrollable urge to move the legs can often disturb sleep. Ignoring the need to move the legs usually only builds up tension until they jerk uncontrollably. If patients experience symptoms during the day, they usually feel compelled to move their legs in order to relieve the symptoms, making it difficult to sit during air or car travel or through classes or meetings.

Late-onset and Early-onset Forms. There appear to be two forms of RLS, early-onset and late-onset. Each form may have different characteristics:

People with early-onset RLS (occurring in the teenage years or earlier) tend to have a family history of the disorder. They also usually have RLS without accompanying pain.

Those with late-onset RLS usually do not have a family history of RLS. Their condition is more likely the result of a problem with the nervous system, and symptoms may include pain in the lower legs.

The medical term for periodic limb movement disorder (PLMD) is nocturnal myoclonus. PLMD symptoms include:

Episodes that usually occur during the night, peaking near midnight, as they do in restless legs syndrome (RLS).

Leg muscles contract and jerk every 20 - 40 seconds during sleep. Such movements may last less than 1 second, or as long as 10 seconds.

Unlike RLS, contractions in PLMD usually do not wake patients. PLMD is distinct from the brief and sudden movements that occur just as people are falling asleep, jolting them awake.

Although 80% of RLS sufferers have PLMD, only about 30% of people with PLMD also have RLS. While treatments for the two conditions are similar, PLMD is a separate syndrome. PLMD is also very common in narcolepsy, a sleep disorder that causes people to fall asleep suddenly and uncontrollably.

Cramps that awaken people during sleep are very common, and they are not part of restless legs syndrome or periodic limb movement disorder. They can be very painful and may cause a person jump out of bed in the middle of the night. They typically affect a specific area of the calf or the sole of the foot.

Circadian Rhythm. In sleep studies, subjects spend about one-third of their time asleep, suggesting that most people need about 8 hours of sleep each day. However, individual adults differ in the amount of sleep they need to feel well rested. Infants may sleep as many as 16 hours a day.

The daily cycle of life, which includes sleeping and waking, is called a circadian rhythm (circadian means "about a day"), or the biological clock. Hundreds of bodily functions follow biologic clocks, but sleeping and waking comprise the most prominent circadian rhythm. The sleeping and waking cycle is about 24 hours long. If confined to windowless apartments, with no clocks or other time cues, sleeping and waking only as their bodies dictate, humans typically live on slightly longer than 24-hour cycles.

The circadian rhythm usually takes the following daily patterns:

Humans prefer daytime activity and nighttime rest.

A natural peak in sleepiness occurs at mid-day, the traditional siesta time.

Daily rhythms interact with other factors that may interfere or change individual patterns:

The fraction-of-a-second-firing of nerve cells in the brain may be faster or slower in different individuals.

The monthly menstrual cycle in women can shift the pattern.

Light signals coming through the eyes reset the circadian cycles each day, so changes in season, or changes in exposures to light and dark, can unsettle the pattern.

The Response in the Brain to Light Signals. The brain's response to light signals is an important key factor in sleep:

Light signals travel to a tiny cluster of nerves in the hypothalamus (in the center of the brain). This cluster is the body's master clock, which is called the supra chiasmatic nucleus (SCN). The SCN is named for its location, which is just above (supra) the optic chiasm, a major junction where nerves transmit information about light from the eyes.

The approach of dusk each day prompts the SCN to signal the nearby pineal gland (named so because it resembles a pinecone) to produce the hormone melatonin.

Researchers think that melatonin acts as the body's time-setting hormone. It also appears to trigger the need to sleep. The longer a person is in darkness, the longer the duration of melatonin secretion. Staying in bright light can decrease the secretion of melatonin.

Sleep consists of two distinct states that alternate in cycles, and reflect differing levels of brain nerve cell activity:

Non-Rapid Eye Movement Sleep. Non-rapid eye movement (NREM) sleep is also called quiet sleep. NREM is further subdivided into three stages of progression:

Stage 1: Light sleep

Stage 2: "True" sleep

Stage 3 to 4: Deep "slow-wave" or delta sleep

With each ascending stage, awakening becomes more difficult. It is not clear what governs NREM sleep in the brain. A balance between certain hormones, particularly growth and stress hormones, may be important for deep sleep.

Rapid Eye-Movement Sleep. Rapid eye-movement (REM) sleep is also called active sleep. Most vivid dreams occur in REM sleep. Brain activity in REM sleep is comparable to that in waking, but the muscles are virtually paralyzed, possibly preventing people from acting out their dreams. Except for vital organs like the lungs and heart, the only muscles not paralyzed during REM sleep are the eye muscles. REM sleep may be critical for learning and for day-to-day mood regulation. When people are sleep-deprived, their brains must work harder than when they are well rested.

The REM/NREM Cycle. The cycle between quiet and active sleep generally follows this pattern:

After about 90 minutes of NREM sleep, eyes move rapidly behind closed lids, giving rise to REM sleep.

As sleep progresses the NREM/REM cycle repeats.

With each cycle, NREM sleep becomes progressively lighter, and REM sleep becomes progressively longer, lasting from a few minutes early in sleep to perhaps an hour at the end of the sleep cycle.

The hypothalamus is a highly complex structure in the brain that regulates many important brain chemicals. Malfunction of this area of the brain may give rise to cluster headaches.

Causes

The main cause of restless legs syndrome (RLS) is unknown. Researchers are investigating neurologic (nervous system) problems that may arise either in the spinal cord or the brain. One current theory suggests that a deficiency in a brain chemical called dopamine causes restless legs syndrome.

RLS may often have a genetic basis, particularly in those who develop it before age 40. When the condition occurs in older adults, it is most likely due to a neurological problem.

The central nervous system is comprised of the brain and spinal cord. The peripheral nervous system includes all peripheral nerves.

People with restless legs syndrome (RLS) often have a family history of the disorder. Researchers have detected specific genetic locations or factors that might be responsible for this condition. Much of the research comes from studies of families with a strong history of RLS-related conditions. In 2005, researchers linked a location on chromosome 12 to RLS. They named this genetic marker RLS1. Locations on chromosomes 14 and 9 may also be associated with hereditary forms of RLS.

Dopamine and Neurologic Abnormalities in the Brain. Some research suggests that neurologic abnormalities involved with restless legs syndrome (RLS) and periodic limb movement disorder (PLMD) start in the brain. A variety of studies support the theory that an imbalance in neurotransmitters (chemical messengers in the brain), notably dopamine and serotonin, may play a part in RLS. Dopamine and serotonin cause numerous nerve impulses that affect muscle movement. The effect is similar to what happens in Parkinson's disease. Moreover, drugs that increase dopamine levels treat both disorders. However, Parkinson's disease itself does not seem to increase the risk for RLS. Nor does RLS early in life predispose to Parkinson's later on.

Neurologic Abnormalities in the Spine. Other research suggests that restless legs syndrome may be due to nerve impairment in the spinal cord. Researchers considered that such abnormalities were likely to start in nerve pathways in the lower spine. However, some patients with RLS have symptoms in the arms, indicating that the upper spine may also be involved.

Neuropathy. Some experts suggest that RLS, particularly if it occurs in older adults, may be a form of neuropathy, which is an abnormality in the nervous system outside the spine and brain. Nevertheless, there is no evidence of a causal relationship.

Iron deficiency, even at a level too mild to cause anemia, has been linked to restless legs syndrome (RLS) in some people. Studies suggest, in fact, that RLS in some people may be due to a problem with getting iron into cells that regulate dopamine in the brain. Some studies have reported RLS in 25 - 30% of people with low iron levels. The common connection between RLS and Parkinson's disease, in turn, may be not having enough iron in these patients.

The cause or causes of periodic limb movement disorder (PLMD) are not clear. Some research suggests that it may be due to abnormalities in the autonomic nervous system, which regulates the involuntary actions of the smooth muscles, heart, and glands.

Risk Factors

Restless legs syndrome (RLS) may affect 2.5 - 15% of the general population. It is more common in women than in men, and its frequency increases with age. The disorder affects an estimated 10 - 28% of adults older than age 65. In about 40% of patients, RLS begins in adolescence.

RLS may be more common than epilepsy and diabetes in children and teens. More than 70% of affected children in one study had at least one biological parent with RLS.

As many as two-thirds of people with restless legs syndrome (RLS) have a family history of the disorder. If so, RLS is more likely to occur before they turn 40. (A family history of RLS is less likely in people who develop it as older adults.) RLS is also more common in people from northern and western Europe, giving added support for a genetic basis for some cases.

Restless legs syndrome (RLS) and periodic leg movement disorder (PLMD) in children are strongly associated with inattention and hyperactivity. One study suggested that a quarter of children diagnosed with attention-deficit hyperactivity disorder (ADHD) also have RLS or PLMD, and this may actually contribute to inattentiveness and hyperactivity. The disorders have much in common, including poor sleep habits, twitching, and the need to get up suddenly and walk about frequently. Some evidence suggests that the link between the diseases may be a deficiency in the brain chemical dopamine.

About 20% of pregnant women report having restless legs syndrome (RLS). The condition usually goes away about a month after delivery. RLS in this population has been strongly associated with deficiencies in iron and the B vitamin folate.

Between 20 - 62% of people undergoing dialysis report restless legs syndrome. Symptoms often disappear after a kidney transplant.

Anxiety can cause restlessness and agitation at night. These symptoms can cause (or strongly resemble) restless legs syndrome.

The following medical conditions are also associated with restless legs syndrome (RLS), although the relationships are not clear. In some cases, these conditions may contribute to RLS, or they may have a common cause. In some cases, they may coexist due to other risk factors:

Osteoarthritis (degenerative joint disease). About 72% of patients with RLS also have osteoarthritis, a common type of arthritis affecting mostly older adults.

Varicose veins. Varicose veins occur in 14% of patients with RLS. Sclerotherapy treatments, in which doctors inject medications into affected veins, may relieve symptoms in such cases.

Obesity

Diabetes -- people with type 2 diabetes may have higher rates of secondary RLS. Nerve pain (neuropathy) related to their diabetes cannot fully explain this increased rate in RLS.

Hypertension

Hypothyroidism (a condition in which the thyroid gland does not make enough hormones)

Fibromyalgia (chronic pain of unknown cause)

Rheumatoid arthritis

Emphysema (a lung disease usually caused by smoking)

Chronic alcoholism

Sleep apnea (pauses in breathing during sleep) and snoring

Chronic headaches

Brain or spinal injuries

Many muscle and nerve disorders. Hereditary ataxia, a group of genetic diseases that affects the central nervous system and causes loss of motor control, is of particular interest. Researchers believe that hereditary ataxia may supply clues to the genetic causes of RLS.

Osteoarthritis is a chronic disease of the joint cartilage and bone, often thought to result from "wear and tear" on a joint, although there are other causes such as congenital defects, trauma, and metabolic disorders. Joints appear larger, are stiff and painful, and usually feel worse the more they are used throughout the day.

Click the icon to see an image of hypothyroidism.

Click the icon to see an image of fibromyalgia.

Click the icon to see an image of rheumatoid arthritis.

Click the icon to see an image of emphysema.

Several environmental and dietary factors can worsen or provoke restless legs syndrome (RLS):

Iron deficiencies. People who are deficient in iron are at risk for restless legs syndrome, even if they do not have anemia

Folic acid or magnesium deficiencies

Smoking

Alcohol abuse

Caffeine (coffee drinking is specifically associated with PLMD)

Stress

Fatigue

Prolonged exposure to cold

Drugs that worsen or provoke the condition include:

Antidepressants

Antipsychotic drugs

Anti-nausea drugs

Beta-blockers (a type of heart medication)

Antihistamines

Oral decongestants

Diuretics

Asthma drugs

Spinal anesthesia (anesthesia-induced restless legs syndrome typically disappears on its own within several months)

About 6% of the general population has periodic limb movement disorder (PLMD). Among the elderly, the prevalence increases to 25 - 58%. Studies suggest that PLMD may be especially common in elderly women. As with RLS, numerous conditions are associated with PLMD. They include sleep apnea, spinal cord injuries, stroke, narcolepsy, and diseases that destroy nerves or the brain over time. Certain medications, including some antidepressants and anti-seizure medications, may also contribute to PLMD.

Complications

Restless legs syndrome rarely results in any serious consequences. But in some cases, severe and persistent symptoms can cause considerable mental distress, chronic insomnia, and daytime sleepiness.

Sleep deprivation, and the daytime sleepiness that follows, is increasingly recognized as a cause of mood disruption and a contributor to industrial errors and motor vehicle crashes.

Effect on Daily Performance and Activities. Studies suggest that sleeplessness worsens many waking behaviors. These include:

Reduced concentration. Deep sleep deprivation appears to impair the brain's ability to process information.

Impaired task performance. Missing several hours of nightly sleep over the course of a week can negatively affect performance levels and mood. In fact, sleep deprivation can cause impaired performance levels comparable to those of intoxicated people.

Effect on learning. Whether sleeplessness significantly impairs learning is unclear. Some studies have reported problems in memorization, although others have found no differences in test scores between people with temporary sleep loss and those with full sleep.

In addition, since restless legs syndrome (RLS) is worse when resting, people with severe RLS may avoid daily activities that involve long periods of sitting, such as going to movies or traveling long distances.

Studies in Swedish working-aged men and women reported that those with restless legs syndrome (RLS) were more apt to be socially isolated, to have frequent daytime headaches or depression, and to complain of reduced libido or problems related to sleepiness.

RLS can contribute to insomnia. Insomnia itself can increase the activity of hormones and pathways in the brain that produce emotional problems. Even modest alterations in waking and sleeping patterns can have significant effects on a person's mood. Persistent insomnia may even predict the future development of mood disorders in some cases.

It is not clear if RLS is responsible for negative mood states or if anxiety or depression contributes to RLS. Anxiety can cause agitation and leg restlessness that resemble RLS, and depression and RLS symptoms also overlap. In addition, certain types of antidepressant drugs -- such as serotonin reuptake inhibitors -- can increase periodic limb movements during sleep.

Diagnosis

A diagnosis of restless legs syndrome or nocturnal leg cramps often relies solely on the patient's description of symptoms. In general, the recommended approach is first to take a sleep and personal history. The doctor may conduct an interview that includes the following questions:

How would you describe your sleep problem?

How long have you had this sleep problem?

How long does it take you to fall asleep?

How many times a week does the problem occur?

How restful is your sleep?

What are the leg problems like (cramps, twitching, crawling feelings)?

What is your sleep environment like? Noisy? Not dark enough?

What medications are you taking (including the use of antidepressants and self-medications -- such as herbs, alcohol, and over-the-counter or prescription drugs)?

Are you taking or withdrawing from stimulants, such as coffee or tobacco?

How much alcohol do you drink per day?

What stresses or emotional factors may be present in your life?

Have you experienced any significant life changes?

Do you snore or gasp during sleep? (This may be an indication of sleep apnea. Sleep apnea is a condition in which breathing stops for short periods many times during the night. It may worsen symptoms of restless legs syndrome or insomnia.)

If you have a bed partner, does he or she notice that you have jerking legs, interrupted breathing, or thrashing while you sleep?

Are you a shift worker?

Keeping a Record of Sleep. To help answer these questions, the patient may need to keep a sleep diary. Every day for 2 weeks, the patient should record all sleep-related information, including responses to questions listed above described on a daily basis. Recording sleep behavior using an extended-play audio or videotape can be very helpful in diagnosing sleep apnea.

A bed partner can help by adding their observations of the patient's sleep behavior.

Some high-risk patients may need to consult a sleep specialist or go to a sleep disorders center before their sleep problem can be diagnosed. At most centers, patients undergo an in-depth analysis, usually supervised by a team of consultants from various specialties, who can provide both physical and psychiatric evaluations. Centers should be accredited by the American Academy of Sleep Medicine.

Among the signs that may indicate a need for a sleep disorders center are:

Insomnia due to psychological disorders

Sleeping problems due to substance abuse

Snoring and sudden awakening with gasping for breath (possible sleep apnea)

Severe restless legs syndrome

Persistent daytime sleepiness

Sudden episodes of falling asleep during the day (possible narcolepsy)

Overnight polysomnography involves several tests to measure different functions during sleep. It is typically performed in a sleep center and may help rule out sleep apnea or confirm the effectiveness of restless legs syndrome (RLS) treatments.

The patient arrives about 2 hours before bedtime without having made any changes in daily habits. Polysomnography electronically monitors the patient as he or she passes, or fails to pass, through the various sleep stages. Polysomnography tracks the following:

Brain waves

Body movements

Breathing

Heart rate

Eye movements

Changes in breathing and blood levels of oxygen

Actigraphy uses a small wristwatch-like device (such as Actiwatch) to monitor sleep quality in people with suspected restless legs syndrome (RLS), periodic leg movement disorder (PLMD), insomnia, sleep apnea, and other sleep-related conditions. Patients can wear the device on their wrists or ankles. It measures and records muscle movements during sleep. For example, with PLMD, actigraphy can provide information on the total duration of movements, the number of occurrences, whether PLMD occurs simultaneously in both legs, and its effects on sleep.

Actigraphy is not as accurate as polygraphy because it cannot measure all the biological effects of sleep. It is more accurate than a sleep log, however, and very helpful for recording long periods of sleep.

The Epworth sleepiness scale uses a simple questionnaire to measure excessive sleepiness during eight situations.

Situation

Chance of Dosing

Sitting and reading

(Indicate a score of 0 to 3)

0 = no chance of dozing

1 = slight chance of dozing

2 = moderate chance of dozing

3 = high chance of dozing

Watching TV

(Indicate a score of 0 to 3)

0 = no chance of dozing

1 = slight chance of dozing

2 = moderate chance of dozing

3 = high chance of dozing

Sitting inactive in a public place

(Indicate a score of 0 to 3)

0 = no chance of dozing

1 = slight chance of dozing

2 = moderate chance of dozing

3 = high chance of dozing

Riding as a passenger in a car for an hour without a break

(Indicate a score of 0 to 3)

0 = no chance of dozing

1 = slight chance of dozing

2 = moderate chance of dozing

3 = high chance of dozing

Lying down to rest in the afternoon when circumstances permit

(Indicate a score of 0 to 3)

0 = no chance of dozing

1 = slight chance of dozing

2 = moderate chance of dozing

3 = high chance of dozing

Sitting and talking to someone

(Indicate a score of 0 to 3)

0 = no chance of dozing

1 = slight chance of dozing

2 = moderate chance of dozing

3 = high chance of dozing

Sitting quietly after a lunch without alcohol

(Indicate a score of 0 to 3)

0 = no chance of dozing

1 = slight chance of dozing

2 = moderate chance of dozing

3 = high chance of dozing

Sitting in a car while stopped for a few minutes in traffic

(Indicate a score of 0 to 3)

0 = no chance of dozing

1 = slight chance of dozing

2 = moderate chance of dozing

3 = high chance of dozing

Score Results

1-6: Getting enough sleep.

4-8: Tends to be sleepy but is average.

9 and over: Very sleepy and suggestive of sleep-disordered breathing. Patient should seek medical advice.

Because of the high association between restless legs syndrome and iron deficiency, a test for low iron stores should be part of the diagnostic workup in restless legs syndrome (RLS). There are two steps in making this diagnosis:

The first step is to determine if a person is actually deficient in iron.

If iron stores are low, the second step is to diagnose the cause of the iron deficiencies, which will help determine treatment.

Determining if Iron Stores are Low: The following findings are important in determining that a person is iron deficient:

Blood cells viewed under the microscope are pale (hypochromic) and abnormally small (microcytic). They are also mostly uneven in shape. These findings suggest iron deficiency, but they can also appear in anemia resulting from chronic disease and in thalassemia.

Hemoglobin and iron levels are low. These findings further suggest iron deficiency, but they can also occur in cases of anemia due to chronic disease.

Ferritin levels are low. Ferritin is a protein that binds to iron, and low levels typically mean the patient does not have enough iron in their body. However, high levels of ferritin in the blood do not always mean a patient has enough iron. For example, pregnant women may have high ferritin levels even in their third trimester, yet still be iron deficient. Ferritin levels may also be normal, or even elevated, in patients with inflammation resulting from anemia due to chronic disease, even if these patients also so not have enough iron in their body.

A test that measures a factor called serum transferrin receptor (TfR) is proving to be very sensitive in identifying iron deficiency in some patients, including the elderly with chronic diseases and possibly pregnant women.

Determining Causes of Iron Deficiency. When iron deficiency anemia is diagnosed, the next step is to determine what causes the iron deficiency itself.

Dietary iron deficiency is most common in children and infants. It is rare in adults.

Heavy menstrual or abnormal uterine bleeding is usually the cause of iron deficiencies in young women. Increased need for iron during pregnancy is also a common cause of iron deficiency in pregnant women.

If doctors suspect internal bleeding as the cause of iron deficiency, they look first to the digestive tract as the possible source. A diagnosis in such cases can often be made if the patient has noticed blood in their stools, (the stool would be black and tarry or red-streaked). Often, however, bleeding may be present but not visible. In such cases, stool tests for this hidden (occult) blood are required. The patient may need additional tests to diagnose the cause of bleeding. One common test is endoscopy, in which a fiberoptic tube is used to look into the gastrointestinal tract. Doctors recommend it particularly when the source of bleeding is unclear.

If the patient's diet suggests low iron intake and doctors cannot find other causes of iron deficiency, they may recommend a month-long trial of iron supplements. If the patient fails to respond, they will need further evaluation.

Certain laboratory tests may be helpful in determining causes of restless legs syndrome (RLS) or conditions that rule it out. They include:

Blood glucose tests for diabetes

Tests for kidney problems

In certain cases, tests for thyroid hormone, magnesium, and folate levels

In addition to other sleep-related leg disorders, a number of other medical conditions may have features that resemble restless legs syndrome (RLS). The doctor will need to consider these disorders in making a diagnosis.

Peripheral Neuropathies. Peripheral neuropathies are nerve disorders in the hands or feet. Several conditions can cause these disorders, and they can produce pain, burning, tingling, or shooting sensations in the arms and legs. Diabetes is a very common cause of painful peripheral neuropathies. Other causes include alcoholism, rheumatoid arthritis, systemic lupus erythematosus, amyloidosis, HIV infection, kidney failure, and certain vitamin deficiencies. Symptoms of peripheral neuropathies may mimic RLS. However, unlike RLS, they are not usually associated with restlessness, movement does not relieve the discomfort, and they do not worsen at bedtime.

Deep Vein Thrombosis. Deep vein thrombosis (DVT) is a blood clot in a deep vein in the body, usually in the leg. It may cause pain, swelling, and aching in the leg where the clot has developed. It can occur in people with heart disease, with varicose veins, during pregnancy, in women from hormonal treatments, from injury to the leg, or from inactivity (such as after surgery or during long flights). In women, it can also result from hormonal treatments. Left untreated, DVT can be a very serious and even life-threatening condition.

This picture shows a red and swollen thigh and leg caused by a blood clot (thrombus) in the deep veins in the groin (iliofemoral veins), which prevents normal return of blood from the leg to the heart.

Intermittent Claudication and Peripheral Artery Disease. Peripheral artery disease (PAD) occurs when atherosclerosis (commonly called hardening of the arteries) affects the feet and legs. In such cases, blocked arteries reduce the flow of oxygen-rich blood to the legs or feet. Intermittent claudication is an important symptom of PAD and occurs in between one-third and one-half of these patients. The word claudication describes the pain that occurs in PAD patients when they exercise, particularly when they walk. In intermittent claudication, blood flows only enough to meet the needs of the person at rest. The result is leg pain during exercise, which disappears during rest.

Click the icon to see an image of peripheral artery disease.

Akathisia. Akathisia is a state of restlessness or agitation, and feelings of muscle quivering. A condition called hypotensive akathisia is caused by failure in the autonomic nervous system. Unlike RLS, it occurs at any time of the day and usually only when the patient is sitting -- not lying down. Drugs used to treat schizophrenia and other psychoses can cause akathisia, as can anti-nausea drugs. The condition also occurs when drugs to treat Parkinson's disease are withdrawn.

Painful Legs and Moving Toes Syndrome. A rare disorder affecting one or both legs, painful legs and moving toes syndrome is marked by a constant, deep, throbbing ache in the limbs and involuntary toe movements. The discomfort may be mild or severe. It gets worse with activity and usually stops during sleep. Usually, the cause is unknown, though it may arise from spinal injuries or herpes zoster infection. The condition is difficult to treat, although the drug baclofen, combined with either clonazepam or carbamazepine, has shown some success. Other treatments that may help include orthotics for the shoes and transcutaneous electrical nerve stimulation (TENS).

Meralgia Paresthetica. An uncommon nerve condition, meralgia paresthetica causes numbness, pain, tingling, or burning on the front and side of the thigh. It usually occurs on one side of the body, and the cause may be compression of the thigh nerve as it passes through the pelvis. It typically occurs in people aged 30 - 60 years, but it can affect people of all ages. It often goes away on its own.

Treatment

The first step in treating a patient who complains of sleeplessness and restless legs syndrome is to try to improve sleep and eliminate possible causes of restless legs syndrome (RLS). Doctors normally try to achieve these goals without the use of drugs, initially. A non-drug approach is a particularly important first step for elderly patients.

The doctor should first try to treat any underlying medical conditions that may be causing restless legs.

If medications may be causing RLS, the doctor should try to prescribe alternatives, if possible.

If the cause cannot be determined, it is best to first try better sleep habits and relaxation methods. These approaches may help, even if the patient needs drug therapy later on.

Some people report help or relief from restless legs syndrome (RLS) with the following behaviors or devices:

Hot baths or cold compresses help some patients.

Ergonomic measures -- for example, patients might find it useful to work at a high stool, where they can dangle their legs. In meetings or during air travel, it is helpful to have an aisle seat.

Changing sleep patterns -- some patients report that symptoms do not occur if they sleep late in the morning. Therefore, if feasible, patients can try changing sleep patterns.

Avoiding caffeine, alcohol, and nicotine also improves some cases of RLS.

Some patients recommend alternative treatments for RLS, such as acupuncture and massage. To date, however, there is not enough data on the effectiveness of these treatments.

Some people have reported benefits from:

Vitamin E (800 - 1,200 IU per day)

Calcium, magnesium, or potassium supplements

Folic acid supplements for people with folate deficiencies

Folate (folic acid) is necessary for the production of red blood cells and for the synthesis of DNA (which controls heredity and is used to guide the cell in its daily activities). Folic acid also helps with tissue growth and cell function. In addition, it helps to increase appetite when needed and stimulates the formation of digestive acids.

Because restless legs syndrome (RLS) is associated with iron insufficiency, people with the condition should get enough iron from their diet. [See In-Depth Report #57: Anemia.] Iron is found in foods either in the form of heme or non-heme iron:

Foods containing heme iron are the best for increasing or maintaining healthy iron levels. Such foods include (in decreasing order of iron-richness) clams, oysters, organ meats, beef, pork, poultry, and fish.

Non-heme iron is less well absorbed. About 60% of the iron in meat is non-heme (although meat itself helps absorb non-heme iron). Eggs, dairy products, and iron-containing vegetables (including dried beans and peas) have only the non-heme form. Other sources of non-heme iron include iron-fortified cereals, bread, and pasta products, dark green leafy vegetables (chard, spinach, mustard greens, kale), dried fruits, nuts, and seeds.

The Effects of Food on Iron Absorption. The absorption of non-heme iron often depends on the food balances in meals. The following are foods that enhance absorption of non-heme iron.

Meat and fish not only contain heme iron, the best form for maintaining stores, but they also help absorb non-heme iron.

Eating more vitamin C-rich foods can enhance absorption of non-heme iron during a single meal. In any case, vitamin C-rich foods are healthy. They include broccoli, cabbage, citrus fruits, melon, tomatoes, and strawberries. One orange or 6 ounces of orange juice can double the amount of iron your body absorbs from plant foods. (Taking vitamin C supplements does not appear to have any significant effect on how much iron your body stores.)

Foods containing riboflavin (vitamin B2) may help enhance the formation of hemoglobin from iron. Sources include liver, dried fortified cereals, and yogurt.

Certain nutrients impede the body's absorption of dietary iron. They include:

Polyphenols (found in tea, coffee, red wine, berries, and apples)

Phytates (found in foods such as seeds, dried beans, soy, and bran). Such foods are typically high in fiber. It is often believed that fiber itself impedes iron absorption, but researchers report that it has little or no effect.

Calcium. Calcium impairs the absorption of heme and non-heme iron. However, calcium intake must be quite high to cause any significant problems.

The Effects of Cooking Methods on Iron. Cooking methods can enhance the amount of iron in your body. Cooking in cast iron pans and skillets is a well-known way to increase the iron content of food. According to one study, boiling, steaming, or stir-frying in utensils composed of any material significantly increased the release of non-heme iron stored in vegetables.

Iron supplements can significantly reduce symptoms in people with restless legs syndrome (RLS) who are also iron deficient. Patients should use them only when dietary measures have failed. Iron supplements do not appear to be useful for RLS patients with normal or above normal iron levels.

Supplement Forms. To replace iron, the preferred forms of iron tablets are ferrous salts, usually ferrous sulfate (Feosol, Fer-In-Sol, Mol-Iron). Other forms include ferrous fumarate (Femiron, FerroSequels, Feostat, Fumerin, Hemocyte, Ircon), ferrous gluconate (Fergon, Ferralet, Simron), polysaccharide-iron complex (Niferex, Nu-Iron), and carbonyl iron (Elemental Iron, Feosol Caplet, Ferra-Cap). Specific brands and forms may have certain advantages. The following are some examples:

Prolonged-release ferrous sulfate (Slow Fe) may enhance iron absorption with fewer side effects than standard ferrous sulfate pills.

FerroSequels contains a stool softener, which helps prevent constipation.

Polysaccharide-iron complex has fewer side effects and equal absorption rates compared to ferrous salts. It is very expensive, however.

Carbonyl iron is composed of very fine tiny uniform spheres of iron powder and may prove to be less toxic than ferrous iron.

Coated or combination pills do not appear to offer any additional advantages and may hinder absorption of the iron.

Regimen. A reasonable approach for patients with RLS is to take 65 mg of iron (or 325 mg of ferrous sulfate) along with 100 mg of vitamin C on an empty stomach, 3 times a day.

IMPORTANT: As few as 3 adult iron tablets can poison, and even kill, children. This includes any form of iron pill. No one, not even adults, should take a double dose of iron if they miss one dose.

Tips for taking iron are:

For best absorption, take iron between meals. (Iron may cause stomach and intestinal disturbances, however. Some experts believe that you can take low doses of ferrous sulfate with food and avoid the side effects.)

Always drink a full 8 ounces of fluid with an iron pill.

Keep tablets in a cool place. Bathroom medicine cabinets may be too warm and humid, which may cause the pills to disintegrate.

Side Effects. Common side effects of iron supplements include the following:

Constipation and diarrhea -- these are rarely severe, although iron tablets can aggravate existing digestive problems such as ulcers and ulcerative colitis.

Nausea and vomiting may occur with high doses, but you can control this by taking smaller amounts. Switching to ferrous gluconate may help some people with severe digestive problems.

Black stools are normal when taking iron tablets. In fact, if they do not turn black, the tablets may not be working effectively. This tends to be a more common problem with coated or long-acting iron tablets.

If the stools are tarry looking as well as black, if they have red streaks, or if cramps, sharp pains, or soreness in the stomach occurs, bleeding in the digestive tract may be causing the iron deficiency, and the patient should call the doctor immediately.

Acute iron poisoning is rare in adults, but can be fatal in children who take adult-strength tablets.

Interactions With Other Drugs. Certain medications, including antacids, can reduce iron absorption.

Iron tablets may also reduce the effectiveness of other drugs, including:

Antibiotics: tetracycline, penicillamine, and ciprofloxacin

Anti-Parkinson's disease drugs: methyldopa, levodopa, and carbidopa

At least 2 hours should elapse between doses of these drugs and doses of iron supplements.

Supplementary Treatments. The following supplements may improve iron absorption:

Adding either ascorbic acid (vitamin C) or succinic acid to ferrous sulfate treatment will improve absorption of iron stores. Ascorbic acid added to iron treatment, however, may worsen some of the side effects. Succinic acid added to ferrous sulfate does not appear to increase side effects.

Some studies have found that the addition of zinc to iron supplements increases hemoglobin levels more than iron alone. Some evidence suggests that zinc affects a hormone called insulin-like growth factor-I (IGF-I), which plays a role in the regulation of red blood cell production.

Exercise earlier in the day may be one of the best ways to achieve healthy sleep. However, vigorous exercise and stimulation (including sexual activity) within 1 - 2 hours of bed time may worsen restless legs syndrome (RLS). A study found that people who walked briskly for 30 minutes, four times a week, improved minor sleep disturbances after 4 months. Regular, moderate exercise, healthful in any case, may help prevent RLS. Patients report that either bursts of excessive energy or long sedentary periods worsen symptoms.

Benign nocturnal leg cramps, sometimes known as a charley horse, are muscle spasms in the calf that can occur one or many times during the night. Cramping may also occur in the soles of the feet. They typically last from a few seconds to a few minutes. Some people experience them regularly, others only on isolated occurrences.

Causes of Nocturnal Leg Cramps. In most cases, the cause of nocturnal leg cramps remains unknown. Among the conditions that might cause leg cramps are:

Calcium and phosphorus imbalances, particularly during pregnancy

Low potassium or sodium (salt) levels

Overexertion, standing on concrete for long periods, or prolonged sitting (especially with the legs contorted)

Having structural disorders in the legs or feet (such as flat feet)

Medical causes of muscle cramping include hypothyroidism, Addison's disease, uremia, hypoglycemia, anemia, and certain medications. Various diseases that affect nerves and muscles, such as Parkinson's, cause leg cramps. Peripheral neuropathy, a complication of diabetes, can cause cramp-like pain, numbness, or tingling in the legs. Patients with kidney disease undergoing dialysis are also prone to leg cramps.

Individuals at Higher Risk for Nocturnal Leg Cramps. Nocturnal leg cramps occur at all ages but peak at different times. They are particularly common in adolescence, during pregnancy, and in older age, affecting up to 70% of adults over age 50 at some point.

Pregnant women and those taking diuretics are also at risk for leg cramps because of low calcium levels and an imbalance in calcium and phosphorus.

Consequences of Nocturnal Leg Cramps. Nocturnal leg cramps, like restless legs syndrome, rarely have any serious consequences. However, they can be extremely painful and long lasting. In some cases, severe and persistent symptoms can cause chronic insomnia and considerable mental distress.

Managing Nocturnal Leg Cramps. Once a cramp begins, straighten the leg, flex the foot upward toward the knee, or grab the toes and pull them toward the knee.

Walking or shaking the affected leg, then elevating it, may also help.

If soreness persists, a warm bath or shower or an ice pack may bring relief.

Lifestyle Tips for Preventing Nocturnal Leg Cramps. Nighttime leg cramps are generally treated with lifestyle changes.

Everyone with leg cramps should drink plenty of water (at least 6 - 8 glasses daily) to maintain adequate fluid levels.

Pregnant women and others who get legs cramps due to low calcium levels should reduce milk intake, because drinking milk does not correct the underlying imbalances in calcium and phosphorus. Instead, they should boost calcium levels by taking nonphosphate calcium supplements.

To prevent cramps from occurring, nightly stretching exercises may be the best preventive measure. Patients should stand about 30 inches from a wall and, keeping the heels flat on the floor, lean forward and slowly move the hands up the wall to achieve a comfortable stretch. A few minutes on a stationary bicycle at bedtime may also help.

While in bed, loose covers should be used to prevent the toes and feet from pointing, which causes calf muscles to contract and cramp. Propping the feet up higher than the torso may also help.

During the week, swimming and water exercises are a good way to keep muscles stretched, and wearing supportive footwear is also important.

Quinine. Quinine had been widely used to prevent leg cramping. The U.S. Food and Drug Administration (FDA) banned its sale over the counter because it reportedly caused some serious, although rare, side effects. These side effects include bleeding problems and heart irregularities. Other, less serious side effects include headaches, vision problems, and rash.

The FDA has since banned the marketing of most quinine drugs, cautioning against the off-label (non-approved) use of the drug to treat RLS. Only one form of the drug, Qualaquin, is approved for sale, for the treatment of some types of malaria. Pregnant women and those with liver problems should avoid quinine in any form.

Supplements. Some small studies indicate that the mineral magnesium, taken as magnesium citrate or magnesium lactate, may provide some benefit to people with leg cramps, including pregnant women.

In one small study, taking vitamin B complex was helpful. Other supplements tried for leg cramps include vitamin E, calcium, and potassium or sodium chloride, but these do not appear to be very effective. Sodium chloride (salt) may be helpful, but Western diets already contain too much sodium.

Medications

The American Academy of Sleep Medicine recommends medications for restless legs syndrome (RLS) or periodic limb movement disorder (PLMD) only for persons who fit strict diagnostic criteria, and who experience excessive daytime sleepiness as a result of these conditions. (Excessive daytime sleepiness results from nighttime sleeplessness due to RLS or PLMD symptoms). Little is known about the best way to treat RLS, but some experts suggest the following:

Over-the-counter pain relievers and possibly mineral and vitamin supplements (particularly folic acid in people who might be deficient) should be the first form of treatment.

People with RLS should have a test for iron deficiency. If they are iron deficient, they should start treatment with iron supplements.

Dopaminergic drugs (drugs that increase levels of dopamine) are the standard medicines for treating severe RLS, PLMD, or both.

Other drugs may be helpful if dopaminergic drugs fail, or for patients who have frequent -- but not nightly -- symptoms. These include opiates (pain relievers), benzodiazepines (sedative hypnotic drugs), or anticonvulsants. However, benzodiazepines and opiates can become habit forming and addictive.

Before taking stronger medications, people should try over-the-counter pain relievers, such as acetaminophen (Tylenol) or non-steroidal anti-inflammatory drugs (NSAIDs), which include ibuprofen (Advil, Motrin, Rufen), naproxen (Anaprox, Naprosyn, Aleve), and ketoprofen (Orudis KT, Aktron).

Although NSAIDs work well, long-term use can cause stomach problems, such as ulcers and bleeding, and possible heart problems. In April 2005, the Food and Drug Administration asked drug manufacturers of NSAIDs to include a warning label on their product that alerts users of an increased risk for heart-related problems and digestive tract bleeding.

Dopaminergic drugs increase the availability of the chemical messenger dopamine in the brain, and are the first-line treatment for severe restless legs syndrome (RLS) and periodic leg movement disorder (PLMD). These drugs significantly reduce the number of limb movements per hour, and improve the subjective quality of sleep. Patients with either condition who take these drugs have experienced up to 100% reduction in symptoms.

Dopaminergic drugs, however, can have severe side effects (they are ordinarily used for Parkinson's disease). They do not appear to be as helpful for RLS related to dialysis as they do for RLS from other causes.

Dopaminergic drugs include dopamine precursors and dopamine receptor agonists.

Dopamine Precursors. The dopamine precursor levodopa (L-dopa) was once a popular drug for severe RLS. The standard preparations (Sinemet, Atamet) combine levodopa with carbidopa, which improves the action of levodopa and reduces some of its side effects, particularly nausea. Levodopa can also be combined with benserazide (Madopar) with similar results, but Sinemet is almost always used in America. (Levodopa combinations are well tolerated and safe.)

Patients typically start with a very low dose taken 1 hour before bedtime. The dosage is increased until the patient finds relief. Patients sometimes need to take an extended form or to take it again during the night.

Levodopa acts fast, and the treatment is usually effective within the first few days of therapy. One study reported that a combination therapy of regular-release L-dopa plus sustained release L-dopa was effective in improving sleep.

Serious common side effects of L-dopa treatment (and, to lesser extent, of dopamine receptor agonists) are augmentation and rebound. Many studies report that augmentation (worsening of symptoms that occur earlier in the day) occurs in up to 70% of patients who take L-dopa. The risk is highest for patients who take daily doses, especially doses at high levels (greater than 200 mg/day). For this reason, patients should use L-dopa only intermittently (fewer than 3 times per week). The drug should be immediately discontinued if augmentation does occur. Following withdrawal from L-dopa, patients can switch to a dopamine receptor agonist.

The rebound effect causes increased leg movements at night or in the morning as the dose wears off, or as tolerance to the drug builds up.

Dopamine Receptor Agonists. Dopamine receptor agonists (also called dopamine agonists) mimic the effects of dopamine by acting on dopamine receptors in the brain. They are now generally preferred to L-dopa. Because they have fewer side effects than L-dopa, including rebound effect and augmentation, these drugs may be used on a daily basis. (Rebound effect is the worsening of symptoms over time; augmentation means the appearance of symptoms earlier in the day. About 30% of patients who take dopamine receptor agonists have reported augmentations symptoms. As the newer drugs are taken for longer periods and at higher doses, however, their augmentation rates may become closer to those of L-dopa.)

Dopamine agonists have been shown to relieve symptoms in 70 - 90% of patients. Dopamine agonists can be ergot-derived (such as cabergoline) or non-ergot derived (such as pramipexole and ropinirole). The newer non-ergotamine derivatives may induce fewer side effects than ergot-derived drugs. Studies on these medications report the following:

Ropinirole (Requip) is a non-ergotamine dopamine agonist. Approved in 2005, ropinirole is the first drug approved specifically for treatment of moderate-to-severe RLS (more than 15 RLS episodes a month). Side effects are generally mild but may include nausea, vomiting, drowsiness, and dizziness.

The Food and Drug Administration (FDA) approved pramipexole (Mirapex) for use in moderate-to-severe RLS in November 2006. However, patients may fall asleep, without warning, while taking this drug, even while performing activities such as driving.

Cabergoline (Dostinex) is also showing promise in clinical trials. In one study, cabergoline was used for RLS after levodopa had either failed or resulted in increased symptoms. Patients in the study reported relief or freedom from symptoms after 4 weeks of use. A 2006 study indicated that a single evening dose of cabergoline improved both day and nighttime limb movements, and sleep disturbances.The FDA announced in March 2007 that the dopamine agonist pergolide (Permax) was voluntarily withdrawn from the market. Studies confirmed that this drug could cause serious damage to the heart valves of patients who take it. These problems have not been reported with ropinirole or pramipexole, which are chemically different then pergolide.

Other Dopamine Agonists. Rotigotine is a unique dopamine agonist that is being developed in patch form for RLS. In May 2007, the FDA approved this patch for treatment of early Parkinson's disease. Other dopamine agonists that have shown some promise in small studies include alpha-dihydroergocryptine, or DHEC (Almirid), and piribedil (Trivastal).

Regimens. The effects of L-dopa are apparent in 15 - 30 minutes. Dopamine receptor agonists, meanwhile, take at least 2 hours to start working. Some doctors recommend regular use of dopamine receptor agonists for patients who experience nightly symptoms, and L-dopa for those whose symptoms occur only occasionally.

Side Effects. Common side effects of dopaminergic drugs vary but may include feeling faint or dizzy (especially when standing up), headaches, abnormal muscle movements, rapid heartbeat, insomnia, bloating, chest pain, and dry mouth. Nausea may be especially common. Adding the drug domperidone may help to relieve this side effect. In rare cases, dopaminergic drugs can cause hallucinations or lung disease.

Because these drugs may cause daytime drowsiness, patients should be extremely careful while driving or performing tasks that require concentration.

Long-term use of dopaminergic drugs can lead to loss of effectiveness (tolerance). Adding a drug called entacapone (Comtan) may prolong the duration of action of carbidopa-levodopa therapy (Sinemet), but it can cause nausea.

Rebound effect, augmentation, and tolerance can reduce the value of dopaminergic drugs in the treatment of RLS. Using the lowest dose possible can minimize these effects.

Withdrawal Symptoms. Patients who withdraw from these drugs typically experience very severe RLS symptoms for the first 2 days after stopping. RLS eventually returns to pre-treatment levels after about a week. The longer a patient uses these drugs, the worse their withdrawal symptoms.

Benzodiazepines, such as clonazepam (Klonopin), are known as sedative hypnotics. Doctors prescribe them for insomnia and anxiety. They may be helpful for some patients with restless legs syndrome (RLS) that disrupts sleep. Clonazepam may be particularly helpful for children with both periodic limb movement disorder and symptoms of attention deficit hyperactivity disorder. The medicine also may be helpful for patients with RLS who are undergoing dialysis.

Side Effects. Elderly people are more susceptible to side effects. They should usually start at half the dose prescribed for younger people, and should not take long-acting forms. Side effects may differ depending on whether the benzodiazepine is long-acting or short-acting.

The drugs may increase depression, a common condition in many people with insomnia.

Breathing problems may occur with overuse or in people with pre-existing respiratory illness.

Long-acting drugs have a very high rate of residual daytime drowsiness compared to others. They have been associated with a significantly increased risk for automobile accidents and falls in the elderly, particularly in the first week after taking them. Shorter-acting benzodiazepines do not appear to pose as high a risk.

There are reports of memory loss (so-called traveler's amnesia), sleepwalking, and odd mood states after taking triazolam (Halcion) and other short-acting benzodiazepines. These effects are rare and probably enhanced by alcohol.

Because benzodiazepines cross the placenta and enter breast milk, pregnant and nursing women should not use them. There are some reports of an association between the use of benzodiazepines in the first trimester of pregnancy and the development of cleft lip in newborns. Studies are conflicting at this point, but, due to other known side effects of benzodiazepines, pregnant women should not use these drugs, if possible.

In rare cases, overdoses have been fatal.

Interactions. Benzodiazepines are potentially dangerous when used in combination with alcohol. Some drugs, such as the ulcer medication cimetidine, can slow the breakdown of benzodiazepine.

Withdrawal Symptoms. Withdrawal symptoms usually occur after prolonged use and indicate dependence. They can last 1 - 3 weeks after stopping the drug and may include:

Gastrointestinal distress

Sweating

Disturbed heart rhythm

In severe cases, patients might hallucinate or experience seizures, even a week or more after they stop taking the drug.

Rebound Insomnia. Rebound insomnia, which often occurs after withdrawal, typically includes 1 - 2 nights of sleep disturbance, daytime sleepiness, and anxiety. The chances of rebound are higher with the short-acting benzodiazepines than with the longer-acting ones.

Narcotics are pain-relieving drugs that act on the central nervous system. They are sometimes prescribed for severe cases of restless legs syndrome (RLS). They may be a good choice if pain is a prominent feature. Some evidence also suggests that narcotics reduce the frequency of periodic leg movements.

There are two types of narcotics, both of which have been used for severe RLS:

Opiates (such as morphine and codeine) come from natural opium. Some patients report relief with the use of the opiate fentanyl (Duragesic), available in skin patch form. An implanted pump that uses morphine and an anesthetic called bupivacaine is showing promise for patients with severe RLS. The pump delivers the drugs to the fluid surrounding the spinal cord (cerebrospinal fluid).

Opioids are synthetic drugs. The most common example is oxycodone (Percodan, Percocet, Roxicodone, Oxycontin). Apomorphine is a morphine derivative. In one study, when injected under the skin at night, it reduced nocturnal discomfort and leg movements in some patients.

Although the use of narcotics for severe RLS is controversial, some studies have suggested that even when the treatments are long-term, they are rarely addictive for pain sufferers except among patients with a history of substance abuse.

The use of such drugs may be beneficial when included as part of a comprehensive pain management program. Such a program involves screening prospective patients for possible drug abuse, and regularly monitoring those who are taking narcotics. Doses should be adjusted as necessary to achieve an acceptable balance between pain relief and side effects. Patients on long-term opiate therapy should also be monitored periodically for sleep apnea, a condition that causes breathing to stop for short periods many times during the night. Sleep apnea may worsen symptoms of RLS, insomnia, and other complaints.

Tramadol. Tramadol (Ultram) is a pain reliever that has been used as an alternative to opioids. In one study, tramadol was very effective for RLS and produced few or no side effects. It has opioid-like properties, but is not as addictive. (However, there are reports of dependence and abuse with this drug as well.) Withdrawal after long-term use (longer than a year) can cause intense symptoms, including diarrhea, insomnia, and even restless legs syndrome itself.

Antiseizure drugs -- such as gabapentin (Neurontin), valproic acid (valproate, divalproex, Depakote, Depakene), and carbamazepine (Tegretol) -- relax blood vessels and are being tested for restless legs syndrome (RLS). Gabapentin, a newer antiseizure drug, is showing particular promise for mild-to-moderate RLS. One study reported that it improved RLS symptoms and sleep, particularly in patients who also experienced pain. It was also effective for periodic leg movement disorder. A new gabapentin product is in phase III clinical trials for the treatment of RLS. The new drug, known as XP13512, converts to gabapentin in the intestines, and therefore may reduce some of the side effects experienced by patients taking antiseizure medications.

Side Effects. All antiseizure drugs have potentially severe side effects. Therefore, patients should try these medications only after non-drug methods have failed. Side effects of many anti-seizure drugs include nausea, vomiting, heartburn, increased appetite with weight gain, hand tremors, irritability, and temporary hair thinning and hair loss (taking zinc and selenium supplements may help reduce this last effect). Some antiseizure drugs can also cause birth defects and, in rare cases, liver toxicity. Gabapentin may have fewer of these side effects than valproic acid or carbamazepine.

Antidepressants. Bupropion (Wellbutrin), a newer antidepressant, may be helpful for restless legs syndrome (RLS). Bupropion is a weak dopamine reuptake inhibitor -- it causes a slight increase in the availability of dopamine in the brain. The drug is not addictive and does not have the severe side effects of other RLS drugs, but more research is needed to determine if it is useful.

Clonidine. Clonidine (Catapres), a drug used for high blood pressure, is helpful for some patients and may be an appropriate choice for patients who have RLS accompanied by hypertension. It also may help patients with RLS who are undergoing hemodialysis.

Baclofen. The anti-spasm drug baclofen (Lioresal) appears to reduce intensity of RLS (although not frequency of movements).

Resources

www.aasmnet.org -- American Academy of Sleep Medicine

www.sleepfoundation.org -- National Sleep Foundation

www.ninds.nih.gov -- National Institute of Neurological Disorders and Stroke

www.nhlbi.nih.gov/about/ncsdr/ -- National Center on Sleep Disorders Research

www.rls.org -- Restless Legs Syndrome Foundation

www.wemove.org -- Worldwide Education and Awareness for Movement Disorders

References

Bogan RK, Fry JM, Schmidt MH, Carson SW, Ritchie SY. Ropinirole in the treatment of patients with restless legs syndrome: a US-based randomized, double-blind, placebo-controlled clinical trial. Mayo Clin Proc. 2006 Jan;81(1):17-27.

Claman DM; Redline S; Blackwell T, Ancoli-Israel S, Surovec S, Scott N, et al. Prevalence and correlates of periodic limb movements in older women. J Clin Sleep Med. 2006 Oct;2(4):438-445.

Merlino G, Fratticci L, Valente M, et al. Association of restless legs syndrome in type 2 diabetes: a case-control study. Sleep. 2007; 30(7): 866-71.

Oertel WH, Benes H, Bodenschatz R, Peglau I, Warmuth R, Happe S, et al. Efficacy of cabergoline in restless legs syndrome: a placebo-controlled study with polysomnography (CATOR). Neurology. 2006 Sep 26;67(6):1040-6.

Partinen M, Hirvonen K, Jama L, Alakuijala A, Hublin C, Tamminen I, et al. Efficacy and safety of pramipexole in idiopathic restless legs syndrome: a polysomnographic dose-finding study--the PRELUDE study. Sleep Med. 2006 Aug;7(5):407-17.

Picchietti D, Winkelman JW. Restless legs syndrome, periodic limb movements in sleep, and depression. Sleep. 2005 Jul 1;28(7):891-8.

Picchietti D. Restless legs syndrome: prevalence and impact in children and adolescents--the Peds REST study. Pediatrics. 2007; 120(2): 253-66.

Stefansson H, Rye DB, Hicks A, et al. A Genetic Risk Factor for Periodic Limb Movements in Sleep. N Engl J Med. 2007;357:639-47.

Winkelman JW, Sethi KD, Kushida CA, Becker PM, Koester J, Cappola JJ, et al. Efficacy and safety of pramipexole in restless legs syndrome. Neurology. 2006 Sep 26;67(6):1034-9.

Winkelmann J, Schormair B, Lichtner P, et al. Genome-wide association study of restless legs syndrome identifies common variants in three genomic regions. Nat Genet (in press). [cited in: Winkelmann J. Periodic Limb Movements in Sleep - Endophenotype for Restless Legs Syndrome? N Engl J Med. 2007; 357:703-05.]

Review Date:
10/22/2007
Reviewed By:
Harvey Simon, MD, Associate Professor of Medicine, Harvard Medical School; Physician, Massachusetts General Hospital.

A.D.A.M., Inc. is accredited by URAC, also known as the American Accreditation HealthCare Commission (www.urac.org). URAC's accreditation program is an independent audit to verify that A.D.A.M. follows rigorous standards of quality and accountability. A.D.A.M. is among the first to achieve this important distinction for online health information and services. Learn more about A.D.A.M.'s editorial policy, editorial process and privacy policy. A.D.A.M. is also a founding member of Hi-Ethics and subscribes to the principles of the Health on the Net Foundation (www.hon.ch).

A.D.A.M. Copyright

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adam.com

Peptic ulcers

FitSugar — Wed, 08 Oct 2008 17:35:38 -0700

In This Report

Highlights

Introduction

Causes

Symptoms

Complications

Risk Factors

Diagnosis

Treatment

Treatment for NSAID-Induced...

Medications

Treatment for Bleeding Ulce...

Lifestyle Changes

Resources

References

HEALTH GUIDE REFERENCE FROM A.D.A.M

Highlights

Risk with cardiovascular medications

While nonsteroidal anti-inflammatory drugs are the major medications responsible for causing peptic ulcers, drugs taken for cardiovascular disease and its risk factors may also cause ulcers. Recent studies have found an association between increased risk of ulcer and the following drugs:

Spironolactone, a common diuretic used in heart failure

Niacin, a drug used to lower "bad" cholesterol and raise "good" cholesterol

Vitamin K antagonists, commonly prescribed anticoagulants

Dipyridamole, a drug for secondary stroke prevention

Low-dose aspirin, prescribed for both heart attack and stroke prevention

Risk of peptic ulcer increases dramatically when these drugs are used in combination. Considering the millions of people who take these medications to prevent a life-threatening cardiovascular event, their impact on peptic ulcer development could be monumental.

Atypical symptoms of GERD

The burning pain of gastroesophageal reflux disease (GERD) can be confused with that of an ulcer. However, GERD pain typically develops after meals and is relieved by antacids. Elderly patients may have different symptoms that can include loss of appetite, weight loss, anemia, vomiting, or difficulty swallowing. A careful examination may be necessary to diagnose the underlying cause, since GERD and peptic ulcer may coexist.

Adjustments in triple therapy

Peptic ulcers are commonly treated with the triple combination of two antibiotics (amoxicillin and clarithromycin) and a proton-pump inhibitor. Therapy usually lasts for 2 weeks. Recent studies indicate that 1 week may be just as effective. In addition, taking the antibiotics in sequence, rather than at the same time, may work better to eliminate H. pylori, the bacteria responsible for most ulcers.

Healing foods

Milk may not be the ideal food for people with peptic ulcers because it encourages the production of stomach acid. However, certain qualities found in fermented milks and yogurts may actually offer protection against gastric ulcers. Likewise, the phenolic compounds found in virgin olive oil appear to kill many strains of H. pylori, including some that have become resistant to antibiotics. Vegetables contain dietary nitrate, which increases nitric oxide in the gut, causing the mucus layer to thicken. This increases protection against H. pylori invasion.

Protection when taking NSAIDs

People who take NSAIDs for pain control have an immediate increased risk of ulcers. Chronic use increases risk dramatically. Taking a proton-pump inhibitor (PPI) or H2 blocker is necessary to reduce this risk. A review of clinical trials found three PPIs [omeprazole (Prilosec), esomeprazole (Nexium), and lansoprazole (Prevacid)] to be more effective than the H2 blocker ranitidine (Zantac). When NSAIDs were discontinued, however, healing rates with ranitidine reached nearly 100%.

Introduction

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), or

The upper part of the small intestine -- the duodenum ( duodenal ulcers). In the U.S., duodenal ulcers are 3 times more common than gastric ulcers.

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 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:

Click the icon to see an image of the stomach.

Hydrochloric acid. A common misbelief 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 important for protecting against H. pylori, the bacteria that causes most peptic ulcers. [Note: An exception is ulcers that occur in Zollinger-Ellison syndrome. This is a rare genetic condition in which very high levels of gastrin, a potent acid, are secreted by tumors in the pancreas or duodenum.]

Pepsin. Pepsin is an enzyme that breaks down proteins in food. Since the stomach and duodenum are also composed of protein, they are also susceptible to the actions of pepsin. Pepsin is, then, also important in the formation of ulcers.

Fortunately, the body has a defense system to protect the stomach and intestine against these powerful substances:

The mucous layer, which coats the stomach and duodenum, forms the first line of defense.

Bicarbonate, which the mucous layer secretes, neutralizes the digestive acids.

Hormone-like substances called prostaglandins help dilate 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 stomach and intestine lining susceptible to the actions of acid and pepsin, increasing the risk for ulcers.

Causes

Before the discovery of the bacterium Helicobacter (H.) pylori, the stomach was believed to be a sterile environment. However, 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 the H. pylori bacteria. This discovery was so important that the researchers were awarded the Nobel Price in Medicine in 2005. The bacteria appear to trigger ulcers in the following way:

H. pylori's corkscrew shape enables it to penetrate the mucous layer of the stomach or duodenum so it can attach itself to the lining.

It 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 lining, leading to ulcers in certain individuals.

It also alters certain immune factors that allow it to evade detection and cause persistent inflammation for a life -- even without invading the mucous membrane.

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

It is also strongly linked to stomach (gastric) cancer and possibly other non-intestinal problems.

Factors that Trigger Ulcers in H. pylori Carriers.H. pylori is found in about 25% of people who do not have peptic ulcers. The magnitude of H. pylori infection, particularly in older people, may not always predict the presence or absence of peptic ulcers. Other variables must to be present to actually trigger ulcers. These may include:

Genetic Factors. Some people harbor genetic strains of H. pylori that may make the bacteria more dangerous and increase the risk for ulcers. The most intensively investigated genetic factor is cytotoxin-associated gene A (CagA), which has been associated with both gastric and duodenal ulcers, as well as with stomach cancer. Other genetic types that may also increase bacterial severity are called vacuolating cytotoxin (vacA) and antigen-binding adhesin (BabA) genotypes. Some of these genetic factors may be more or less important for development of ulcers, depending on ethnicity.

Immune Abnormalities. Some experts suggest that certain individuals have abnormalities in the immune response of the intestine, 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 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 ability of the immune system to protect against endotoxins.

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. For example, a 2001 study suggested that about half of ulcers are not caused by H. pylori. Instead, they tend to be caused by regular use of nonsteroidal anti-inflammatory drugs (NSAIDs), which include aspirin and other common pain relievers. Genetic factors or, rarely, Crohn's disease or Zollinger-Ellison syndrome, also cause ulcers.

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 cases of acute duodenal perforation show no evidence of H. pylori, and why duodenal ulcers can recur even after H. pylori has been eradicated.

A 2006 study published in the Journal of Biological Chemistry indicates that a protein called decay-accelerating factor (DAF) acts as receptor for H. pylori. Animal studies show that blocking this interaction renders H. pylori harmless to the stomach. Researchers hope the discovery leads to new drugs that can reduce the risk of peptic ulcer.

Long-term use of NSAIDs is the second most common cause of ulcers, and the rate of NSAID-caused ulcers is increasing. About 20 million people take prescription NSAIDs regularly, and more than 25 billion tablets of over-the-counter brands are sold each year in the U.S. alone. The most common NSAIDs are aspirin, ibuprofen (Advil), and naproxen (Aleve, Naprosyn), although many others are available. Patients with NSAID-caused ulcers should stop taking these drugs.

There is no doubt NSAIDs increase the risk of ulcers and gastrointestinal (GI) bleeding. The risk of bleeding is continuous for as long as a patient takes these drugs and may persist for about one 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.

Specific NSAIDs pose greater or lesser risks for ulcers and bleeding. No NSAIDs, however, even over-the-counter brands, should be used long-term except under a doctor's direction.

Lowest Risk

Medium Risk

Highest Risk

Nabumetone (Relafen)

Etodolac (Lodine)

Salsalate

Sulindac (Clinoril)

Aspirin. Even low-dose ("baby") aspirin (81 mg) may pose some risk

Ibuprofen (Motrin, Advil, Nuprin, Rufen)

Naproxen (Aleve, Naprosyn, Naprelan, Anaprox)

Diclofenac (Voltaren), Tolmetin (Tolectin)

NOTE: Drugs in the medium risk group vary in risk. For example, studies show that naproxen is twice as likely as ibuprofen to be associated with hospitalization from GI bleeding.

Flurbiprofen (Ansaid), Piroxicam (Feldene), Fenoprofen Indomethacin (Indocin), Meclofenamate (Meclomen)

Ketoprofen (Actron, Orudis KT). Note: Ketoprofen is often considered a medium-risk drug, but one study reported that taking the drug in low doses for as little as 1 week causes significant GI injury.

Certain drugs other than NSAIDs may cause or aggravate ulcers, particularly those taken for cardiovascular disease and its risk factors. A review of more than 306,000 primary care patients found that spironolactone, a common diuretic prescribed in heart failure, was associated with a 2.7% increased risk of ulcer or upper GI bleeding. Exacerbation of peptic ulcers is a rare but noted side effect of niacin, a drug that can reduce LDL cholesterol and raise HDL cholesterol. Low-dose aspirin, dipyridamole, and vitamin K antagonists such as Coumadin nearly double the risk of upper GI bleeding. When these drugs are used in combination, the risk soars.

Risk of GI perforation was seen in phase 3 clinical trials of bevacizumab, the first vascular endothelial growth factor agent (VEGF) approved by the FDA. This drug has been shown to increase survival and stop the progression of metastatic colorectal cancer when used in combination with chemotherapy. While the benefits of bevacizumab outweigh the risks, GI perforation is very serious. If it occurs, the drug must be discontinued.

The least common major cause of peptic ulcer disease is Zollinger-Ellison syndrome (ZES).

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

Radiation treatments

Bacterial or viral infections

Alcohol abuse

Physical injury

Burns

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 (gastrinomas) produce excessive amounts of gastrin, a hormone that stimulates gastric acid formation. These tumors are usually malignant, 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 malignant, must be removed and acid production suppressed to relieve the recurrence of the ulcers.

Who Gets ZES? The incidence of ZES in the United States is estimated at 1 case per million people per year, and at 0.1 - 1% among patients with peptic ulcers. The mean age at onset is 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 have no history of NSAID use. Diarrhea may precede ulcer symptoms. Ulcers occurring in the second, third, or fourth portions of the duodenum or the jejunum (the middle section of the small intestine) are signs of ZES. GERD is more prevalent and often more severe in patients with ZES, and can be complicated by ulcerations and 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). Previously, removing the stomach was the only option.

Symptoms

Dyspepsia. The most common symptoms of peptic ulcer are known collectively as dyspepsia. Peptic ulcers can occur without dyspepsia or any other gastrointestinal symptom, especially when caused by NSAIDs. Dyspepsia may be persistent or recurrent and can encompass a variety of symptoms in the upper abdomen, including:

Pain or discomfort

Bloating

A feeling of fullness. People with severe dyspepsia are unable to drink as much fluid as people with mild or no dyspepsia.

Hunger and an empty feeling in the stomach, often 1 - 3 hours after a meal

Mild nausea (Vomiting, in fact, may relieve symptoms.)

Regurgitation (sensation of acid backing up into the throat.)

Belching

Ulcer Pain. The pain of ulcers can be either localized in one place or diffuse. 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 the pain is often relieved by eating a meal.

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 heart attack.

Because ulcers can cause hidden bleeding, patients may experience the symptoms of anemia, including fatigue and shortness of breath.

A sudden onset of severe symptoms may indicate intestinal obstruction, 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 entire stomach contents (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.

Peptic ulcers may lead to emergency situations. Severe abdominal pain with or without evidence of bleeding may indicate a perforation of the ulcer through the stomach or duodenum. Vomiting of a substance that resembles coffee grounds or the presence of black tarry stools may indicate serious bleeding.

Complications

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 caused by H. pylori or NSAIDs can be very serious if they 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. NSAID-related bleeding and stomach problems may be responsible for as many as 107,000 hospital admissions and 16,500 deaths each year.

Because there are usually 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 the presence of another serious, unstable medical condition. Populations at greatest risk are the elderly and those with other serious conditions, such as heart problems.

H. pylori is strongly associated with certain cancers. Some studies have also linked it to a number of non-gastrointestinal illnesses as well, although the evidence is inconsistent.

Stomach Cancers. Stomach cancer, also called gastric cancer, is the second most common cause of cancer worldwide. In developing countries where the rate of H. pylori is very high, the risk of stomach cancer is 6 times higher than in the U.S. An important 2001 study strongly supported previous work that found a causal link between H. pylori infection and stomach cancer. In this study, uninfected people did not develop stomach cancer. However, the stomach cancer rates for H. pylori-associated conditions were 4.7% for nonulcer dyspepsia, 3.4% for gastric ulcers, and 2.2% of stomach polyps. Experts now suggest that H. pylori may be as carcinogenic to the stomach as cigarette smoke is to the lungs.

Eradication of H. pylori may reduce the risk of stomach cancer, but not eliminate it. A Japanese study found that continued risk is associated with degree of mucosal atrophy before H. pylori eradication therapy is started. This is something than can be measured during an endoscopy.

The process most likely starts in childhood. Infection with H. pylori promotes a precancerous condition called atrophic gastritis. This 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 proliferate in the stomach.

Onset of H. pylori infection in adulthood poses a lower risk, since the development of atrophic gastritis takes years, and an adult is likely to die of other causes first. Other factors, such as specific genetic strains and diets, might also influence a higher 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 virulent H. pylori strain called cytotoxin-associated gene A (CagA) may also be a particular risk factor for precancerous changes.

Interestingly, 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.

Pancreatic Cancer. H. pylori has recently been linked to pancreatic cancer. The excess risk is high in patients with unoperated gastric ulcers -- 20% after 15 years and 50% after the first hospitalization. Surgery decreased the risk dramatically. Unoperated duodenal ulcers, on the other hand, were not associated with increased risk of pancreatic cancer.

Heart Disease. Some research has reported a very high rate of H. pylori infection in men with coronary artery disease, but more recent work has found no relationship between the bacteria and heart disease. A 2001 study suggested that the only relationship between H. pylori and heart disease may be that people with both tend to be in lower socioeconomic groups. Further studies are needed.

Other Diseases. H. pylori has also been weakly associated with other nonintestinal disorders, including migraine, Raynaud's disease (marked by cold extremities), and some skin disorders, such as chronic hives.

Risk Factors

About 25 million 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 is rare in children. Men have twice the risk of ulcers as women. The risk of duodenal ulcers tends to rise beginning around age 25 and continues until age 75; gastric ulcers peak at age 55 - 65.

Peptic ulcers are less common than they once were. Research suggests that ulcer rates have even declined in areas with widespread H. pylori infection. The increased use of proton-pump inhibitor drugs may be responsible for this trend.

H. pylori grows and colonizes only in the intestinal tracts of primates. The bacteria are most likely transmitted directly from person to person. Still, little is yet known about its transmission.

Who Is Infected with H. pylori? About half the world's adults are infected with H. pylori. The bacteria are nearly always acquired during childhood and persist throughout life, if not treated. The prevalence in children ranges from less than 10% to more than 80%, with the highest infection rates (3 - 10%) in developing countries and the lowest (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.

How Does the Bacteria Pass from Person to Person? It is not entirely clear how the bacteria are transmitted. One study did not find that infected students posed any risk for their classmates. Transmission within families may be the most important route for H. pylori. A 2002 study reported that spouses of people with peptic ulcers are at significantly higher risk for ulcers, suggesting that the bacteria may be transmitted during intimate contact. Some evidence suggests that bacteria may spread during GI tract illness, particularly when vomiting occurs. The bacteria also may be passed in stools. Since H. pylori can live in water, but not apparently in food, the bacteria may also be transmitting through sewage-contaminated water.

Who Is at Risk for Ulcers from H. pylori? Although H. pylori infection is common, ulcers in children are very rare, and only a minority of infected adults develops ulcers. Some known risk factors include smoking, alcohol use, having a relative with peptic ulcers, being male, and the presence of the cytotoxin-associated gene A (CagA). Experts are unable to determine, however, any single factor or group of factors that can determine which infected patients are most likely to develop ulcers.

Between 15 - 25% of patients who have taken NSAIDs regularly will have evidence of one or more ulcers, but in most cases these ulcers are very small. Given the widespread use of NSAIDs, however, the potential total number of people who can develop serious problems may be very large. Long-term NSAID use can damage the stomach and, possibly, the small intestine.

In April 2005, the FDA asked manufacturers of prescription NSAIDs to include with their products the same boxed warning used for the COX-2 inhibitor celecoxib (Celebrex). This boxed warning emphasizes the increased risk for cardiovascular events and GI bleeding in people taking these drugs. (Pharmaceutical companies are trying to develop new COX-2 inhibitors without these dangerous side effects. Early safety studies of the novel COX-2 inhibitor known as CS-706 showed its effect on gastric mucosa to be the same as placebo.)

The FDA also requested manufacturers of over-the-counter NSAIDs to revise their labels to include more specific language concerning potential cardiovascular and GI risks. Due to its proven heart benefits, aspirin was excluded from these labeling revisions.

Frequent Users of NSAIDs. Anyone who uses NSAIDs regularly is at risk for gastrointestinal problems. Even low-dose aspirin (81 mg) may pose some risk, although the risk is lower than with standard doses. In one 4-year study, 4.5% of regular NSAID users were hospitalized for GI bleeding. The highest risk, however, was found in people who require long-term use of very high-dose NSAIDs, notably patients with rheumatoid arthritis. Other people who take high doses of NSAIDs include those with chronic low back pain, fibromyalgia, and chronic stress.

Contributing Factors. Certain factors add to the risk for ulcers in NSAID-users:

Age 65 and older

History of peptic ulcers or upper gastrointestinal bleeding

Other serious ailments, such as congestive heart failure

Use of other medications, such as the anticoagulant warfarin (Coumadin), corticosteroids, or the osteoporosis drug alendronate (Fosamax)

Alcohol abuse

Those infected with H. pylori. A 2002 study reported that the combination of NSAID use and H. pylori posed a 3.5-fold greater risk of ulcers than either factor alone. However, not all studies have reported the higher risk in infected patients.

Stress and Psychological Factors. Although stress is no longer considered a cause of ulcers, studies still suggest that stress may predispose a person to ulcers or prevent existing ulcers from healing. Some experts estimate that social and psychological factors play a contributory role in 30 - 60% of peptic ulcer cases, whether they are caused by H. pylori or NSAIDs. Some experts even believe that the anecdotal relationship between stress and ulcers is so strong that treatment of psychological factors is warranted.

Smoking. Smoking increases acid secretion, reduces prostaglandin and bicarbonate production, and decreases mucosal blood flow. Results of studies on the actual effect of smoking on ulcers, however, are mixed. Some evidence suggests that smoking delays the healing of gastric and duodenal ulcers. One study reported that after ulcers healed, about half of nonsmokers experienced a relapse of their ulcer disease after 1 year, but that all heavy smokers relapsed after 3 months. Other studies have found no increased risk for ulcers in smokers. In any case, any impact of smoking on ulcers does not seem to be affected by the presence of H. pylori.

Tobacco use and exposure may cause an acceleration of coronary artery disease and peptic ulcer disease. It is also linked to reproductive disturbances, esophageal reflux, hypertension, fetal illness and death, and delayed wound healing.

Diagnosis

Peptic ulcers are always suspected in patients with persistent dyspepsia (bloating, belching, and abdominal pain). Dyspepsia, however, occurs in 20 - 40% of people who live in industrialized nations, and only about 15 - 25% of these people actually have ulcers. A number of steps are needed to make an accurate diagnosis of ulcers.

The doctor will ask for a thorough report of a patient's dyspepsia and other important symptoms, such as weight loss or fatigue, present and past medication use (especially chronic use of NSAIDs), family members with ulcers, and drinking and smoking habits.

In addition to peptic ulcers, a number of conditions, notably gastroesophageal reflux disease (GERD) and irritable bowel syndrome, cause dyspepsia. Often, however, no cause can be determined. In such cases, the symptoms are referred to collectively as functional dyspepsia.

Peptic ulcer symptoms, particularly abdominal pain and chest pain, may resemble those of other conditions, such as gallstones or heart attack. Certain features may help to distinguish these different conditions. However, symptoms often overlap, and it is impossible to make a diagnosis based on symptoms alone. A number of tests are needed.

The following disorders may be confused with peptic ulcers:

GERD. About half of patients with GERD also have dyspepsia. With GERD or other problems in the esophagus, the main symptom is usually heartburn, a burning pain that radiates up to the throat. It typically develops after meals and is relieved by antacids. The patient may have difficulty swallowing and may experience regurgitation or acid reflux. Elderly patients with GERD are less likely to have these symptoms, but instead may experience loss of appetite, weight loss, anemia, vomiting, or dysphagia (difficulty or painful swallowing). [See In-Depth Report #85: Gastroesophageal Reflux Disease.]

Heart Events. Cardiac pain, such as angina or a heart attack, is more likely to occur with exercise and may radiate to the neck, jaw, or arms. In addition, patients typically have distinct risk factors for heart disease, such as a family history, smoking, high blood pressure, obesity, or high cholesterol. [See In-Depth Report #12: Heart Attack.]

Gallstones. The primary symptom in gallstones is typically a steady gripping or gnawing pain on the right side under the rib cage, which can be quite severe and can radiate to the upper back. Some patients experience pain behind the breastbone. The pain is often precipitated by a fatty or heavy meal, but gallstones almost never cause dyspepsia. [See In-Depth Report #10: Gallstones and Gallbladder Disease.]

Irritable Bowel Syndrome. Irritable bowel syndrome can cause dyspepsia, nausea and vomiting, bloating, and abdominal pain. It occurs more often in women than in men.

Dyspepsia may also occur with gastritis, stomach cancer, or as a side effect of certain drugs, including NSAIDs, antibiotics, iron, corticosteroids, theophylline, and calcium blockers.

When ulcers are suspected, the doctor will prescribe tests to detect bleeding. These may include a rectal exam, a complete blood count, and a fecal occult blood test (FOBT). The FOBT tests for hidden (occult) blood in stools. Typically, the patient is asked to supply up to 6 stool specimens in a specially prepared package. A small quantity of feces is smeared on treated paper, which reacts to hydrogen peroxide. If blood is present, the paper turns blue.

Traditional radiology tests have not yet proven valuable for diagnosing ulcers. However, radiologists in France who performed multidetector computed tomography (MDCT) scans on preoperative patients with proven GI perforations found the technology to be highly accurate in pinpointing the location of the perforations.

Simple blood, breath, and stool tests can now detect H. pylori with a fairly high degree of accuracy. It is not entirely clear, however, which individuals should be screened for H. pylori.

Candidates for Screening. Some doctors currently test for H. pylori only in individuals with dyspepsia who also have high-risk conditions, such as:

Strong indication for ulcers, such as weight loss, anemia, or indications of bleeding

History of active ulcers

Risk factors for stomach cancer or other complications from ulcers

Smokers and those who experience regular and persistent pain on an empty stomach may also be good candidates for screening tests. Some doctors argue that testing for H. pylori may be beneficial for patients with dyspepsia who are regular NSAID users. In fact, given the possible risk for stomach cancer in H. pylori- infected people with dyspepsia, some experts now recommend that any patient with dyspepsia lasting longer than 4 weeks should have a blood test for H. pylori. This is a subject of considerable debate, however.

Specific Screening Tests for H. pylori. The following screening tests used or under investigation for H. pylori:

Breath Test. A simple test called the carbon isotope-urea breath test (UBT) can identify up to 99% of people who harbor H. pylori. Up to 2 weeks before the test, the patient must discontinue taking any antibiotics, bismuth-containing agents such as Pepto-Bismol, and proton-pump inhibitors (PPIs). As part of the test, the patient swallows a special substance containing urea (a compound in mammals metabolized from nitrogen) that has been treated with carbon atoms. If H. pylori is present, the bacteria convert the urea into carbon dioxide, which is detected and recorded in the patient's exhaled breath after 10 minutes.

Blood Tests. Blood tests are used to measure antibodies to H. pylori, with results available in minutes. Diagnostic accuracy is reported at 80 - 90%. One such important test is called enzyme-linked immunosorbent assay (ELISA). An ELISA test of the urine is also showing promise in children.

Stool Test. A test to detect genetic fingerprints of H. pylori in the feces appears to be as accurate as the breath test for initial detection of the bacteria and for detecting recurrences after antibiotic therapy.

It should be noted that such tests are not as accurate as endoscopy, an invasive procedure, which is needed to confirm a diagnosis of H. pylori. The breath and stool tests, however, can be particularly useful after treatment to determine if a patient has been cured.

Test and Treat. Depending on the results of the screening tests, some doctors take the following steps:

Approach for Noninfected Individuals. People who do not have evidence of H. pylori on a blood or breath test are typically given a 4-week course of acid-suppressing medication, usually a PPI such as omeprazole (Prilosec).

Approach for H. pylori-Infected Individuals. Patients with evidence of bacterial infection are given antibiotics. If this does not relieve symptoms, they are given a 6-week course of the PPI omeprazole (Prilosec). (Whether to give antibiotics to infected patients with non-ulcer dyspepsia is controversial and is discussed in the section, What Are the Guidelines for Treating Peptic Ulcers Caused by H. pylori?)

If symptoms persist, endoscopy is usually performed. Endoscopy is an invasive procedure, but is the only procedure in which a biopsy of stomach tissue can be taken, making it the most accurate test.

Experts debate whether endoscopy should be performed on all patients who do not respond to initial medication, since it does not appear to add any useful information on treatment choices, unless there is evidence or suspicion of bleeding or serious complications.

While endoscopy is the gold standard for diagnosing upper GI disorders, because it allows doctors to biopsy the stomach, 3-dimensional CT imaging may also be valuable. Researchers in China compared the results of endoscopy to the results of noninvasive CT imaging performed to diagnose GI disease. They found that the CT imaging correctly diagnosed 50 of 52 cases, including 5 cases of peptic ulcer disease. Three-dimensional CT imaging clearly showed the GI tract lesions. It is currently considered a valuable complement to endoscopy.

Endoscopy is a procedure used to evaluate the esophagus, stomach, and duodenum using a long, thin tube tipped with a tiny video camera (endoscope). When combined with biopsy, endoscopy is the most accurate procedure for detecting the presence of peptic ulcers, bleeding, and stomach cancer, or for confirming the presence of H. pylori.

Appropriate Candidates for Endoscopy. Because endoscopy is invasive and expensive, it is unsuitable for screening everyone with dyspepsia. Most individuals with these symptoms are managed effectively without endoscopy. Endoscopy is usually reserved for patients with dyspepsia who also have risk factors for ulcers, stomach cancer, or both. Such factors include the following:

Having so-called "alarm" symptoms (unexplained weight loss, gastrointestinal bleeding, vomiting, difficulty swallowing, or anemia).

Being over 45 (when the risk for stomach cancer increases).

There is some debate whether patients under 45 with persistent dyspepsia and no alarm symptoms should have endoscopy.

The Procedure. Endoscopy may be performed in a hospital, doctor's office, or outpatient surgery center, and typically involves the following:

The doctor administers a local anesthetic using an oral spray and an intravenous sedative to suppress the gag reflex and relax the patient.

The doctor then places the thin, flexible plastic tube into the patient's mouth and down the esophagus into the stomach.

A tiny camera in the endoscope allows the doctor to see the surface of the esophagus, stomach, and duodenum, and to search for abnormalities.

The doctor will remove about 10 small tissue samples (biopsies), which will be tested for H. pylori.

In endoscopy, the doctor places a long, thin, flexible tube (called an endoscope) down the patient's throat and into the stomach and duodenum. A camera and light on the tip of the endoscope enables the doctor to check for abnormalities. Tiny samples may be taken to check for H. pylori bacteria, a cause of many peptic ulcers. If a bleeding ulcer is found, it may be sealed with a burning tool (cauterized) during the procedure.

Note: Some evidence suggests that patients who take PPIs should stop taking the medication 2 weeks before an endoscopy, since it may mask ulcers.

Capsule Endoscopy.Capsule endoscopy involves swallowing a capsule the size of a large vitamin, which contains tiny camera, light source, and radio transmitter. The device takes pictures as it passes through the intestinal tract. At this point, its benefits are limited to the small intestine, so it is unlikely to play a role in the diagnosis of peptic or gastric ulcers. However, capsule endoscopy has the potential to be an important tool for the diagnosis of obscure upper GI bleeding. Patients who have used it have usually found it painless and preferable to conventional endoscopy.

An upper GI (gastrointestinal) series was the standard diagnostic method for peptic ulcers until the introduction of adequate tests for detecting H. pylori. In an upper GI series, the patient drinks a solution containing barium. X-rays are then taken, which may reveal inflammation, active ulcer craters, or deformities and scarring due to previous ulcers. Endoscopy is more accurate, although it is more invasive and expensive.

Click the icon to see an illustrated series detailing treatment of GI bleeding.

Stool tests may show traces of blood that are not visible to the naked eye, and blood tests may reveal anemia in those who have bleeding ulcers. If Zollinger-Ellison syndrome is suspected, blood levels of gastrin should be measured.

Treatment

Antibiotic regimens that eradicate H. pylori can cure peptic ulcers and are now the standard medications used for ulcers in infected individuals who are not taking NSAIDs. Eliminating H. pylori can also cure the rare MALT lymphomas caused by this bacterium. Other drugs, such as proton-pump inhibitors or H2 blockers, are useful for relieving ulcer symptoms.

Patients with Clear Evidence of Ulcers. Antibiotics are clearly indicated for patients who have both ulcers and H. pylori infection. Despite such clear indications, however, European and American studies continue to suggest that many doctors only treat symptoms and not the ulcers themselves. Studies also suggest that most doctors do not counsel patients on the potential dangers of NSAIDs and other drugs that can cause ulcers.

There is considerable debate about whether to test for H. pylori and treat infected patients who have dyspepsia, but no evidence of ulcers.

The best approach for treating dyspepsia is highly controversial. Options include the following:

Test and Treat. This approach involves testing for H. pylori and eradicating the bacteria in infected patients.

Prescribing potent acid-suppressing agents. This approach generally employs a trial of potent acid-suppressing drugs called proton-pump inhibitors (PPIs), such as omeprazole (Prilosec) or esomeprazole (Nexium).

In either case, endoscopy is usually performed if symptoms persist after 4 weeks. Some evidence suggests that PPIs may mask ulcers, so patients taking these drugs may need to discontinue them for 2 weeks before endoscopy.

Arguments for Testing and Treating Patients with Dyspepsia. The argument supporting testing and treating patients with nonulcer dyspepsia is as follows:

Protection against ulcers. Some evidence suggests that antibiotic treatments for infected patients with dyspepsia may prevent ulcers from developing. A 2002 study found that antibiotic regimens to eradicate H. pylori greatly decreased the likelihood of ulcers in infected patients with nonulcer dyspepsia who were chronic NSAID users.

Protection against gastric cancer. Some evidence suggests that eradicating H. pylori may prevent or delay the onset of stomach cancer in people with long-term dyspepsia who are infected with the bacteria. A large 2001 study conducted in Japan, where gastric cancer is especially common, found that such cancers developed in about 3% of infected patients with nonulcer dyspepsia. However, none occurred in dyspeptic patients who were treated with antibiotics for H. pylori.

Arguments against Testing and Treating Patients with Dyspepsia. The arguments against testing and treating are as follows:

Lack of significant effect on symptoms. Studies are mixed on whether antibiotics have much effect on dyspepsia symptoms. In a 2003 study, overall symptom scores after 1 year were not significantly different between dyspeptic patients who were treated for H. pylori and patients who were maintained on PPIs.

Lower rates of H. pylori in the U.S. The number of people with H. pylori infection is declining in the U.S., possibly making the test-and-treat approach too expensive for the number of people it helps.

Increased risk for gastroesophageal reflux disease (GERD). A number of studies suggest that H. pylori in the intestinal tract protects against GERD, which in severe cases can be a risk factor for cancer of the esophagus. Eliminating H. pylori may also have other adverse effects.

Overuse of antibiotics. Concern that such treatments without clear evidence of ulcers will lead to unnecessary antibiotic prescriptions, increasing the risk for side effects. Overuse may also contribute to a growing public health problem -- the emergence of bacteria that are resistant to antibiotics.

The standard treatment regimen for H. pylori uses 2 antibiotics and a PPI. Cure rates after antibiotic treatment range from 70 - 90%. A typical regimen contains three drugs:

A PPI. These drugs include omeprazole (Prilosec), lansoprazole (Prevacid), esomeprazole (Nexium), and rabeprazole (Aciphex). PPIs are important for all types of peptic ulcers, and are a critical partner in antibiotic regimens. They reduce acidity in the intestinal tract, and increase the ability of antibiotics to destroy H. pylori.

Two antibiotics. The standard antibiotics are clarithromycin (Biaxin) and amoxicillin. Some doctors substitute the antibiotic metronidazole (Flagyl) for either clarithromycin or amoxicillin.

This combination treatment is typically taken for at least 14 days. Many studies, however, suggest that a 7-day treatment may work just as well. A report published in 2006 evaluated a shorter course of treatment using the PPI rabeprazole and 2 antibiotics. They found that a 4-day treatment eliminated H. pylori and was associated with fewer side effects. A study published in 2007 comparing 1- and 2-week treatments with amoxicillin, clarithromycin, and omeprazole for H. pylori eradication found both regimens to be similar in efficacy, safety, and compliance.

Interestingly, an Italian study indicated that giving antibiotics sequentially instead of at the same time may be even more effective. The researchers found that patients who took amoxicillin for 5 days, followed by clarithromycin for 5 days, had higher H. pylori eradication rates (89%) than those who took both antibiotics for 10 days (77%).

A 2007 study showed that eradication rates with this 3-drug regimen could be improved, and side effects reduced, by adding probiotics ("good" bacteria) and the milk protein bovine lactoferrin. These products are often found in yogurts and other forms of fermented milk.

Follow-Up. Follow-up testing for the bacteria should be done no sooner than 4 weeks after therapy is completed. Test results before that time may not be accurate.

In most cases, drug treatment relieves ulcer symptoms. However, symptom relief does not always indicate success, nor does persistence of dyspepsia necessarily mean that treatment has failed. Heartburn and other symptoms from GERD, for example, can worsen and require acid-suppressing medication.

Failure. Treatment fails in about 15% of patients, mostly when they fail to adhere to the regimen. Compliance with standard antibiotic regimens may be poor for the following reasons:

The triple-drug regimens are complicated and require many pills. Helicide or two-drug combinations may help offset this problem.

About 30% of patients suffer side effects from the H. pylori regimen. Gastrointestinal problems are very common, and severe diarrhea can occur.

Treatment may also fail if the patients harbor strains of H. pylori that are resistant to the antibiotics. When this happens, different drugs are tried.

Reinfection after Successful Treatment. Studies in developed countries indicate that once the bacteria are eliminated, recurrence rates are below 1% per year. Reinfection with the bacteria is possible, however, in areas where the incidence of H. pylori is very high and sanitary conditions are poor. In such regions, reinfection rates are 6 - 15%.

Weight Gain. Some patients may gain weight.

Gastroesophageal Reflux Disease. Of ongoing interest are reports of a lower incidence of H. pylori in patients with GERD. There are some important unanswered questions associated with this issue:

Is the lower incidence of H. pylori in GERD patients significant, and does the bacteria actually protect against GERD? Studies have not conclusively found any significant risk for GERD in people who are not infected with H. pylori, except possibly in certain regions. In a 2003 study, the absence of H. pylori infection in people with GERD was more pronounced in Asian patients than in those from Europe and North America. That being said, guidelines for eradication of H. pylori infection published in 2007 by the European Helicobacter Study Group state that "Eradication of H. pylori infection does not cause gastroesophageal reflux disease (GERD) or exacerbate GERD, and may prevent peptic ulcer in patients who are naive users of NSAIDs."

Does eliminating the bacteria with antibiotic therapy actually produce GERD in some people? One study observed that patients cured of H. pylori infection were twice as likely to develop GERD as those who remained infected. However, a 2003 analysis of 8 studies reported no higher risk for GERD after antibiotic treatments. In addition, GERD patients did not experience worsening of symptoms. Longer follow-up studies are needed however to determine the long-term consequences, if any.

What is the proper management of people who have GERD and H. pylori infection? Patients with severe GERD usually require on-going therapy with PPIs, which are powerful acid-suppressors. Some evidence suggests that in such patients, the combination of H. pylori and chronic acid suppression may lead to atrophic gastritis, a precancerous condition in the stomach. Guidelines then advocate eliminating the bacteria with antibiotics. There is some concern that once the bacteria are eliminated, however, GERD may worsen, which can pose a risk for Barrett's esophagus, which is also a precancerous condition. On the encouraging side, however, evidence to date does not suggest any higher risk for more serious GERD complications after H. pylori is eliminated.

Effects on Other Gastrointestinal Infections. In children, there is some evidence that H. pylori protects against E. coli and other GI infections, particularly those that cause diarrhea. If this is true, treating infected children for H. pylori should be done only if the bacteria are causing harm.

Click the icon to see an animation on ulcer treatment.

Treatment for NSAID-Induced Ulcers

Preventing Ulcers or Rebleeding Caused by NSAIDs. If NSAID-caused ulcers or bleeding are identified, patients should:

Get tested for H. pylori and, if they are infected, take antibiotics.

Possibly use a PPI. Studies suggest these medications lower the risk for NSAID-caused ulcers, although they do not completely prevent them.

People who still need to take NSAIDs should:

Use the lowest NSAID dose possible.

Try the prescription drugs misoprostol (Cytotec) or Arthrotec. Misoprostol works as well as a PPI, however, it has many side effects. Arthrotec is a combination of misoprostol and the NSAID diclofenac.

A warning to women: misoprostol can induce labor at any stage of pregnancy. Pregnant women should not use the drug.

Healing Existing Ulcers. A number of drugs are used to treat NSAID-caused ulcers. PPIs -- omeprazole (Prilosec), lansoprazole (Prevacid), or esomeprazole (Nexium) -- are used most often. Other drugs that may be useful include H2 blockers, such as famotidine (Pepcid AC), cimetidine (Tagamet), and ranitidine (Zantac). Sucralfate is another drug used to heal ulcers and reduce the stomach upset caused by NSAIDs.

COX-2 Inhibitors (Coxibs). Coxibs block an inflammation-promoting enzyme called COX-2. This drug class was initially thought to work as well as NSAIDs, while causing less gastrointestinal distress. However, following numerous reports of cardiovascular events, the FDA banned rofecoxib (Vioxx) and valdecoxib (Bextra) from use in the U.S. Celecoxib (Celebrex) is still available, but patients should discuss with their doctor whether this drug is appropriate and safe for them.

Arthrotec. Arthrotec is a combination of misoprostol and the NSAID diclofenac. It may reduce the risk for gastrointestinal bleeding. One study found that patients taking Arthrotec had 65 - 80% fewer ulcers than those who took NSAIDs alone.

Acetaminophen. Acetaminophen (Tylenol, Anacin-3) is the most common alternative to NSAIDs. Acetaminophen is inexpensive and generally safe. It poses far less of a risk of gastrointestinal problems than NSAIDs. It does have some adverse effects, however, and the daily dose should not exceed 4 grams (4,000 mg); some studies suggest that ulcer risk is increased even in doses exceeding 2 grams (2,000 mg) a day, if the drug is used on a long-term basis. Patients who take high doses of acetaminophen for long periods are also at risk for liver damage, particularly if they drink alcohol. It may pose a small risk for serious kidney complications in people with preexisting kidney disease, although acetaminophen remains the drug of choice for patients with impaired kidney function.

Tramadol. Tramadol (Ultram) is a pain reliever that has been used as an alternative to opioids. It has opioid-like properties, but is not as addictive. However, dependence and abuse have been reported. It can cause nausea, but does not cause severe gastrointestinal problems, as NSAIDs can. Some patients experience severe itching. A combination of tramadol and acetaminophen (Ultracet) provides more rapid pain relief than tramadol alone and more durable relief than acetaminophen alone. Side effects are the same as for each of these agents.

Medications

The following drugs are sometimes used in the treatments of peptic ulcers caused by either NSAIDs or H. pylori. They are described in alphabetical order.

Many antacids are available without prescription and are the first drugs recommended to relieve heartburn and mild dyspepsia. They play no major role in either the prevention or healing of ulcers, but help in the following ways:

All rely on various combinations of three basic compounds -- magnesium, calcium, or aluminum -- to neutralize stomach acid.

They may defend the stomach by increasing acid-buffering bicarbonate and mucus secretion.

It is generally believed that liquid antacids work faster and are more potent than tablets, although some evidence suggests that both forms work equally well.

Basic Salts Used in Antacids. There are three basic salts used in antacids:

Magnesium. Magnesium compounds are available in the form of magnesium carbonate, magnesium trisilicate, and, most commonly, magnesium hydroxide (Milk of Magnesia). The major side effect of these magnesium compounds is diarrhea.

Calcium. Calcium carbonate (Tums, Titralac, and Alka-2) is a potent and rapid-acting antacid, but it can cause constipation. There have been rare cases of hypercalcemia (elevated levels of calcium in the blood) in people taking calcium carbonate for long periods of time. Hypercalcemia can lead to kidney failure.

Aluminum. The most common side effect of antacids containing aluminum compounds (Amphogel, Alternagel) is constipation. Maalox and Mylanta are combinations of aluminum and magnesium, which balance the side effects of diarrhea and constipation. People who take large amounts of antacids containing aluminum may be at risk for calcium loss and osteoporosis. Long-term use also increases the risk of kidney stones. People who have recently experienced GI bleeding should not use aluminum compounds.

Interactions with Other Drugs. Antacids can reduce the absorption of a number of drugs. Conversely, some antacids increase the potency of certain drugs. The interactions can be avoided by taking these other drugs 1 hour before or 3 hours after taking the antacid.

Drugs that are absorbed less well if taken with antacids

Drugs that are made more potent by antacids

Tetracycline

Ciprofloxacin (Cipro)

Propranolol (Inderal)

Captopril (Capoten)

Ranitidine (Zantac)

Famotidine (Pepcid AC)

Valproic acid

Sulfonylureas

Quinidine

Levodopa

H. pylori is usually highly sensitive to certain antibiotics, particularly amoxicillin, and to antibiotics in the macrolide class, such as clarithromycin. Either type of agent serves effectively as a second antibiotic in a three-drug regimen. Other antibiotics that are sometimes used include tetracycline, metronidazole, and ciprofloxacin.

Amoxicillin is the most common form of penicillin. It is inexpensive, but many people are allergic to it.

Clarithromycin (Biaxin) is a macrolide and is the most expensive antibiotic used against H. pylori. It is very effective, but there is growing bacterial resistance to this drug. Resistance rates tend to be higher in women and increase with age. Researchers fear that resistance will increase as more people use the drug.

Tetracycline is effective, but this medicine has unique side effects, including skin reactions to sunlight, possible burning in the throat, and tooth discoloration. Pregnant women cannot take tetracycline.

Ciprofloxacin (Cipro), a fluoroquinolone, is also sometimes used in ulcer regimens.

Metronidazole (Flagyl) was the mainstay in initial combination regimens for H. pylori. As with clarithromycin, however, there continues to be growing bacterial resistance to the drug. Today, about 25 - 35% of H. pylori bacteria are metronidazole-resistant.

Side Effects of Antibiotics.

The most common side effects of nearly all antibiotics are gastrointestinal problems such as cramps, nausea, vomiting, and diarrhea.

Allergic reactions can also occur with all antibiotics, but are most common with medications derived from penicillin or sulfa. These reactions can range from mild skin rashes to rare, but severe -- even life-threatening -- anaphylactic shock.

Some drugs, including certain over-the-counter medications, interact with antibiotics; patients should report to all medications they are taking to their doctor.

Antibiotics double the risk of vaginal infections in women.

Compounds that contain bismuth are often used in the three-drug antibiotic regimens. They destroy the cell walls of H. pylori bacteria. The only bismuth compound available in the U.S. has been bismuth subsalicylate (Pepto-Bismol), although a drug combination of the H2 blocker ranitidine and bismuth citrate (Tritec) has been released. High doses can cause vomiting and depression of the central nervous system, but the doses given for ulcer patients rarely cause side effects.

H2 blockers interfere with acid production by blocking histamine, a substance produced by the body that encourages acid secretion in the stomach. H2 blockers were the standard treatment for peptic ulcers until antibiotic regimens against H. pylori were developed. These drugs cannot cure ulcers, but they are useful in certain cases. They are effective only for duodenal ulcers, however.

Four H2 blockers are currently available over-the-counter in the U.S.: famotidine (Pepcid AC), cimetidine (Tagamet), ranitidine (Zantac), and nizatidine (Axid). All have good safety profiles and few side effects. There are some differences between these drugs:

Famotidine (Pepcid AC). Famotidine is the most potent H2 blocker. The most common side effect is headache, which occurs in 4. 7% of people who take it. Famotidine is virtually free of drug interactions, but it may have significant adverse effects in patients with kidney problems.

Cimetidine (Tagamet). Cimetidine has few side effects; about 1% of people taking cimetidine experience mild temporary diarrhea, dizziness, rash, or headache. Cimetidine interacts with a number of commonly used medications, including phenytoin, theophylline, and warfarin. Long-term use of excessive doses (more than 3 grams a day) may cause impotence or breast enlargement in men. These problems resolve after the drug is discontinued.

Ranitidine (Zantac). Ranitidine interacts with very few drugs. In one study, ranitidine provided more pain relief and healed ulcers more quickly than cimetidine in people younger than age 60, but there was no difference in older patients. A common side effect of ranitidine is headache, which occurs in about 3% of people who take it.

That being said, a literature review of clinical trials showed that the PPIs are more effective than the H2 blockers in healing ulcers in people who take NSAIDs. After 8 weeks of treatment, healing rates of both gastric and duodenal ulcers were:

92% and 88% with esomeprazole 40 mg and 20 mg (vs 74% with ranitidine).

87% and 84% with omeprazole 40 mg and 20 mg (vs 64% with ranitidine).

And 73 - 74% and 66 - 69% with lansoprazole 30 mg and 15 mg (vs 50 - 53% with ranitidine).

However, healing rates with ranitidine reached nearly 100% when NSAIDs were discontinued.

Nizatidine (Axid). Nizatidine is nearly free of side effects and drug interactions.

Long-Term Concerns. In most cases, these H2 blockers have good safety profiles and few side effects. Because H2 blockers can interact with other drugs, be sure to tell your doctor about any other drugs you are taking. There are also some concerns about possible long-term effects -- for example, that long-term acid suppression with these drugs may cause cancerous changes in the stomach in patients who also have untreated H. pylori infection. More research is needed. However, the following concerns are real:

Liver damage. This is more likely with ranitidine than other H2 blockers, but is rare in any event.

Kidney-related complications. With famotidine, adverse effects on the central nervous system in patients with even moderate kidney insufficiency have been reported, resulting in anxiety, depression, and mental disturbances.

Increased risk for pneumonia in hospitalized patients.

Ulcer perforation and bleeding. Some experts are concerned that the use of acid-blocking drugs may actually increase the risk for serious complications by masking the ulcer's symptoms.

Misoprostol (Cytotec) increases prostaglandin levels in the stomach lining, which protects against the major intestinal toxicity of NSAIDs.

Actions against Ulcers. Misoprostol can reduce formation of ulcers in the upper small intestine by two-thirds and in the stomach by three-fourths. It does not neutralize or reduce acid, so although the drug is helpful for preventing NSAID-induced ulcers, it is not useful in healing existing ulcers.

Side Effects.

Diarrhea and other gastrointestinal problems are severe enough to cause 20% of patients to stop taking the drug. Taking misoprostol after meals should minimize these effects. One study indicated that taking the drug 2 - 3 times a day, instead of the standard regimen of 4 times, may prove to be just as effective and cause fewer side effects.

Misoprostol can induce abortion or cause birth defects and should not be taken by pregnant women. If pregnancy occurs during treatment, the drug should be discontinued at once and the doctor contacted immediately.

Actions against Ulcers. PPIs are the drugs of choice for managing patients with peptic ulcers from any cause. They suppress the production of stomach acid by blocking the gastric acid pump -- the molecule in the stomach glands that is responsible for acid secretion.

PPIs can be used either as part of a multidrug regimen for H. pylori or alone for preventing and healing NSAID-caused ulcers. One retrospective study found that adding a PPI to diclofenac therapy reduced hospitalization for ulcers by 60%. They are also useful in treating ulcers caused by Zollinger-Ellison syndrome. Some people carry a gene that reduces the effectiveness of PPIs. This gene is present in 18 - 20% of people of Asian descent.

Standard Brands. Most PPIs are available by prescription as oral drugs. There is no evidence that one brand of PPI works better than another. Brands approved for ulcer prevention and treatment include:

Omeprazole (generic, Prilosec OTC)

Esomeprazole (Nexium)

Lansoprazole (Prevacid)

Rabeprazole (Aciphex)

Possible Adverse Effects.

Side effects are uncommon, but may include headache, diarrhea, constipation, nausea, and itching.

Pregnant women and nursing mothers should avoid taking PPIs, although recent studies suggest that these drugs do not increase the risk of birth defects.

PPIs may interact with certain drugs, such as antiseizure agents (such as phenytoin), antianxiety drugs (such as diazepam), and blood thinners (such as warfarin).

Long-term use of high-dose PPIs may produce vitamin B12 deficiency, but studies are needed to confirm this risk.

In theory, long-term use of PPIs by people with H. pylori may reduce acid secretion enough to cause atrophic gastritis (chronic inflammation of the stomach), a risk factor for stomach cancer. Long-term use of PPIs may also mask symptoms of stomach cancer and delay diagnosis. At this time, however, there have been no reports of an increase in stomach cancer with long-term use of these drugs.

Sucralfate (Carafate) seems to work by adhering to the ulcer crater and protecting it from further damage by stomach acid and pepsin. It also promotes the defensive processes of the stomach. Sucralfate has an ulcer-healing rate similar to that of H2 blockers. Other than constipation, which occurs in 2.2% of patients, the drug has few side effects. Sucralfate does interact with a wide variety of drugs, however, including warfarin, phenytoin, and tetracycline.

Treatment for Bleeding Ulcers

When a patient comes to the hospital with bleeding ulcers, endoscopy is usually performed. This procedure is critical for the diagnosis, determination of treatment options, and treatment of bleeding ulcers.

In high-risk patients or those with evidence of bleeding, options include watchful waiting with medical treatments or surgery. The first critical steps for massive bleeding are to stabilize the patient and support vital functions with fluid replacement and possibly blood transfusions. People on NSAIDs should discontinue them, if possible.

Depending on the intensity of the bleeding, patients can be released from the hospital within a day or kept up to 3 days after endoscopy. Bleeding stops spontaneously in about 70 - 80% of patients, but about 30% of patients who come to the hospital for bleeding ulcers need surgery. Endoscopy is the surgical procedure most often used for treating bleeding ulcers and patients at high-risk for rebleeding. It is usually combined with medications, such as epinephrine and intravenous proton-pump inhibitors.

Between 10 - 20% of patients require more invasive procedures for bleeding, usually major abdominal surgery.

Endoscopy is important for both diagnosing and treating bleeding ulcers. The doctor first places a thin, flexible plastic tube called an endoscope into the patient's mouth and down the esophagus into the stomach.

Endoscopy for Diagnosing Bleeding Ulcers and Determining Risk of Rebleeding. With endoscopy, doctors are able to detect the signs of bleeding, such as active spurting or oozing of blood from arteries. Endoscopy can also detect specific features in the ulcers referred to as stigmata, which indicate a higher or lower risk of rebleeding.

Such features include the following:

Low risk (5 -15%) for bleeding: flat dot; a clean or white base.

High risk (30 - 50%) for bleeding: swollen but nonbleeding blood vessels; blood clots that adhere to ulcers.

According to one study, if patients with these high-risk features are untreated, their risk for rebleeding after endoscopy ranges from about 10% on the first day after endoscopy to about 3% by the third day. Identifying and treating patients with stigmata can reduce these risks. Other factors that increase the risk for rebleeding include bleeding disorders, very low blood pressure, other serious medical conditions, and bleeding that started after hospitalization.

After endoscopy, high-dose PPI therapy has been shown to significantly reduce the rate of rebleeding, need for surgery, and death from hemorrhage. The medication may be given intravenously, but studies show that oral PPI therapy is probably just as effective.

Endoscopy as Treatment. Endoscopy is usually used to treat bleeding from visible vessels that are less than 2 mm in diameter. This approach also appears to be very effective in preventing rebleeding in patients whose ulcers are not bleeding, but who have high-risk features (swollen blood vessels or clots adhering to ulcers).

The following is a typical endoscopy procedure:

The surgeon passes a probe through an endoscopic tube and applies electricity, heat, or small clips to coagulate the blood and stop the bleeding. This procedure also causes fluid buildup, which helps to compress the blood vessels.

In high-risk cases, the doctor may inject epinephrine (commonly known as adrenaline) directly into the ulcer to enhance the effects of the heating process. Epinephrine activates the process leading to blood coagulation, narrows the arteries, and enhances blood clotting.

Intravenous (IV) administration of a PPI (usually omeprazole or pantoprazole) significantly prevents rebleeding and appears to be cost-effective. In one study, the use of IV PPIs reduced the risk of bleeding from 23% to 7%. (Oral PPIs are also effective, but studies are needed to compare their effectiveness versus IV PPIs.) A PPI may also be useful for initial bleeding episodes when endoscopy is unsuccessful, inappropriate, or unavailable.

Intravenous H2 blockers are often used, but a major analysis reported no benefit in bleeding duodenal ulcers, although they may be effective in gastric ulcers.

Endoscopy is effective in controlling bleeding in more than 85% of appropriate candidates. If rebleeding occurs, a repeat endoscopy is effective in about 75% of patients. Those who fail to respond require major abdominal surgery. The most serious complication from endoscopy is perforation of the stomach or intestinal wall, which occurred in about 1.4% of patients in a large 2002 study.

While endoscopy and clipping are routine treatment for bleeding ulcers in the U.S., a Korean study found little difference in outcomes between clipping (plus H2 therapy) and oral PPI therapy alone. In a randomized test of 129 patients, hemostasis (end of bleeding) was achieved in 93.5% of patients after clipping and 92.5% of patients on oral PPIs at 24 hours. The rate of rebleeding was 6.9% with clipping and 7.5% with PPIs.

Other Medical Considerations. Certain agents may be warranted after endoscopy:

Patients who harbor the H. pylori bacteria, even when the bleeding has been caused by NSAID use, should be treated with antibiotic therapy to eliminate the bacteria. Triple therapy, including antibiotics, to eliminate H. pylori immediately after endoscopy is warranted in most patients infected with the bacteria.

Somatostatin (a hormone used to prevent bleeding in cirrhosis) is also useful for reducing persistent peptic ulcer bleeding or the risk of recurrence. Researchers are investigating adding other therapies, such as fibrin glue, a blood clotting factor. To date, no therapy has proven to be more effective than current treatments.

Major abdominal surgery for bleeding ulcers is now generally performed only when endoscopy fails or is not appropriate. Certain emergencies may require surgical repair, such as when an ulcer perforates the wall of the stomach or intestine, causing sudden intense pain and life-threatening infection.

Surgical Approaches. The standard major surgical approach uses a wide abdominal incision and standard surgical instruments (called open surgery). Laparoscopic techniques employ small abdominal incisions and the insertion of tubes that contain miniature cameras and instruments. Laparoscopic techniques are increasingly being used for perforated ulcers. Surgery is not effective for upper GI ulceration caused by chronic NSAID use.

Major Surgical Procedures. There are a number of surgical procedures aimed at long-term relief of ulcer complications. These include:

Click the icon to see an illustrated series detailing a gastrectomy procedure.

Vagotomy, in which the vagus nerve is cut to interrupt messages from the brain that stimulate acid secretion in the stomach. This surgery may impair stomach emptying. A recent variation that cuts only parts of the nerve may reduce this complication.

Antrectomy, in which the lower part of the stomach is removed. This part manufactures the hormone responsible for stimulation of digestive juices.

Pyloroplasty, which enlarges the opening into the small intestine so that stomach contents can pass into it more easily.

Antrectomy and pyloroplasty are usually performed with vagotomy.

Lifestyle Changes

In the past, it was common practice to tell people suffering from peptic ulcers to consume small, frequent amounts of bland foods. Exhaustive research conducted since that time has shown that a bland diet is not effective in reducing the incidence or recurrence of ulcers, and that eating numerous small meals throughout the day is no more effective than eating three meals a day. Large amounts of food should still be avoided, because stretching the stomach can result in painful symptoms.

Fruits and Vegetables. The good news is that a diet rich in fiber may cut the risk of developing ulcers in half and speed healing of existing ulcers. Fiber found in fruits and vegetables is particularly protective; vitamin A contained in many of these foods may increase the benefit. Some studies on associations between specific food chemicals and ulcers are as follows:

In one study, apples and yams appeared to be especially helpful.

Apples, celery, cranberries, onions, red wine, and green and black tea are also high in natural chemicals known as flavonoids, which appear to inhibit H. pylori growth and have many other health benefits. Cranberry juice specifically may have properties that help prevent H. pylori from infecting the intestinal lining.

Grapefruit has antioxidant properties that may help heal ulcers.

Studies on rats have found that dietary nitrate increases nitric oxide in the gut and causes the mucus layer to thicken. Pretreatment with nitrate provided dramatic protection against diclofenac-induced ulcers. High levels of dietary nitrate are found in many vegetables.

Laboratory experiments suggest that sulforaphone, a compound found in broccoli and broccoli sprouts, may be lethal to even drug-resistant strains of H. pylori.

Tea has chemicals that may help protect against cancers in the stomach and esophagus.

Milk. Milk actually encourages the production of acid in the stomach, although moderate amounts (2 - 3 cups a day) appear to do no harm. Animal studies show that a milk protein called bovine alpha-lactalbumin protects against gastric ulcers caused by stress. Certain probiotics, which are "good" bacteria added to yogurt and other fermented milk drinks, may also have gastric protective qualities.

Coffee and Carbonated Beverages. Coffee (both caffeinated and decaffeinated), soft drinks, and fruit juices with citric acid increase stomach acid production. Although no studies have proven that any of these drinks contribute to ulcers, consuming more than 3 cups of coffee per day may increase susceptibility to H. pylori infection.

Spices and Peppers. Studies conducted on spices and peppers have yielded conflicting results. The rule of thumb is to use these substances moderately, and to avoid them if they irritate the stomach.

Garlic. Some studies suggest that high amounts of garlic may have some protective properties against stomach cancer, although a recent study concluded that it offered no benefits against H. pylori and, in high amounts, can cause considerable GI distress.

Olive Oil. Studies from Spain have shown that phenolic compounds in virgin olive oil may have strong bactericidal activity against 8 strains of H. pylori, 3 of which are resistant to antibiotics.

Vitamins. Although no vitamins have been shown to protect against ulcers, H. pylori appears to impair absorption of vitamin C, which may play a role in the higher risk of stomach cancer.

Some evidence exists that exercise may help reduce the risk for ulcers in some people. In one study, exercise was associated with a lower risk for duodenal, but not gastric, ulcers in men. In this study, exercise appeared to have no effect on ulcer development in women.

Stress relief programs have not been shown to promote ulcer healing, but they may have other health benefits.

Melatonin is a hormone found in the brain that is normally associated with sleep. Researchers have observed that the GI tract is rich in melatonin, and that the hormone may have properties that help prevent ulcers, reduce acid secretion, and improve blood flow. It is not known whether this would benefit people with peptic ulcers, but it appears to warrant some research. In the U.S., melatonin is classified as a dietary supplement and not a drug, so its quality and effectiveness are uncontrolled. The U.S. is the only developed nation that does not regulate this agent.

Resources

http://digestive.niddk.nih.gov -- National Digestive Diseases Information Clearinghouse

www.gastro.org -- American Gastroenterological Association

www.acg.gi.org -- American College of Gastroenterology

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Vaira D, Zullo A, Vakil N, et al. Sequential therapy versus standard triple-drug therapy for Helicobacter pylori eradication: a randomized trial. Ann Intern Med. 2007;146(:556-563.

Verhamme K, Mosis G, Dieleman J, Stricker B, Sturkenboom M. Spironolactone and risk of upper gastrointestinal events: population-based case-control study. BMJ. 2006;333(7563):330. Epub 2006 Jul 13.

Yeomans ND, Svedberg LD, Naesdal J. Is ranitidine therapy sufficient for healing peptic ulcers associated with non-steroidal anti-inflammatory drug use? Int J Clin Pract. 2006;60(11):1401-407.

Zagari RM, Bianchi-Porro G, Fiocca R, Gasbarrini G, Roda E, Bazzoli F. Comparison of 1 and 2 weeks of omeprazole, amoxicillin and clarithromycin treatment for Helicobacter pylori eradication: the HYPER study. Gut. 2007;56(4):475-479.

Review Date:
6/22/2007
Reviewed By:
Harvey Simon, MD, Associate Professor of Medicine, Harvard Medical School; Physician, Massachusetts General Hospital.

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Ulcerative colitis

FitSugar — Wed, 08 Oct 2008 17:35:30 -0700

In This Report

Highlights

Introduction

Causes

Symptoms

Complications

Risk Factors

Diagnosis

Dietary Factors

Symptom Management

Medications

Surgery

Resources

References

HEALTH GUIDE REFERENCE FROM A.D.A.M

Highlights

Drug Approval

In 2007, the FDA approved LIALDA, the first once-daily mesalamine pill for treating mild-to-moderate ulcerative colitis. Other types of mesalamine need to be taken several times a day.

Genetic Research

Scientists have made an important discovery by identifying a gene associated with inflammatory bowel disease. In a 2006 paper published in Science, researchers announced that variations in the interleukin-23 receptor (IL23R) gene can either increase or decrease the risk for developing ulcerative colitis and Crohn’s disease.

Clostridium Difficile

Patients with ulcerative colitis are particularly susceptible to Clostridium difficile, a nasty bacterial infection that causes severe diarrhea. According to several 2007 studies, C. difficile is becoming increasingly common among these patients. Experts recommend that doctors monitor patients with ulcerative colitis for signs of this difficult-to-treat infection.

Pregnancy

Women with inflammatory bowel disease have twice the risk of pregnancy complications as healthy women, according to a 2006 review in Gut. Premature birth, low birth weight, and birth defects are among the complications. Active flares of disease during pregnancy especially increase the risks for problems.

Infliximab (Remicade)

Infliximab (Remicade) is helpful for promoting remission and healing in patients with moderate-to-severe ulcerative colitis who have not responded to other drugs, according to a 2006 review in the Cochrane Database.

Infliximab works by blocking the effects of tumor necrosis factor (TNF), a substance that plays a role in inflammatory diseases. Infliximab is the only biologic drug approved for treatment of ulcerative colitis. Researchers are studying other types of biologic drugs as well.

According to a 2007 consensus statement from the American Gastroenterological Association, infliximab should be used only for patients who have not been helped by other drugs, such as immunosuppressants and corticosteroids. It is not recommended as a first-line treatment for ulcerative colitis.

Introduction

Inflammatory bowel disease (IBD) is a general term that covers two disorders:

Ulcerative colitis

Crohn's disease

Some evidence suggests that they are part of a biologic continuum, but at this time they are considered distinct disorders with somewhat different treatment options. The basic distinctions are location and severity. As many as 10% of patients with IBD have features and symptoms that match the criteria for both disorders, at least in the early stages. (This is called indeterminate colitis.)

Crohn's disease, also called regional enteritis, is a chronic inflammation of the intestines that is usually confined to the ileum, the terminal portion of the small intestine. Ulcerative colitis is a similar inflammation of the colon, or large intestine. These and other inflammatory bowel diseases have been linked with an increased risk of colorectal cancer.

Ulcerative Colitis. Ulcerative colitis occurs only in the large intestine. Ulcers form in the inner lining, or mucosa, of the colon or rectum, often resulting in diarrhea, blood, and pus. The inflammation is usually most severe in the sigmoid and rectum and usually diminishes higher in the colon. It is sometimes divided into one of four categories depending on the location of the disease:

Click the icon to see an image of the structure of the colon.

Proctitis. Disease only in the rectum (the lowest part of the large intestine that connects with the anus). Constitutes about 30% of cases.

Proctosigmoiditis. Disease in the rectum and sigmoid (the next portion of the intestine leading up from the rectum). Constitutes about 30% of cases.

Left-Sided Colitis. Disease in the left side of the large intestine. Constitutes about 40% of cases.

Pancolitis. Disease in entire colon. Very uncommon.

Click the icon to see an image of the types of ulcerative colitis.

In most patients the location of the disease does not change, but as many as 30% of patients with proctitis or proctosigmoiditis will experience some progression.

Crohn's Disease. Crohn's disease is an inflammation that extends into the deeper layers of the intestinal wall. It is found most often in the area bridging the small and large intestines, specifically in the ileum and the cecum, which is sometimes referred to as the ileocecal region. Crohn's disease less frequently occurs in other parts of the gastrointestinal tract, including the anus, stomach, esophagus, and even the mouth. It may affect the entire colon, form a string of contiguous ulcers in one part of the colon, or develop as multiple scattered clusters of ulcers skipping healthy tissue in between. [See In-Depth Report #103: Crohn's disease.]

The gastrointestinal (GI) tract (the digestive system) is a tube that extends from the mouth to the anus. It is a complex organ system that first carries food from the mouth down the esophagus to the stomach and then through the small and large intestine to be excreted through the rectum and anus.

Esophagus. The esophagus, commonly called the food pipe, is a narrow muscular tube, about 9 1/2 inches long that begins below the tongue and ends at the stomach.

Stomach. In the stomach, acids and stomach motion break food down into particles small enough so that nutrients can be absorbed by the small intestine.

Small Intestine. The small intestine, despite its name, is the longest part of the gastrointestinal tract and is about 20 feet long. Food that passes from the stomach into the small intestine first passes through three parts:

First it enters the duodenum

Then the jejunum, and

Finally the ileum

Most of the digestive process occurs in the small intestine.

Large Intestine. Undigested material, such as plant fiber, is passed to the large intestine, mostly in liquid form. The large intestine is approximately 6 feet long and is the final portion of the digestive tract. It follows the small intestine and includes the cecum, the appendix, the colon, and the rectum, which extends to the anus.

Cecum and Appendix. The cecum and the appendix are located in the lower-right quadrant of the abdomen.

Colon. The colon absorbs excess water and salts into the blood. The remaining waste matter is converted to feces through bacterial action. The colon is divided into four major sections:

The first section, the ascending colon, extends upward from the cecum on the right side of the abdomen.

The second section, the transverse colon, crosses the upper abdomen to the left side.

The third section extends downward on the left side of the abdomen toward the pelvis and is called the descending colon.

The final section is the sigmoid colon.

Rectum and Anus. Feces are stored in the descending and sigmoid colon until they pass through the rectum and anus. The rectum extends through the pelvis from the end of the sigmoid colon to the anus.

Click the icon to see an image of the digestive system.

Click the icon to see an image of the stomach.

Click the icon to see an image of the small intestine.

Click the icon to see an image of the large intestine.

Causes

Inflammatory bowel disease (IBD) can have many causes. Often, genetic problems in the intestine allow viruses or bacteria to trigger an immune response that causes inflammation and injury in the intestines. In IBD, the defense systems appear to be impaired, either from defects in the mucosal lining that provides a barrier in the intestine or an inability to make repairs after injury.

The Immune System's Infection Fighters. The primary infection-fighting units are two types of white blood cells: lymphocytes and leukocytes.

Lymphocytes include two subtypes known as T cells and B cells. Both types of cells are designed to recognize foreign invaders (antigens) and to launch an offensive or defensive action against them:

B cells produce antibodies, substances that can either ride along with a B cell or travel on their own to attack the antigen.

T cells have special receptors attached to their surface that recognize the specific antigen.

T cells are further categorized as killer T cells or helper T cells.

Killer T cells directly attack antigens that occur in any cells that contain a nucleus.

Helper T cells also recognize antigens, but their role is two-fold. They stimulate B cells and other white cells to attack the antigen. They also produce cytokines, powerful immune factors that have an important role in the inflammatory process.

Helper T Cells and Inflammatory Bowel Disease. The actions of the helper T cells (TH cells) are of special interest in inflammatory bowel disease:

TH cells stimulate other white blood cells called B cells to produce antibodies. In this case, however, they appear to direct the B cells to produce autoantibodies, which are directed against the body's own cells.

TH cells also secrete or stimulate the production of powerful immune factors called cytokines. In small amounts, cytokines are indispensable for healing. If overproduced, however, they can cause serious damage, including inflammation and cellular injury. Cytokines, particularly specific ones known as tumor necrosis factor, interferon-gamma, and interleukins, cause intestinal inflammation and damage, which, in a vicious cycle, attract even more helper T cells.

Helper T cells are further categorized as TH1 and TH2. An imbalance in these two types appears to occur in inflammatory bowel disease (IBD), although each disorder has a different balance:

Patients with ulcerative colitis favor a TH2 response, which activates the interleukins IL-5, IL-6, and IL-10. These proteins affect mostly mucosal areas in the intestine.

Research indicates that Crohn's disease patients have increased activity in TH1 cells, which activates interleukin-2 (IL-2) and interferon-gamma. These substances affect intestinal cells. Tumor necrosis factor may be a particularly potent immune factor in Crohn's disease. It is important in properties that regulate inflammation and cell proliferation. If genetic or other factors increase production of this immune compound, it can lead to great harm.

Interleukin 6 appears to play a part in both IBDs. Interleukin 6 inhibits a natural process called apoptosis,in which cells self-destruct. As a result, cells proliferate faster than they die, causing an excessively strong immune response.

Adhesion Molecules. Increased levels of certain molecules called E-selectin and intercellular adhesion molecule-1 (ICAM-1) also appear to play a major role in the inflammatory process by causing damaging immune factors to accumulate on intestinal cells.

Matrix Metalloproteinase. Greater activity of enzymes called matrix metalloproteinase has been detected in the colons of patients with IBD. Such increased levels tend to break down the extracellular matrix, a barrier composed of structural proteins and elastic fibers that surrounds and supports cells, in this case in the colon. Researchers suggest that this activity may cause persistent damage once the inflammatory process has triggered IBD.

Although the causes of inflammatory bowel disease are not yet known, genetic factors certainly play some role. Between 10 - 20% of people with ulcerative colitis have family members with the disease. Several identified genes and chromosome locations play a role in the development of ulcerative colitis, Crohn's disease, or both. Genetic factors appear to be more important in Crohn's disease, although there is evidence that both conditions have some genetic defects in common.

In 2006, scientists identified variations in the interleukin-23 receptor (IL23R) as an important genetic link to both Crohn’s disease and ulcerative colitis. Interleukin 23 is a cytokine that plays an important part in the inflammatory response and inflammatory diseases. Interestingly, scientists found that certain variations in the IL23 receptor gene can either increase or decrease the risk for inflammatory bowel disease.

One theory suggests that viruses or bacteria within the intestine may alter properties in the lining and intestinal tract. Over time, these changes may trigger the injurious processes that lead to inflammatory bowel disease.

Some studies report that children with IBD may have had more and earlier childhood infections. The measles virus has been of particular interest. However, according to the U.S. Centers for Disease Control, and many studies, the measles virus does not cause Crohn’s or IBD. In addition, studies conclusively report that the measles, mumps, and rubella (MMR) vaccine does not cause Crohn’s disease, ulcerative colitis, or autism.

Inflammatory bowel disease is much more prevalent in industrialized nations and in higher-income groups. Diet may play some role, although studies have been conflicting over its importance.

Symptoms

The two major inflammatory bowel diseases (IBDs), ulcerative colitis and Crohn's disease, share certain characteristics:

Symptoms usually appear in young adults.

Symptoms can develop gradually or have a sudden onset.

Both are chronic. In either disease, symptoms may flare up (relapse) after symptom-free periods (remission) or symptoms may be continuous without treatment.

Symptoms can be mild or very severe and disabling.

The severity of symptoms and relapse rates of both IBDs vary with seasons, with the highest risk in the winter and autumn and lowest in summer.

The two disorders, however, have different symptom profiles. It is important to differentiate between them, since they require different treatments.

Symptoms

Ulcerative Colitis (UC)

Crohn's Disease (CD)

Diarrhea

Recurrent diarrhea is very common, but onset may be very gradual and mild or it may not be present. Feces may also contain mucus.

Recurrent diarrhea is fairly common.

Rectal bleeding

Blood is almost always present in stools. It may be readily visible or visible using only a microscope (called occult blood).

Bleeding not as common as in UC, but can occur.

Constipation

Constipation can be a symptom of UC, but not as common as diarrhea. Can occur during flare-ups. May occur when the inflamed rectum triggers a reflex response in the colon that causes it to retain the stool.

Constipation in Crohn's disease is usually a symptom of obstruction in the small intestine.

Abdominal symptoms

Pain is not prominent symptom, but can vary. May cause vague discomfort in the lower abdomen, an ache around the top of the hipbone, or cramps in the middle of the abdomen. Severe pain can occur during flare-ups. Vomiting and nausea.

Hallmark symptom is recurrent episodes of pain in the lower right part of the abdomen or above the pubic bone. Often preceded by and relieved by defecation. Bloating, nausea, and vomiting may also occur. Intestinal pain may also be an indication of a serious condition, such as an abscess, or a perforation of the intestinal wall.

Fever

May occur with severe attacks.

Usually low-grade. Spiking fever and chills indicates complications.

Loss of appetite, weight loss, and impaired growth in children

Often not evident in mild or even moderately severe UC. Occasionally impairs growth in children and teenagers.

Common. Typical weight loss is 10 -20% of normal. Commonly impairs growth in children and teenagers.

Abnormal defecation: Increased frequency, a feeling of incomplete evacuation, and tenesmus (a painful urge for a bowel movement even if the rectum is empty). Fecal incontinence.

Symptoms may be mild or severe.

Can occur in active stages.

Anal ulcers and fistulas: (channels that can burrow between organs, loops of the intestine, or between the intestines and skin).

Almost never a symptom.

Fistulas and ulcers around the anus may be early symptoms of CD.

Neurologic or psychiatric symptoms

No.

May be early signs of Crohn's disease when accompanied by gastrointestinal problems.

Complications

Surgical removal of the colon is the only cure for ulcerative colitis, but the disease varies greatly in severity. In one 10-year study, 87% of patients went into complete remission after a single attack, and only 8% developed a chronic persistent condition. Mortality rates were about the same as in the general population, although they were higher in patients with UC with severe initial attacks or extensive disease. Surgical and medical treatments have complications of their own that can be very severe.

Ulcerative colitis is considered mild if a patient has the following symptoms:

Four or fewer bowel movements a day

Only occasional blood in the stool

A normal temperature and pulse rate

Normal hemoglobin or red blood cell count

No abnormalities observed on x-rays of the colon.

Ulcerative colitis is considered serious if the following symptoms are present:

More than six movements a day

Frequent-to-persistent blood and mucus in the stool (in serious cases, stool is liquid and looks like anchovy sauce)

Fever

A rapid pulse

Anemia

Abnormal x-rays of the colon

Tenderness in the abdomen when pressed, with possible distention

Malabsorption and Malnutrition. Malabsorption is the inability of the intestines to absorb nutrients. In IBD, this occurs as a result of bleeding and diarrhea, as a side effect from some of the medications, and as a result of surgery. Malnutrition typically develops rapidly after the condition has been present for some time.

Toxic Megacolon. Toxic megacolon is a serious complication that can occur if inflammation spreads into the deeper layers of the colon. In such cases, the colon enlarges and becomes paralyzed. In severe cases, it may rupture, which is a life-threatening event needing emergency surgery. Symptoms include weakness and abdominal pain and bloating. You may be disoriented or groggy. X-rays are needed to confirm the diagnosis, but barium enemas and colonoscopies should not be performed. Medications used for pain and diarrhea, such as opiates and drugs that reduce spasms of the colon, may increase the risk of toxic megacolon. People with ulcerative colitis have a higher than normal risk, although this is still not common. Its incidence is decreasing with treatment advances.

Toxic megacolon is characterized by extreme inflammation and distention of the colon. Common symptoms are pain, distention of the abdomen, fever, rapid heart rate, and dehydration. This is a life-threatening complication that requires immediate medical treatment.

Bleeding. Bleeding due to ulcers in the colon is a common complication of UC. It can increase the risk for anemia. In some cases, bleeding can be massive and dangerous, requiring surgery.

Intestinal Infections. Inflammatory bowel disease can increase patients’ susceptibility to Clostridium difficile, a species of intestinal bacteria that causes severe diarrhea. As its name implies, C. difficile is difficult to treat and is resistant to many types of antibiotics. It is usually acquired in a hospital. However, several 2007 studies indicated that C. difficile is increasing among patients with inflammatory bowel disease and that many patients acquire this infection outside of the hospital setting. Patients with ulcerative colitis are at particularly high risk.

Colorectal Cancers. Patients with ulcerative colitis have a higher than normal risk for cancers of the colon and rectum. About 5 - 8% of patients with ulcerative colitis will develop colorectal cancer within 20 years of their ulcerative colitis diagnosis. The risk of colorectal cancer increases with the duration and severity of the ulcerative colitis condition. The presence of inflammatory polyps (pseudopolyps) more than doubles the risk. Some research suggests that anti-inflammatory drugs, such as 5-ASA, may help reduce the risk of cancer. Doctors also advise that patients with ulcerative colitis receive regular (every 1 - 3 years) colonoscopy exams to help screen for cancer. According to a 2006 study, patients with ulcerative colitis who are diagnosed with colorectal cancer have a worse prognosis, and poorer survival, than those without ulcerative colitis. [See In-Depth Report #55: Colon and rectal cancers.]

Click the icon to see an image of the colonoscopy procedure.

People with inflammatory bowel disease (IBD) have a higher risk of developing other inflammatory diseases that affect the lungs and central nervous system.

Asthma. According to a 2005 study, people with IBD are 1.5 times more likely to have asthma than people without IBD. Of all the conditions that can accompany IBD, asthma is the most common. People with IBD are also at increased risk for bronchitis and other lung inflammations.

Eyes. Inflammation in parts of the eye is a common complication. Retinal disease, including detachment can occur but is rare. People with accompanying arthritic complications may be at higher risk for eye problems.

Joints. Inflammation causes arthritis and stiffness in the joints.

Bones. Low body weight and calcium loss from corticosteroids contribute to osteoporosis (bone loss). However, ulcerative colitis itself causes less bone loss than Crohn’s disease.

Click the icon to see an image of osteoporosis.

Heart. People with IBD have more than three times the risk of developing pericarditis (inflammation of the sac enclosing the heart) than healthy people

Anemia. People with ulcerative colitis have a higher than normal risk for anemia.

Liver and Gallbladder Disorders. People have a higher than average risk for mild but not severe liver abnormalities. There is a higher risk (although rare) for primary sclerosing cholangitis, which is persistent inflammation of the bile duct that can later cause serious obstruction.

Skin Disorders. Patients with ulcerative colitis have a higher risk for skin disorders and may experience ulcer eruptions called pyoderma gangrenosum that heal in the center and spread.

Thromboembolism (Blood Clots). People with ulcerative colitis are at higher risk for blood clots, especially in the legs and pelvic area.

Click the icon to see an image depicting a thrombus.

Kidney Disorders. People with ulcerative colitis have a higher than normal risk for kidney stones.

Click the icon to see an image of kidney stones.

Lung Involvement. Lung involvement may develop but it can progress for years without symptoms.

Mouth Sores. There is a slightly higher than average risk for mouth sores and infections in people with ulcerative colitis , but they are uncommon and lower than those with Crohn's disease.

Delayed Growth and Development in Children. Children with ulcerative colitis are at slightly higher than average risk for delayed growth, but their risk is lower than the risk is for people with Crohn's disease.

Fertility. Fertility rates in women are close to normal, but ulcerative colitis surgery can increase the risk for infertility. Prematurity rates are high with both types of IBD.

Hodgkin's Disease. Patients with ulcerative colitis may be at higher risk for Hodgkin's disease, according to a 2000 study. The risk of other cancers was not increased, however.

Menstrual Problems in Women. Menstrual problems are common, including premenstrual disorder, abnormal bleeding, and pain. Pain with intercourse occurs in about half of patients. Sexual function may be impaired, not only because of the emotional impact, but also by treatment of side effects and complications of the diseases, such as fistulas.

Pregnancy. Inflammatory bowel disease doubles the risk of pregnancy complications. According to a 2007 review, women with inflammatory bowel disease are nearly twice as likely to give birth prematurely. Children born to mothers with this disease are more than twice as likely to be below normal weight and to have birth defects. If a woman experiences active bouts of disease during the course of her pregnancy, her risk for complications increases.

Neurologic Factors. Inflammatory bowel disease has been associated with neurologic complications, including a higher risk for dementia, movement disorder, and stroke. People with IBD have a higher risk for developing multiple sclerosis and inflammation of the optic nerve (optic neuritis).

Emotional Factors. The emotional consequences of ulcerative colitis cannot be overestimated. Eating becomes associated with fear of abdominal pain before the end of the meal. Frequent attacks of diarrhea can cause such a strong sense of humiliation that social isolation and low self-esteem may result. ulcerative colitis takes a serious toll on work, family, and social activities. According to a 2005 survey, 40% of patients report incapacitating symptoms at least 180 days per year. Adolescents with IBD may have added problems that increase emotional distress, including weight gain from steroid treatments and delayed puberty.

Risk Factors

About 1 - 2 million Americans suffer from inflammatory bowel disease (IBD). Crohn's disease was once thought to be far less common than ulcerative colitis, but the two conditions are now estimated to occur about equally. The incidence may vary depending on gender, age, and geography:

Men and women have equal risk for ulcerative colitis.

IBD is diagnosed most often in young people ages 10 - 19, but it can occur at any age. A smaller peak onset occurs in people ages 50 - 80. About 2% of IBD cases appear in children below age 10.

Ulcerative colitis is most common among people of European descent. People of African descent have a lower incidence than Caucasians. Low incidence regions include Asia and South America. Ethnically, Ashkenazi Jewish people have a particularly high risk.

Ulcerative colitis may disproportionately affect people of higher socioeconomic classes, but evidence for this is inconclusive.

Smoking. Smokers have lower than average rates of ulcerative colitis (but higher than average rates of Crohn's disease). Some patients with ulcerative colitis, in fact, have reported that their disorder began after they quit smoking, and many studies have reinforced the association between smoking and protection against ulcerative colitis. (This information is certainly no encouragement to smoke. Rather, patients should ask their doctor about trials using nicotine replacement aids.)

Breast-feeding. Breast-feeding appears linked to lower risk for ulcerative colitis.

Left-Handedness. People who are left-handed have a significantly higher risk for both inflammatory bowel diseases as well as for certain other diseases associated with immune system abnormalities.

Depression. One study reported that patients with ulcerative colitis were more likely to have a history of depression or anxiety than those without inflammatory bowel disease. Some researchers suggest that depression may alter the immune system and make people more susceptible to ulcerative colitis.

Diagnosis

The doctor will take your medical history and perform a thorough physical examination. The disease is particularly difficult to diagnose in children, in whom inflammatory bowel disease (IBD) may be mistaken for an infection or even depression if other characteristic symptoms, such as bloody diarrhea and weight loss, are not present. Slow growth may be a key feature in making a diagnosis, particularly of Crohn's disease, in children.

Several laboratory tests may be taken, such as the following:

Blood tests are used for various purposes. An increased number of white blood cells may indicate the presence of inflammation. Blood tests are used to determine the presence of anemia and to measure liver enzymes. (They are abnormal in about 3% of ulcerative colitis cases.) New blood tests that measure certain antibodies may make it easier to differentiate Crohn's disease from ulcerative colitis in children.

A stool sample is taken and examined for blood, infectious organisms, or both.

Endoscopic Procedures. Flexible sigmoidoscopy and colonoscopy are endoscopic procedures. They are important in the diagnosis of both ulcerative colitis and Crohn's disease. Both procedures involve snaking a fiberoptic tube called an endoscope through the rectum to view the lining of the colon. The doctor may also insert instruments through the endoscope to remove a tissue sample for a biopsy.

Sigmoidoscopy, which is used to examine the rectum and left (sigmoid) colon, lasts about 10 minutes and is done without sedation. It may be mildly uncomfortable, but it is not painful. Ulcerative colitis almost always involves the lower left colon and rectum and is diagnosed using sigmoidoscopy. The doctor usually observes an evenly distributed inflamed surface lining the intestine, and the bowel wall bleeds easily when touched with a swab.

Colonoscopy allows a view of the entire colon and requires a sedative, but it is still performed on an outpatient basis. It is helpful for distinguishing between Crohn's disease and ulcerative colitis and in screening for colon cancer.

Patients diagnosed with ulcerative colitis may also need periodic endoscopies to evaluate their condition when symptoms flare up. However, a 2005 study suggested that these routine endoscopies may not be necessary. The study found that doctors can get as much information about a person's disease when patients self-report their symptoms as they can from endoscopies.

X-rays and Barium Enema. The double-contrast barium enema, which uses an x-ray image, is less expensive than a colonoscopy for viewing the entire colon. Although not as accurate as colonoscopy, it is very valuable in diagnosing both Crohn's disease and ulcerative colitis in early stages. In patients with active ulcerative colitis, this procedure may increase the risk for toxic megacolon.

A barium enema is a valuable diagnostic tool that helps detect abnormalities in the large intestine (colon). A barium enema, along with colonoscopy, remains standard in the diagnosis of colon cancer, ulcerative colitis, and other diseases of the colon.

X-rays of the abdomen are also useful when a patient has a severe attack of ulcerative colitis. In such cases, the edges of the colon are swollen and irregular. X-rays may also reveal thickened walls and other signs of severity.

Ultrasound. Intestinal wall ultrasound may be useful for identifying the extent and severity of Crohn's disease. Although it is unclear if ultrasound is useful for an initial diagnosis, one study indicated that, when used by experienced professionals, it is effective for identifying Crohn's disease or ulcerative colitis.

Other Imaging Procedures. Magnetic resonance spectroscopy (MRS) is a variant of magnetic resonance imaging (MRI) that may prove to be useful for differentiating between Crohn's disease and ulcerative colitis.

Positron emission tomography (PET) and computed tomography (CT) scans may be useful for determining the extent of the disease on the intestine and for detecting abscesses and other complications of advanced IBD.

A promising experimental technique called virtual colonoscopy allows three-dimensional imaging of the colon without using invasive instruments. The procedure involves pumping air into the colon and scanning the intestine using computed tomography (CT) or magnetic resonance imaging (MRI). It is very safe, requires no sedation, and takes only about 10 minutes.

Endoscopy

Ulcerative colitis almost always involves the lower left colon and rectum and can be diagnosed using sigmoidoscopy. Crohn's disease may require colonoscopy as well. Endoscopy often reveals ulcers, diseased regions that have a cobblestone-like appearance in Crohn's disease, but not in ulcerative colitis.

X-Rays (Barium Enema) or Computed Tomography Scans

In ulcerative colitis, inflammation is usually evenly distributed on the surface lining of the intestine, and the bowel wall bleeds easily when touched with a swab. The pattern observed in Crohn's disease is usually one of scattered patches of ulcers that are deep, thick, and large.

Crohn's disease produces pockets (fissures) or channels (fistulas). They do not occur with UC.

In ulcerative colitis the ileum (the lower part of the small intestine) is often dilated while it is narrowed in Crohn's disease.

Laboratory Tests

Tissue samples obtained from a patient with Crohn's disease may reveal granulomas, small collections of inflammatory cells. Granulomas may also be present in other conditions, however. Tissue samples should also be examined for the presence of cancerous cells.

About 70% of tests for antibodies in people with UC will show perinuclear-staining antineutrophil cytoplasmic antibodies. Over 50% of Crohn's people have anti-Saccharomyces cerevisiae antibodies. Such tests are expensive and infrequently performed, but they may be useful in cases of uncertainty.

Irritable Bowel Syndrome. Irritable bowel syndrome (IBS), also known as spastic colon, functional bowel disease, and spastic colitis, cause many of the same symptoms as inflammatory bowel disease. Bloating, diarrhea, constipation, and abdominal cramps are all symptoms of IBS. Irritable bowel syndrome is not caused by inflammation, however, and no fever or bleeding occurs. Behavioral therapy may be helpful in treating IBS. (Psychological therapy does not improve inflammatory bowel disease.)

Microscopic Colitis. Microscopic colitis causes chronic watery diarrhea, but the colon lining shows little or no signs of inflammation. It may be genetically linked to celiac sprue. Most patients can expect to improve.

Celiac Sprue. Celiac sprue, or celiac disease, is an intolerance to gluten (found in wheat) that triggers inflammation in the small intestine and causes diarrhea, vitamin deficiencies, and stool abnormalities. It occurs in a lot of people with inflammatory bowel disease (IBD) and is usually first noticed in children.

Click the icon to see foods to avoid when you have celiac sprue.

Interstitial Cystitis. Interstitial cystitis (IC) is an inflammation of the bladder wall that occurs almost exclusively in women. Some evidence suggests that the risk for IBD in these patients is 100 times above that in the general population and that there may be some common factor to both conditions. The average age of a patient with IC is 40, but 25% of cases occur in women under age 30. Symptoms are very similar to urinary tract infections, but no bacteria are present. Pain during sex is a very common complaint in these patients, and stress may intensify symptoms.

Infections. If endoscopy reveals inflammation, a doctor must always rule out possible infections before a diagnosis of inflammatory bowel disease can be confirmed.

Acute Appendicitis. Crohn's disease may cause tenderness in the right lower part of the abdomen, where the appendix is located, that resembles an appendicitis.

Cancer. Colon or rectal cancers must always be ruled out when symptoms of IBD occur.

Intestinal Ischemia. Symptoms similar to irritabel bowel syndrome can be caused by blockage of blood flow in the intestine. This is more likely to occur in elderly people.

Dietary Factors

Malnutrition is very common in ulcerative colitis, although it tends to be more severe in Crohn's disease. Some experts recommend that children with inflammatory bowel disease increase their calorie and protein intake by 150% of the daily recommended allowance for their specific ages and heights. Studies indicate that nutritional support in children is as important as medications for achieving remission. People whose weights are normal or no less than 90% of normal do not need to add extra calories.

Fluids (Non-Caffeinated). Drinking plenty of water is extremely important. It not only benefits the intestine but also helps prevent kidney stones, which are common in inflammatory bowel disease (IBD). Vegetable juice and sports drinks may be helpful for restoring important minerals.

Protein. Proteins are very important for growth in children and for repair of cells. Diarrhea can cause protein deficiency and so patients may need more protein than the general population.

Complex Carbohydrates. Complex carbohydrates, found in whole grains, fruits, and vegetables, should make up half of your calories. Fresh fruit (such as apples, grapefruit, oranges, plums, blueberries, raspberries, and strawberries) might be specifically protective for IBD and may also reduce the risk for colon cancer. (Simple sugars can increase inflammation, however, so you should avoid dried fruits and high-sugar fruits, such as grapes, pineapple, and watermelon.)

Foods made up of complex carbohydrates are also often a good source of fiber. Fiber may help reduce damage in the intestinal tract caused by UC, and may even help protect against cancer. Oat bran is of particular interest. In the intestinal tract, this whole grain increases levels of a fatty acid called butyrate, which may help reduce GI symptoms due to ulcerative colitis. However, high-fiber foods can cause gas, bloating, and pain, particularly in people with IBD. Available commercial products (Beano) can reduce gas. Eating small, frequent meals can also help.

Potassium-rich Foods. Potassium rich foods help protect the intestine. They may also reduce the risk for kidney stones. Such foods include bananas, oranges, pears, cantaloupes, tomatoes, dried peas and beans, nuts, potatoes, and avocados.

Fish Oil. Omega-3 fatty acids, which are found in oily fish, have been associated with protection against inflammation, including in the intestinal tract. Some studies have even reported lowered use of anti-inflammatory medications in people who consume fish oil. Such fatty acids are also available in supplements as docosahexaenoic (DHA) and eicosapentaneoic (EPA) acids. Standards for optimal amounts and forms of omega-3 fatty acids have not yet been established, however.

Omega-3 fatty acids, found plentifully in oily fish, flaxseed, and canola oils, may help people with inflammatory bowel disease.

Exclusion diets are those that eliminate certain allergenic foods or those that might irritate the intestine. To determine these foods, patients use a so-called elimination-and-challenge approach. First, they remove all suspect foods from their diet for 2 weeks and then reintroduce one food every 3 days. Patients then watch for any symptoms that might indicate an allergic or irritant response, including gastrointestinal problems, headaches, and flushing. Elimination diets, however, are very difficult to maintain, and it is not clear if they prevent relapse.

Typical foods to avoid are:

Saturated fats, found in animal and dairy products. People with inflammatory bowel disease should limit fats. Some studies have found an association between high-fat intake and later development of ulcerative colitis. Animal (saturated) fats are often suspected in IBD.

Milk products. Some people with inflammatory bowel disease are lactose intolerant (unable to digest the sugar lactose, found in milk products). However, milk, along with the calcium it contains, has been associated with a lower risk for colon cancer. Taking lactase tablets or specially prepared dairy products may help. (Many lactose-intolerant people are still able to eat yogurt with active cultures, which could be helpful for IBD.)

Foods associated with inflammation (alcohol, simple sugars, and caffeine). Fruits may be protective, but you should avoid dried fruits or high-sugar fruits, such as grapes, watermelon, or pineapple.

Products containing corn or gluten (those made from wheat, oats, barley, or triticale).

Common allergenic foods, such as soy, eggs, peanuts, tomatoes.

Foods that may irritate the intestine, particularly so-called Brassica vegetables (cabbage, Brussels sprouts, broccoli, cauliflower, kale).

Kidney stones are painful and common complications in people with inflammatory bowel disease (IBD), particularly in people who have had intestinal surgery. People with IBD are at risk for the most common types of stones -- those composed of either calcium oxalate or uric acid crystals. The following are some considerations in reducing the risk for stones:

The most important dietary recommendations for reducing the risk for kidney stones are increasing fluid and restricting sodium intake.

Limiting protein is recommended for reducing kidney stones. However, people with IBD who have frequent diarrhea are protein deficient. Sufficient protein, particularly in children with IBD, is very important and should be weighed against any risk for stones.

You should increase intake of potassium-rich foods.

You should try to correct any dietary habits that cause acidic or alkaline imbalances in the urine that promote stone formation.

Many kidney stones are formed from calcium-oxalate stones. You should avoid or limit intake oxalate-rich foods, such as beets, beet tops, black tea, chenopodium, chocolate, cocoa, dried figs, ground pepper, lamb quarters, lime peel, nuts, parsley, poppy seeds, purslane, rhubarb, sorrel, spinach, and Swiss chard. A high calcium diet does not appear to increase the risk for kidney stones as long as it also contains plenty of fluids and dietary potassium and phosphate. Importantly, calcium is associated with protection against colon cancer and osteoporosis -- two conditions that are associated with IBD.

People who have stones associated with short-bowel syndrome should eat less fat and foods containing oxalates. In these people, calcium may bind to unabsorbed fat instead of to oxalates, which increase oxalate levels.

The general recommendations for avoiding kidney stones must be tailored to the dietary requirements of IBD. You should work with your doctor to develop an individualized plan.

Researchers are currently investigating a mix of bacteria (called probiotics), specific foods (called prebiotics) that are metabolized by these bacteria, and the compounds they produce (called synbiotics). Some evidence suggests that alone or in combination, they may have significant benefits in the intestine.

Probiotics are helpful bacterial strains that by themselves may provide a barrier against harmful bacteria, possibly through various mechanisms, such as by excreting certain acids (lactate, acetate) that inhibit harmful bacteria or competing with them for nutrients. Evidence is now suggesting that probiotics may help maintain remission in patients with IBD. They are also proving to be effective in people with pouchitis -- a common surgical complication. The most well-known probiotics are the lactobacilli strains, such as acidophilus, which is found in yogurt and other fermented milk products. Others, such as bifidobacteria and GG lactobacilli, however, may prove to be more important in inflammatory bowel disease (IBD). Other probiotics include lactobacilli rhamnosus, casel, plantarium, bulgaricus, salivarius, Enterococcus faecium, and Streptococcus thermophilus.

Prebiotics are specific non-digestible molecules called fructo-oligosaccharides, which stimulate the growth of probiotics. These molecules are found in many foods, including Jerusalem artichokes, onions, salsify, bananas, honey, garlic, and leeks. (However, some of these foods themselves can irritate the intestine in patients with IBD.)

Researchers are investigating probiotics, prebiotics, or both for intestinal protection, including benefits for patients with IBD. Foods and supplements containing these substances are available in the U.S. and overseas. To date, however, no studies have determined any clear benefits from any specific organism or formulation.

Vitamins. Deficiencies of vitamins A, C, E, B12, and folate (a B vitamin) may result from malabsorption. In general, vitamin supplements may be recommended for everyone with IBD, particularly for children to avoid growth retardation. Vitamins A, C, and E are antioxidants, which protect the body against damaging particles. Folic acid supplements are particularly important for patients who must restrict fresh fruits and vegetables and for those taking sulfasalazine. Folate deficiencies may contribute to the increased risk for colon cancer in patients with ulcerative colitis. Monthly injections of vitamin B-12 may be necessary. Vitamin D is necessary for bone protection. Because some vitamins, such as A and D, can be toxic in high doses, patients should discuss specific dosages with their doctors.

Mineral Supplements. Supplements of calcium, magnesium, zinc, selenium, and iron may be needed to offset deficiencies in patients with severe IBD. Zinc is specifically important for gastrointestinal health. Calcium and magnesium are critical for health and strong bones. Selenium is a potent antioxidant. Iron supplements may be required for anemia. A doctor should advise patients carefully on the correct dosages since minerals can be toxic in high levels.

Symptom Management

The following are some ways of managing diarrhea, constipation, or both:

To reduce mild-to-moderate diarrhea, take one teaspoon of psyllium hydrophilic colloid (Metamucil) twice a day in a glass of water.

Anti-diarrhea drugs, such as loperamide (Imodium) and atropine/diphenoxylate (Lomotil), may help. In very ill patients, large doses of some drugs, such as Lomotil, can trigger the onset of toxic megacolon.

Opiates or drugs used to relax muscle spasms may help relieve mild-to-moderate diarrhea and abdominal cramps, but they should be used for very short periods and not for severe cases.

Bulk-type laxatives can help constipation.

Iron supplements may be required for anemia. Intravenous (IV) iron with or without erythropoietin (a hormone that acts in the bone marrow to increase the production of red blood cells) is effective for severe anemia in inflammatory bowel disease that does not respond to iron alone. Crohn's disease patients benefit from the combination. Patients with ulcerative colitis usually improve on IV iron alone.

Antidepressants may help relieve emotional problems. However, inflammatory bowel disease is not a psychological disorder, and such drugs will not affect the basic illness.

Acetaminophen (Tylenol) and nonsteroidal anti-inflammatory drugs (NSAIDs) are used for relieving mild pain. NSAIDs include aspirin, ibuprofen (Advil, Motrin), naproxen (Aleve), and celecoxib (Celebrex), the only COX-2 inhibitor left on the market. NSAIDs have been thought to cause symptom flare-ups in patients with inflammatory bowel disease (IBD). However, a comprehensive 2006 study concluded that these drugs are as safe for patients with IBD as for other people, and that they can help prevent relapse as well as provide short-term pain relief. Still, long-term use of NSAIDs can cause stomach bleeding and, with the exception of aspirin, may increase the risks for heart attack and stroke. Acetaminophen can cause liver damage if taken in high doses or combined with alcoholic drinks. Discuss with your doctor whether acetaminophen, NSAIDs, or other pain relievers are appropriate for you.

Although stress is not a cause of inflammatory bowel disease, there are reports of an association between stress and symptom flare-ups. Patients with inflammatory bowel disease (IBD), in fact, may have a more exaggerated physical response to stressful events than people without IBD. Although no evidence exists to confirm that stress reduction techniques, such as relaxation methods, meditation, or cognitive therapy, manage the disease, they might be helpful.

Castor Oil Pack. Some people report relief from the use of a castor oil pack for 3 consecutive days. The oil is applied directly to the skin and then covered with a clean soft cloth and plastic wrap. A hot water bottle or heating pad is then placed over the pack for 30 - 60 minutes.

Acupuncture. Acupuncture may help relieve symptoms in some patients.

Medications

Drugs cannot cure inflammatory bowel disease, but they can help reduce the inflammation and accompanying symptoms in up to 80% of patients. The primary goal of drug therapy is to reduce inflammation in the intestine.

Drugs Used. Drug therapies for ulcerative colitis aim to resolve symptoms (induce remission) and prevent flare-ups (maintain remission).

Aminosalicylates. Mild-to-moderate ulcerative colitis is usually treated with aspirin-like medications called aminosalicylates, or 5-ASAs. These drugs are also used to treat relapses. They may be administered rectally in patients who have mild-to-moderate disease that occurs only in the lower intestine. They may also be taken by mouth.

Corticosteroids. Corticosteroids (steroids) may be added or used alone to reduce acute inflammation. (Because of their significant side effects, they are not recommended for long-term use and maintenance therapy). Steroids may be administered rectally as an alternative to an aminosalicylate if the disease is limited to the lowest parts of the intestine. Forms taken by mouth may treat moderate-to-severe cases. People who do not respond to less aggressive treatments may need intravenous steroids.

Immunosuppressants. Drugs that suppress the immune system (immunosuppressants) are useful, either alone or in combinations, for disease that does not respond to other treatments or for maintenance of remissions.

Biologic Drugs. Unlike drugs that are made from chemicals, biologic drugs are produced from living organisms. Biologics are designed to stimulate the immune system and interfere with specific proteins (cytokines) involved with the inflammatory response. Infliximab (Remicade) is the first biologic drug approved for ulcerative colitis. It blocks a cytokine called tumor necrosis factor (TNF).

Determining Success. Therapy is considered successful if it can push the disease into remission (and keep it there) without causing significant side effects. The patient's condition is generally considered in remission when the intestinal lining has healed and symptoms such as diarrhea, abdominal cramps, and tenesmus (straining painfully or ineffectively to defecate or urinate) are normal or close to normal.

Aminosalicylates contain the compound 5-aminosalicylic acid, or 5-ASA, which helps reduce inflammation. These drugs are used to prevent relapses and maintain remission in mild-to-moderate Crohn’s disease.

The standard aminosalicylate drug is sulfazine (Azulfidine). This drug combines the 5-ASA drug mesalamine with sulfapyridine, a sulfa antibiotic. While sulfazine is cheap and effective, the sulfa component of the drug can cause unpleasant side effects, including headache, nausea, and rash.

Patients who cannot tolerate sulfazine or who are allergic to sulfa drugs have other options for aminosalicylate drugs, including mesalamine (Asacol, Pentasa), olsalazine (Dipentum), and balsalazide (Colazal). These drugs, like sulfazine, are taken as pills several times a day. In 2007, the Food and Drug Administration approved LIALDA, the first once-daily mesalamine pill for patients with ulcerative colitis. Mesalamine is also available in enema (Rowasa) and suppository (Canasa) forms.

Mesalamine can cause kidney problems and should be used with caution by patients with kidney disease. Common side effects of aminosalicylate drugs include:

Abdominal pain and cramps (mesalamine, balsalazide)

Diarrhea (mesalamine, olsalazine)

Gas (mesalamine)

Nausea (mesalamine)

Hair loss (mesalamine)

Headache (mesalamine, balsalazide)

Dizziness (mesalamine)

All mesalamine preparations, including sulfasalazine, appear to be safe for children and women who are pregnant or nursing.

General Guidelines. Corticosteroids (commonly called steroids) are powerful anti-inflammatory drugs. They are used only for active ulcerative colitis. Steroids are frequently combined with other drugs to produce more rapid symptom relief and to allow quicker withdrawal, although such combinations do not improve remission time. Because they have serious long-term effects, steroids are not useful for maintenance therapy. Patients who are malnourished are less likely to respond to steroids, and those who had an initial inadequate response to steroids are also less likely to do well with repeat therapy.

Corticosteroid Types. Prednisone (Deltasone), methylprednisolone (Medrol), and hydrocortisone (Cortef, Cortisol) are the most common corticosteroids. Newer steroids, such as budesonide (Entocort), affect only local areas in the intestine and do not circulate throughout the body. Such drugs may avoid the widespread side effects that are a serious problem with long-term treatment using older conventional steroids.

Administering Corticosteroids. Most corticosteroids can be taken as a pill. For patients who cannot take oral forms, methylprednisolone and hydrocortisone may also be given intravenously or rectally as a suppository, enema, or foam. The severity or location of the condition often determines the form.

Side Effects of Corticosteroids. Standard steroids can have distressing and sometimes serious long-term side effects, including:

Susceptibility to infection

Weight gain (particularly increased fatty tissue on the face and upper trunk and back)

Acne

Excess hair growth

High blood pressure (hypertension)

Weakened bones (osteoporosis)

Cataracts and glaucoma

Diabetes

Muscle wasting

Menstrual irregularities

Upper gastrointestinal ulcers

Personality change, including irritability, insomnia, psychosis, and depression; such emotional changes are sometimes severe enough to produce suicidal thoughts

Withdrawing from Corticosteroids. Once the intestinal inflammation has subsided, steroids must be withdrawn very gradually in order to give the body time to recover its own ability to produce natural steroids. Withdrawal symptoms, including fever, malaise, and joint pain, may occur if the dosage is lowered too rapidly. If this happens, the dosage is increased slightly and maintained until symptoms are gone. More gradual withdrawal is then resumed.

Immunosuppressant drugs are now being used for long-term therapy, especially for very active inflammatory bowel disease that does not respond to standard treatments. Such drugs suppress or restrain actions of the immune system and therefore its inflammatory response, which causes ulcerative colitis. Immunosuppressants can prevent relapse, even when used alone, and in some studies have proved to help maintain remissions in ulcerative colitis for up to 2 years.

Azathioprine (Imuran, Azasan) and 6-mercaptopurine (6-MP, Purinethol) are the standard oral immunosuppressant drugs. However, it can take 3 - 6 months for these drugs to have an effect. To speed up the response, they are sometimes prescribed along with a corticosteroid drug. Lower steroid doses are then needed, resulting in fewer side effects. Corticosteroids may also be withdrawn more quickly. For this reason, immunosuppressants are sometimes referred to as steroid-sparing drugs.

Other pill forms of immunosuppressants include cyclosporine A (Sandimmune, Neoral) and tracrolimus (Prograf). Cyclosporine A is also given intravenously to patients with severe ulcerative colitis. These drugs are quicker-acting than azathiopine and 6-mercaptopurine. Cyclosporine A generally takes 1 - 2 weeks to take effect. Methotrexate (MTX, Rheumatrex) is another fast-acting type of injectable immunosuppressant that is effective for Crohn’s disease. However, methotrexate does not appear to be helpful for ulcerative colitis. (Antibiotics, which are used to treat Crohn's disease, are also not helpful for ulcerative colitis.)

General side effects of immunosuppressants may include nausea, vomiting, and liver or pancreatic inflammation. Patients should receive frequent blood tests to monitor bone marrow, liver, and kidneys. Patients who take cyclosporine A or tacrolimus need to have their blood pressure and kidney function checked regularly. Immunosuppressants are usually not recommended for women who are pregnant or breast-feeding.

Biologic response modifiers are genetically engineered drugs that target specific proteins involved with the body’s inflammatory response. One such drug, infliximab (Remicade), was approved in 2005 for treatment of moderate-to-severe ulcerative colitis in patients who have not responded to other drugs, such as corticosteroids. In 2006, infliximab was approved to help maintain as well as induce remission. Doctors do not recommend infliximab as a first-line drug for ulcerative colitis.

Infliximab targets an inflammatory immune factor known as tumor necrosis factor (TNF). Studies indicate that infliximab may reduce ulcerative colitis symptoms and help patients achieve remission. Infliximab may also help heal ulcers and inflammation of the colon’s inner lining (mucosa). Some patients who take infliximab may be able to avoid surgical removal of the colon.

Infliximab is given as a 2-hour intravenous infusion in a doctor’s office. After the first dose, the patient receives a second dose 2 weeks later, and a third dose 6 weeks after that. After these three doses, the drug is given every 8 weeks.

Common side effects may include a skin reaction at the injection site, stomach pain, and coughing. Potential serious side effects include tuberculosis, pneumonia, and other respiratory infections; lymphoma (a type of cancer); liver failure; and aplastic anemia. Infliximab is not appropriate for most patients with heart failure.

Researchers are currently studying other biologic drugs for treatment of ulcerative colitis. These investigational drugs include adalimumab (Humira), which is approved for Crohn’s disease, and visilizumab (Nuvion), rituximab (Rituxan), basiliximab (Simulect), and golimumab (CNTO 148). To date, however, infliximab is the only biologic drug approved for treatment of ulcerative colitis.

Interferon. Interferons suppress important inflammatory factors in the immune system. They are used in treating multiple sclerosis. Research suggests that the drug interferon (IFN) beta-1a (Avonex, Rebif) may help patients with ulcerative colitis. Side effects include flu-like symptoms and reactions at the site of injection. More research is needed.

Rosiglitazone. The diabetes drug rosiglitazone (Avandia) is being studied as a short-term treatment for mild-to-moderate ulcerative colitis in patients who are not helped by 5-aminosalicylic acid (5-ASA) drugs. Research presented at the 2007 Digestive Disease Week conference indicated that rosiglitazone may have some benefit for select patients. However, this drug has been associated with increased risk for heart failure, and possibly heart attack, in patients with diabetes. More research is needed.

Alicaforsen. Antisense drugs bind to target RNA and block the production of key proteins. Alicaforsen is an antisense drug that inhibits an intercellular adhesion molecule (ICAM-1) thought to play a pivotal role in the inflammatory process. Several clinical trials of alicaforsen enemas have reported encouraging results for improvement of ulcerative colitis symptoms. More research is needed.

Adsorptive Granulocyte and Monocyte Apheresis (GMA). Adsorptive apheresis is a process in which the fluid part of the blood, called plasma, is removed from blood cells. The procedure involves withdrawing blood from the patient, filtering it through a device, and then infusing the filtered blood back into the patient. The process removes inflammatory antibodies and other immunologically active substances. It is used for patients with rheumatoid arthritis and may be helpful for patients with ulcerative colitis. Some clinical trials have reported promising results for treatment of refractory ulcerative colitis. More research is needed.

Parasites. Inflammatory bowel disease is rare in countries where intestinal infection with parasites called helminthes is common. Small studies are reporting significant remission rates in patients with Crohn's disease or ulcerative colitis who have swallowed the eggs of a specific parasitic worm. The parasite does not invade tissue or spread other diseases. The parasite induces production of specific T cells, called TH-2, which are immune factors that may be protective against overactivity of cytokines that trigger inflammatory bowel disease. More research, however, is needed.

Surgery

In 20% of people with ulcerative colitis, drug therapy is not effective, and surgery to remove diseased sections is necessary. In these people, part, or all ,of the colon is removed, depending on the extent of the disease. Surgeries may also be required because of hemorrhage, chronic illness, perforation of the colon, or to prevent colon cancer. Studies report that surgery improves the quality of life in most patients. Some experts are urging, in fact, that many patients should consider intestinal surgery in the early stages of the disease.

Proctocolectomy is removal of the entire colon, including the lower part of the rectum and the sphincter muscles that control bowel movements. It can achieve a complete cure, but it is a last resort. There are different variations that may be performed depending on various factors. The procedure must be performed only on patients in whom it is absolutely clear that ulcerative colitis, and not Crohn’s disease, is causing the inflammatory bowel disease (IBD). Discovering underlying Crohn's disease or other problems during the procedure can increase the risk for complications.

Ileostomy. In some proctocolectomies, the surgeon creates an opening in the abdominal wall (called a stoma) to allow passage of waste material. This part of the procedure is referred to as an ileostomy, and the stoma is created in the lower right corner of the abdomen. The surgeon then connects cut ends of the small intestine to this opening. A bag is placed over the opening and accumulates waste matter. It requires emptying several times a day.

Ileoanal Anastomosis. Ileal pouch anal anastomosis (IPAA), also simply called ileoanal anastomosis, has now largely replaced ileostomy because it preserves part of the anus and allows for more normal bowel movements. The procedure creates a natural pouch to collect waste, rather than using an ileostomy bag. The standard procedure involves:

The colon is removed as in proctocolectomy, but the surgeon only strips the superficial diseased inner layer of the rectum, leaving the sphincter muscles intact.

The anus is then attached to the ileum (the final portion of the small intestine leading to the colon).

A pouch is constructed out of the small bowel above the anus. The pouch is able to collect waste material, and the patient can pass bowel movements normally through the anus, although they are watery and more frequent than normal (five or six times a day). Closing the pouch with a staple, rather than hand-sewn stitches, achieves better continence rates.

A temporary abdominal opening (ileostomy) is usually required, but it is typically closed up in a second operation a few months later.

Flatulence is the most socially distressing problem. Unfortunately many of the fiber rich vegetables and whole grains that can benefit patients with ulcerative colitis can also cause gas. (Surgical patients should avoid or chew thoroughly insoluble fiber foods, such as popcorn, olives, and vegetable skins, which can obstruct the stoma.) Some pouching systems have filters that can help limit flatulence. Typically, flatulence occurs 2 - 4 hours after eating, which may help patients time their meals to ensure privacy afterward.

Patients must increase fluid intake, and include not only water but also broth, sports drinks, and vegetable juice to maintain appropriate levels of sodium and potassium.

Patients should avoid time-released, coated, or large pills, which often are not completely absorbed and may block the stoma.

The ileostomy does not interfere with bathing or showering or most physical activity. (Patients should avoid contact sports.) As a rule, the surgeries do not impair sexual function. If it does, according to one study, taking sildenafil (Viagra) restores sexual function to near or complete improvement in 80% of men.

Complications are common with any intestinal operation. In about 5 - 10% of IPAA procedures, complications occur that require conversion to an ileostomy. In general, patient satisfaction is very high with this procedure. Over 80% of patients report better or much better quality of life 5 years after the procedure. According to one study, 90% of patients can expect to have a functioning pouch for at least 20 years. Most patients can postpone their bowel movements until they are convenient. Bowel movements still average about seven a day.

Pouchitis. Inflammation of the pouch (pouchitis) is the most common complication of the pouch procedures, and one study reported its occurrence in up to 60% of patients. Symptoms include rectal bleeding, cramps, and fever. It can usually be easily treated. According to one study, however, in about 10% of these patients the condition becomes chronic, and the pouch may need to be removed. Metronidazole (Flagyl) is effective in treating active flare-ups of pouchitis. Evidence also suggests that the use of a probiotic (VSL-3) helps maintain remission in chronic pouchitis.

Irritable Pouch Syndrome. Irritable pouch syndrome is a problem that includes frequent movements, an urgent need to defecate, and abdominal pain. There are no signs of inflammation, however, as there are with pouchitis. Stress and diet play a role in this condition, and it is usually relieved after a bowel movement.

Fecal Incontinence. About 70% of patients are fully continent indefinitely after the procedure. (In other words, they experience no leakage.) The other patients typically experience occasional spotting and minor leakage, which is manageable.

Infertility. IPAA triples the risk of infertility in women with ulcerative colitis. The surgery may cause scarring or blocking of fallopian tubes, which increases the risk of infertility. About 48% of women who undergo this procedure become infertile

Severe scarring at the incision occurs in more than half of patients. One study found that placing an experimental absorbable membrane made from hyaluronate (a natural lubricating substance) along the incision reduced the rate of scarring up to 15%. When the rectum is removed, there is a small danger of injury to the nerves that control erection and bladder function.

Small bowel obstruction may occur with some of the procedures. If this occurs in pouch procedures, the pouch may need to be removed.

Pelvic infection occurs in less than 10% of pouch procedures (more often after hand-sewn than stapled anastomoses), and it occurs almost four times more often in men than in women. It is also more common in patients with ulcerative colitis who also have toxic megacolon.

Valve leakage may occur or the catheter may become blocked in continent ileostomies. In at least 10% of these procedures, the valve needs to be repaired later on.

Some studies have also reported that appendectomy (removal of the appendix) protects against ulcerative colitis. It may be that removing the appendix alters the T cell balance in the immune system that then works in favor of people with UC. One study suggested, however, that specific inflammatory conditions leading to appendicitis were the protective factors -- and only in people under age 20. (An appendectomy may actually increase the risk for Crohn's disease.)

Click the icon to see an illustrated series detailing an appendectomy surgery.

Resources

www.ccfa.org -- Crohn's & Colitis Foundation of America

www.gastro.org -- American Gastroenterological Association

www.acg.gi.org -- American College of Gastroenterology

www2.niddk.nih.gov -- National Digestive Diseases Information Clearinghouse

References

Clark M, Colombel JF, Feagan BC, Fedorak RN, Hanauer SB, Kamm MA, et al. American gastroenterological association consensus development conference on the use of biologics in the treatment of inflammatory bowel disease, June 21-23, 2006. Gastroenterology. 2007 Jul;133(1):312-39.

Cornish J, Tan E, Teare J, Teoh TG, Rai R, Clark SK, et al. A meta-analysis on the influence of inflammatory bowel disease on pregnancy. Gut. 2007 Jun;56(6):830-7. Epub 2006 Dec 21.

Duerr RH, Taylor KD, Brant SR, Rioux JD, Silverberg MS, Daly MJ, et al. A genome-wide association study identifies IL23R as an inflammatory bowel disease gene. Science. 2006 Dec 1;314(5804):1461-3. Epub 2006 Oct 26.

Lawson MM, Thomas AG, Akobeng AK. Tumour necrosis factor alpha blocking agents for induction of remission in ulcerative colitis. Cochrane Database Syst Rev. 2006 Jul 19;3:CD005112.

Rodemann JF, Dubberke ER, Reske KA, Seo da H, Stone CD. Incidence of Clostridium difficile infection in inflammatory bowel disease. Clin Gastroenterol Hepatol. 2007 Mar;5(3):339-44.

Review Date:
8/30/2007
Reviewed By:
Harvey Simon, MD, Associate Professor of Medicine, Harvard Medical School; Physician, Massachusetts General Hospital.

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Symptoms	Ulcerative Colitis	Crohn's Disease
Diarrhea	Recurrent diarrhea is very common, but onset may be very gradual and mild or it may not be present. Feces may also contain mucus.	Recurrent diarrhea is fairly common.
Rectal Bleeding	Blood is almost always present in stools. It may be readily visible or visible only using a microscope (called occult blood).	Bleeding not as common as in UC, but can occur.
Constipation	Constipation can be a symptom of UC, but not as common as diarrhea. Can occur during flare-ups. May occur when the inflamed rectum triggers a reflex response in the colon that causes it to retain the stool.	Constipation in Crohn's disease is usually a symptom of obstruction in the small intestine.
Abdominal Symptoms	Pain is not prominent symptom, but can vary. May cause vague discomfort in the lower abdomen, an ache around the top of the hipbone, or cramps in the middle of the abdomen. Severe pain can occur during flare-ups. Vomiting and nausea.	Main symptom is recurrent episodes of pain in the lower right part of the abdomen or above the pubic bone. Often preceded by and relieved by defecation. Bloating, nausea, and vomiting may also occur. Intestinal pain may also be an indication of a serious condition, such as an abscess, or a perforation of the intestinal wall.
Fever	May occur with severe attacks.	Usually low-grade. Spiking fever and chills indicates complications.
Loss of appetite, weight loss, and impaired growth in children	Often not evident in mild or even moderately severe UC. Occasionally impairs growth in children and teenagers.	Common. Typical weight loss is 10 - 20% of normal. Commonly impairs growth in children and teenagers.
Abnormal defecation: Increased frequency, a feeling of incomplete evacuation, and tenesmus (a painful urge for a bowel movement even if the rectum is empty). Fecal incontinence.	Symptoms may be mild or severe.	Can occur in active stages.
Anal ulcers and fistulas: (channels that can burrow between organs, loops of the intestine, or between the intestines and skin).	Almost never a symptom.	Fistulas and ulcers around the anus may be early symptoms.
Neurologic or psychiatric symptoms	No.	May be early signs of Crohn's disease when accompanied by gastrointestinal problems.


Endoscopy	Ulcerative colitis almost always involves the lower left colon and rectum and can be diagnosed using sigmoidoscopy. Crohn's disease may require colonoscopy as well. Endoscopy often reveals ulcers, diseased regions that have a cobblestone-like appearance in Crohn's disease, but not in ulcerative colitis.
X-Rays (Barium Enema) or Computed Tomography Scans	In ulcerative colitis, inflammation is usually evenly distributed on the surface lining of the intestine, and the bowel wall bleeds easily when touched with a swab. The pattern observed in Crohn's disease is usually one of scattered patches of ulcers that are deep, thick, and large. Crohn's disease produces pockets (fissures) or channels (fistulas). They do not occur with UC. In ulcerative colitis the ileum (the lower part of the small intestine) is often dilated while it is narrowed in Crohn's disease.
Laboratory Tests	Tissue samples obtained from a patient with Crohn's disease may reveal granulomas, small collections of inflammatory cells. Granulomas may also be present in other conditions, however. Tissue samples should also be examined for the presence of cancerous cells. About 70% of antibody tests for patients with UC will show immune factors called perinuclear-staining antineutrophil cytoplasmic antibodies, and over 50% of Crohn's patients have anti-Saccharomyces cerevisiae antibodies. Each antibody group shows up only occasionally in the other disorder. Researchers are also investigating other antibodies, such as antilaminaribioside and antichitobioside, which may serve as new markers for Crohn’s disease.


Laparoscopy	Open Cholecystectomy
Treatment of choice for most adult gallstone patients with or without symptoms, who have electively chosen to have their gallbladders removed.	Patients who have had extensive previous abdominal surgery.
Most patients with acute cholecystitis not accompanied by infection or perforation. (Up to 30% will need to convert to open surgery, depending on the severity of the condition.)	Patients with complications of acute cholecystitis (empyema, gangrene, perforation of the gallbladder).
Patients with acalculous gallbladder disease (without stones) who choose to have surgery. (if the patients have inflammation, however, the procedure of choice is percutaneous cholecystostomy to drain the gallbladder.	Very elderly patients. (Those over 80 are likely to have lower complication rates from open cholecystectomy than laparoscopy, although laparoscopy may even be appropriate in these patients.)
Patients with residual gallbladder stones after endoscopic sphincterotomy for common bile duct stones.
Candidates when experienced surgeons are available: Patients with acute gallstone pancreatitis that has subsided. Severely obese patients Patients with prior surgery in the upper abdomen. Patients with severely infected gallbladders. Pregnant women with symptomatic gallstones.	Seriously ill patients with acute cholecystitis who do not respond to fluid aspiration (percutaneous cholecystostomy).


Endoscopic Retrograde Cholangiopancreatography (ERCP)	Laparoscopic Common Bile Duct Exploration	Open Common Bile Duct Exploration (Choledocholithotomy)
Before gallbladder surgeries when there is strong suspicion that common bile duct stones are present. After gallbladder surgeries in which the surgeon detects stones in the common bile duct (only if there are experts in ERCP and equipment is available). For patients with gallstone cholangitis (serious infection in the common bile duct). In such cases urgent ERCP plus antibiotics is required. When acute pancreatitis is caused by gallstones. In such cases urgent ERCP plus antibiotics is required. (The use of ERCP compared to conservative treatment has been controversial. One study reported that only patients who had infection and persistent obstruction in the ducts benefited from urgent ERCP intervention. In a 2000 analysis of four studies, however, ERCP significantly improved survival rates and reduced complications.)	As an alternative to ERCP before gallbladder surgeries when there is high suspicion of common bile duct stones. (Should be performed only in centers with expertise in this procedure, where it may actually be preferable to ERCP.) During gallbladder surgeries when common duct stones are detected or highly suspected. (Only for centers with expertise in this procedure.)	During or after some gallbladder operations when stones are detected. If procedure is laparoscopy, surgeon may convert to open procedure. Less often used now. When ERCP or laparoscopic procedures are not available.


Situation	Chance of Dosing
Sitting and reading	(Indicate a score of 0 to 3) 0 = no chance of dozing 1 = slight chance of dozing 2 = moderate chance of dozing 3 = high chance of dozing
Watching TV	(Indicate a score of 0 to 3) 0 = no chance of dozing 1 = slight chance of dozing 2 = moderate chance of dozing 3 = high chance of dozing
Sitting inactive in a public place	(Indicate a score of 0 to 3) 0 = no chance of dozing 1 = slight chance of dozing 2 = moderate chance of dozing 3 = high chance of dozing
Riding as a passenger in a car for an hour without a break	(Indicate a score of 0 to 3) 0 = no chance of dozing 1 = slight chance of dozing 2 = moderate chance of dozing 3 = high chance of dozing
Lying down to rest in the afternoon when circumstances permit	(Indicate a score of 0 to 3) 0 = no chance of dozing 1 = slight chance of dozing 2 = moderate chance of dozing 3 = high chance of dozing
Sitting and talking to someone	(Indicate a score of 0 to 3) 0 = no chance of dozing 1 = slight chance of dozing 2 = moderate chance of dozing 3 = high chance of dozing
Sitting quietly after a lunch without alcohol	(Indicate a score of 0 to 3) 0 = no chance of dozing 1 = slight chance of dozing 2 = moderate chance of dozing 3 = high chance of dozing
Sitting in a car while stopped for a few minutes in traffic	(Indicate a score of 0 to 3) 0 = no chance of dozing 1 = slight chance of dozing 2 = moderate chance of dozing 3 = high chance of dozing
Score Results 1-6: Getting enough sleep. 4-8: Tends to be sleepy but is average. 9 and over: Very sleepy and suggestive of sleep-disordered breathing. Patient should seek medical advice.


Symptoms	Ulcerative Colitis (UC)	Crohn's Disease (CD)
Diarrhea	Recurrent diarrhea is very common, but onset may be very gradual and mild or it may not be present. Feces may also contain mucus.	Recurrent diarrhea is fairly common.
Rectal bleeding	Blood is almost always present in stools. It may be readily visible or visible using only a microscope (called occult blood).	Bleeding not as common as in UC, but can occur.
Constipation	Constipation can be a symptom of UC, but not as common as diarrhea. Can occur during flare-ups. May occur when the inflamed rectum triggers a reflex response in the colon that causes it to retain the stool.	Constipation in Crohn's disease is usually a symptom of obstruction in the small intestine.
Abdominal symptoms	Pain is not prominent symptom, but can vary. May cause vague discomfort in the lower abdomen, an ache around the top of the hipbone, or cramps in the middle of the abdomen. Severe pain can occur during flare-ups. Vomiting and nausea.	Hallmark symptom is recurrent episodes of pain in the lower right part of the abdomen or above the pubic bone. Often preceded by and relieved by defecation. Bloating, nausea, and vomiting may also occur. Intestinal pain may also be an indication of a serious condition, such as an abscess, or a perforation of the intestinal wall.
Fever	May occur with severe attacks.	Usually low-grade. Spiking fever and chills indicates complications.
Loss of appetite, weight loss, and impaired growth in children	Often not evident in mild or even moderately severe UC. Occasionally impairs growth in children and teenagers.	Common. Typical weight loss is 10 -20% of normal. Commonly impairs growth in children and teenagers.
Abnormal defecation: Increased frequency, a feeling of incomplete evacuation, and tenesmus (a painful urge for a bowel movement even if the rectum is empty). Fecal incontinence.	Symptoms may be mild or severe.	Can occur in active stages.
Anal ulcers and fistulas: (channels that can burrow between organs, loops of the intestine, or between the intestines and skin).	Almost never a symptom.	Fistulas and ulcers around the anus may be early symptoms of CD.
Neurologic or psychiatric symptoms	No.	May be early signs of Crohn's disease when accompanied by gastrointestinal problems.