FitSugar

Partner Yoga Pose: Shoulderstand on Bridge

FitSugar — Fri, 12 Sep 2008 10:00:00 -0700

Some partner yoga poses are a little more challenging than others like this one - Shoulderstand on Bridge. It requires strength for the person on the bottom to hold the Half Wheel and it also requires balance for the person on top to hold Shoulderstand. Since this pose involves one person being upside down, it also requires trust and communication. I love that this video shows both the man and woman taking turns and switching positions. It's common to think the woman wouldn't be strong enough to be on the bottom, but she is!

For detailed instructions on how to give this pose a try read more.

Partner #1 (guy) comes into Half Wheel (Bridge), with his elbows bent and his hands underneath his lower back.
Partner #2 (woman) stands at Partner #1's feet, holds onto his shins, and rests her shoulders on his thighs so her head hangs down. Partner #1 can gently squeeze Partner #2's head to add a little support.
Then Partner #2 lifts or jumps her feet up so her hips are over her shoulders and her spine is straight. When she feels stable, she straightens her legs and comes into Shoulderstand (or I think of it more as a supported Headstand).
Even though it seems like this pose is more challenging for the person on the top since she's working hard to stay balanced, the person on the bottom is also doing a lot of work to keep his thighs stable and hold his partner up. So it's important for both partners to talk to each other during this pose, and let the other person know if they need a break.
To release this pose, Partner #2 folds at her hips and places her feet gently back on the ground and stands up. Then they switch positions and try it again.

Fit's Tips: If you're a little nervous about falling over, have a trusted friend stand next to you so they can catch you in case you start to lose your balance.

Strike a Yoga Pose: Half Wheel

FitSugar — Tue, 04 Sep 2007 03:30:00 -0700

Backbending poses are great for opening your heart and chest, both figuratively and literally. I love this particular backbend because not only does it increase flexibility in your spine, but it also stretches out your shoulders and the back of your neck. Because it doesn't require a lot of energy, it has both a calming and energetic effect on the body and mind.

Sanskrit Name: Setu Bandha Sarvangasana
English Translation: Bridge Pose
Also Called: Half Wheel

Want to know how to get into Half Wheel? Then read more

Begin lying flat on your back with your arms along the sides of your body, with your palms facing down.
Bend your knees and place your feet flat on the floor. Walk your heels as close as you can to your bum, and turn your heels out slightly so the outside edges of your feet are parallel with the outside edges of your mat.
With your palms and feet pressing firmly into the ground, lift your hips up. Try to keep your thighs parallel.
Stay here, or clasp your hands together below your pelvis, extending through your arms. I like to rock my weight from side to side so that I can pull my shoulders in and bring my shoulder blades closer together.
Stay here for 5 or more deep breaths. Try to keep lifting the hips up as high as you can, and gaze towards your belly. You can watch to make sure you are doing ujayi breathing correctly. Your stomach should remain still, and you should be able to see your ribs expanding and contracting with each complete breath.
After you've had enough, gently drop your bum back onto the ground. You can repeat this pose again after taking a break, or stretch through your lower back by hugging your knees into your chest.

Fit's Tips: Half Wheel pose and the knee hug counterpose is great to do if you suffer from lower back pain.

Partner Yoga Pose: Double Bridge

FitSugar — Fri, 12 Jun 2009 09:00:00 -0700

If you're looking to increase flexibility in your neck and spine, half wheel is the pose to do. It also tones your glutes, hamstrings, and quads, so it's a great pose to include in your stretching routine. To make it slightly more challenging and offer support to a friend doing a modified shoulderstand, do this pose called double bridge.

To see a picture of how to get into this pose, read more.

Partner #1 (man) lies on his back, brings his feet over his head, and comes into Plow pose.
Partner #2 (woman) sits behind him with her knees bent. Both partners clasp hands.
Partner #1 lifts his legs up to the ceiling, bends his knees, and gently places the soles of his feet on his partner's knees. He presses firmly into her knees and lifts his hips up so his thighs and torso are in one straight vertical line.

Once Partner #1 is stable, Partner #2 lifts her hips off the floor, coming into Half Wheel.
They stay like this for at least five breaths, and then Partner #2 lowers her hips to the floor. Partner #1 comes back to Plow pose, and then Partner #2 does Plow. Partner #1 lowers his spine onto the floor, bends his knees, and places his feet on the floor. Now each partner is in position to switch roles and repeat the pose.

Source

How to Choose and Use an Exercise Ball

FitSugar — Fri, 17 Apr 2009 10:00:00 -0700

Yoga ball, exercise ball, gym ball, fitness ball - whatever you call it, it's a must have for all active people. An exercise ball can be used for both stretching and toning exercises, but if you're new to this piece of gym equipment, here are some things you should know.

When choosing an exercise ball, you should know they come in three sizes, depending on your height. Check the list below to see which size is right for you before purchasing one.

4'11" to 5'4" height: 55 cm ball
5'4" to 5'11" height: 65 cm ball
5'11" to 6' 7" height: 75 cm ball

Now that you know which size ball to use, here are some ways you can use it:

Use the ball as a weight bench. Lie across it on your back and do chest presses, tricep presses, or lying pec flies to work your upper body. Since you're using your legs to keep your body stable, you end up toning your glutes, quads, and hamstrings as well.

To see the other exercise ball ideas, read more.

Use it to elevate parts of your body. Raising your upper or lower body on a ball can help target specific muscle groups more effectively. Try doing push-ups or bridge leg lifts with a ball and you'll end up working many muscles at one time.
Do ab work. Crunches, abdominal twists, and bicycle crunches are so much more challenging on a ball, since lying on one engages your abs even before you start doing any exercises.
Do yoga and Pilates moves. You can tone and increase flexibility by using a ball to do basic poses and exercises. Do backbends and back strengthening exercises such as prone leg raises. A ball can also support your body weight to help you balance when trying challenging poses such as Scorpion.

Source

Cirrhosis

FitSugar — Wed, 08 Oct 2008 17:35:41 -0700

HEALTH GUIDE REFERENCE FROM A.D.A.M

Highlights

Drug Approval

In 2007, the Food and Drug Administration approved HepaGram B, an injectable immune globulin that can help prevent recurrence of hepatitis B following liver transplantation.

Primary Biliary Cirrhosis

Primary biliary cirrhosis is an autoimmune liver disease that increases the risk for liver cancer. According to a 2007 study, specific risk factors may help predict which patients with primary biliary cirrhosis are at particularly high risk of developing liver cancer. These risk factors include older age, being male, history of blood transfusion, and any signs of portal hypertension (high pressure of the blood in the portal vein, which leads to the liver) or cirrhosis.

Hepatitis C and Cirrhosis

Patients with cirrhosis who are infected with a particular hepatitis C genotype (1b) have a high risk of developing liver cancer, indicates a 2007 study. These patients should receive regular monitoring so that liver cancer can be detected in its earliest stages.
Interferon drug therapy can help reduce -- but not entirely eliminate -- the risk of liver cancer developing in patients with hepatitis C-related cirrhosis.

Hemochromatosis

Hemochromatosis, also called “iron overload,” is an iron disorder that increases the risk for cirrhosis. Hereditary hemochromatosis is one of the most common genetic diseases in the United States, and experts have debated whether all people should get screened for it. In 2006, the U.S. Preventive Services Task Force (USPSTF) released updated guidelines concerning hemochromatosis screening. The USPSTF does not recommend routine screening in the general population. However, people who have family histories of hemochromatosis, or who show signs or symptoms of this disorder, should get tested.

Encephalopathy

Lactulose, a drug that helps remove ammonia from the body, can help improve cognitive function and quality of life for people with hepatic encephalopathy, suggests a 2007 study. Hepatic encephalopathy, a complication of liver disease, affects the brain and nervous system.

Introduction

Cirrhosis is an irreversible result of various disorders that damage liver cells over time. Eventually, damage becomes so extensive that the normal structure of the liver is distorted and its function is impaired.

Cirrhosis is a chronic liver disease that causes damage to liver tissue, scarring of the liver (fibrosis - nodular regeneration), progressive decrease in liver function, excessive fluid in the abdomen (ascites), bleeding disorders (coagulopathy), increased pressure in the blood vessels (portal hypertension), and brain function disorders (hepatic encephalopathy). Excessive alcohol use is the leading cause of cirrhosis.

The disease process often takes the following path:

Scarring. The main damage in cirrhosis is triggered by scarring (fibrosis) that occurs from injuries due to alcohol, viruses, or other assaults. Normal clumps and form nodules around the scarred areas. The scar tissue and regenerated nodules act like small dams and alter the flow of blood and bile in and out of the liver.

Altered Blood and Bile Flow. The changes in blood and bile flow have significant consequences, with both the liver and other organs responding to the altered flow:

The spleen overproduces nitric oxide, a gas that causes blood vessels in the spleen to relax and open.
The small blood vessels and bile ducts in the liver itself, however, narrow (constrict). (Blood vessels in other organs, including the kidney, also narrow.)
Blood flow coming from the intestine into the liver is slowed by the narrow blood vessels. It backs up through the portal vein and seeks other routes.
New, abnormally twisted and swollen veins called varices form in the stomach and lower part of the esophagus in order to compensate for the backup blood.
Bile also builds up in the bloodstream, resulting in high levels of bilirubin, which causes a yellowish cast in the skin called jaundice.
Fluid buildup also occurs in the abdomen (called ascites), and swelling in the arms and legs is common.

Changes in Liver Size. The liver enlarges in the first phases of the disease. In advanced stages, the liver sometimes shrinks, a condition called postnecrotic cirrhosis.

The liver is the largest organ in the body. In the healthy adult, it weighs about 3 pounds. The liver is wedge-shaped, with the top part wider than the bottom. It is located immediately below the diaphragm and occupies the entire upper right quadrant of the abdomen.

Vital Functions. The liver performs over 500 vital functions. Damage to the liver can impair these and many other processes. Among them are the following:

Processing Healthful Nutrients. It processes all of the nutrients the body requires, including proteins, glucose, vitamins, and fats.

Bile Production. The liver produces bile, a green-colored fluid that helps the body absorb fats and fat-soluble vitamins. Bile is formed from bilirubin, a yellow-green pigment produced from the breakdown of hemoglobin, the oxygen-carrying component in red blood cells. Bile contains bile salts, fatty acids, cholesterol, and other substances. Bile travels from the liver to the gallbladder, where it is stored until after a meal. It is then secreted into the intestines where it helps digest fat.

Eliminating Toxins. One of the liver's major functions is to render harmless potentially toxic substances, including alcohol, ammonia, nicotine, drugs, and harmful by-products of digestion.

Recycling Blood. The liver and spleen removes old red blood cells from the blood. The iron contained in them is recycled in the bone marrow to make new red blood cells.

The Liver's Architecture. The vital processes the liver performs rely on well-organized liver architecture.

The Building Blocks. The basic building blocks of the liver are the following structures:

Bile ducts
Blood vessels
Working liver tissue (called the parenchyma)
Supportive (connective) tissue

The Architecture. The liver is a built on a framework of lobes:

The lobes. The liver is divided into two major lobes, a right and a smaller left, that are separated by tough, fibrous connective tissue.
The lobules. The liver's two major lobes contain about 100,000 smaller lobes, called lobules. Each lobule contains microscopic columns of liver cells and blood vessels. Bracing the corners of each lobule column are an artery and a vein that carry blood and a bile duct that drains bile.
The arteries and veins. The arteries bring oxygen-rich blood to nourish the liver cells. The veins supply the liver cells with blood containing the nutrients and toxins that the liver cells process. A central vein runs through each column and collects the processed blood from both sources. These veins join to form the hepatic vein.
The bile ducts. The bile ducts in the column corners collect bile draining from tiny canals around the liver cells. These ducts eventually join to form the large common bile duct that leads from the liver to the gallbladder.

The Liver's Blood Supply. The liver is rich in blood. It holds about a pint, or 13% of the body's supply. It is furnished with blood from two large vessels, the hepatic artery and the portal vein, and is drained of blood by the hepatic vein. (The word "hepatic" derives from the Latin word for liver.)

The hepatic artery. This artery supplies blood from the heart directly to the liver. This blood nourishes the liver.

The portal vein. The portal vein carries to the liver blood that has been circulating through the stomach, spleen, and intestine. The liver processes this blood, extracting nutrients and toxins.

The hepatic vein. This vein carries blood from the liver and connects to the inferior vena cava, a large vein that carries blood back to the heart.

Click the icon to see an image of the liver.

Causes

Several processes can lead to cirrhosis.

Alcoholism particularly endangers the liver. Alcoholic cirrhosis (also sometimes referred to as portal, Laennec's, nutritional, or micronodular cirrhosis) is the primary cause of cirrhosis in the U.S. It is estimated to be responsible for 44% of deaths from cirrhosis in North America. Some experts believe this estimate is low. One Canadian study found alcohol to be the major contributor in 80% of all cirrhosis deaths.

The relationship between alcohol and cirrhosis is generally as follows:

Alcohol is absorbed from the small intestine, and the blood carries it directly into the liver, where it becomes the preferred energy source.
In the liver, alcohol converts to toxic chemicals, such as acetaldehyde (AcH), which trigger the production of powerful immune factors called cytokines. These molecules in large amounts can cause inflammation and tissue injury. They are proving to be major culprits in the destructive process in the liver. AcH is particularly being researched because it plays a role in most actions of alcohol, including damaging effects on the liver that may lead to cirrhosis.
The injured liver eventually is unable to break down fatty acids, compounds that make up fat. Over time, then, fat accumulates, further impairing the liver's ability to absorb oxygen and increasing its susceptibility to injury. During the initial phase, the fat-laden liver becomes greatly enlarged, but it eventually shrinks as cirrhosis develops.

Chronic hepatitis, both hepatitis B and hepatitis C, is the second leading cause of cirrhosis. Chronic hepatitis C is the more dangerous form and accounts for one-third of all cirrhosis cases. About 5 - 20% of patients with chronic hepatitis C, and 5 - 10% of patients with chronic hepatitis B, eventually develop cirrhosis over the course of several decades. The longer a patient has had chronic hepatitis, the greater the risk for eventually developing cirrhosis. A 2005 study indicated that cirrhosis develops in 70% of patients who have had hepatitis C for more than 60 years.

The hepatitis virus can produce inflammation in liver cells, causing injury or destruction. If the condition is severe enough, the cell damage becomes progressive, building a layer of scar tissue over the liver. In advanced cases, as with alcoholic cirrhosis, the liver shrivels in size, a condition called postnecrotic or posthepatic cirrhosis.

Hepatitis C is a virus-caused liver inflammation which may lead to jaundice, fever, and cirrhosis. The people most at risk for contracting and spreading hepatitis C are those who share needles for injecting drugs and health care workers or emergency workers who may be exposed to contaminated blood.

Autoimmune liver diseases include autoimmune hepatitis and primary biliary cirrhosis. Like other autoimmune disorders, these conditions most likely develop because a genetically defective immune system attacks the body's own cells and organs. People who have one of these liver diseases also often have other autoimmune conditions, including systemic lupus erythematosus, rheumatoid arthritis, Sjögren syndrome, scleroderma, inflammatory bowel disease, glomerulonephritis, and hemolytic anemia.

Autoimmune Hepatitis. Autoimmune chronic hepatitis occurs when an abnormal immune response causes an attack on the liver cells. It accounts for about 20% of all chronic hepatitis cases. Autoimmune chronic hepatitis typically occurs in women age 20 - 40 who have other autoimmune diseases. Some research indicates that the postmenopausal period may be another peak in incidence of AIH among women. About 30% of patients are men, however, and in both genders there is often no relationship to another autoimmune disease. In general, no major risk factors have been discovered for this condition.

Suspects for triggering this hepatitis include the measles virus, a hepatitis virus, or the Epstein-Barr virus, which causes mononucleosis. It is also possible that a reaction to a drug or other toxin that affects the liver also triggers an autoimmune response in some people.

Click the icon to see an image of mononucleosis.

Primary Biliary Cirrhosis. Up to 95% of primary biliary cirrhosis (PBC) cases occur in women, usually around age 50. In people with PBC, the immune system attacks and destroys cells in the liver’s bile ducts. Like many autoimmune disorders, the causes of PBC are unknown. Recent research indicates the following risk factors:

Family history of PBC
Family history of Sjögren syndrome (another autoimmune disorder)
Individual history of urinary tract infections (UTI)
History of smoking
History of nail polish use
Hormone replacement therapy
Exposure to toxins from hazardous waste sites

This research suggests that environmental factors (chemicals, cigarette smoke) or infectious organisms (bacteria that causes UTI) may trigger PBC in patients who are genetically susceptible to the disease. Women who have never been pregnant appear less likely to develop PBC.

Nonalcoholic fatty liver disease (NAFLD) resembles alcoholic liver disease, but it occurs in people who do not drink a lot of alcohol. Obesity and type 2 diabetes are the two main causes of a fatty liver. Some evidence suggests that insulin resistance (the primary problem in type 2 diabetes) is a major factor in development of a fatty liver. A diet high in fatty foods may also be a risk factor, as dietary fat accumulates in the liver. Due to the recent rise in childhood obesity, NAFLD is increasingly occurring in children. In fact, NAFLD is now the most common liver disease in American children.

Nonalcoholic fatty liver disease can lead to nonalcoholic steatohepatitis (NASH). Liver inflammation and injury, as well as a fatty liver, characterize NASH. NASH occurs in about half of people with diabetes and up to 75% of obese people.

Nonalcoholic fatty liver disease is usually benign and very slowly progressive. But, in certain patients it can lead to cirrhosis, liver failure, or liver cancer. About 8 - 20% of people with nonalcoholic steatohepatitis go on to develop cirrhosis. A 2006 study indicated that NASH-related cirrhosis causes fewer deaths than cirrhosis that is caused by chronic hepatitis C. However, many patients with NASH have coronary artery disease and heart failure and have a high risk of dying from heart disease.

Weight reduction and diabetes and cholesterol management are the primary approaches to controlling these diseases.

Hemochromatosis is a disorder of iron metabolism. This disease interferes with the way the body normally gets rid of iron. People with hemochromatosis absorb too much more iron from the food that they eat. The iron overload accumulates in organs in the body. When excess iron deposits accumulate in the liver, they can cause cirrhosis.

There are two main forms of hemochromatosis:

Primary hemochromatosis, also called hereditary hemochromatosis, is an inherited genetic disease.
Secondary hemochromatosis results from other conditions, such as anemia and alcoholism.

Hereditary hemochromatosis is one of the most common genetic diseases, especially among Caucasians. About 1 in every 200 Americans carries the gene that causes this disease. Although experts do not recommend that everyone get screened for hemochromatosis, people who have a family history of this disease, or who show symptoms (joint pain, fatigue, abdominal pain), should get tested. Left untreated, hemochromatosis can lead to serious damage of the liver, heart, and pancreas.

Hemochromatosis is treated with phlebotomy, a procedure that involves removing about a pint of blood once or twice a week. Starting phlebotomy treatment before organ damage occurs can help prevent cirrhosis. If, however, cirrhosis has already developed, patients have a high risk for developing liver cancer even if iron levels are normalized.

Inherited Diseases. Cirrhosis can be caused by several inherited diseases, including:

Cystic fibrosis
Alpha-1 antitrypsin deficiency
Galactosemia
Glycogen storage diseases
Wilson's disease

Other Rare Causes. Rare causes of cirrhosis include:

Schistosomiasis, caused by a parasite found in the Far East, Africa, and South America.
Small intestine bypass surgery (rarely, if ever, performed anymore).
Long-term or high level exposure to certain chemicals and drugs can cause cirrhosis, including arsenic, methotrexate, and toxic doses of vitamin A.

Cancers that have metastasized to the liver, blood clots in the hepatic or portal vein, or obstructions in the bile duct can cause changes that resemble cirrhosis.

Risk Factors

Cirrhosis affects about 3 million Americans a year. However, because about 2.7 - 4 million people harbor hepatitis C, the rates of cirrhosis could dramatically increase over the next few years.

Only 10% of heavy drinkers develop advanced liver disease. Not eating when drinking and consuming a variety of alcoholic beverages are factors that increase the risk for liver damage. Still, the amount of alcohol consumed and the patterns of drinking are only weak predictions of risk. Other risk factors have been identified that may increase the danger to the liver:

Obesity is a major factor for all stages of liver disease.
Women develop liver disease at lower quantities of alcohol intake than men. The reason for this may be due to women's inability to metabolize alcohol as quickly as men, so it stays in the bloodstream longer.
Genetic factors that regulate the immune responses in the intestine also play a role in increasing the risk for liver injury from alcoholism.

Risk Factors for Developing Cirrhosis from Hepatitis C. Overall, between 10 - 15% of patients with chronic hepatitis C develop cirrhosis. The risk varies widely, however. The following conditions put people with hepatitis C at higher risk for liver damage:

Overall the risk for progression is highest in men -- particularly African-Americans -- who were older at the time of infection. The risk is much lower in women and children (2 - 4%).
Moderate-to-heavy alcohol users. (Even one or two alcoholic drinks a day increase the risk for liver injury in hepatitis C patients.)
Having a specific genetic type of the virus. There are six main genetic types and more than 90 subtypes, which can differ significantly in their effects and response to treatment. Genotype 1 is the most serious and is the cause of up to three quarters of the cases in the U.S. The other common forms are types 2 (15%) and 3 (7%), which pose less danger.
Co-infection with hepatitis B. Co-infection with B significantly affects the outcome of these patients and may be more common than previously believed. This co-condition may cause superinfections with very serious consequences, reduce these patients' responses to interferon therapy, and increase their risk of liver cancer. Patients with hepatitis C should be immunized against hepatitis B.
Co-infection with HIV.
A history of transfusions. (In one report, the risk in middle-aged patients with a history of transfusions was 20 - 30%).
Being diabetic and overweight, particularly if fat is distributed in the abdomen (an apple-shape). This condition poses a higher risk for nonalcoholic fatty liver disease (NASH), which in turn is apt to become scarred and cirrhotic.

Weight gain in the area of and above the waist (apple type) is more dangerous than weight gained around the hips and flank area (pear type). Fat cells in the upper body have different qualities than those found in hips and thighs.

Having large iron stores in the liver.
High exposure to toxic chemicals or environmental contaminants.

Because there are millions of Americans now infected with chronic hepatitis C, doctors have been justifiably concerned that there will be a significant number of cases of liver failure and liver cancer in the coming years. Computer analyses have suggested that mortality rates from hepatitis C-related cirrhosis or liver cancer will double or triple over the next 20 years. Fortunately, improved therapies may significantly reduce these discouraging estimates.

Researchers are working on developing a genetic test to identify patients with chronic hepatitis C who are most at risk of developing cirrhosis. In 2007, scientists announced they had made progress on a test that measures variations in seven genes to calculate a “Cirrhosis Risk Score.” The researchers hope that this experimental test may eventually help doctors decide which patients should receive early treatment with alpha-interferon and ribavirin.

Risk Factors for Developing Cirrhosis from Hepatitis B. The great majority of people with chronic persistent hepatitis B have a good long-term outlook. Between 5 - 10%, however, become carriers of the virus, and 5 - 10% of these individuals eventually develop cirrhosis. The addition of hepatitis D is a particular danger and increases the risk for cirrhosis. Seven genetic types of hepatitis B virus (designated A to G) have now been identified, which may help researchers determine the patients who may have a better outlook than others. Genotype C is the most common form and is more aggressive than genotype B, which also responds better to treatment.

Primary biliary cirrhosis accounts for only 0.6 - 2% of deaths from cirrhosis. In patients with chronic persistent autoimmune hepatitis, the outlook is very favorable, and survival rates are equal to the general population. If it becomes active, it must be treated. Left untreated, the 5-year survival rates of primary biliary cirrhosis are 50%.

Obesity increases the risk for nonalcoholic fatty liver disease (NAFLD), a condition that can lead to nonalcoholic steatohepatitis (NASH). Studies estimate that 8 - 20% of people with NASH eventually develop cirrhosis. A 2006 study found that people with NAFLD and elevated liver enzymes have a high risk of developing end-stage liver disease. People with NASH had an especially poor prognosis for survival. Losing weight is important for overweight people with NASH and may help to delay disease progression. A 2003 study of more than 11,000 patients indicated that obesity increases the risk of death from cirrhosis in people who drink little or no alcohol, but not among those who drink alcohol.

Symptoms

Many people experience few symptoms at the onset of cirrhosis.

Early symptoms include:

Fatigue and loss of energy.
Loss of appetite and nausea.
Spider angiomas may develop on the skin. These are pinhead-sized red spots from which tiny blood vessels radiate.

Patients in later stages may develop the following symptoms:

Jaundice. This yellowish cast to the skin and eyes occurs because the liver cannot process bilirubin for elimination from the body.

Jaundice is a condition produced when excess amounts of bilirubin circulating in the bloodstream dissolve in the subcutaneous fat (the layer of fat just beneath the skin), causing a yellowish appearance of the skin and the whites of the eyes. With the exception of normal newborn jaundice in the first week of life, all other jaundice indicates overload or damage to the liver, or inability to move bilirubin from the liver through the biliary tract to the gut.

The palms of the hands may be reddish and blotchy, a condition known as palmar erythema.
Loss of body hair.
Abnormalities in hormone-affected organs. In men with alcoholic cirrhosis, the testicles may atrophy, and their breasts may become swollen, sometimes painfully.
Ascites. A swollen belly is a sign of ascites, the most common major complication of cirrhosis, which occurs when fluid accumulates in the abdomen. Fever, abdominal pain, and tenderness when the belly is pressed indicate that the fluid is infected, but infection can occur without any symptoms.
Fluid buildup and swelling (edema) in legs.

People with primary biliary cirrhosis may have severe generalized itching and often develop small fatty yellow lumps called xanthomas on the eyelids, hands, and elbows. They may have an unpleasant condition called steatorrhea, in which the feces contain excessive fat, causing them to float and to be very foul smelling.

Click the icon to see an image of a xanthoma.

Complications

Cirrhosis is the eleventh leading cause of death by disease in the United States, killing more than 25,000 people each year. A damaged liver affects almost every bodily process, including the functions of the digestive, hormonal, and circulatory systems. The most serious complications are those associated with so-called decompensation, which occur when cirrhosis progresses. They include the following:

Bleeding and fluid buildup (ascites).
Infections.
Damage to the brain (encephalopathy). Impaired brain function occurs when the liver cannot detoxify harmful substances.

Liver cancer is also a long-term risk with cirrhosis.

Cirrhosis is irreversible, but the rate of progression can be very slow, depending on its cause and other factors. Five-year survival rates are about 85% and can be lower or higher depending on severity.

For example, alcoholics with cirrhosis who abstain can have a 5-year or more survival rate of as high as 85%. For those who continue drinking, the chance for living beyond 5 years is no higher than 60%.
In patients with hepatitis B or C, the 5-year survival rate after a diagnosis of cirrhosis is 71 - 85%.
About two-thirds of patients with primary biliary cirrhosis never develop symptoms and can have a normal lifespan. Once symptoms of liver damage, such as jaundice, occur, however, the average survival time declines. In one study of women diagnosed with primary biliary cirrhosis, about 36% developed symptoms over an 11-year period, and 11% either died or required liver transplantation.

Unfortunately, doctors are usually unable to determine when cirrhosis first occurred, which makes it difficult to determine prognosis.

In cirrhosis, liver cell damage slows down blood flow. This causes a backup of blood through the portal vein, a condition called portal hypertension. The effects of portal hypertension can be widespread and serious, including fluid buildup and bleeding.

Ascites and Fluid Buildup. Ascites is fluid buildup in the abdomen. It is uncomfortable and can reduce breathing function and urination. Ascites is usually caused by portal hypertension, but it can result from other conditions. Swelling can also occur in the arms, legs, and spleen. Although ascites itself is not fatal, it is a marker for severe progression. Once ascites occurs, only half of patients survive after 2 years. Some doctors refer to the phases of cirrhosis as preascitic and ascitic. Some doctors even believe that ascites signals the need for liver transplantation, particularly in alcoholic cirrhosis.

Variceal Bleeding. One of the most serious repercussions of portal hypertension is the development of varices, blood vessels that enlarge to provide an alternative pathway for blood diverted from the liver. In about two-thirds of patients, they form in esophagus. Varices pose a high risk for rupture and bleeding because of the following characteristics:

They are thin-walled.
They are often twisted.
They are subject to high pressure.
Internal bleeding from these varices (variceal bleeding) occurs in 20 - 30% of patients with cirrhosis. The risk of death from a single episode can reach 70%.

Bleeding commonly recurs within 2 weeks of the first episode, but after 6 weeks, the risk for recurrence is the same as for patients who have not had a bleeding event.

Factors that predict variceal bleeding include:

Ascites
Encephalopathy
Large veins

Factors that can increase the danger for a bleeding episode in high-risk individuals include the following:

Moderate-to-intense exercise
Bacterial infection
Certain times of the day. Eating increases portal pressure, and there is a greater risk for bleeding in the evening. A lesser but still significant risk occurs in the early morning.

It is important for patients to be screened for esophageal varices and treated with preventive beta blockers if they show signs of risk. Between 30 - 40% of patients with cirrhosis have bleeding. The risk of dying from this complication is 20 - 35%. Some doctors recommend that all newly diagnosed patients be screened using endoscopy. Screening should also be considered for all previously diagnosed patients who have not been screened but would benefit from preventive treatments.

Portal hypertension can cause several secondary complications, including kidney failure. Non-steroidal anti-inflammatory drugs, such as naproxen, may increase the risk for kidney failure.

Gastrointestinal bleeding can occur from abnormal blood clotting, which can be a result of a combination of complications associated with cirrhosis. They include vitamin K deficiencies and thrombocytopenia -- a drop in platelets (the blood cells that normally initiate the clotting process). Some research now suggests that thrombocytopenia itself may be associated with more advanced liver failure.

Bacterial infections are very common in advanced cirrhosis, and may even increase the risk for bleeding. Most bacterial infections, including those in the urinary, respiratory, or gastrointestinal tracts, develop when patients are in the hospital. Abdominal infections are a particular problem in cirrhosis and occur in up to 25% of patients with cirrhosis within a year of diagnosis.

Mental impairment is a common event in advanced cirrhosis. In severe cases, the disease causes encephalopathy (damage to the brain), with mental symptoms that range from confusion to coma and death. A combination of conditions associated with cirrhosis causes this serious complication:

Buildup in the blood of harmful intestinal toxins, particularly ammonia.
An imbalance of amino acids that affect the central nervous system.

Encephalopathy is often triggered by certain conditions, including:

Gastrointestinal bleeding
Constipation
Excessive dietary protein
Infection
Surgery
Dehydration

Alcoholics with cirrhosis are believed to be at higher risk for this complication than are nonalcoholic cirrhosis, but one study suggested that alcoholics simply tend to have more severe cirrhosis. Even minimal hepatic encephalopathy (MHE) can have detrimental effects on functional ability. One study suggested that MHE impairs the ability to safely drive a car, and that all patients with cirrhosis be tested for MHE.

Symptoms of Encephalopathy. Early symptoms of hepatic encephalopathy include forgetfulness, unresponsiveness, and trouble concentrating. Sudden changes in the patient's mental state, including agitation or confusion, may indicate an emergency condition. Other symptoms include bad fruity-smelling breath and tremor. Late stage symptoms of encephalopathy are stupor and eventually coma.

Hepatorenal syndrome occurs if the kidneys drastically reduce their own blood flow in response to the altered blood flow in the liver. It is a life-threatening complication of late-stage liver disease that occurs in patients with ascites. Symptoms include dark colored urine and a reduction in volume, yellowish skin, abdominal swelling, mental changes (delirium, confusion), jerking or coarse muscle movement, nausea, and vomiting.

People with cirrhosis have an increased risk for liver cancer. Hepatitis B and C themselves increase the risk for liver cancer, regardless of the presence of cirrhosis. Hepatitis B infection is the leading cause of liver cancer.

For hepatitis C-related cirrhosis, a 2007 study indicated that patients with cirrhosis who are infected with genotype 1b hepatitis C have a greater risk of developing liver cancer than patients infected with other types of hepatitis C genotypes. (Genotype 1 is the most common type of hepatitis C in the United States.)

People with primary biliary cirrhosis also face a high risk of liver cancer. According to a 2007 study, several factors can indicate the increased likelihood of developing liver cancer. These factors include older age, male gender, history of blood transfusion, and signs of portal hypertension or cirrhosis.

About 30% of patients with chronic liver disease develop osteoporosis (loss of bone density), which is twice the usual incidence. Patients with primary biliary cirrhosis have a particularly high risk for osteoporosis. Treating osteoporosis in patients with cirrhosis can be complicated. One study found that calcitriol (a form of vitamin D) is especially helpful in preventing bone loss in patients with cirrhosis.

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 may reduce and even reverse loss of bone density.

Nearly all patients with cirrhosis are insulin resistant. Insulin resistance is a primary feature in type 2 diabetes and occurs when the body is unable to use insulin. This hormone is important for delivering blood sugar and amino acids into cells and helps determine whether these nutrients will be burned for energy or stored for future use.

One study reported that nearly a quarter of patients with cirrhosis had gallstones.

Click the icon to see an image of gallstones.

They may also face a higher than average risk for certain abnormal heart rhythms. Peptic ulcers, sleep disorders, and respiratory problems are also more common in people with cirrhosis than in the general population.

Diagnosis

A physical examination may reveal the following in a patient with cirrhosis:

The cirrhotic liver is firm and often enlarged. The liver may feel rock-hard. (In advanced stages of cirrhosis, the liver may become small and shriveled.)
The left side can often be felt by the doctor when pressing on the abdomen.

If the abdomen is swollen, the doctor will check for ascites by tapping the flanks and listening for a dull thud and feeling the abdomen for a shifting wave of fluid.

Measuring Liver Enzymes (Aminotransferases). Enzymes known as aminotransferases, including aspartate (AST) and alanine (ALT), are released when the liver is damaged. Measurements of these enzymes, particularly ALT, are the least expensive and most noninvasive tests for determining severity of the underlying liver disease and monitoring treatment effectiveness. Enzyme levels vary, however, and are not always an accurate indicator of disease activity. (For example, they are not useful in detecting progression to cirrhosis.)

Radioimmunoassays. To identify a particular virus that may be causing hepatitis, blood tests called radioimmunoassays are performed. Typically, radioimmunoassays identify particular antibodies, which are molecules in the immune system that attack specific antigens. (Antigens are any molecules that the body considers threatening or dangerous, and can be targeted by antibodies.)

An antigen is a substance that can provoke an immune response. Typically antigens are substances not usually found in the body.

Some of these tests can pinpoint hepatitis antigens directly. These tests, however, have limitations:

There may not be enough antibodies for blood tests to detect for up to weeks or months after hepatitis develops. Blood tests that are taken too early, then, may miss these signs of infection.
Antibodies also persist after patients recover, so a positive antibody test can indicate a previous infection but does not necessarily determine if the infection is active.

The assays for individual hepatitis viruses may differ.

Polymerase Chain Reaction. In some cases of hepatitis C, a polymerase chain reaction (PCR), may be performed. A PCR is able to make multiple copies of the genetic material (the RNA) of the virus to the point where it is detectable.

Screening for Hepatitis C Virus. In 2004, the U.S. Preventive Services Task Force (USPSTF) recommended against routine screening for the hepatitis C infection in the general population due to low prevalence of the disease. In addition, it "found no evidence that screening for HCV infection in adults at high risk leads to improved long-term health outcomes" and found insufficient evidence to recommend for or against such screening. However, the USPSTF did advise testing in those with signs or symptoms of liver disease. The failure to recommend testing in the high-risk population goes against current recommendations made by the Centers for Disease Control and Prevention, the National Institutes of Health, and other professional organizations. In response to the study, published in the Annals of Internal Medicine, the American Association for the Study of Liver Diseases issued a statement saying that halting such screening would be a "terrible mistake with grave consequences," pointing out that the study itself underscored some key infection-related data that strongly emphasizes the need for screening in high-risk populations.

A liver biopsy is the only definite method for diagnosing cirrhosis. It also helps determine its cause, treatment possibilities, the extent of damage, and the long-term outlook. For example, hepatitis C patients who show no significant liver scarring when biopsied appear to have a low risk for cirrhosis.

The biopsy may be performed using various approaches, including:

Percutaneous Liver Biopsy. This approach uses a needle inserted through the abdomen to obtain a tissue sample from the liver. Various forms of needles are used, including those that use suction or those that cut out the tissue. If cirrhosis is suspected, a cutting needle is the better tool. This approach should not be used in patients with bleeding problems, and it must be used with caution in patients with ascites or severe obesity.

Click the icon to see an image of liver biopsy.

Transjugular Liver Biopsy. This approach uses a catheter (a thin tube) that is inserted in the jugular vein in the neck and threaded through the hepatic vein (which leads to the liver). A needle is passed through the tube, and a suction device collects liver samples. This procedure is risky but may be used for patients with severe ascites.
Laparoscopy. This procedure requires a small abdominal incision through which the doctor inserts a thin tube that contains small surgical instruments and a tiny camera to view the surface of the liver. This is generally reserved for staging cancer or for ascites with unknown causes.

Biopsies can be dangerous, so they cannot be performed on patients who have test results that indicate clotting problems, on those who have had previous liver biopsies, or who have ascites.

Certain blood tests are used to determine liver function. They include the following:

Serum albumin concentration. Serum albumin measures protein in the blood (low levels indicate poor liver function).
Prothrombin time (PT). The PT test measures in seconds the time it takes for blood clots to form (the longer it takes the greater the risk for bleeding).
Bilirubin. One of the most important factors indicative of liver damage is bilirubin, a red-yellow pigment that is normally metabolized in the liver and then excreted in the urine. In patients with hepatitis, the liver cannot process bilirubin, and blood levels of this substance rise, sometimes causing jaundice.

The results of these tests along with the presence of specific complications (ascites and encephalopathy) are used for calculating the Child-Pugh Classification. This is a staging system (A to C) that helps doctors determine the severity of cirrhosis.

Very high levels of serum alkaline phosphatase, an enzyme produced in the liver, and high levels of immune factors called mitochondrial antibodies are usually present in blood tests of patients with primary biliary blood cirrhosis. Bilirubin measurements appear to be important factors in determining its severity.

Fatty liver is suspected when a patient has elevated liver enzymes. The doctor will take imaging tests of the liver using ultrasound, computed tomography, or magnetic resonance imaging. A liver biopsy is the standard test for confirming a diagnosis of fatty liver disease and for distinguishing NAFLD from nonalcoholic steatohepatitis (NASH). Several studies in 2006 and 2007 suggested that a blood test for cytokeratin-18 (CK-18), a protein found in liver cells, may be an effective noninvasive approach for diagnosing NASH. Doctors hope that this simple blood test may eventually be able to replace liver biopsy.

Several imaging tests can be used to diagnose cirrhosis and its complications.

Imaging Techniques. Magnetic resonance imaging (MRI), computed tomography (CT), and ultrasound are all imaging techniques that are useful in detecting and defining the extent of cirrhosis. Such tests can reveal ascites, an enlarged spleen, an irregular liver surface, reversed portal vein blood flow, and liver cancer. Sometimes they can even detect abnormally large blood vessels in the liver. In some cases, images from ultrasound and CT can be misinterpreted as cancer. MRI is most useful for ruling out or confirming cancer.

Click the icon to see an image of an MRI scan.

Click the icon to see an image of a CT scan.

Liver Scans. Sometimes liver scans are performed using a small radioactive tracer and a special camera that records information provided by the tracer as it passes through the liver:

Arteriography uses dye injected into the hepatic arteries that show up on x-ray.
Splenoportography uses dye injected into the spleen, which allows the doctor to measure portal vein pressure. This procedure is risky.

Hepatic vein wedge pressure involves insertion of a catheter into the hepatic veins. The blood pressure in the veins of the liver is then measured. The result is an indicator of portal vein pressure. If pressure is high, cirrhosis is likely. A low measurement is a favorable sign.

Endoscopy. Some doctors recommend endoscopy for patients newly diagnosed with mild-to-moderate cirrhosis in order to screen for esophageal varices. (These are abnormal blood vessels in the esophagus that increase the risk for bleeding). In this test, a fiber optic tube is inserted down the throat. The tube contains tiny cameras to view the inside of the esophagus, where varices are most likely to develop. Endoscopy is the only procedure for detecting varices, but it is not clear if screening for varices in patients without severe cirrhosis is any more beneficial than simply putting them immediately on preventive drugs -- whether or not varices have been identified.

Paracentesis. If ascites is present, paracentesis is performed to determine its cause. This procedure involves using a thin needle to withdraw fluid from the abdomen. The fluid is tested for different factors to determine the cause of ascites:

Bacteria cultures and white blood cell counts. (These are used to determine the presence of infection.)
Protein levels. Low levels of protein in the fluid plus a low white blood cell count suggest that cirrhosis is the cause of the ascites.

The appearance of the fluid is helpful in determining problems:

A cloudy fluid plus a high white blood cell count means an infection is present.
Bloody fluid suggests the presence of a tumor.

Screening for Liver Cancer. Patients with cirrhosis are usually screened for liver cancer using ultrasound and tests for a substance called alpha-fetoprotein (AFP). It is not known whether such screening has much impact on survival, because it is not very sensitive and has a high rate of false positives (suggesting the presence of cancer when it is not actually present). Screening is not necessary in patients without cirrhosis.

Treatment

The only treatment for alcoholic cirrhosis is to stop drinking. Individuals with alcoholic cirrhosis are typically malnourished and require increased calories and rigorous nutritional support, which can improve survival rates.

Interferons Alone and in Combination with Ribavirin. Pegylated interferon combined with ribavirin is the gold standard treatment for chronic hepatitis C in both adults and children. It achieves response rates of up to 50% for patients infected with HCV genotype 1 (the most common genotype form in the U.S.) and up to 80% for patients infected with genotypes 2 or 3. Interferon alone is usually reserved for patients who cannot tolerate ribavarin.

A 2005 clinical trial of patients with chronic hepatitis C and cirrhosis found that interferon treatment reduced the risk of liver cancer and significantly improved chance of survival. The study emphasizes the importance and substantial benefits of interferon therapy. A 2007 study of patients with hepatitis C-related cirrhosis also indicated that interferon therapy can help reduce the risk of liver cancer and overall risk of death from liver disease.

A number of natural and synthetic interferons are available:

Natural interferons include interferon alfa-2a (Intron) and interferon alfa-2b (Roferon).
Pegylated interferons (PegINF) are long-acting formulations of interferon. They include alfa-2b (Peg-Intron) or alfa-2a (Pegasys). These drugs are used in combination with ribavarin (Copegus, Rebetol).
Alfacon-1 (Infergen), also called consensus interferon, is a genetically modified interferon. A combination of alfacon-1 with ribavirin is proving to help some patients who had been resistant to ribavirin with interferon.

A 2005 study suggested that some patients with hepatitis C genotypes 2 or 3 may be able to benefit from a shorter course of combination treatment (12 weeks) than the standard 24-week treatment duration. A shorter treatment time may reduce the risk of side effects. However, a 2007 study in the New England Journal of Medicine found that 16 weeks of combination therapy in patients with these genotypes did not work as well as the 24-week regimen. Given the significant side effects associated with combination pegylated interferon and ribavarin treatment, particularly anemia, researchers are actively investigating how to identify which patients may be able to succeed with shorter treatment duration.

PegINF combinations are proving to slow progression of scarring, and have even achieved improvement in some patients who already have cirrhosis. Whether the combination treatment protects against future liver cancer is still unclear. (A higher total dose, rather than a longer duration of treatment, may be the critical factor for protection.)

Side Effects of Combination Treatment. The side effects of the combination include those of both interferon and ribavirin. Interferon side effects may occur more often in the combination treatment. Combination treatment side effects may include:

Anemia occurs in about 22% of patients who take combination treatment versus 1% who take interferon alone. This complication is reversible and usually stabilizes after 1 - 2 months of treatment. However, some patients may become so anemic that they have to stop the medication. Since anemia can worsen heart disease, patients with a history of significant heart problems should not be treated with ribavirin. Other nucleoside analogues are being investigated that may have a lower risk for anemia than ribavirin.
Flu-like symptoms, such as fever, headaches, and muscle aches, are the most common side effect.
Reduced white blood cell count.
Skin disorders, such as dry skin and rash.
Coughing and shortness of breath.
Gastrointestinal symptoms (nausea, indigestion, lack of appetite).
Emotional and psychological symptoms, such as severe sleep disturbances, depression, irritability, and anxiety.
Combination treatment in pregnant women poses a very high risk for birth defects.

The current drugs used for hepatitis C still do not meet the needs of all patients. They are expensive, have significant side effects, do not work in half the patients who take them, and are unsuitable in many others. Investigation is ongoing to find better solutions. Drugs showing promise include:

Albinterferon alfa-2b (Albuferon). This long-acting form of interferon-alfa may have fewer side effects and require less dosing than pegylated interferons. It is currently being tested in combination with ribavarin in Phase II trials for patients with genotype 1 chronic hepatitis C.
Thymosin Alpha 1 (Zadaxin), also called thymalfasin, is a synthetic version of a peptide derived from the thymus gland (which is responsible for maturation of immune factors called T-cells). It is being used for hepatitis B and is under investigation for hepatitis C in combination with interferon.
Celgosivir. Celgosivir is a new type of antiviral drug, which blocks alpha-glucosidase, an enzyme involved in viral replication. Celgosivir is being studied in combination with pegylated interferon alfa-2b and ribavirin. The drug is derived from the Australian chestnut tree.
Eltrombopag (Revolade). Thrombocytopenia, reduced production of blood platelets, is a condition that affects patients with hepatitis C and cirrhosis. Patients with thrombocytopenia cannot tolerate standard antiviral therapy. Researchers hope that eltrombopag, a drug that stimulates platelet production, may help normalize platelet levels so that they can start antiviral drug treatment.
Statins. Statin drugs are used for the treatment and management of cholesterol. Researchers are studying whether they may help improve liver enzyme levels in patients with hepatitis C.

Of interest are studies using phlebotomy (which is simply drawing blood) to reduce iron levels. In one study, maintenance therapy with this procedure reduced liver inflammation and possibly slowed progression of cirrhosis.

An ounce of prevention is worth a pound of cure, and the phrase resoundingly holds true in the case of hepatitis B. Today, a vaccine against hepatitis B is available. It can prevent hepatitis B and, therefore, also prevent liver cancer. The American Academy of Pediatrics and the Centers for Disease Control and Prevention currently recommend that all babies born in the United States receive a hepatitis B vaccine at birth.

Six drugs are currently approved in the United States for treatment of chronic hepatitis B:

Peginterferon alfa-2a (Pegasys)
Interferon-alfa-2b (Intron)
Adefovir (Hepsera)
Lamivudine (Epivir)
Entecavir (Baraclude)
Telbivudine (Tyzeka)

These drugs block the replication of hepatitis B in the body. Some also help boost the immune system. A doctor will decide which drug to prescribe based on a patient’s age, disease severity, and other factors. Each drug has various advantages and disadvantages in terms of cost, efficacy, side effects, and likelihood of drug resistance. A combination of drugs may also be prescribed.

Peginterferon alfa-2a. Peginterferon alfa-2a (Pegasys) was approved in 2005 for treatment of chronic hepatitis B. (Peginterferon is also called pegylated interferon.) The drug was previously approved in 2002 for treatment of chronic hepatitis C. Pegasys prevents the hepatitis B virus from replicating and also helps boost the immune system. It is given as a weekly injection. Peginterferon is sometimes prescribed in combination with lamivudine (Epivir).

Interferon Alpha. For many years, interferon alfa-2b (Intron) was the standard drug for hepatitis B. The drug is usually taken by injection every day for 16 weeks. (It does not appear to help hepatitis D.) Unfortunately, even in hepatitis B, the virus recurs in almost all cases, although this recurring mutation may be weaker than the original strain. Administering the drug for longer periods may produce sustained remission in more patients while still being safe. Interferon is also effective in eligible children, although long-term effects are unclear.

Lamivudine, Entecavir, and Telbivudine. These drugs are classified as nucleoside analogs. Lamivudine (Epivir or 3TC) is an antiretroviral drug that is used to treat human immunodeficiency virus (HIV) as well as hepatitis B. Studies suggest that lamivudine reduces viral count in over half of hepatitis B patients who take it as sole therapy for about a year. It is less expensive than interferon-alfa and has fewer side effects, but may not work as well as interferon-alfa for long-term therapy. A major problem with lamivudine is the development of mutated viral strains that become resistant to the drug, particularly in areas where the virus is common. About 20% of patients who take lamivudine develop drug resistance.

In 2005, the Food and Drug Administration (FDA) approved entecavir (Baraclude) for treatment of adults with chronic hepatitis B. In clinical trials, entecavir worked better than lamivudine for treating hepatitis B. Entecavir appears to have less risk of drug resistance than lamivudine. Studies also suggest that it may be a good alternative treatment for patients who have developed resistance to lamivudine. Questions have been raised about the drug’s possible cancer risks. Ongoing studies are evaluating this risk.

In 2006, the FDA approved telbivudine (Tyzeka), the newest nucleoside analog drug, for treatment of chronic hepatitis B.

Adefovir. Adefovir (Hepsera) belongs to a class of antiviral drugs called nucleotide analogs. (Nucleotides are related to nucleosides but have a slightly different chemical structure.) Nucleotide analogs block an enzyme involved in the replication of viruses. Adefovir costs more than lamivudine, but may be effective against lamivudine-resistant strains of hepatitis B. The drug must be taken on a long-term basis. A 2006 study indicated that when patients stopped taking adefovir after 48 weeks, the hepitatis B virus resumed replication. Patients who took the drug for a longer period (144 weeks) continued to benefit from treatment. Another 2006 study indicated that for some patients, adefovir remains effective for up to 5 years, although resistance occurs in about 20% of patients.

Drug Warnings. In 2004, the FDA issued two drug warnings for patients with hepatitis B. The HIV drug tenofovir (Viread) should not be used to treat patients with HIV who are co-infected with hepatitis Bas the drug may increase hepatitis severity. The lymphoma drug rituximab (Rituxan) may reactivate hepatitis B. Patients with lymphoma should be screened for hepatitis B. In 2007, the FDA revised the label for entecavir (Baraclude); patients who are co-infected with hepatitis Band HIV should take entecavir only if they are also taking antiviral HIV drugs.

Emtricitabine is a nucleoside analog drug used to treat HIV and AIDS. It is being investigated for chronic hepatitis B.
Pegylated interferon alfa-2b (Peg-Intron) and alfa-2a (Pegasys) are approved for treatment of chronic hepatitis C. They are being investigated alone and in combination with other drugs, such as ribavirin (Copegus, Rebetol), for treatment of hepatitis B. The combination of pegylated interferon and ribavirin is the standard treatment for hepatitis C.
Thymosin Alpha 1 (Zadaxin), also called thymalfasin, is a synthetic version of a substance derived from the thymus gland (which is responsible for maturation of immune factors called T-cells). It appears to be safe for hepatitis B patients when used alone or in combination with interferon. It is approved in many countries, but not the United States.

Ursodeoxycholic Acid (UDCA) and Drugs Used to Slow Progression. At this time no medication can cure primary biliary cirrhosis. Ursodiol, ursodeoxycholic acid (Actigall), or UDCA has been the standard drug used for primary biliary cirrhosis. Several studies have reported that it slows progression and helps prevent the need for liver transplantation.

It has no effect on symptoms, including itching and fatigue. Some drugs, such as colchicine, corticosteroids, or immunosuppressants, are being investigated for use in combination with UDCA. Long-term controlled trials are needed to determine the value of UDCA alone or with other drugs.

Drugs for Itching. Itching is a major problem with this disease. Cholestyramine, taken with meals, is the first choice for relieving itching. Several other drugs have been used or investigated, including low doses of the drug naltrexone and phototherapy.

Drugs for Impaired Fat Absorption. Because primary biliary cirrhosis affects fat absorption, patients may need high doses or injections of important fat-soluble vitamins, including K, D, A, and E.

Treatment of Nonalcoholic Fatty Liver Disease. Weight loss is the most important method for managing nonalcoholic fatty liver disease (NAFLD) and preventing progression to nonalcoholic steatohepatitis (NASH) and, eventually, cirrhosis. Diabetes and cholesterol control are also important. Investigators are studying whether various drugs used to treat type 2 diabetes may help treat NAFLD and NASH.

Other research is focusing on antioxidant vitamins, such as vitamin E.

In 2005, the National Institutes of Health launched two trials to study treatment of nonalcoholic fatty liver disease and nonalcoholic steatohepatitisin adults and children. Children with NAFLD will receive vitamin E, metformin, or placebo. In the adult trial, patients with NASH will receive vitamin E, pioglitazone, or placebo.

Secondary Biliary Cirrhosis. Secondary biliary cirrhosis caused by blockage in the bile ducts can be relieved by surgery.

Autoimmune Hepatitis. Autoimmune hepatitis is treated with the corticosteroid prednisone and also sometimes immunosuppressants, such as azathioprine (Imuran).

Hemochromatosis. For hemochromatosis, weekly bleedings (phlebotomies) may be performed until iron levels are normal, then repeated as needed. If treatment is given before cirrhosis develops, life expectancy may be normal.

Wilson's Disease. D-penicillamine is the drug most used for Wilson's disease.

There are no current safe and effective therapies for liver scarring (fibrosis). However, recent insights into the cellular and molecular mechanisms responsible for scarring have led to the development of specific, antifibrotic drugs that target the primary injury and inhibit abnormal cell mechanisms. Such drugs, now in very early testing, could one day help prevent or reduce the progression of liver scarring or the progression to liver cancer.

Liver transplantation may be indicated for the following:

Patients who have developed life-threatening cirrhosis and who have a life expectancy of more than 12 years.
Patients with liver cancer that has not spread beyond the liver.

Survival rates after transplantation are similar among those who have hepatitis B, hepatitis C, or alcoholic liver disease. Current 5-year survival rates after liver transplantation are about 75%. Patients also report improved quality of life and mental functioning after liver transplantation. Patients should seek medical centers that perform more than 50 transplants per year and produce better-than-average results.

Unfortunately, there are many more patients waiting for liver transplants than there are available organs. Fortunately, more procedures are now being performed using liver tissue from a living donor. In these cases, surgeons replace the patient’s diseased liver with a part of the liver taken from a donor. The donor’s liver regenerates to full size within a few weeks of surgery, and the recipient’s liver also regrows.

Transplantation surgery generally takes 4 - 12 hours to perform, and patients stay in the hospital for up to 3 weeks after the surgery. Most patients return to normal or near-normal activities 6 - 12 months following the transplant. For the rest of their lives, patients need to take immunosuppressive medication to prevent rejection.

Liver Transplantation in Patients with Hepatitis. One of the primary problems with many hepatitis patients is recurrence of the virus after transplantation.

One study of patients with hepatitis C reported 5-year risks of 80% for viral recurrence and 10% for cirrhosis. A 2004 study found that the hepatitis C virus recurs with more severity with liver donations from living donors than livers taken from cadavers.
Viral recurrence is also high in patients with hepatitis B. In 2007, the FDA approved HepaGram B, an immune globulin, to prevent recurrence of hepatitis B after transplantation. Patients need to receive HepaGram B injections on a lifelong basis.

Liver Transplantation in Autoimmune Liver Diseases. Patients who require transplantation for primary biliary cirrhosis are those who develop major complications of portal hypertension and liver failure or who have poor quality of life and short survival without the procedure. Survival rates after transplantation are excellent.

The outlook is also good for patients who have autoimmune hepatitis who require a transplant. Survival rates are about 90% after 1 year, and 70 - 80% after 5 years. Rejection usually occurs in those patients whose immune systems are very compromised.

Liver Transplantation in Alcoholism. There is considerable controversy over whether liver transplantation should be performed in alcoholics with cirrhosis who are unlikely to abstain. One French study reported no differences in survival, transplant rejection, and other indicators of success and failure after transplantation between alcoholics and non-alcoholics and between alcoholics who abstained and those who relapsed after the procedure.

Click the icon to see an illustrated series detailing a liver transplant.

Lifestyle Changes

A healthy lifestyle is particularly important for people with cirrhosis.

Healthy Foods. Because important antioxidant vitamins are depleted in the cirrhotic liver, patients should maintain a diet rich in fresh fruits, vegetables, and whole grains.

Coffee and Tea. Coffee appears to help lower the risk of cirrhosis, especially among heavy drinkers. A 2006 study indicated that people who drank 1 - 3 cups of coffee a day reduced their risk of alcoholic cirrhosis by 40%. Those who drank 4 or more cups reduced their risk by 80%. Researchers think that there is some ingredient in coffee (other than caffeine) that is responsible for this apparent protection. Studies on tea have been mixed. Some studies report that tea also lowers the risk of chronic liver disease, while others have found no effect.

Antioxidant Supplements. There is some preliminary laboratory evidence that various antioxidant supplements -- including vitamin E, selenium, and S-adenosylmethionine (SAMe) -- may help protect against liver damage and cirrhosis. Supplements, however, are not recommended for people with liver disease except with the advice of a doctor. Some vitamins, such as vitamins D and A, are metabolized in the liver and can be toxic.

Iron Restrictions. Elevated iron levels have been associated with cirrhosis from many causes. Patients should avoid iron-rich foods, such as red meats, liver, and iron-fortified cereals, and should avoid cooking with iron-coated cookware and utensils.

Supplemental Nutritional Products. Supplemental nutritional beverages may be helpful, particularly for patients with both alcoholism and cirrhosis. In one study, patients with both alcoholism and cirrhosis drank Ensure every day as a supplement to their regular diet. After 6 months they showed significant improvement in many signs of overall health compared to those who did not consume the beverage.

Vitamin B1 (Thiamine). Thiamine binds to iron and helps reduce iron load in the liver. One small study suggested it may be helpful for patients with chronic hepatitis B. It is not known if it has any benefit for cirrhosis. Pork is high in the vitamin, but more healthful sources include dried fortified cereals, oatmeal, corn, nuts, cauliflower, sunflower seeds and vitamin pills.

Like most vitamins, vitamin B1 may be obtained in the recommended amount with a well-balanced diet, including some enriched or fortified foods.

Omega-3 Fatty Acids. Some research suggests that supplements of omega-3 fatty acids (found in fish oil and evening primrose oil) may help protect the diseased liver.

Click the icon to see an image of omega-3 fatty acids.

Protein and Soy. High-quality dietary protein may be especially helpful for patients with ascites and for repairing muscle mass, but excessive protein loads may trigger encephalopathy. Protein solutions have been devised that provide beneficial amino acids without including those that increase this risk. There is no limit on vegetable proteins, such as those from soy.

Salt Restriction. Restricting salt consumption to less than 2,000 mg a day is particularly important for patients with ascites. The less salt the better.

Zinc. In some studies, taking zinc supplements have lowered ammonia levels in some patients who were zinc-deficient, a common problem in cirrhosis. Zinc replacement may reduce frequency and severity of muscle cramps and may even help protect against encephalopathy.

Fluid restriction is not usually necessary, but patients with severe ascites should discuss limiting fluid with their doctors.

Exercise increases the risk for portal pressure and variceal bleeding. One study reported that taking a beta-blocker may reduce this risk, although patients should discuss this with their doctor.

Infections can have a severe impact on the liver. Although most respiratory infections generally affect only the lungs, one small study suggested influenza may directly affect the liver in patients with cirrhosis and exacerbate the disease process. Researchers in the study advise annual flu shots for people with cirrhosis.

Patients should be aware that manufacturers of herbal remedies and dietary supplements do not need FDA approval to sell their products. Just like a drug, herbs and supplements can affect the body's chemistry, and therefore have the potential to produce side effects that may be harmful. There have been several reported cases of serious and even lethal side effects from herbal products. Patients should always check with their doctors before using any herbal remedies or dietary supplements.

Among the natural substances being investigated for liver disease are ginseng, glycyrrhizin (a compound in licorice), catechin (found in green tea), SAMe, and silymarin (found in milk thistle).

Silymarin. Silymarin is a chemical found in the milk thistle herb. It is one of the most popular, and most studied, herbal remedies for liver disease. Some studies have indicated that silymarin may help improve liver enzyme levels. However, a 2005 review found that milk thistle did not help reduce deaths from liver disease caused by alcohol or hepatitis.

S-adenosylmethionine. S-adenosylmethionine (SAMe) is a chemical found in all parts of the body, which declines with age. It has been investigated for years in Europe for arthritis, depression, and liver disease. Some preliminary studies suggest it may provide some protection against liver damage and scarring and may improve survival rates in alcoholic patients with cirrhosis. It is very expensive, however, and as with all unregulated products, long-term side effects, drug interactions, and other factors are not fully known.

The following warnings are of particular importance for people with liver disease:

Kava kava (an herb used for anxiety and tension) can be toxic to the liver and cause severe hepatitis and even liver failure if taken excessively.

Abdominal Infections

Antibiotics are administered when fluid examination and tests for ascites indicate infection. For a first episode, the antibiotic cefotaxime is typically administered intravenously, requiring hospitalization. Treatment usually lasts 10 days, but research indicates that 5 days may be sufficient for certain patients. Some research indicates that the oral antibiotic ofloxacin may work as well with fewer complications, allowing patients to be treated at home.

In advanced cirrhosis, the risk for serious abdominal infection is high, and the antibiotic norfloxacin is often prescribed preventively against specific organisms that infect the abdominal cavity. One study reported, however, that patients who took norfloxacin became susceptible to Staphylococcal infections. Long-term treatments with norfloxacin or similar antibiotics may increase the risk for fungal infections after liver transplantation.

Encephalopathy

The first step in managing encephalopathy (damage to the brain) is to treat any precipitating cause, such as:

High ammonia levels
Bleeding
Low oxygen
Dehydration
Infection
Use of sedatives

Some studies indicate that manganese poisoning may be partially responsible for encephalopathy in cirrhosis. Studies are needed to determine if drugs that remove manganese improve this complication.

Ammonia is the leading toxin in causing encephalopathy related to cirrhosis. Mild encephalopathy is managed by directing therapy toward eliminating ammonia in the intestine:

The first step is to restrict animal protein, substituting meats and dairy products with vegetable protein, such as soy, and amino acid supplements.
Enemas, which clean out the intestine, may be effective.
Lactulose (Cephulac, Chronulac, Constulose, Duphalac, Enulose) and lactitol, known as disaccharides, help lower blood ammonia levels and have been shown to be effective in improving cognitive function and quality of life in people with mild encephalopathy.
Antibiotics, such as metronidazole, rifamycin, or neomycin, are effective in reducing levels of ammonia-producing bacteria in the intestine, although long-term use of these drugs can cause toxic side effects. Rifaximin (Xifaxan), another antibiotic, was approved in 2005 for treatment of hepatic encephalopathy.
L. acidophilus is the probiotic found in live culture yogurt. Researchers are studying whether L. acidophilus food or supplements can aid in improving liver and cognitive functions.
Researchers are investigating whether exercise can help remove ammonia from the body and improve encephalopathy.

Investigational Drugs. Certain drugs, such as rifaximin (Xifaxan) and flumazenil (Mazicon, Romazicon), are under investigation for treating encephalopathy. Flumazenil is typically administered to counteract the effects of sedatives.

Ascites

Nearly all patients with ascites (fluid accumulation in the abdomen) can benefit from the following measures:

Abstaining from alcohol. (Sometimes abstaining from alcohol is enough to improve this complication.)
Restricting salt.
Taking diuretics, usually spironolactone (Aldactone) and furosemide (Lasix). Previously, spironolactone was usually given alone, but experts now use it by itself only in patients with minimal fluid buildup. Patients should be monitored carefully for excessive and too-fluid loss, which can set off complications, including hypokalemia (dangerously low potassium levels), kidney failure, or encephalopathy. Weight loss from diuretics usually should not exceed 1 - 2 pounds per day, but there is no limit for patients with massive swelling.

Doctors often recommend bed rest for patients with ascites, but studies do not support its benefits. Restricting fluid is not usually necessary unless sodium levels in the blood are very low.

Patients with recurring ascites, or ascites that does not respond to standard diuretics after a month (refractory ascites), may require procedures to reduce fluid.

Large-Volume Paracentesis. Large-volume paracentesis is the current standard procedure and involves the following:

Large volumes of fluid are removed through a tube in the abdomen. Research indicates that 4 - 6 liters are usually effective and safe.
Albumin (protein) may be administered intravenously. This helps prevent a sudden drop in blood flow in the arteries. One study suggested that terlipressin, a drug that constricts blood vessels, may be as effective.
If the ascites does not respond to treatments, the patient may need paracentesis every 2 weeks or more frequently, and up to 10 liters may need to be removed.

Patients who need this procedure are probably not complying with dietary requirements.

Transjugular Intrahepatic Portosystemic Shunt. Studies have been mixed on whether transjugular intrahepatic portosystemic shunt (TIPS) improves survival without transplantation compared to large-volume paracentesis. An important 2003 study reported that although TIPS reduced the number of paracenteses, there was no improvement in survival rates. In addition, patients who were given TIPS had a higher risk for encephalopathy than those given large-volume paracentesis. In general, TIPS should be a second-line option for ascites that does not respond to diuretics.

Peritoneovenous Shunting. Peritoneovenous shunting is an older, more invasive, procedure involving insertion of a tube, or shunt, under the skin that routes the fluid from the abdomen into the jugular vein. The procedure can have serious complications, including infection, blood clots, encephalopathy, and rupture of blood vessels in the esophagus. It is now generally reserved for patients who are not candidates for repeat paracentesis or liver transplantation.

Hepatorenal syndrome can occur in patients with ascites. This is a life-threatening condition in which the kidneys fail in trying to compensate for altered blood flow in the liver. Studies suggest that terlipressin may be an effective treatment in combination with albumin for hepatorenal syndrome.

Researchers are testing certain drugs that may correct the imbalances in circulation that lead to portal hypertension and ascites. Of particular interest are drugs called nonpeptide vasopressin antagonists, also referred to as aquaretics. They may reverse the dilation in blood vessels that lead to salt and fluid retention.

The prognosis for patients with ascites is poor, even with intensive procedures. Liver transplantation should be considered for patients when ascites does not respond to treatments and when poor liver function or other complications, such as peritonitis or kidney failure, are present.

Bleeding Episodes

Preventing an Initial Bleeding Episode. About half of patients with mild-to-moderate cirrhosis have esophageal varices (enlarged veins in the esophagus). In such patients, the risk for bleeding within 2 years is as high as 35%. Bleeding is fatal in half of these patients. In general, experts recommend preventive drugs for such patients, even if they have not been screened with endoscopy -- the procedure needed to actually detect varices. Beta-blockers are the only medications to date that have some preventive effects, but others are under investigation.

Guidelines for Treating Bleeding Episodes. The doctor should first be certain that bleeding is caused by portal hypertension and ruptured varices and not by other conditions. For example, patients with cirrhosis are also at higher than average risk for bleeding peptic ulcers.

Saline or Ringers solution (a fluid and electrolyte replenisher) followed by red blood cells and plasma is administered immediately to replace lost blood.

The next step is to immediately achieve normal blood clotting (hemostasis) in order to stop the current bleeding episode and prevent early recurrence, which typically occurs 3 - 5 days after a bleeding episode.

In general it is a two-pronged approach using drugs and endoscopy procedures.

Drugs. Either octreotide or vasopressin are typically used to reduce portal pressure and blood flow.
Endoscopy. Endoscopy involves insertion of a thin tube containing a tiny camera followed by surgery to make repairs. Endoscopic sclerotherapy is the most common procedure. Emergency sclerotherapy is often used as first-line therapy for variceal bleeding, but a major 2002 analysis suggested that it is no more effective than drugs for stopping bleeding, and it has potentially serious adverse effects.

A combination of drugs and endoscopy is the best approach for stopping bleeding compared to endoscopy alone. It is not clear if there is any difference in long-term survival, however.

Prevent Bleeding Recurrence. Rebleeding is common after an episode. Beta-blocker drugs are typically used, although they are not effective for many patients.

Preventing Complications. The patient who is experiencing a bleeding episode is at high risk for other complications, including pneumonia, bacterial infections, and hepatic encephalopathy. Bacterial infections can also impair blood clotting. Preventive oral antibiotics are often problematic in these patients. One study suggested that intravenous ciprofloxacin may be helpful.

Beta-Blockers. Beta-blockers, typically propranolol (Inderal) or nadolol (Corgard), reduce the heart rate and can lower portal vein pressure in many patients and so reduce variceal bleeding. Carvedilol (Coreg), a newer drug, may be even more effective, but more research is needed. Beta-blockers are also used as a primary approach for prevention of recurring bleeding. Nevertheless, they fail to reduce portal pressure in nearly 40% of patients with cirrhosis. They may not be appropriate for patients with type 1 diabetes, asthma, emphysema, and chronic bronchitis. They must be taken for at least 2 years and most likely longer to sustain a survival advantage.

Other Drugs. Other drugs are being used or investigated, mostly in combination with beta-blockers, to reduce recurrence rates.

Isosorbide mononitrate is a nitrate, a type of drug commonly used for angina. Combinations with beta-blockers appear to prevent rebleeding more effectively than beta-blockers alone. It is not clear if the combination improves any other aspects of the disease. The nitrate may also be an alternative drug for patients who cannot tolerate beta-blockers. Studies have failed to show any survival advantage, however, when isosorbide mononitrate is used alone.
The diuretic spironolactone may be helpful in combination with a beta-blocker for reducing both ascites and rebleeding after an initial episode.
Angiotensin II receptor antagonists, including losartan (Cozaar), are being studied for lowering portal pressure.

Somatostatinand Similar Drugs. Somatostatin is a natural hormone that constricts blood vessels. This drug or synthetic derivatives (octreotide and vapreotide) may be more effective than the common procedure, endoscopic sclerotherapy, for controlling bleeding. No single drug is more effective than another. Their benefits for improving overall survival, however, are still uncertain, and a major analysis of current studies found no effects on survival rates with either octreotide or somatostatin.

Somatostatin, the natural hormone, controlled variceal bleeding in 87% of patients in one study, but it is short acting.
Octreotide (Sandostatin) is a derivative of somatostatin and is longer acting. It has largely replaced the older drug. It is very safe, even for heart patients, and has few serious side effects.
Vapreotide (Octastatin) also resembles somatostatin. One study concluded that a combination of vapreotide and endoscopic treatment is more effective than endoscopic treatment alone for controlling bleeding, but the combination therapy did not improve mortality rates at 42 days. The study suggested that these drugs should be taken for 5 days.

Vasoconstrictors. Vasoconstrictors narrow the blood vessels and reduce flow in the spleen. They are particularly effective when used with nitroglycerin.

Vasopressin (Pitressin) is the most commonly used vasoconstrictor. It poses a risk to the heart, however, and it is not clear whether it is actually helpful.
Terlipressin is a synthetic version of vasopressin that is proving to be as effective as sclerotherapy in controlling bleeding. It also lacks vasopressin's side effects and may prove to prolong survival and serve as a bridge for patients waiting for liver transplantation.

Endoscopic procedures use a tube inserted down through the esophagus, containing microcameras and tiny instruments. Endoscopy is used both to diagnose the disease and stop bleeding. The two standard procedures are band ligation and sclerotherapy. In general, a combination of drug therapies and an endoscopic procedure is the usual approach for preventing a bleeding recurrence.

Endoscopic Band Ligation. In endoscopic band ligation, latex bands are wrapped around the bleeding varices, shutting off the blood supply. It is the method of choice to control of bleeding and, in weekly sessions, to prevent rebleeding, because it has a lower risk for complications than sclerotherapy. Recurrence rates are higher with band ligation, however. Studies are mixed on whether weekly treatments with band ligation are any more effective in preventing rebleeding than beta-blockers plus isosorbide mononitrate. A combination of medications plus band ligation is under investigation.

Investigators are studying argon plasma coagulation (APC) after band ligation to prevent variceal recurrence and rebleeding. This procedure uses argon gas to deliver electric currents that coagulate and stop bleeding.

Endoscopic Sclerotherapy. Endoscopic sclerotherapy is only effective against bleeding in the esophagus. The endoscopic tube is inserted through the mouth. A sclerosant (a solution that toughens the tissue around the variceal blood vessels) is injected to stop the bleeding. The procedure is repeated over a period of 2 - 3 months. Repeat treatments appear to reduce rebleeding and death. Minor complications (usually ulcers in the mucus membranes) are common, and serious complications can occur (narrowing or perforation of the esophagus and leakage at the injection site.)

Balloon tamponade has been available for years, but it is now used only for bleeding that cannot be controlled by drugs or endoscopy. It uses a tube inserted through the nose and down through the esophagus until it reaches the upper part of the stomach. A balloon at the tube's end is inflated and positioned tightly against the esophageal wall. It is usually deflated in about 24 hours. Serious complications can occur, the most dangerous being rupture of the esophagus. Recurrence of bleeding is common.

Shunts are used for patients who are still bleeding in the esophagus after endoscopic sclerotherapy or who are bleeding in the stomach. Choices include the following:

Transjugular intrahepatic portosystemic shunt (TIPS)
A surgical shunt

Shunt operations usually eliminate variceal bleeding, but encephalopathy and shunt failure are frequent complications. Doctors do not recommend shunts as elective surgery for high-risk patients who are candidates for liver transplantation, since shunts make this operation more difficult.

Transjugular Intrahepatic Portosystemic Shunt.A transjugular intrahepatic portosystemic (or portal-systemic) shunt (TIPS) involves the following:

The patient only requires a local anesthetic and a sedative.
A long needle is inserted into the jugular vein in the neck and passed down through the vena cava, a large vein that conducts blood back to the heart. This serves to widen the vein.
The surgeon makes an incision in the hepatic vein in the liver and creates a connection to the portal vein.
A cylindrical wire-mesh stent is inserted into this connecting vein.
The stent now acts as a shunt, which reroutes blood around the scarred liver.

TIPS is a good choice for bleeding that is not controlled by endoscopy, particularly when it is performed shortly after a bleeding episode. It also reduces ascites.

It is not useful as the first choice for stopping an initial bleeding episode or for preventing rebleeding, however, since it poses a high risk for encephalopathy. This complication outweighs its benefits compared to endoscopy for initial treatment and to beta-blockers for preventing recurrence. Blockage or closure of the shunt can develop over time.

TIPS is generally recommended for only patients who:

Cannot tolerate sclerotherapy
Are unlikely or unable to comply with the repeated procedures necessary for sclerotherapy
Have poor blood circulation

Surgical Shunts. There are two types of surgical shunts:

A portal shunt, or portal systemic shunt. It was introduced in 1945 and was the first significant treatment for bleeding varices. It relieves pressure in the portal vein by surgically joining it to the inferior vena cava, a large vein that conducts blood back to the heart. It poses a high risk for encephalopathy and does not appear to improve survival, so is not used often.
A variation called the H-graft portacaval shunt is a partial shunt that is proving to be effective for treating bleeding. It controls bleeding in 90% of patients and has a lower encephalopathy rate than the complete portal shunt or TIPS. In fact, early studies report that it may have lower rates for transplantation and death than TIPS.
A distal splenorenal shunt (DSRS) preserves blood flow through the portal vein while relieving pressure on the varices by joining the left kidney vein to the splenic vein. (The splenic vein returns blood from the spleen and is one of two veins that form the portal vein.) Studies show that DSRS has similar mortality rates compared to the portal shunt but lower rates of encephalopathy afterwards. Patients with alcoholic cirrhosis fare worse with DSRS than nonalcoholic patients. It is probably best used as an elective operation in patients with good liver function who continue to bleed in spite of endoscopy.

Resources

www2.niddk.nih.gov -- National Institute of Diabetes and Digestive and Kidney Diseases
www.aasld.org -- American Association for the Study of Liver Diseases
www.liverfoundation.org -- American Liver Foundation
www.gastro.org -- American Gastrointestinal Association
www.cdc.gov/ncidod/diseases/hepatitis -- Centers for Disease Control and Prevention, Hepatitis
www.hepfi.org -- Hepatitis Foundation International
www.pbcers.org -- Primary Biliary Cirrhosis Organization
www.organdonor.org -- National Transplant Society
www.unos.org -- United Network for Organ Sharing
www.organdonor.gov -- US government organ donor site

References

Bruno S, Crosignani A, Maisonneuve P, Rossi S, Silini E, Mondelli MU. Hepatitis C virus genotype 1b as a major risk factor associated with hepatocellular carcinoma in patients with cirrhosis: A seventeen-year prospective cohort study. Hepatology. 2007 Aug 6; [Epub ahead of print]

Bruno S, Stroffolini T, Colombo M, Bollani S, Benvegnu L, Mazzella G, et al. Sustained virological response to interferon-alpha is associated with improved outcome in HCV-related cirrhosis: a retrospective study. Hepatology. 2007 Mar;45(3):579-87.

Ekstedt M, Franzen LE, Mathiesen UL, Thorelius L, Holmqvist M, Bodemar G, et al. Long-term follow-up of patients with NAFLD and elevated liver enzymes. Hepatology. 2006 Oct;44(4):865-73.

Huang H, Shiffman ML, Friedman S, Venkatesh R, Bzowej N, Abar OT, et al. A 7 gene signature identifies the risk of developing cirrhosis in patients with chronic hepatitis C. Hepatology. 2007 Aug;46(2):297-306.

Prasad S, Dhiman RK, Duseja A, Chawla YK, Sharma A, Agarwal R. Lactulose improves cognitive functions and health-related quality of life inpatients with cirrhosis who have minimal hepatic encephalopathy. Hepatology. 2007 Mar;45(3):549-59.

Suzuki A, Lymp J, Donlinger J, Mendes F, Angulo P, Lindor K. Clinical predictors for hepatocellular carcinoma in patients with primary biliary cirrhosis. Clin Gastroenterol Hepatol. 2007 Feb;5(2):259-64. Epub 2006 Dec 15.

U.S. Preventive Services Task Force. Screening for hemochromatosis: recommendation statement. Ann Intern Med. 2006 Aug 1;145(3):204-8.

Whitlock EP, Garlitz BA, Harris EL, Beil TL, Smith PR. Screening for hereditary hemochromatosis: a systematic review for the U.S. Preventive Services Task Force. Ann Intern Med. 2006 Aug 1;145(3):209-23.

Review Date:
8/31/2007
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

Carpal tunnel syndrome

FitSugar — Wed, 08 Oct 2008 17:34:56 -0700

In This Report

Highlights
Introduction
Symptoms
Causes
Risk Factors
Prognosis
Prevention
Diagnosis
Treatment
Surgery
Resources
References

HEALTH GUIDE REFERENCE FROM A.D.A.M

Highlights

Overview

Several medical conditions can increase the risk for, or even cause, carpal tunnel syndrome (CTS). Diabetes, hypothyroidism, rheumatoid arthritis, osteoarthritis, obesity, and pregnancy are the main conditions associated with CTS. Many of the underlying diseases that contribute to the development of CTS are also associated with more severe forms of CTS.

Most workers who use their hands and wrists repetitively are at risk for CTS. This is especially true if they work in cold temperatures and have medical conditions that make them susceptible to CTS.

Being overweight consistently turns up as a risk factor for CTS and may play a direct causal role in CTS.

Treatment News:

Several physical therapy techniques have been shown to improve hand strength and function in patients with mild-to-moderate CTS.
Short periods of traction have also been successful in producing long-term relief in patients who have failed other conventional treatments.
Injections of botulinum toxin (Botox) show promise in treating carpal tunnel syndrome.

Risk Factors:

A Swedish study of neurological diseases found CTS to be the second most commonly occurring nerve, nerve root, and nerve plexus disorder among siblings hospitalized with the same condition. Although the study could not distinguish between genetic and environmental causes, clusters of CTS in families may suggest an inherited predisposition.

Introduction

Carpal tunnel syndrome (CTS) is a disorder marked by weakness and pain in the hand and wrist. CTS occurs in the nerves of the hands -- not the muscles, as some people believe. The symptoms of CTS can be incapacitating.

To understand how carpal tunnel syndrome arises, it is important to know the parts of the hand and wrist that are involved.

The Carpal Tunnel. The carpal tunnel is a passageway that forms beneath the strong, broad transverse ligament. This ligament is a bridge that extends across the lower palm and connects the bones of the wrist (carpals), which form an arch below the tunnel.

The Median Nerve and Flexor Tendons. The median nerve and nine flexor tendons pass under the ligament bridge and through the carpal tunnel (similar to a river). They extend from the forearm and up into the hand:

The flexor tendons are fibrous cords that connect to muscles of the fingers (two to each finger) and one to the thumb. They allow flexing of the fingers and clenching of the fist.
The median nerve plays two important roles. It supplies sensation to the thumb, index, middle, and ring fingers, and to the flexor tendons. It provides function for the muscles at the base of the thumb (the thenar muscle).

The median nerve travels through a compartment in the wrist called the carpal tunnel. The ligaments that transverse the nerve are not very flexible. Any swelling within the wrist compartment can put excessive pressure on structures such as the blood vessels and the median nerve. Excessive pressure can constrict blood flow and cause nerve damage. The symptoms from the compression cause pain, loss of sensation, and decreased function in the hand.

It is not completely known how the process leading to carpal tunnel syndrome actually evolves, and how nerve conduction (the passing of the nerve signal) through the wrist becomes changed. In general, carpal tunnel syndrome develops when the tissues around the median nerve swell and press on the nerve. Early in the disorder, the process is reversible. Over time, however, the insulation on the nerves may wear away, and permanent nerve damage may develop.

The following events have been observed in the hands of people with carpal tunnel syndrome:

The protective lining of tendons (called the tenosynovium) swells within the carpal tunnel. Some research suggests that this swelling is caused by build-up of fluid (called synovial fluid) under the lining. Synovial fluid lubricates and protects the tendons.
The transverse ligament, the band of fibrous tissue that forms the roof over the median nerve, becomes thicker and broader.
The swollen tendons and thickened ligament compress the median nerve fibers, just as stepping on a hose slows the flow of water through it. The effect is to reduce blood flow and oxygen supply to the nerve, slowing the transmission of nerve signals through the carpal tunnel. Some cases of carpal tunnel syndrome may be due to enlargement of the median nerve rather than compression by surrounding tissues.

The result is pain, numbness, and tingling in the wrist, hand, and fingers. Only the little finger is unaffected by the median nerve.

Click the icon to see a depiction of carpal tunnel syndrome.

Symptoms

Symptoms of carpal tunnel syndrome usually progress gradually over weeks and months and sometimes years. Anyone with recurrent or persistent pain, numbness and tingling, or weakness of the hand should consult a doctor for a diagnosis. Symptoms often develop as follows:

Initial symptoms include pain in the wrist and hand. Symptoms commonly occur in both hands. (Even when only one hand is painful, the other hand often shows signs of nerve conduction abnormalities on testing.)
Early on, the patient also usually reports numbness, tingling, burning, or some combination on the palm side of the index, middle, and ring fingers. (Typically the fifth finger has no symptoms.) Such sensations may radiate to the forearm or shoulder.
Over time, the hand may become numb, and patients may lose the ability to feel heat and cold. Patients may experience a sense of weakness and a tendency to drop things.
Patients may feel that their hands are swollen even though there is no visible swelling. This symptom may actually prove to be an important indicator of greater severity.

Symptoms may occur not only when the hand is being used but also at night when the patient is at rest. Even in cases where work is suspected as the cause, symptoms typically first occur outside of work. In fact, the disorder may be distinguished from similar conditions by pain occurring at night after going to bed.

Causes

Biologic Causes. Carpal tunnel syndrome (CTS) is considered an inflammatory disorder caused by repetitive stress, physical injury, or medical conditions. It is often very difficult, however, to determine the precise cause of carpal tunnel syndrome. No tests are available to identify a specific cause. Except in patients with certain underlying diseases, the biologic mechanisms leading to carpal tunnel syndrome are unknown. Although an overactive immune response that causes inflammation and damage in the joints or muscles is responsible for a number of arthritic conditions, similar problems are not likely to play an important role in CTS. More likely, reduced blood flow and lack of oxygen are important in the process leading to progressive swelling and scarring.

Working Conditions versus Medical Problems. Although some studies suggest that more than half of CTS cases are associated with workplace factors, there is no strong evidence of a cause and effect relationship. In fact, most studies now strongly suggest that carpal tunnel syndrome is primarily associated with medical or physical conditions such as diabetes, osteoarthritis, hypothyroidism, and rheumatoid arthritis. CTS also tends to occur in people with certain genetic or environmental risk factors such as obesity, smoking, alcohol abuse, or significant mental stress. Of all nerve, nerve root, and nerve plexus disorders, CTS has one of the highest familial risks, implying some type of genetic origin. When such susceptible people are subjected to repetitive hand or wrist work, the risk for CTS can become significant. CTS, then, is very likely to be due to convergences of factors that lead to nerve damage in the hand.

Worker's Compensation and CTS. The issues surrounding workers' compensation are particularly troubling in determining accurately whether labor conditions cause carpal tunnel pain. CTS is a major contributor to workers' compensation cases.

High Force and Vibration. Even though medical and physical conditions may be the initial culprits leading to CTS, certain working conditions are especially related to nerve damage -- if not to pure cases of CTS. Work that involves high force or vibration is particularly hazardous, as is repetitive hand and wrist work in cold temperatures.

In addition to CTS, other disorders of hand and wrist result from these work-related movements. They include the following:

Hand-arm vibration syndrome -- tingling and numbing that persist even after the vibration stops
Cumulative trauma (repetitive stress) disorder
Overuse syndromes
Chronic upper limb pain syndrome

All of these problems are generally associated with repetitive and forceful use of the hands, resulting in damaged muscles and bones of the upper arms.

Psychosocial Factors in the Workplace. Studies indicate that psychosocial factors in the workplace, such as intense deadlines, a poor social work environment, and low levels of job satisfaction, are major contributors to carpal tunnel pain. Such psychosocial conditions are more likely to be important factors in contributing to CTS in office workers, although they also complicate the condition in workers whose work is primarily physical.

A number of medical conditions increase the risk for or even cause CTS. The main conditions associated with CTS are diabetes, hypothyroidism, rheumatoid arthritis, osteoarthritis, obesity, and pregnancy. Many of the underlying diseases that contribute to the development of CTS are also associated with more severe forms of CTS.

Diabetes. CTS is a very common feature of diabetic neuropathy, one of the major complications of diabetes. Neuropathy is decreased or distorted nerve function; it particularly affects sensation. Symptoms include numbness, tingling, weakness, and burning sensations, usually starting in the fingers and toes and moving up to the arms and legs. About 6% of patients with CTS have diabetes. A 2005 study reported that an estimated 85% of patients with type 1 diabetes develop CTS. Development of CTS was related to the patient's age and the length of time they had diabetes. The development of diabetes-related complications, such as kidney disease, is not related to the development of CTS in people with diabetes.

Autoimmune Diseases. In autoimmune diseases, the body's immune system abnormally attacks its own tissue, causing widespread inflammation, which, in many cases, affects the carpal tunnel of the hand. Such autoimmune diseases include rheumatoid arthritis, systemic lupus erythematosus, and hypothyroidism. Some experts believe that CTS may actually be one of the first symptoms in a number of these diseases. Studies also suggest that CTS patients with these disorders are more likely to have severe CTS that requires surgery.

Diseases that Affect Muscle and Bones. Arthritis, gout, and other medical conditions that damage the muscles, joints, or bones in the hand may cause changes that lead to CTS. In fact, in one 2000 study, susceptibility to muscle and bone diseases was the major risk factor for CTS in British women. Osteoporosis (loss of bone density), although not a direct cause of CTS, increases the risk for wrist fractures that can lead to CTS.

Injuries and Previous Surgeries. Injuries, fractures, and operations that affect the forearm, wrist, or hand may lead to CTS, sometimes many years after the event.

Structural Abnormalities. Inborn abnormalities in the bones of the hand, wrist, or forearm may contribute to CTS.

Chronic Kidney Insufficiency. People who undergo hemodialysis for chronic kidney damage often experience a build-up in the hand of a certain type of protein called beta 2-microglobulin. This build-up can result in CTS. The longer the person has been receiving hemodialysis, the greater the risk of CTS. Certain drugs and procedures (particularly one procedure called hemodiafiltration) are being investigated as having the potential to reduce microglobulin build-up. It is hoped such new methods will delay the need for carpal tunnel surgery in patients undergoing long-term hemodialysis.

Other Diseases. A number of other medical conditions may cause or increase susceptibility to CTS:

Down syndrome
Amyloidosis (a progressive disorder of the connective tissues)
Acromegaly (a disease that leads to abnormally large hands and feet due to excessive growth hormone)
Tumor on the median nerve (removal of the tumor often resolves the CTS in such cases)

Medications. According to case reports, a number of medications may increase the risk for temporary CTS. They include certain medications that affect the immune system (such as interleukin-2), and anticlotting drugs (such as warfarin). There has been conflicting evidence as to whether corticosteroids and hormone replacement therapy may increase risk. More research is warranted before a causal association can be established.

Bone dislocations and fractures can narrow the carpal tunnel, thereby exerting pressure on the median nerve.

Being overweight consistently turns up as a risk factor for CTS and may play a direct causal role on CTS. Greater body mass appears to reduce nerve flow speed into the hand. Obesity is also related to poor physical fitness, which may also increase risk. A 2005 analysis indicated that weight is strongly linked to the onset of CTS in patients under the age of 63 years, but may be a less important factor as they get older.

Hormonal fluctuations in women play a role in CTS. Such fluctuations may cause fluid retention and other changes in the body that cause swelling. Fluid retention is one reason that CTS may develop during pregnancy.

CTS is strongly associated with a family history of the disorder. Many of these cases can be attributed to physical characteristics or medical conditions associated with CTS, which also run in families. However, in one study, 17% of family clusters of CTS were not associated with any such medical conditions, suggesting the genetic factors may be important in some people. Carpal tunnel syndrome that develops in young people is most likely to have a genetic component.

A 2000 study suggested that some patients with CTS may have a genetic defect that produces higher levels of a certain collagen subtype. Collagen is the protein used to build all connective tissue, muscle, bones, and ligament. The collagen found in CTS patients tends to produce stiffness.

Other genetic factors that may contribute to this disorder include abnormalities in certain genes that regulate myelin, a fatty substance that serves as insulation for nerve fibers.

Risk Factors

Evidence suggests that about 3% of women and 2% of men will be diagnosed with carpal tunnel syndrome during their lifetimes, with peak prevalence in women older than 55. Still, determining how many people actually have CTS is very difficult. Many people report CTS symptoms and have normal test results. Other people have no symptoms and abnormal results. Furthermore, some evidence suggests that, after an apparent a decline in cases, the prevalence of CTS is rising.

A large 2005 study of more than 1,000 patients found that the severity of CTS was mild in 42% of patients, moderate in 18%, and severe in 40%. Patients were an average of about 48 years old. More than five times as many women then men participated in the study.

Older people are at higher risk than younger adults. It is very rare in children.

Many studies indicate that women have a significantly higher risk for carpal tunnel syndrome than men do. According to the National Institutes of Health, women are three times more likely than men to experience carpal tunnel syndrome. The explanation for this greater risk is unknown but may be related to the smaller size of women's carpal tunnel.

Hormonal changes appear to play a major role in CTS.

A 2005 study reported that 17% of pregnant women had CTS. Nearly one-quarter of those had it in both wrists. Early studies have presented conflicting reports regarding when CTS is most likely to occur during pregnancy. One found that most cases occurred in the third trimester, and weight gain increased the risk. Another concluded that CTS developed at any point during the pregnancy. New-onset CTS during pregnancy that is severe and persistent enough to require treatment is uncommon. Most cases go away on their own after delivery. However, in one study, 11% of women reported CTS six months after delivery, and 4.3% of them still had the condition a year afterward.

Breastfeeding has also been linked to flare-ups of inflammatory disorders such as CTS. Breastfeeding temporarily lowers the level of natural steroid hormones.

CTS has also been shown to increase during:

The postpartum period
Menopause

Other conditions that are more specific to women than men may increase their risk for carpal tunnel syndrome:

The hand-intensive nature of housework and typing may contribute to a higher incidence of CTS in women.
Women are also at a much higher risk for autoimmune disorders than men are; such disorders are significantly linked to CTS.

People with close relatives who have carpal tunnel syndrome have a higher risk of developing CTS themselves. This risk may be due to family histories of medical conditions associated with CTS, obesity, or genetic factors.

A number of illnesses, skeletal abnormalities, and injuries can predispose individuals to carpal tunnel syndrome, including autoimmune diseases and arthritic conditions.

At high risk are those whose occupations combine force and repetition of the same motion in the fingers and hand for long periods.

Virtually all workers who use their hands and wrists repetitively are at risk for CTS, particularly if they work in cold temperatures and have factors or medical conditions that make them susceptible.

Computer Users and Typists. Repetitive typing and key entry is highly associated with missing work due to CTS. The risk for CTS in this group, however, is still much lower than with occupations involving heavy labor. Although more than 10% of the computer users complain of CTS symptoms, the evidence implicating computer use as a major cause of CTS is weak. One small 2001 study reported that nerve conduction tests on frequent computer users showed the same rate of CTS (3.5%) as in the general population.

A 2003 study found an association between mouse-use (not keyboard use) and CTS. Typing speed may affect risk in some cases, however. For example, the fingers of typists whose speed is 60 words per minute exert up to 25 tons of pressure each day. In one study, typists with CTS struck the keys with greater force than those without the disorder. A large Danish study showed no increased risk of CTS among people who use computers at work. Another study of workers who used computers heavily (up to 7 hours per day) found no increased risk of CTS among them.

Other Very High-Risk Workers. Workers in the meat and fish packing industries and those who assemble airplanes have the highest risk for CTS, according to one study. Meat packers complained of pain and loss of hand function as long ago as the 1860s. Even today, the incidence of carpal tunnel syndrome in the meat, poultry, and fish packing industries may be as high as 15%. A 2005 study of automobile assembly workers found that the estimated annual rate of CTS ranged from 1 - 10%.

Musicians. Musicians are at very high risk for CTS and other problems related to the muscles and nerves in the hands, upper trunk, and neck. In one study, 20% reported CTS or other nerve disorders in the hands and wrists.

Highest to Lowest Numbers of CTS Events by Job. The following is a list of occupations published by the Bureau of Labor Statistics in 2002 rating workers with highest to lowest total numbers of CTS-related events:

Assemblers
Cashiers
Secretaries
General office clerks
Laborers, non-construction
Bookkeepers, accounting, and auditing clerks
Welders and cutters
Data-entry employees
Textile sewing machine operators
Order clerks
Supervisors and proprietors, sales occupations
Machine operators (unspecified)
Truck drivers
Insurance adjusters, examiners, and investigators
Electrical and electronic equipment assemblers
Packaging and filling machine operators
Janitors and cleaners
Bank tellers
Production inspectors, checkers, and examiners

SOURCES: Bureau of Labor Statistics, U.S. Department of Labor, April 2002

At Home and At Play. People who intensively cook, knit, sew, do needlepoint, play computer games, do carpentry, or extensively use power tools are at increased risk for CTS. Long-distance cycling may make symptoms of carpal tunnel syndrome worse.

Square Wrists. Some (but not all) studies have reported a higher risk for CTS in people with square wrists (the thickness and width are about the same) than in those with the more common rectangular wrists.

Palm Shape. In one study, patients with palms that were both shorter and wider than average, and who also had shorter third fingers, were more likely to have CTS than those without these hand characteristics.

Poor Upper Back Strength. Some researchers claim that poor upper back strength makes people more susceptible to poor posture and injuries in the upper extremities, including carpal tunnel syndrome.

Cigarette smoking slows down blood flow, so that smokers have worse symptoms and slower recovery than nonsmokers do. Increased alcohol intake has been associated with CTS in people with other risk factors.

Poor nutrition, previous injuries, and stress can increase one's risk for carpal tunnel syndrome. In addition, high levels of so-called “bad” cholesterol (low-density lipoprotein, or LDL) have also been linked to an increased risk of CTS.

Prognosis

Carpal tunnel syndrome can range from a minor inconvenience to a disabling condition, depending on its cause and persistence and the individual characteristics of the patient. Many cases of CTS are mild, and when symptoms are of short duration, they often resolve (disappear) on their own. Once a woman with pregnancy-associated CTS gives birth, for instance, the swelling in her wrists and other symptoms almost always subside. Proper treatment of other medical conditions that cause CTS can often help reduce wrist swelling.

In severe untreated cases, however, the thenar muscles at the base of the thumb may whither, and loss of sensation may be permanent. CTS can become so crippling that people can no longer do their jobs or even perform simple tasks at home.

Carpal tunnel syndrome exacts a psychological toll. Anyone who cannot use his or her hands is likely to be depressed and suffer from low self-esteem. People may suffer from daily pain. In severe cases, they may be unable to perform ordinary tasks, such as driving a car or carrying groceries. And equally or even more distressing, they may have to give up enjoyable sports and hobbies.

According to a 2005 report from the Bureau of Labor Statistics, among the major disabling diseases and illnesses, carpal tunnel syndrome was associated with the longest average time away from work (28 days).

Employees with CTS who try to work through the disorder often put more stress on the wrists to compensate for the weakness and pain. The end result is to make the condition worse and impair work performance.

Eventually, the worker with CTS may be forced to give up his or her livelihood. In one study, nearly half of all patients with CTS changed jobs within 30 months of an initial diagnosis. And because of the controversy surrounding the issue of carpal tunnel syndrome and workers compensation, it is not always certain that the worker will receive compensation payments.

Prevention

Because multiple factors may cause carpal tunnel syndrome, there is no single mode of prevention. Treating any underlying medical condition is certainly important. Simple common sense may help minimize some risk factors predisposing a person to work-related CTS or other cumulative trauma disorders. A patient can learn how to adjust the work area, handle tools, or perform tasks in ways that put less stress on the hands and wrists. Proper posture and exercise programs to strengthen the fingers, hands, wrists, forearms, shoulders, and neck may help prevent CTS.

Many companies are now taking action to help prevent repetitive stress injuries. In a major survey, 84% reported that they were modifying equipment, tasks, and processes. Nearly 85% were analyzing their workstations and jobs, and 79% were buying new equipment. It should be stressed, however, that there has been no evidence that any of these methods can provide complete protection against CTS. The optimal corporate approach, if possible, is to reallocate workers suffering from repetitive stress injuries to other jobs.

Altering the way a person performs repetitive activities may help prevent inflammation in the hand and wrist from progressing into carpal tunnel syndrome. For example, replacing old tools with ergonomically designed new ones can be very helpful.

Rest Periods and Avoiding Repetition. Anyone who does repetitive tasks should begin with a short warm-up period, take frequent breaks, and avoid overexertion of the hand and finger muscles whenever possible. Employers should be urged to vary tasks and work content.

A 2001 study conducted by the National Institute for Occupational Safety and Health reported that even taking multiple "microbreaks" (about 3 minutes each) reduces strain and discomfort without decreasing productivity. Such breaks may include the following:

Shaking or stretching the limbs
Leaning back in the chair
Squeezing the shoulder blades together.
Taking deep breaths

Good Posture. Good posture is extremely important in preventing carpal tunnel syndrome, particularly for typists and computer users.

The worker should sit with the spine against the back of the chair with the shoulders relaxed.
The elbows should rest along the sides of the body, with wrists straight.
The feet should be firmly on the floor or on a footrest.
Typing materials should be at eye level so that the neck does not bend over the work.
Keeping the neck flexible and head upright maintains circulation and nerve function to the arms and hands. One method for finding the correct head position is the "pigeon" movement. Keeping the chin level, glide the head slowly and gently forward and backward in small movements, avoiding neck discomfort.

Good Office Furniture. Poorly designed office furniture is a major contributor to bad posture. Chairs should be adjustable for height, with a supportive backrest. Custom-designed chairs, made for people who do not fit in standard chairs, can be expensive. However, the costs are often offset by the savings in medical expenses that follow injuries related to bad posture.

Voice Recognition Software. For CTS patients who must use a computer frequently, a variety of voice recognition software packages (ViaVoice, Voice Xpress, Dragon NaturallySpeaking, IListen) are now available, enabling virtually hands-free computer use.

Keyboard and Mouse Tips. Anyone using a keyboard and mouse has some options that may help protect the hands.

The tension of the keys should be adjusted so they can be depressed without excessive force.
The hands and wrists should remain in a relaxed position to avoid excessive force on the keyboard.
A 2003 study suggested that mouse-use poses a higher risk than keyboard use. Replacing the mouse with a trackball device and the standard keyboard with a jointed-type keyboard are helpful substitutions.
Wrist rests, which fit under most keyboards, can help keep the wrists and fingers in a comfortable position.
Some people recommend keeping the computer mouse as close to the keyboard and the user's body as possible, to reduce shoulder muscle movement.
The mouse should be held lightly, with the wrist and forearm relaxed. New mouse supports (ErgoCat) are also available that relieve stress on the hand and support the wrist.
Some people cut their mouse pads in half to reduce movement.

Innovative keyboard designs may reduce hand stress:

Alternative geometry keyboards (Microsoft Natural Keyboard, Apple Adjustable Keyboard) allow the user to adjust and modify hand positions as well as adjust key tension. Most have a split or "slanted" keyboard that places the wrists at an angle. Studies suggest they are useful in promoting a neutral position for the wrist.
The continuous passive motion (CPM) keyboard lifts and declines gently and automatically every three minutes to break tension on the hands and wrist. A report of a clerical worker with CTS who used this device found an overall improvement of 10 words per minute in the typing tests, a decrease in disability score and symptom severity, and an improvement in function.
A keyless keyboard (orbiTouch) is an innovative device that uses two domes. The typist covers the domes with his or her hands and slides them into different positions that represent letters.

The force placed on the fingers, hands, and wrists by a repetitive task is an important contributor to CTS. To alleviate the effect of force on the wrist, tools and tasks should be designed so that the wrist position is the same as it would be if the arms dangled in a relaxed manner at the sides.

No task should require the wrist to deviate from side to side or to remain flexed or highly extended for long periods.
The handles of hand tools such as screwdrivers, scrapers, paint brushes, and buffers should be designed so that the force of the worker's grip is distributed across the muscle between the base of the thumb and the little finger, not just in the center of the palm.
People who need to hold any tools (including pencils and steering wheels) for long periods of time should grip them as loosely as possible.
In order to apply force appropriately, the ability to feel an object is extremely important. Tools with textured handles are helpful.
If possible, people should avoid working at low temperatures, which reduces sensation in hands and fingers.
Power tools and machines should be designed to minimize vibrations.
Wearing thick gloves, when possible, may lessen the shock transmitted to the hands and wrists. One 2001 study found, however, that wearing gel-padded gloves clearly increased comfort but did not actually protect against compression-induced CTS.

Hand and wrist exercises may help reduce the risk of developing carpal tunnel syndrome. Isometric and stretching exercises can strengthen the muscles in the wrists and hands, as well as the neck and shoulders, improving blood flow to these areas. Performing the simple exercises described below for 4 to 5 minutes every hour may be helpful.

Wrists

Exercise 1.

Make a loose right fist, palm up, and use the left hand to press gently down against the clenched hand.
Resist the force with the closed right hand for 5 seconds. Be sure to keep the wrist straight.
Turn the right fist palm down, and press the knuckles against the left open palm for 5 seconds.
Finally, turn the right palm so the thumb-side of the fist is up, and press down again for 5 seconds.
Repeat with the left hand.

Exercise 2.

Hold one hand straight up shoulder-high with fingers together and palm facing outward. (The position looks like a shoulder-high salute.)
With the other hand, bend the hand being exercised backward with the fingers still held together and hold for 5 seconds.
Spread the fingers and thumb open while the hand is still bent back and hold for 5 seconds.
Repeat five times for each hand.

Exercise 3. (Wrist Circle)

Hold the second and third fingers up, and close the others.
Draw five clockwise circles in the air with the two finger tips.
Draw five more counterclockwise circles.
Repeat with the other hand.

Fingers and Hand

Exercise 1.

Clench the fingers of one hand into a fist tightly.
Release, fanning out the fingers.
Do this five times. Repeat with the other hand.

Exercise 2.

To exercise the thumb, bend it against the palm beneath the little finger, and hold for 5 seconds.
Spread the fingers apart, palm up, and hold for 5 seconds.
Repeat five to 10 times with each hand.

Exercise 3.

Gently pull the thumb out and back and hold for 5 seconds.
Repeat five to 10 times with each hand.

Forearms (stretching these muscles will reduce tension in the wrist)

Place the hands together in front of the chest, fingers pointed upward in a prayer-like position.
Keeping the palms flat together, raise the elbows to stretch the forearm muscles.
Stretch for 10 seconds.
Gently shake the hands limp for a few seconds to loosen them.
Repeat frequently when the hands or arms tire from activity.

Neck and Shoulders

Exercise 1.

Sit upright and place the right hand on top of the left shoulder.
Hold that shoulder down, and slowly tip the head down toward the right.
Keep the face pointed forward, or even turned slightly toward the right.
Hold this stretch gently for 5 seconds.
Repeat on the other side.

Exercise 2.

Stand in a relaxed position with the arms at the side.
Shrug the shoulders up, then squeeze the shoulders back, then stretch the shoulders down, and then press them forward.
The entire exercise should take about 7 seconds.

Diagnosis

Carpal tunnel syndrome (CTS) is most accurately diagnosed using the patients' descriptions of symptoms, and electrodiagnostic tests that measure nerve conduction through the hand. If electrodiagnostic testing is not available, then symptom descriptions and a series of physical tests are useful.

Diagnosing CTS, however, is not straightforward. Only a small fraction of patients exhibit all three factors necessary for a clear diagnosis:

Classic CTS symptoms
Specific physical findings
Abnormal electrodiagnostic test results

Many people have abnormal electrodiagnostic test results without classic symptoms or any symptoms at all. Furthermore, about 15% of the population has symptoms consistent with CTS, but most do not show test results indicating the disorder. In fact, in a 2001 study, some patients who had symptoms, but whose nerve and physical tests were normal, still experienced relief after CTS surgery.

Many cases of CTS are a combination of a medical problem exacerbated by repetitive stress factors at work. The patient should give the doctor a detailed history and description of any complaints, in any part of the body. The patient should report in detail any daily activities that require repetitive hand or wrist actions, abnormal postures, or other regular situations that could affect the nerves in the neck, shoulders, and hands. The patient should report whether the symptoms are more likely to appear at night, or after particular tasks.

Questionnaires. The use of specific questionnaires that score results are quite accurate in assessing the severity of the condition.

Hand Diagram. A diagram of the hand and wrist, usually divided into six regions, is a very useful diagnostic tool. Patients are asked to indicate where their symptoms are, including pain, numbness, or tingling, by locating the affected areas on the diagram. They may also be asked to rate the severity of their symptoms. A diagnosis is probable if at least two of fingers 1, 2, or 3 have these symptoms, and if there is pain in or near the wrist. CTS is possible if at least one of these fingers has symptoms. It is unlikely if there are no symptoms in these fingers, the palm, or the wrist.

One of the most important first steps in diagnosing CTS is to rule out any underlying medical disorders that may be contributing to the condition. Experts emphasize the need to fully examine patients presenting with symptoms of CTS. Relying only on CTS symptoms, and personal or work histories may result in the failure to detect (and thus properly treat) underlying medical conditions that could be serious. If the doctor suspects that an underlying medical condition may be exacerbating the symptoms, laboratory tests will be performed. The doctor may take an x-ray, for example, to check for arthritis or fractured bones.

Raynaud's Phenomenon. A diagram of the hand and wrist, usually divided into six regions, is a very useful diagnostic tool. Patients are asked to indicate the location of their symptoms -- including pain, numbness, or tingling -- by locating the affected areas on the diagram. They may also be asked to rate the severity of their symptoms. A diagnosis is probable if at least two of fingers 1, 2, or 3 have these symptoms, and if there is pain in or near the wrist. CTS is possible if at least one of these fingers has symptoms. It is unlikely if there are no symptoms in these fingers, the palm, or the wrist.

Arthritic Conditions. Arthritic conditions, including rheumatoid arthritis, gout, and osteoarthritis, can all cause pain in the hands and fingers that may mimic carpal tunnel disease. The treatment for these conditions, however, is different.

Muscle and Nerve Diseases. Any disease or abnormality that affects the muscles and nerves, including those in the spine, may produce symptoms in the hand that mimic carpal tunnel syndrome.

About 25% of patients with suspected work-related cumulative trauma or repetitive stress disorders have evidence of other conditions that resemble, but are not, carpal tunnel syndrome. A definitive diagnosis is often difficult. Most require treatments similar to those used for CTS: rest, immobilization, steroid injections, and even surgery if conservative management is unsuccessful.


Location	Description
The Median Nerve in Other Locations	Repetitive work can cause pressure on the median nerve in locations other than the wrist and can also affect other nerves in the arm and hand. The branch of the median nerve that runs through the palm of the hand can be damaged directly by repeated pounding or by the use of certain tools requiring a strong grip using the palm, such as needle-nosed pliers. The median nerve can also be pinched in the forearm.
Guyon's Canal Syndrome (Commonly called ulnar tunnel syndrome)	The ulnar nerve can, like the median nerve, can be trapped as a result of repetitive stress. When this nerve is trapped, the condition is sometimes referred to as ulnar tunnel syndrome. It is more correctly known as Guyon's canal syndrome, however, since this is the name of the passage through which the ulnar nerve passes. General symptoms are similar to carpal tunnel syndrome, but patients experience loss of sensation in the ring and little finger and in the outer half of the palm. It can be a separate problem, although it commonly occurs with CTS. In such cases, release surgery for CTS usually also relieves the ulnar nerve entrapment. The ulnar nerve can also be affected at the elbow.
De Quervain's Tenosynovitis	Tenosynovitis is swelling of the slippery covering of the tendons that move the thumb. When it causes pain on the side of the wrist and forearm right below the base of the thumb, it is known as De Quervain's tenosynovitis. (Finklestein's Test may help identify this. Make a fist that encloses the thumb, and bend the wrist sideways and down away from the thumb. If it causes pain, it is likely to be De Quervain's tenosynovitis.) It may be treated with splints or corticosteroid injections. In severe cases release surgery is effective.
Digital Flexor Tenosynovitis (Trigger or Snapping Finger)	Digital flexor tenosynovitis, commonly called trigger or snapping finger, is brought on when a tendon thickens, leaving the finger or thumb in a bent position. This disorder usually occurs when the tendons thicken and form a knot and may arise in those with hypothyroidism, diabetes, gout, rheumatoid arthritis, or connective tissue disorders. It can cause pain and a clicking sound when the trigger finger or thumb is bent and straightened. It can be effectively treated with corticosteroid injections.
Thoracic Outlet Syndrome	Thoracic outlet syndrome is caused by compression of nerves and blood vessels running down the neck into the arm. It can produce symptoms very similar to CTS. Other symptoms may include Raynaud's phenomenon (changes in sensation and temperature in the hand). The compression occurs at the first rib in the front of the shoulder. This may happen after an accident or simply from chronic slouching posture. A doctor may be able to diagnose the condition by detecting diminished blood flow in the arm as the patient raises the affected hand and turns his or her head toward the opposite side. Although the condition is uncommon, a correct diagnosis is important to differentiate it from CTS, since treatments differ. Surgery may be required to relieve pressure on the nerves and blood vessels.

The following findings are helpful in identifying carpal tunnel syndrome:

Less sensitivity to pain where the median nerve runs through to the fingers
Thumb weakness
Inability to tell the difference between one and two sharp points on the fingertips (this is a late sign of carpal tunnel)

Flick Signal. One important and simple test of carpal tunnel is the "flick" signal:

The patient is asked, "What do you do when your symptoms are worse?"
If the patient responds with a motion that resembles shaking a thermometer, then the doctor can strongly suspect carpal tunnel.

Testing for Thumb Weakness. Two questions are useful in determining thumb weakness:

Can the thumb rise up from the plane of the palm?
Can the thumb stretch so that its pad rests on the pad of the little finger pad?

Provocation Tests. Certain tests are conducted to produce symptoms:

Phalen's Test. In Phalen's test, the patient rests the elbows on a table and lets the wrists dangle with fingers pointing down and the backs of the hands pressed together. If symptoms develop within a minute, CTS is indicated. (If the test lasts for more than a minute even patients without CTS may develop symptoms.) This test may be particularly important in determining the severity of CTS and assessing the results of treatment.
Tinel's Sign. In the Tinel's sign test, the doctor taps over the median nerve to produce a tingling or mild shock-sensation.
Pressure Provocation Test. The doctor presses over carpal tunnel for 30 seconds to produce tingling or shock in the median nerve.
Tourniquet Test. This test employs an inflatable cuff that applies pressure over the median nerve to produce tingling or small shocks.
Hand Elevation Test. The patient raises their hand overhead for 2 minutes to produce symptoms of CTS. The test was recently proven to be accurate and may provide useful information when combined with the Tinel's and Phalen's tests.

Electrodiagnostic tests analyze the electric waves of nerves and muscles. These tests can help detect median nerve compression in the carpal tunnel.

Electrodiagnostic tests are the best methods for confirming a diagnosis of CTS at this time. Doctors who perform these tests should be certified by the American Board of Electrodiagnostic Medicine, which uses rigorous standards in qualifying doctors. Specific electrodiagnostic tests, called nerve conduction studies and electromyography, are the most common ones performed:

Nerve Conduction Studies. To perform nerve conduction studies, surface electrodes are first fastened to the hand and wrist. Small electric shocks are then applied to the nerves in the fingers, wrist, and forearm to measure how fast a signal travels through the nerves that control movement and sensation. In suspected cases of CTS, nerve conduction tests can identify over 85% of true carpal tunnel syndrome cases and eliminate 95% of those that are not true CTS. They are less accurate in identifying mild CTS, however. Patients should be sure their practitioners perform tests that compare a number of internal responses -- not just routine testing that records only the responses of muscles located in the palm at the base of the thumb), and those on the second or third fingers.

Nerve conduction tests can also detect causes of symptoms that mimic CTS but should be attributed to other problems, such as pinched nerves in the neck or elbow or thoracic outlet syndrome.

Electromyography. To perform electromyography, a fine, sterile, wire electrode is inserted briefly into a muscle, and the electrical activity is displayed on a viewing screen. Electromyography can be quite painful and is less accurate than nerve conduction. Some experts question, in fact, whether it adds any valuable diagnostic information. They suggest it be limited to unusual cases or when other tests indicate that the condition is aggressive and may increase the risk for rapid, significant injury.
Portable electrodiagnostic testing. Portable electronic devices (such as NC-Stat, Neurosentinel, and the Nervepace digital electroneurometer) are being evaluated for measuring nerve conductivity. They are relatively quick and easy to use on a large scale in an industrial facility. However, the Advancing Association of Neuromuscular and Electrodiagnostic Medicine maintains that these devices are experimental and are not effective substitutes for standard electrodiagnostic studies.

Limitations. Electrodiagnostic studies are not well standardized, and certain conditions can skew the results of either test:

Obesity can slow the speed of electrical conduction.
Anxiety can slow the speed of electrical conduction.
Women and the elderly normally have slower conduction times than younger adult men.
Temperature also affects nerve conduction speed. When undergoing testing, doctors should strictly control room temperature to lessen its impact.

Ruling out other causes is extremely important in order to avoid unnecessary surgery for CTS. Modifications and improvements of these tests are continually being made.

Note: People with abnormal results who have no CTS symptoms are at no higher risk for CTS than those with normal results and no symptoms.

A diagnosis of carpal tunnel syndrome may follow testing the affected hand for numbness, tingling, weakness or pain in specific areas. Muscle and nerve conduction tests may also help affirm or rule out carpal tunnel syndrome.

Ultrasound. Ultrasound imaging, a relatively inexpensive technique that uses sound waves, is showing promise. Studies indicate that it can identify up to 85% of CTS cases, and some suggest it is as effective as electrodiagnostic tests. It may be effective for ruling out other causes of hand pain, such as tendon injuries, tenosynovitis (swelling of the tendon lining), cysts, and blood clots in the median artery (a rare complication that can cause the sudden onset of CTS symptoms). However, results are mixed on its accuracy. Newer color Doppler ultrasound and other technological advances are improving the results achieved with this technique. A 2005 study comparing high-resolution ultrasonography with electromyography found that ultrasonography may be helpful for estimating the symptom severity and problems with nerve conduction.

MRI. Magnetic resonance imaging (MRI), an advanced imaging technique, is being adapted to distinguish weak nerve signals from surrounding tissue, so that eventually it may be able to precisely diagnose CTS. However, studies in 2002 note that it requires special expertise, has limited diagnostic accuracy, and is still too expensive at present for routine use. MRI is accurate in diagnosing carpal tunnel syndrome about 80% of the time, compared to about 85% using electrodiagnostic tests, which remains the preferred method of diagnosis. MRI may be most effective for detecting any internal injuries, tumors, arthritis, or joint damage that might be causing the problem. It may also be valuable in selecting surgical candidates when electrodiagnostic tests produce unusual results or indicate more severe disease than expected. Additionally, an MRI may be useful for evaluating patients if surgery fails to bring relief.

Treatment

It is critical to begin treating early phases of carpal tunnel syndrome before the damage progresses. A conservative approach to CTS, which may include corticosteroid injections and splinting, is the first step in treating this disorder.

Nevertheless, relapse is common, and studies suggest that surgery is a better option for severe CTS. In one study, 89% of patients who had conservative treatments suffered a recurrence of symptoms within a year. Conservative treatments work best in men under 40. They do not work as well in young women. The conservative approach is also most successful in patients with mild carpal tunnel syndrome. Even among these patients, however, one study found that 60% of patients can expect a relapse. Some researchers are reporting better results when specific exercises for carpal tunnel syndrome are added to the program of treatments.

Limiting Movement. If possible, the patient should avoid activities at work or home that may aggravate the syndrome. The affected hand and wrist should be rested for 2 to 6 weeks. This allows the swollen, inflamed tissues to shrink and relieves pressure on the median nerve. If the injury is work related, the worker should ask to see if other jobs are available that will not involve the same actions. Few studies have been conducted on ergonomically designed furniture or equipment, or on frequent rest breaks. However, it is reasonable to ask for these if other work is not available.

Conservative Treatment Approach. In a major analysis, the following conservative approaches were shown to provide symptom relief:

Wrist splints
Corticosteroids (steroids). Injected or short-term oral corticosteroids may be tried if other methods fail.
Yoga. In one study, 8 weeks of regular yoga practice reduced pain significantly more than splinting.
Manual therapy, a type of physical therapy

A major analysis of other conservative approaches found that patients had no significant relief from nonsteroidal anti-inflammatory drugs (NSAIDs). NSAIDs include common pain relievers such as aspirin and ibuprofen (Advil). The same report also found no benefits from diuretics, magnet therapy, laser acupuncture, vitamin B6, exercise, or chiropractic care. Other approaches being investigated include omega-3 fatty acid supplements and cognitive-behavioral therapy.

Underlying Conditions. It is important to treat any underlying medical condition that might be causing carpal tunnel syndrome. For example, reducing inflammation in rheumatoid arthritis or other forms of inflammatory disorders that directly cause CTS is very helpful.

Hypothyroidism and diabetes are diseases that are associated with an increased risk of CTS. The treatments for such diseases may offer some relief for CTS symptoms. For example, insulin helps nerves heal. A study of patients with CTS and type 2 diabetes found that patients who had an initial steroid injection followed by 7 weekly insulin injections had significantly less pain than those who received sham therapy (placebo). More research is needed on the effects of insulin injections in patients with CTS.

Wrist splints are used to keep the wrist from bending. They are not as beneficial as surgery for patients with moderate to severe CTS, but they appear to be helpful in specific patients. In one study, the best success rates were in patients with mild to moderate nighttime symptoms of less than a year's duration. In selected patients, up to 80% reported fewer symptoms, usually within days of wearing the splint.

Although typically the splint is worn at night or during sports, one 2000 study reported that wearing it full time is most beneficial. (In the study, few patients actually complied with the regimen and wore them full time, but any regular use appeared to improve nerve function and symptoms.) The splint is used for several weeks or months, depending on the severity of the problem, and may be combined with hand and finger exercises. A 2005 study reported that a 6-week course of at-night splinting reduced symptom severity in people with CTS and that the benefits were still evident after 1 year.

Corticosteroid Injections. Corticosteroids (also called steroids) reduce inflammation. If restriction of activities and the use of painkillers are unsuccessful, the doctor may inject a corticosteroid into the carpal tunnel. Some experts recommend them for patients with CTS whose symptoms are intermittent, and there is no evidence of a permanent injury. In CTS, steroid injections (such as cortisone or prednisolone) shrink the swollen tissues and relieve pressure on the nerve. Evidence strongly suggests that they offer relief in more than 75% of CTS patients. It should be noted that the pain may increase for a day or two after the injection, and skin color may change.

A study comparing the benefits of two steroid injections (8 weeks apart) to a single injection in the treatment of CTS found the patients did not significantly benefit from the second shot. One injection is therefore enough to achieve the maximum benefit of this treatment.

Unfortunately, in most cases, steroid injections provide only temporary relief, although studies comparing steroid injection to surgery have produced conflicting results. In a major analysis, after 1 month, injections were no more effective than placebo (sham) injections.

However, a recent analysis compared the effects of local steroid injection versus surgery in patients with new CTS of at least 3 months' duration. Over the short term, local steroid injection was better than surgery for relieving symptoms of CTS. And after 1 year, local steroid injection was as effective as surgery. Another study compared steroid injection with open-release surgery and found that the surgery resulted in better outcomes, but not improved grip strength, in patients with CTS over a 20-week period.

Most doctors limit steroid injections to about three per year, since they can cause complications, such as rupture of tendons, nerve irritation, or more widespread side effects such as hypertension or elevated blood sugar levels.

Low-Dose Oral Corticosteroids. Oral corticosteroids are medicines taken by mouth. Short-term (1 to 2 weeks), low-dose use of corticosteroids may provide long-term relief. People with diabetes should not take oral corticosteroids.

Yoga. Some evidence suggests that yoga practice may be specifically very helpful for carpal tunnel, since yoga postures are designed to stretch, strengthen, and balance upper body joints. In one study, people who practiced yoga for 8 weeks experienced significantly reduced symptoms compared to wrist splints or no treatment at all. Two other small studies also reported improvement in pain relief. Positive effects may take a few weeks of regular practice of at least two sessions a week.

General Exercise Program. Some experts have reported that people who are physically fit, including athletes, joggers, and swimmers, have a lower risk for cumulative trauma disorders. Although there is no evidence that exercise can directly improve CTS, a regular exercise regimen using a combination of aerobic and resistance training techniques strengthens the muscles in the shoulders, arms, and back, helps reduce weight, and improves overall health and well-being. In one 2001 study, CTS patients experienced symptom relief and signs of improved nerve conduction after 10 months of participation in an aerobic exercise program (such improvements appeared to be due to both weight loss and higher oxygen levels in the blood). One study found that most people with CTS felt improvement after two months of physical therapy that included exercises to improve balance and posture. People with any chronic medical condition or with risk factors for heart disease should check with their doctors about an appropriate exercise regimen.

If symptoms subside, the patient may proceed with a supervised program of joint mobilization and hand and wrist strengthening and stretching, usually offered by physical or occupational therapists. Hand and wrist exercises may be most beneficial for patients with mild to moderate disease who are also treated with splints and other conservative measures. Graston Instrument-Assisted Soft-Tissue Mobilization (GISTM) and Soft-Tissue Moblization (STM) techniques have been shown to improve nerve conduction, wrist strength, and wrist motion.

Ultrasound employs high-frequency sound waves directed toward the inflamed area. The sound waves are converted into heat in the deep tissues of the hand, which opens the blood vessels and allows oxygen to be delivered to the injured tissue. A major analysis suggested this approach may be effective when used for seven weeks or more.

Nonsteroidal anti-inflammatory drugs (NSAIDs), which include aspirin and ibuprofen (Advil), are the most common pain relievers used for CTS. They block prostaglandins, the substances that dilate blood vessels and cause inflammation and pain. Unfortunately, as with most other medications used for carpal tunnel syndrome, there are few well-conducted studies to determine their role in CTS. To date, there is no evidence that they offer any significant relief, and regular use can have serious side effects.

NSAIDs Used. Non-steroidal anti-inflammatory drugs (NSAIDs) are commonly used to relieve joint pain and inflammation. There are dozens of NSAIDs. The following are the most common:

Over-the-counter NSAIDs include aspirin, ibuprofen (Advil, Nuprin, Motrin IB, Rufen), naproxen (Aleve), and ketoprofen (Actron, Orudis KT).
Prescription NSAIDs include ibuprofen (Motrin), naproxen (Naprosyn, Anaprox), flurbiprofen (Ansaid), diclofenac (Voltaren), tolmetin (Tolectin), ketoprofen (Orudis, Oruvail), dexibuprofen (Seractil), and indomethacin (Indocin).

Regular use of even over-the-counter NSAIDs may be hazardous for anyone. Long-term use can cause stomach problems, such as ulcers and bleeding, and possible heart problems. In April 2005, the Food and Drug Administration (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. NSAIDS have been associated with the following side effects:

Ulcers and gastrointestinal bleeding are the major danger with long-term use of NSAIDs.
Increased blood pressure -- most NSAIDs appear to pose this risk, with higher risks observed with piroxicam (Feldene), naproxen (Aleve), and indomethacin (Indocin). Sulindac has the smallest effect; aspirin has no risk. People with hypertension, severe vascular disease, kidney, or liver problems, and those taking diuretics, must be closely monitored if they need to take NSAIDs.
Delay in emptying of the stomach -- this could interfere with the actions of other drugs. The elderly are at special risk.
Kidney abnormalities -- these have been reported in people taking NSAIDs, which resolve when the drugs are withdrawn. Report any sudden weight gain or swelling to a doctor. Anyone with kidney disease should avoid these drugs.

Other side effects include:

Dizziness
Tinnitus (ringing in the ear)
Headache
Skin rash
Depression
Confusion or bizarre sensation (in some higher-potency NSAIDs, notably indomethacin)
Possible higher risk for miscarriage (particularly if the NSAID is taken for more than a week or around the time of conception)
There is a slight risk for liver abnormalities.

COX-2 Inhibitors (Coxibs). COX-2 inhibitors block an inflammation-promoting enzyme called COX-2. This class of drugs was initially believed to work as well as traditional NSAIDs, but with fewer stomach problems. However, numerous reports of heart attacks and stroke have prompted the FDA to re-evaluate the risks and benefits of the COX-2s. Rofecoxib (Vioxx) and valdecoxib (Bextra) have been withdrawn from the U.S. market following reports of heart attacks in patients taking the drugs. At the time of this update, Celecoxib (Celebrex) was still available, but labeled with strong warnings and a recommendation that it be prescribed at the lowest possible dose for the shortest duration possible. Patients should ask their doctor whether the drug is appropriate and safe for them.

Ice and Warmth. Ice may provide benefit for acute pain. Some patients have reported that alternating warm and cold soaks have been beneficial. (If hot applications relieve pain, most likely the problem is not caused by CTS but by another condition producing similar symptoms.)

Anesthetic Injections. In some cases, injections of an anesthetic (such as lidocaine) may be helpful. A recent small study compared a painkilling lidocaine patch with a combination lidocaine-steroid injection. The study found the daily use of a 5% lidocaine patch reduced pain as well as the injections. More patients in the patch group reported satisfaction with their treatment. The lidocaine patch is less painful than injections because it is worn on the skin and doesn't require a shot. Doctors noted improvements in 88% of the patients in the patch group, compared with 74% of the patients in the injections group.

Pheresis. The word "pheresis" means to carry. In the case of carpal tunnel, pheresis is a technique being investigated to deliver (to carry) a corticosteroid cream deep within the wrist. One such technique called iontophoresis uses an electrical current, and another called phonophoresis uses ultrasound. One study recently found steroid injections to be superior to iontophoresis and phonophoresis in the treatment of CTS.

Diuretics. Diuretics such as trichlormethiazide reduce fluid in the body. They are sometimes used to treat CTS. However, studies have not reported any significant benefits with these agents.

Low-Level Laser Therapy. Some investigators are working with low-level laser therapy (LLLT), which generates extremely pure light in a single wavelength. The procedure is painless, but studies are mixed on whether it is any more effective than sham treatment. One major analysis reported that laser therapy was more effective over time than steroid injections (although it does not appear to provide much immediate relief.) A 2004 study comparing LLLT with a sham (inactive) therapy reported no significant differences in outcomes between the two groups.

Muscle Stimulation. Two investigative procedures called automated or electrical twitch obtaining intramuscular stimulation (ATOIMS or ETOIMS) are showing promise. ATOIMS uses an automated mechanical device that vibrates the muscle using a tiny pin. (The sensation is described as similar to a mosquito bite.) ETOIMS uses an extremely mild electrical current. They can also be used together. Both approaches cause the muscles to twitch and then relax until the process is completed. Discomfort is minimal. Small studies are reporting some help in relieving a number of conditions that cause chronic pain, including carpal tunnel syndrome.

Traction. Small studies of a hand traction device showed improvement in some patients. The device, called C-TRAC, significantly improved pain, tingling, and numbness in patients who had failed a minimum of 4 months of therapy with conservative treatments such as NSAIDs, night hand splinting, acupuncture, and hand therapy. Patients used the C-TRAC device for 5 minutes three times daily for four weeks, then as needed to maintain long-term improvement.

Many alternative therapies are offered to sufferers of carpal tunnel syndrome and other repetitive stress disorders. Few, however, have any proven benefit. People should carefully educate themselves about how alternative therapies may interact with other medications or impact other medical conditions, and should check with their doctor before trying any of them.

Vitamin B6. Vitamin B6 (pyridoxine) is often used for carpal tunnel syndrome. Studies have not supported its benefits, however, either in oral or cream form. It should also be noted that excessively high doses of vitamin B6 can be toxic and cause nerve damage.

Acupuncture. Acupuncture may be beneficial. New techniques employing painless laser acupuncture may prove to be particularly effective. The National Institutes of Health issued a Consensus Statement on Acupuncture in 1997, which declared this ancient form of treatment useful as a supplement to standard treatment or even as part of a comprehensive management program for CTS.

Chiropractic Therapies. Chiropractic techniques have been useful for some people whose condition is produced by pinched nerves. In one small study, the technique was as effective as medications or wrist splints for relief of pain, though further research is needed.

Magnets. Magnets are a popular but unproven therapy for pain relief. One small study of patients who wore magnets attached to their wrists showed no benefits over those who wore a nonmagnetic placebo (sham) device, although both groups did experience pain relief, perhaps due to a placebo response.

Botulinum toxin type A. Intracarpal injections of botulinum toxin type A (Botox) have been reported to relieve carpal tunnel syndrome in more than half of the small number of patients tested. The product has been safely used to relieve headaches, myofacial pain, and other neuropathic pains.

Generally, manufacturers of herbal remedies and dietary supplements do not need FDA approval to sell their products. Just like a drug, herbs and supplements can affect the body's chemistry, and therefore have the potential to produce side effects that may be harmful. There have been a number of reported cases of serious and even lethal side effects from herbal products. Always check with your doctor before using any herbal remedies or dietary supplements.

Several herbal and homeopathic remedies are sold for pain relief. A small 2002 British study suggested that preparations containing arnica, a popular remedy for swelling and bruising, may ease discomfort following surgery for carpal tunnel, but a 2003 study reported no advantages compared to placebo (an inactive substance).

Research indicates that anxiety, depression, and even pain related to CTS can be relieved to some extent with cognitive behavioral therapy. The focus of this therapeutic approach is to change negative thinking about one's ability to manage pain. Cognitive behavioral therapy is particularly helpful in defining and setting limits. It may be expensive and not covered by insurance, although the therapy is usually of short duration, typically six to 20 one-hour sessions, plus homework, which usually includes attempting a task that the patient has avoided because of negative thinking. Even if people cannot afford this type of therapy, support groups for carpal tunnel syndrome and other sufferers of repetitive stress injuries can be very helpful for exchanging information, specific advice, and solace. Stress management techniques can also be useful in dealing with the psychological and emotional issues accompanying these injuries.

Surgery

Every year more than 200,000 people in the US undergo surgeries for carpal tunnel syndrome. Surgery for CTS is among the most common hand surgeries. In various trials, 70 - 90% of patients who underwent surgery were free of nighttime pain afterward.

Although evidence strongly suggests that surgery is more effective than conservative approaches (at least in patients with moderate to severe CTS), the decision about whether to have surgery to correct CTS, and when to have it, is a troubling one for patients. Electrodiagnostic and other tests used to confirm the presence of CTS are not very useful in determining the best candidates for surgery. For example, results suggesting severe CTS may not relate at all to surgical success or the lack of it.

In general, patients with the following characteristics are less likely to respond to conservative treatment and, therefore, might benefit from surgery:

Older than 50 years of age
Symptoms lasting 10 months or longer
Continual numbness
Muscles in the base of the palm have begun to shrink
Symptoms occur within 30 seconds during a Phalen's test

According to a 2002 study, if none of these factors are present, conservative therapies (splinting and anti-inflammatory agents) are effective in two thirds of patients. However, the conservative approach was ineffective in 60% of patients if only one of these factors were present, in 83% with only two of them, and in virtually all patients who had three or more.

Surgery does not cure all patients, and because it permanently cuts the carpal ligament, some wrist strength is often lost. A number of experts believe that release surgery is performed too often. They recommend aggressive conservative treatment (such as splints, anti-inflammatory agents, and physical therapy) before choosing the more invasive option (surgery). Nevertheless, other experts argue that CTS is often progressive and will worsen over time without surgery. Furthermore, evidence now shows that surgery is better than splints and conservative measures for the relief of pain. Factors that may increase the chances for successful surgery:

Having surgery performed within 3 years of the diagnosis of the disorder
Being in good general health
Having very slow nerve conduction results, but also having some muscle strength before surgery
Symptoms are worse at night than during the day

Factors that may reduce the chances for success:

Being elderly may affect the chances of successful surgery. However, a study found that the majority of patients over age 65 who had surgery were either completely or very satisfied.
Having very severe symptoms before surgery may reduce the chance for successful surgery.
Performing heavy manual labor, particularly working with vibrating tools, may lead to a less successful surgery. Medical evidence has found that only slightly more than half the people who used vibrating hand-held tools were symptom-free 3 years after a CTS operation.
Having very poor nerve conduction results before surgery may reduce the chance for successful surgery. However, some patients with severe symptoms who have normal neurological and physical test results, could still experience significant relief from CTS surgeries.
Patients who are on hemodialysis have good initial success, but approximately half deteriorate in about a year and a half.
Alcohol abuse can negatively affect the results of CTS surgery.
Poor mental health can lead to less successful surgery.
Patients with diabetes and high blood pressure may be more likely to require a second operation.

Factors that make no difference in results:

Patients whose CTS is due to nerve damage from medical conditions, such as diabetes, rheumatoid arthritis, or hypothyroidism. Such patients appear to have the same outcome as those without such conditions, and such disorders should not preclude them from surgery.

Open Release Surgery. Traditionally, surgery for CTS entails an open surgical procedure performed in an outpatient facility. In this procedure, the carpal ligament is cut free (released) from the median nerve. The pressure on the median nerve is therefore relieved. The surgery is straightforward.

In treating carpal tunnel syndrome, surgery may be required to release the compressed median nerve. The open release procedure involves simply cutting the transverse carpal ligament.

The Mini-Open Approach. In recent years, more surgeons have adopted a "mini" open -- also called short-incision -- procedure. This surgery requires only a one-inch incision, but it still allows a direct view of the area (unlike endoscopy, which is viewed on a monitor). The mini-open approach may allow for quicker recovery while avoiding some of the complications of endoscopy, although few studies have investigated its benefits and risks. In a 2005 report, the mini-open approach was directly compared with open release surgery. The recovery time in patients receiving the mini-open approach was shorter than with the open approach, and results were about the same 30 months after the surgery.

Endoscopy. Endoscopy for carpal tunnel syndrome is a less invasive procedure than standard open release.

A surgeon makes one or two 1/2-inch incisions in the wrist and palm, and inserts one or two endoscopes (pencil-thin tubes).
The surgeon then inserts a tiny camera and a knife through the lighted tubes.
While observing the underside of the carpal ligament on a screen, the surgeon cuts the ligament to free the compressed median nerve.

Patients report less pain than those who had the open release procedure, and return to normal activities in about half the time. Nevertheless, at this time the best evidence available does not show any significant long-term advantages of endoscopy over open release in terms of muscle or grip strength or dexterity. The endoscopic approach may even carry a slightly higher risk of pain afterward. This may be due to a more limited view of the hand with endoscopy. (In the open release procedure, the surgeon has a full view of the structures in the hand.) One report indicated a nearly 3-fold increased risk of reversible nerve injury with endoscopic carpal tunnel release, compared with open carpal tunnel release. On the other hand, a recently published review of 486 patients, who had a total of 753 endoscopic release procedures, showed an extremely low number of complications following the procedure. This study calls into the question the widely held belief that endoscopy carries a higher risk of complications. The study also noted that 90% of the patients returned to their original line of work.

Timing for Recovery. Patients should expect the following course:

For some patients, release surgery relieves CTS symptoms of numbness and tingling immediately.

People who have the operation on both hands are completely incapacitated for about two weeks and must have someone to help them at home.
Returning to strenuous work right after surgery may cause the symptoms to return. Patients generally stay out of work for at least a month and often much longer, depending upon the type of surgery and severity of the condition. Recovery time appears to be faster with endoscopy than with open release.
Immediately after surgery patients usually experience a decline in grip strength and dexterity. Studies have reported a wide range of recovery in this area. In one study, grip and pinch strengths reached better levels than before surgery within 6 weeks. In another study, however, grip strength and dexterity did not return to before-surgery levels until 25 weeks after open surgery. The scar may remain tender for up to a year.
Peak improvement (the best level of improvement a patient can reach) may take a long time; in one study, it took an average of almost 10 months.

Physical Therapy. Physical therapy is very important to help rebuild wrist strength. While physical therapy does not reduce the recurrence (return) of symptoms or improve the long-term benefits of surgery, it does accelerate recovery after surgery. Hand exercises can help restore circulation, muscle strength, and joint flexibility in the hand and wrist. Wearing a splint to immobilize the wrist after surgery has no benefits.

Treatment failure and complication rates of CTS surgery vary.

Complications after surgery may include the following:

Nerve damage with tingling and numbness (usually temporary)
Infection
Scarring
Pain
Stiffness. Loss of some wrist strength is a complication that affects between 10% and a third of patients. Endoscopy may have better results than open release. Some patients who have jobs requiring significant strength of the hand and wrist may not be able to perform them after surgery. Such workers may also have problems in other parts of the upper body, including elbows and shoulders. These problems do not go away with surgery and can persist. Studies indicate that between 10 - 15% of patients change jobs after a CTS operation.

If pain and symptoms return, the release procedure may be repeated.

Reasons for procedure failure include:

Incomplete release of the ligament
Extensive scarring
Recurrence of the disorder due to underlying medical conditions

Patients who had open release surgery appear more likely to require repeat operations compared with those who have had endoscopic surgery.

Neurolysis. In severe cases or when scarring is extensive after surgery, surgeons may choose to sever the nerves that are responsible for the pain, using a procedure called external or internal neurolysis. The procedure may extend recovery time substantially, and the need for repeat surgeries may be higher in those who undergo the procedure. One report indicated that neurolysis should be considered if there has not been any recovery within 3 months after surgery, after which improvement is unlikely. It is unclear if this approach offers any benefits over conservative measures to free the nerve from surrounding scar tissue.

Implants. In another procedure for recurrent carpal tunnel syndrome, doctors may take muscle flaps or even fatty tissue from other parts of the body and implant them at the site of the nerve injury. Such flaps enhance the development of new blood vessels, provide padding, and possibly serve as a bed for nerve regrowth. These implants may be used with or without cutting the nerve. Another procedure called vein wrapping uses grafts taken from veins to help protect the scarred nerves.

Resources

www.aanem.org -- Advancing Association of Neuromuscular and Electrodiagnostic Medicine
www.apta.org -- American Physical Therapy Association
www.aoec.org -- The Association of Occupational and Environmental Clinics
www.aaos.org -- American Academy of Orthopaedic Surgeons
www.assh.org -- American Society for Surgery of the Hand
www.ampainsoc.org -- American Pain Society
www.iasp-pain.org -- Association for the Study of Pain
www.aan.com -- American Academy of Neurology
www.nih.gov/niams -- National Institute of Arthritis and Musculoskeletal and Skin Diseases
www.ninds.nih.gov -- National Institute of Neurological Disorders and Stroke
www.nlm.nih.gov/medlineplus/carpaltunnelsyndrome.html -- Information on CTS
www.cdc.gov/niosh/homepage.html -- National Institute for Occupational Safety and Health
www.workerscompensationinsurance.com -- Resources for injured workers
www.keybowl.com -- orbiTouch keyboard
www.ergodevices.com -- Hand and wrist support keyboard

References

Tsai CP, Liu CY, Lin KP, Wang KC. Efficacy of botulinum toxin type a in the relief of carpal tunnel syndrome: A preliminary experience. Clin Drug Investig.2006;26:511-515.

Burke J, Buchberger DJ, Carey-Loughmani MT, et al. A pilot study comparing two manual therapy interventions for carpal tunnel syndrome. J Manipulative Physiol Ther.2007;30:50-61.

Hemminki K, Li X, Sundquist K. Familial risks for nerve, nerve root and plexus disorders in siblings based on hospitalizations in Sweden. J Epidemiol Community Health. 2007;61:80-84.

Porrata H, Porrata A, Sosner J. New carpal ligament traction device for the treatment of carpal tunnel syndrome unreposnive to conservative therapy. J Hand Ther. 2007;20:20-28.

Review Date:
3/14/2007
Reviewed By:
Harvey Simon, MD, Associate Professor of Medicine, Harvard Medical School; Physician, Massachusetts General Hospital.

A.D.A.M. Copyright

adam.com

Colds and the flu

FitSugar — Wed, 08 Oct 2008 17:35:26 -0700

In This Report

Highlights
Introduction
Diagnosis
Complications
Risk Factors
Prevention
Treatment
Medications
Resources
References

HEALTH GUIDE REFERENCE FROM A.D.A.M

Highlights

Vaccine News:

On September 28, 2007, the U.S. Food and Drug Administration (FDA) approved a new brand of inactivated influenza ("flu") vaccine, Alfuria, for adults aged 18 years or older. This vaccine is given by injection.
On September 19, 2007, the FDA approved the use of the live flu vaccine (FluMist) in healthy children as young as 2 years of age. This vaccine, given in the form of a nose spray, was previously approved for healthy children and non-pregnant adults aged 5 - 49.

Drug Resistance:

The World Health Organization reports that resistance to the anti-viral drug oseltamivir (Tamiflu) can develop with extensive use. Oseltamivir is one of two drugs the CDC recommends for treating the flu. It is also the current recommended treatment for the H5N1 avian flu virus.

Drug Recalls:

In October 2007, drug manufacturers voluntarily withdrew from the market all oral cough and cold products, including decongestants, aimed at children under 2, due to potential harm from misuse. The U.S. Food and Drug Administration (FDA) recommends against using these products to treat children under age 2. The FDA is currently reviewing the safety of cough and cold medicines in children ages 2 - 11 years.

Emerging Virus:

A new, more virulent strain of adenovirus has reportedly emerged in the United States in 2006. The adenovirus family causes upper respiratory infections, pneumonia, and several other diseases. The new strain of adenovirus 14 causes severe respiratory illness that has resulted in several deaths.

Introduction

Upper respiratory tract infections affect the airways in the nose, ears, and throat.

Structures of the throat include the esophagus, trachea, epiglottis, and tonsils.

The infections can be caused by viruses, bacteria, or other microscopic organisms. In most cases, these infections lead to colds or mild influenza (flu) and are temporary and harmless. In rare cases, flu can be severe, or the infections may turn into pneumonia.

Organisms that cause these upper respiratory tract infections are generally spread by:

Direct contact (such as hand-to-mouth)
Coughing or sneezing

The common cold (medically known as infectious nasopharyngitis) is the most common upper respiratory tract infection. More than 200 viruses can cause colds. The most common cause is the rhinovirus, which is responsible for about half of all colds. Symptoms usually develop 1 - 3 days after being exposed to the virus.

A cold usually progresses in the following manner:

It nearly always starts rapidly with throat irritation and stuffiness in the nose.
Within hours, full-blown cold symptoms usually develop, which can include sneezing, mild sore throat, fever, minor headaches, muscle aches, and coughing.
Fever is low-grade or absent. In small children, however, fever may be as high as 103°F for 1 or 2 days. The fever should go down after that time, and be back to normal by the 5th day.
Nasal discharge is usually clear and runny the first 1 - 3 days. It then thickens and becomes yellow to greenish.
The sore throat is usually mild and lasts only about a day. A runny nose usually lasts 2 - 7 days, although coughing and nasal discharge can persist for more than 2 weeks.

A new, more virulent strain of adenovirus has reportedly emerged in the United States in 2006. The adenovirus family causes upper respiratory infections (it is one of the many viruses that cause the common cold). It also causes pneumonia, conjunctivitis, and several other diseases. The new strain of adenovirus 14 causes severe respiratory illness that has resulted in several deaths. Some patients who contracted this new viral disease had to be hospitalized, sometimes in intensive care units.

Every year, influenza strikes millions of people worldwide. Influenza epidemics are most serious when they involve a new strain, against which most people around the world are not immune. Such global epidemics (pandemics) can rapidly infect more than one fourth of the world's population. For example, the Spanish flu in 1918 and 1919 killed an estimated 20 million people in the U.S. and Europe and 17 million people in India. With modern society's dependence on air travel, an influenza pandemic could potentially inflict catastrophic damage on human lives, and disrupt the global economy.

The influenza virus mutates (changes) rapidly as it moves from species to species. Most Type A influenza strains (the most common strains) first develop in migratory waterfowl populations. While most avian influenza (bird flu) virus strains are relatively harmless, a few develop into "highly pathogenic avian influenza," which can be very deadly for domesticated poultry and livestock. As recent events have shown, these strains can also be deadly to humans. People can become infected by these bird flu strains through contact with contaminated chickens and pigs. The medical community is now greatly concerned about the H5N1 bird flu virus, which has infected and even killed people in several countries.

Symptoms of influenza. Patients usually feel sick 1 - 4 days after exposure to the influenza (flu) virus. The flu usually involves:

Abrupt onset of severe symptoms, which include headache, muscle aches, fatigue, and high fever (up to 104°F).
Cough (which is usually dry but can be severe) and sometimes a runny nose and sore throat.
Children may experience vomiting, diarrhea, and ear infections, as well as other flu symptoms.
The symptoms usually resolve in 4 - 5 days, although some people can experience coughing and feelings of illness for more than 2 weeks. In some cases, flu can become more severe or make other conditions worse.

Transmitting the Virus. The flu virus is spread primarily when a person with the flu coughs or sneezes near someone else. Adults with flu typically spread it to someone else from 1 day before symptoms start to about 5 days after symptoms develop. Children can spread the infection for more than 10 days after symptoms begin, and young children can transmit the virus 6 days or even earlier before the onset of symptoms. People with severely compromised immune systems can transmit the virus for weeks or months.

Flu Strains. A virus is a cluster of genes wrapped in a protein membrane, which is coated with a fatty substance that contains molecules called glycoproteins. Strains of the flu are identified according to the number of membranes and type of glycoproteins present.

Click the icon to see an image of a virus.

The two major flu strains are referred to as A and B:

Influenza A is the most widespread and can infect animals and humans. Influenza A is the cause of the major pandemics (worldwide epidemics) of influenza that have occurred so far. It is usually further categorized by two subtypes based on two substances that occur on the surface of the viruses: hemagglutinin (H) and neuraminidase (N).
Influenza B infects only humans. It is less common than type A, but is often associated with specific outbreaks, such as in nursing homes.

The vast majority of flu cases are type A. Influenza A usually causes more severe disease than type B. There is some concern, however, that since influenza B has been less common in the past few years, some people, particularly small children, may have fewer antibodies to it and so may be at higher risk for severe infection.

Although the risk of lethal viruses is generally low, scientists are greatly concerned about a particular virus called H5N1, which causes avian influenza. Since 1997, the H5N1 virus has triggered deadly outbreaks in poultry across Southeast Asia. As of Janaury 15, 2008, 350 people had been infected with the bird flu in 12 countries. Of these people, 217 have died, according to the World Health Organization. No cases have been seen in the United States.

So far, the virus has spread from birds to humans. The virus does not seem to be easily spread from person to person. However, scientists and public health officials are monitoring the spread of H5N1 and working to contain it. Efforts include slaughtering infected birds, developing new vaccines, and stockpiling antiviral drugs such as oseltamivir (Tamiflu). Many poor nations have limited resources and already contend with other serious health problems, including HIV-AIDS. If H5N1 does mutate and spread, the consequences could be especially severe for these countries.

In April 2007, the FDA approved a vaccine to protect humans from avian influenza. Currently this vaccine is not being used for routine immunization. However, if the avian flu develops the ability to spread fairly easily from human to human, this vaccine may be made available.

Diagnosis

Differentiating between a cold and flu may be difficult. Cold symptoms are nearly always less severe than those of the flu.


Symptoms	Cold	Flu
Fever	Rare	Common and high (102-104°F); lasts 3 - 4 days
Headache	Rare	Almost always present
General aches and pains	Mild, if they occur at all	Often severe
Fatigue, exhaustion, and weakness	Mild, it they occur at all	Extreme exhaustion is early and severe; can last 2 - 3 weeks
Stuffy nose	Nearly always	Sometimes
Sneezing	Very common	Sometimes
Sore throat	Common	Sometimes
Chest discomfort and cough	Mild-to-moderate, hacking cough	Common, can be severe
Source: National Institute of Allergy and Infectious Disease

Several available tests can isolate and identify the viruses responsible for some respiratory infections. They are generally not needed, since most cases of the flu are self-evident. However, such tests can be very helpful in confirming or ruling out the flu. If a doctor believes a diagnosis would help, samples using a swab should be taken from the nasal passages or throat within 4 days of the first symptoms.

A nasopharyngeal culture is a test used to identify disease-causing organisms in nasal secretions. Nasopharyngeal cultures are useful in identifying Bordetella pertussis and Neisseria meningitidis (types of bacteria). The culture may help determine appropriate antibiotic therapy.

Several rapid tests for the flu can produce results in less than 30 minutes, but vary on the specific strain or strains that they can detect. They are not as accurate as a viral culture, however, in which the virus is reproduced in the laboratory. Culture results can take 3 - 10 days. Blood tests can also document the infection several weeks after symptoms appear.

In February 2006, the U.S. Food and Drug Administration approved a new, faster test for diagnosing H5 strains of avian influenza in people suspected of having the virus. The test is called the Influenza A/H5 (Asian lineage) Virus Real-time RT-PCR Primer and Probe Set. The test gives preliminary results within 4 hours. Older tests required 2 - 3 days. It checks for the presence of the Influenza A H5 strain. If the presence of this strain is confirmed through the rapid test, further testing will be needed to determine the exact subtype of the virus. For example, the current strain of concern is H5, subtype N1, designated as H5N1 for short.

Ruling out Allergic Rhinitis. Symptoms of allergic rhinitis include nasal obstruction and congestion, which are similar to the symptoms of a cold. People with allergies, however, are likely to have the following:

Thin, clear, and runny nasal discharge
An itchy nose, eyes, or throat
Recurrent sneezing

There are two forms of allergic rhinitis:

Symptoms that appear only during allergy season are called allergic rhinitis, commonly known as hay or rose fever. [For more information, see In-Depth Report #77: Allergic rhinitis.]
Allergens in the house, such as house dust mites, molds, and pet dander, can cause year-long allergic rhinitis, referred to as perennial rhinitis.

Click the icon to see an image of common allergens.

Ruling out Sinusitis. The signs and symptoms suggestive of true acute sinusitis include the following:

A return of congestion and discomfort after initial improvement in a cold (called double sickening)
Purulent (pus-filled) nasal secretion
A lack of response to decongestant or antihistamine
Pain in the upper teeth or pain on one side of the head
Pain above or below both eyes when leaning over

Children with sinusitis are less likely to have facial pain and headache and may only develop a high fever or prolonged upper respiratory symptoms (such as a daytime cough that does not improve for 11 - 14 days). When the diagnosis is unclear or complications are suspected, further tests may be required. [For more information, see In-Depth Report #62: Sinusitis.]

Acute Bronchitis. Acute bronchitis is usually caused by a virus and in most cases is self-limiting. The cough it causes typically lasts for about 7 - 10 days, but in about half of patients, coughing can last for up to 3 weeks, and 25% of patients continue to cough for over 1 month.

Atypical Pneumonia. Pneumonia caused by atypical organisms (for example, Mycoplasma pneumonia, chlamydia, Legionella) can cause symptoms similar to the flu. Only laboratory tests can diagnose the difference. [For more information, see In-Depth Report #64: Pneumonia.]

Ruling out More Serious Viral Infections. Respiratory syncytial virus (RSV) and, possibly human parainfluenza viruses (HPV), are proving to be important causes of serious respiratory infections in infants, the elderly, and people with damaged immune systems. (Both also cause mild conditions.) RSV may be a much more common cause of flu-like symptoms than previously thought.

Pertussis. Pertussis (whooping cough) was a very common childhood illness throughout the first half of the century. Although immunizations caused a decline in cases to only 1,700 in the U.S. in 1980, the incidence has risen recently, with almost 30,000 cases reported between 1997 and 2000 (17 infants died of the disease in 2000). Many more cases are reported worldwide.

Nearly half of pertussis cases now occur in people 10 years of age or older, perhaps due to waning immunity in adolescents and adults. Such cases may be greatly underreported. Up to 25% of adults who see a doctor for persistent cough may actually have pertussis. It may go undiagnosed, however, because symptoms are usually mild, and adults are unlikely to have the classic "whooping" cough. This is of some concern because such adults may unknowingly infect unvaccinated children. The younger the patient, the higher the risk for severe complications, including pneumonia, seizures, and even death. Children younger than 6 months are at particular risk because protection is incomplete, even with vaccination.

In addition to common cold viruses, other, less frequent causes of sore throat include the following:

Strep throat
Foodborne and waterborne infections (Streptococcus C and G)
An uncommon organism called Arcanobacterium haemolyticum (infection with this bacterium can mimic strep throat and may even cause a rash)
Infectious mononucleosis ("mono")
Herpesvirus 1

Group A Streptococcal bacteria is the most common bacterial cause of the severe sore throat known commonly as "strep throat." It occurs mostly in school age children, but people of all ages are susceptible. (Strep throat constitutes about 12% of all sore throat cases seen by doctors.)

The symptoms of strep throat include the following:

A sudden onset of severe sore throat
Difficulty in swallowing
Fever
Headache
Stomach pain
Vomiting

Only about half of patients with strep throat have such clear-cut symptoms. Furthermore, half of people who have these symptoms do not actually have strep throat.

How Is Strep Throat Diagnosed? Most cold-related sore throats are caused by viruses and require no treatment. They usually do not last more than a day. When the sore throat persists and is very painful the doctor will want to rule out or confirm the presence of the strep bacteria.

The doctor will look for redness and pus-filled patches on the tonsils and back of the throat. Enlarged tonsils are less likely to indicate a strep throat.
The doctor will feel the sides of the neck for swollen lymph nodes. If the lymph nodes are not swollen, it is less likely to be a strep throat.
A cotton swab is used to take a sample of pus in the throat for a throat culture.

A throat culture is the most effective and least expensive test for confirming the presence of strep throat. It takes 24 - 48 hours to obtain a result.

Rapid Antigen-Detection Test for Strep Throat. A faster test, called the rapid strep antigen test, uses chemicals to detect the presence of bacteria in a few minutes. A positive result nearly always means that streptococcal bacteria is the cause of the infection. The test, however, fails to detect 10 - 20% of cases, so a culture may still be necessary to catch any missed infections, particularly in children.

How Serious is Strep Throat? The use of antibiotics has removed the threat of most complications from streptococcus infection in the throat (strep throat). However, untreated strep throat could lead to the following complications:

Abscess in the tonsils
Scarlet fever
Rheumatic fever (rare in the U.S.)

How Is Strep Throat Treated? Strep throat infections require antibiotics. Antibiotics prevent a serious complication called rheumatic fever, which can result in permanent damage to the heart. Fortunately, this complication occurs rarely in United States anymore. If started on time, antibiotic treatment of strep throat will almost always prevent this complication. In addition, antibiotics shorten the recovery time from strep throat.

The following antibiotics are generally used to treat strep throat:

Penicillin is usually the antibiotic of choice unless the patient is allergic. A full 10 days may be necessary. Amoxicillin, a form of penicillin, is proving to be effective when taken in a single daily dose for 10 days.
Macrolide antibiotics. Erythromycin is known as a macrolide antibiotic and is the first choice for patients with penicillin allergies. A 10-day regimen is needed. Another macrolide, azithromycin, can be given as a single daily dose and may be effective in 5 days. It is expensive, however, and bacterial resistance to macrolides is growing, so it should not be given as a first choice.
Cephalosporins are very effective in eradicating the bacteria.

Antibiotics are very commonly inappropriately prescribed for non-strep sore throats. One study reported that an estimated 6.7 million American adults visited their doctors because of sore throat between 1989 and 1999, with 73% of them receiving antibiotics. Studies indicate, however, that fewer than half of adults and far fewer children with even strong signs and symptoms for strep throat actually have strep infections.

Parents should be comforted that a delay in antibiotic treatment while waiting for lab results does not increase the risk that the child will develop serious long-term complications, including acute rheumatic fever. If a patient is severely ill, however, it is reasonable to begin administering antibiotics before the results are back. If the culture is negative (there is no evidence of bacteria), the doctor should call the family to make certain the patient stops taking the antibiotics and any remaining pills are discarded.

Children who have a sore throat and who have had rheumatic fever in the past should receive antibiotics immediately, even before culture results are back. Children with a sore throat who have a family member with strep throat or rheumatic fever should also receive immediate antibiotic treatment.

Complications

Colds rarely cause serious complications. In about 1% of cases, a cold can lead to other complications, such as sinus or ear infections. It can also aggravate asthma and, in uncommon situations, increase the risk for lower respiratory tract infections.

Ear Infections. The rhinovirus infection, a major cause of colds, also commonly predisposes children to ear infections, possibly by obstructing the Eustachian tube, which leads to the middle ear. Viruses may even attack the ear directly.

Sinusitis. Between 0.5 - 5% of people with colds develop sinusitis, an infection in the sinus cavities (air-filled spaces in the skull). Sinusitis is usually mild, but if it becomes severe, antibiotics generally eliminate further problems. In rare cases, however, sinusitis can be serious.

Lower Respiratory Tract Infections. The common cold poses a risk for bronchitis and pneumonia in nursing home patients, and in other people who may be vulnerable to infection. Some experts believe that the rhinovirus may play a more significant role than the flu in causing lower respiratory infections in the vulnerable population.

Aggravation of Asthma. Rhinovirus infections can aggravate asthma in both children and adults. In fact, rhinovirus has been reported to be the most common infectious organism associated with asthma attacks. Colds may promote allergic inflammation of the airways, and increase the intensity their responsiveness for weeks.

The flu is usually self-limited and not serious. However, each year in the United States, more than 200,000 people are hospitalized due to complications of the flu. An estimated 36,000 people die each year of influenza-related complications. People at highest risk for serious complications are those over 65 years old and those with chronic medical conditions. Influenza A is the most severe strain. Influenza B tends to be milder.

Pneumonia. Pneumonia is the major serious complication of influenza and can be very serious. It can develop about 5 days after viral influenza. More than 90% of the deaths caused by influenza and pneumonia occur among older adults. Flu-related pneumonia nearly always occurs in high-risk individuals, such as the following:

People with weakened immune systems, such as AIDS patients
Elderly patients, particularly patients in nursing home
Very young children -- [it may be difficult to tell whether pneumonia is related to influenza or caused by respiratory syncytial virus (RSV)]
Hospitalized patients and anyone with serious medical conditions, such as diabetes, heart, circulation, or lung disorders, particularly chronic lung disease
Drug abusers who use needles

Combinations of these factors further increase the risk. It should be noted that pneumonia is an uncommon outcome of influenza in healthy adults.

Complications in the Central Nervous System in Children. Influenza increases the risk for complications in the central nervous system of small children. Febrile seizures are the most common neurologic complication in children The risks decline after a child turns 1 year old, but are still high in children aged 3 - 5 years old.

Risk Factors

The very young and the very old are at higher risk for upper respiratory tract infections and their associated complications.

Children. Young children are prone to colds and may have 8 to 12 of them every year. Millions of cases of influenza develop in American children and adolescents each year.

Before the immune system matures, all infants are susceptible to uppper respiratory infections, with a possible frequency of one cold every 1 - 2 months. Smaller nasal and sinus passages also make younger children more vulnerable to colds than older children and adults. Upper respiratory infections gradually diminish as children grow, until at school age their rate of such infections is about the same as an adult's. There is almost never cause for concern when a child has frequent colds, unless the colds become unusually severe or more frequent than usual.

The Elderly. The elderly have diminished cough and gag reflexes, and their immune systems are often weaker. They are therefore at greater risk for serious respiratory infections than the young and middle-aged adults.

The risk of respiratory infections is increased by exposure to cigarette smoke, which can injure airways and damage the cilia (tiny hair-like structures that help keep the airways clear). Toxic fumes, industrial smoke, and other air pollutants are also risk factors. Parental smoking increases the risk of respiratory infections in their children.

People with AIDS and other medical conditions that damage the immune system are extremely susceptible to serious infections.

Cancers, especially leukemia and Hodgkin's disease, put patients at risk. Patients who are on corticosteroid (steroid) treatments, chemotherapy, or other medications that suppress the immune system are also prone to infection.

People with diabetes are at a higher risk for the flu.

Certain genetic disorders predispose people to respiratory infections. They include sickle-cell disease, cystic fibrosis, and Kartagener syndrome (which results in malfunctioning cilia).

Much evidence suggests that stress increases one's susceptibility to a cold. In one study, people with high stress levels averaged 2.7 upper respiratory infections during a 6-month period and those reporting low stress averaged 1.5 infections. Another study found the duration of colds in children with chronic, year-round colds decreased with help of a stress management program. Stress appears to increase the risk for a cold regardless of lifestyle or other health habits. And once a person catches a cold or flu, stress can make symptoms worse.

It is not clear why these events occur. Some experts believe that stress alters specific immune factors, which cause inflammation in the airways. One study reported that the only people who got sick after experiencing short stress were those whose body responded to stress with high levels of cortisol, a stress hormone, coupled with a low immune response.

In people who already have colds, exercise has no effect on the illness' severity or duration of the infection. High-intensity or endurance exercises, however, appear to suppress the immune system while they are being performed. Some highly trained athletes, for instance, report being susceptible to colds after strenuous events. People should avoid strenuous physical activity when they have high fevers or widespread viral illnesses. Note: Very low fat diets appear to worsen this dampening effect on the immune system. A higher fat-diet may help correct this imbalance (omega-3 fatty acids, found in fish and canola oil, are preferred). Whether carbohydrate loading provides much additional value is not clear.

Colds and flus occur predominantly in the winter. Flu season typically starts in October and lasts into mid March.

The reasons for this seasonal bias are not due to the cold itself, but to other factors. Certainly, flus and colds are more likely to be transmitted in winter because people spend more time indoors and are exposed to higher concentrations of airborne viruses. Dry winter weather also dries up nasal passages, making them more susceptible to viruses. Some experts theorize that the high rates of viral infections in winter may be due to certain immune factors, which react to light and dark and affect a person's susceptibility to viruses.

Traveling in close contact with people, whether on trains, planes, or buses, can increase the risk for respiratory infections.

Children who attend day care may have an increased risk of colds. However, one study suggested that although children in day care centers incur higher rates of the common cold in the preschool years, they have lower cold rates in their first years of regular school. The colds they catch in day care, then, may bestow some immunity to future colds for a few years. By age 13, such protection has worn off. There is also some evidence that frequent colds in young children may help protect against future allergies and asthma.

Prevention

Because colds and flus are easily spread, everyone should always wash their hands before eating and after going outside. Ordinary soap is sufficient. Waterless hand cleaners that contain an alcohol-based gel are also effective for every day use and may even kill cold viruses. (They are less effective, however, if extreme hygiene is required. In such cases, alcohol-based rinses are needed.)

Antibacterial soaps add little protection, particularly against viruses. In fact, one study suggests that common liquid dish washing soaps are up to 100 times more effective than antibacterial soaps in killing respiratory syncytial virus (RSV), which is known to cause pneumonia. Wiping surfaces with a solution that contains one part bleach to 10 parts water is very effective in killing viruses.

Colds are not caused by insufficiently warm clothes or by going outside with wet hair.

Foods Containing Lactobacilli (Good Bacteria). Researchers are also studying the possible protective value of certain strains of lactobacilli bacteria found in the intestines. Some of these strains, particularly acidophilus, are used to make yogurt. According to one Finnish study, children attending day care who ate milk containing the strain lactobacilli GG 10 - 20% fewer respiratory infections. (The strain used was not the kind found in most commercial yogurt products.)

Vitamins. Studies are mixed whether vitamin supplements protect against upper respiratory infections. Large doses of vitamin C, for example, may help reduce the duration of a cold, but they do not appear to protect against one in the first place, even after exposure to a cold virus. Two studies on multivitamins reported opposite results, with one finding fewer infections and one finding no difference. It is possible that vitamin C or multivitamin supplements may be helpful in specific people, such those who are vitamin deficient or have medical problems that impair their immune systems.

Treatment

The following are some food and fluid recommendations. Most will not cure a cold, but they may help a person deal better with the symptoms:

Drinking plenty of fluids and getting lots of rest when needed is still the best bit of advice to ease the discomforts of the common cold. Water is the best fluid and helps lubricate the mucous membranes. (There is no evidence that drinking milk will increase or worsen mucus, although milk is a food and should not serve as fluid replacement.)
Chicken soup does indeed help congestion and body aches. The hot steam from the soup may be its chief advantage, although laboratory studies have actually reported that ingredients in the soup may have anti-inflammatory effects. In fact, any hot beverage may have similar soothing effects from steam. Ginger tea, fruit juice, and hot tea with honey and lemon may all be helpful.
Spicy foods that contain hot peppers or horseradish may help clear sinuses.
Foods rich in vitamins A and C are always recommended and may be helpful during a respiratory infection. They include oranges, kiwi, and tomatoes for vitamin C, and sweet potatoes, spinach, and broccoli for vitamin A.

Different studies have found that large doses of vitamin C may reduce the duration of a cold. Some precautions against taking high doses of vitamin C include the following:

High doses of vitamin C may cause headaches, intestinal and urinary problems, and even kidney stones.
Because vitamin C increases iron absorption, people with certain blood disorders, such as hemochromatosis, thalassemia, or sideroblastic anemia, should avoid high doses of this vitamin.
Large doses of vitamin C can also interfere with anticoagulant medications ("blood thinners"), blood tests used in diabetes, and stool tests.
Vitamin E or multivitamin supplements do not appear to be helpful in reducing symptoms of the cold.

Zinc appears to have certain important effects on the immune system and it may have a direct effect on viruses. How it works is not entirely clear, however. Zinc preparations in lozenge or nasal gel form are now available as cold treatments. Studies are very mixed on the effects of zinc on colds. The variance may be due to different zinc preparations. A review of available studies comparing zinc treatment to placebo ("sugar pill") found only one high-quality study, which showed that zinc nasal gels might provide a benefit. The overall benefit of zinc in the prevention of colds remains unproven. In any case, no one with an adequate diet and a healthy immune system should take zinc for prolonged periods, for the purpose of preventing colds.

Side Effects. Side effects, particularly of the lozenges form, include the following:

Dry mouth
Constipation
Nausea
Bad taste (possibly only with zinc gluconate lozenges)
Severe vomiting, dehydration, and restlessness (signs of overdose, seek medical help)
Allergic response (rare)

Food and Drug Interactions. Zinc may also interact with drugs or other elements:

It may reduce absorption of certain antibiotics.
Foods high in calcium or phosphorus may reduce zinc absorption.
In high doses and for long periods of time, zinc can cause copper deficiencies.

Many people take medications to reduce mild pain and fever. Adults most often choose aspirin, ibuprofen (Advil), or acetaminophen (Tylenol).

The following are recommendations for children:

Acetaminophen (Tylenol) or ibuprofen (usually Advil or Motrin) are the typical pain-relievers parents give their children. Most pediatricians advise such medications for children who run fevers over 101°F. Some suggest alternating the two agents, although there is no evidence that this regimen offers any benefits, and it might be harmful.
Aspirin and aspirin-containing products are virtually never recommended for children or adolescents. Reye syndrome, a very serious condition, has been associated with aspirin use in children who have flu symptoms or chicken pox.

Nasal strips (such as Breathe Right) are placed across the lower part of the nose and pull the nostrils open. These strips may open the nasal passages and ease congestion due to a cold, sinusitis, or hay fever. As of yet, there is no scientific evidence that they offer such benefits.

A nasal wash can be helpful for removing mucus from the nose. A saline solution can be purchased at a drug store or made at home. One study reported that neither a homemade solution (using one teaspoon of salt and one pinch of baking soda in a pint of warm water) nor a commercial hypertonic saline nasal wash had any effect on symptoms. Further, one preliminary study found that over-the-counter saline nasal sprays that contain benzalkonium chloride as a preservative may actually worsen symptoms and infection.

Some physicians, however, advocate a traditional nasal wash that has been used for centuries and is different from that used in most studies. It contains no baking soda and uses more fluid for each dose and less salt. The nasal wash should be performed several times a day.

A simple method for administering a nasal wash:

Lean over the sink head down.
Pour some solution into the palm of the hand and inhale it through the nose, one nostril at a time.
Spit the remaining solution out.
Gently blow the nose.

The solution may also be inserted into the nose using a large rubber ear syringe, available at a pharmacy. In this case, the process is the following:

Lean over the sink head down.
Insert only the tip of the syringe into one nostril.
Gently squeeze the bulb several times to wash the nasal passage.
Then press the bulb firmly enough so that the solution passes into the mouth.
The process should be repeated in the other nostril.

Nasal-delivery decongestants are applied directly into the nasal passages with a spray, gel, drops, or vapors. Nasal forms work faster than oral decongestants and have fewer side effects. They often require frequent administration, although long-acting forms are now available. Ingredients and brands of nasal decongestants include the following:

Long Acting Nasal-Delivery Decongestants. They are effective in a few minutes and remain so for 6 - 12 hours. The primary ingredient in long-acting decongestant is:

Oxymetazoline: Brands include Vicks Sinex (12-hour brands), Afrin (12-hour brands), Dristan 12-Hour, Good Sense, Nostrilla, Neo-Synephrine 12-Hour
Xylometazoline: Inspire, Otrivin, Natru-vent

Short-Acting Nasal-Delivery Decongestants. The effects usually last about 4 hours. The primary ingredients in short-acing decongestants are:

Phenylephrine: Neo-Synephrine (mild, regular, high-potency), 4-Way, Dristan Mist Spray, Vicks Sinex
Naphazoline (Naphcon Forte, Privine)

Dependency and Rebound. The major hazard with nasal-delivery decongestants, particularly long-acting forms, is a cycle of dependency and rebound effects. The 12-hour brands pose a particular risk for this effect. This effect works in the following way:

With prolonged use (more than 3 - 5 days), nasal decongestants lose effectiveness and even cause swelling in the nasal passages.
The patient then increases the frequency of their dose. The congestion worsens, and the patient responds with even more frequent doses, in some cases as often as every hour.
Individuals then become dependent on them.

Tips for Use. The following precautions are important for people taking nasal decongestants:

When using a nasal spray, spray each nostril once. Wait a minute to allow absorption into the mucosal tissues, and then spray again.
Keep the nasal passages moist. All forms of nasal decongestants can cause irritation and stinging. They also may dry out the affected areas and damage tissues.
Do not share droppers and inhalators with other people.
Use decongestants only for conditions requiring short-term use, such as before air travel or for a single-allergy attack. Do not take them more than 3 days in a row. With prolonged use, nasal decongestants become ineffective and result in the so-called rebound effect and dependence.
Discard sprayers, inhalators, or other decongestant delivery devices when the medication is no longer needed. Over time, these devices can become reservoirs for bacteria.
Discard the medicine if it becomes cloudy or unclear.

Oral decongestants also come in many brands, which mainly differ in their ingredients. The most common active ingredient is pseudoephedrine (Sudafed, Actifed, Drixoral).

Side Effects of Decongestants. Decongestants have certain adverse effects, which are more apt to occur in oral than nasal decongestants and include the following:

Agitation and nervousness
Drowsiness (particularly with oral decongestants and in combination with alcohol)
Changes in heart rate and blood pressure

Avoid combinations of oral decongestants with alcohol or certain drugs, including monoamine oxidase inhibitors (MAOI) and sedatives

Individuals at Risk for Complications from Decongestants. People who may be at higher risk for complications are those with certain medical conditions, including disorders that make blood vessels highly susceptible to contraction. Such conditions include the following:

Heart disease
High blood pressure
Thyroid disease
Diabetes
Prostate problems that cause urinary difficulties
Migraines
Raynaud's phenomenon
High sensitivity to cold
Emphysema or chronic bronchitis

Anyone with the above conditions should not use either oral or nasal decongestants without a doctor's guidance. In addition, people taking medications that increase serotonin levels, such as certain antidepressants, anti-migraine agents, diet pills, St. John's wort, and methamphetamine, should avoid decongestants. The combinations can cause blood vessels in the brain to narrow suddenly, causing severe headaches and even stroke.

Others who should use these drugs with caution are the following (consult your health care provider):

Anyone who is pregnant.
Children: Children appear to metabolize decongestants differently than adults. Decongestants should not be used at all in infants and small children under the age of 2, according to a new recommendation from an advisory panel of the Food and Drug Administration. These children are at particular risk for side effects that depress the central nervous system. Such symptoms cause changes in blood pressure, drowsiness, deep sleep, and, rarely, coma. Studies have also shown that these cough and cold products generally are not effective in the treatment of children under 6 years of age.

In October 2007, drug manufacturers voluntarily withdrew from the market all oral cough and cold products, including decongestants, aimed at children under 2, due to potential harm from misuse.

Major studies have indicated that over-the-counter cough medicines are not very effective, but they are also not harmful.

For thick phlegm, patients may try cough medications that contain guaifenesin (Robitussin, Scot-Tussin Expectorant), which loosens mucus. Patients should not suppress coughs that produce mucus and phlegm. It is important to expel this substance. To loosen phlegm, patients should drink plenty of fluids and use a humidifier or steamer.
For patients with a dry cough, a suppressant may be useful, such as one that contains dextromethorphan (Drixoral Cough, Robitussin Maximum Strength Cough Suppressant).

Medications that contain both a cough suppressant and an expectorant are not useful and should be avoided. Medicated cough drops that contain dextromethorphan are not very useful. A patient is just as likely to find relief from hard candy or lozenges.

Prescription cough medications with small doses of narcotics are available. They are usually reserved for lower respiratory infections with significant coughs.

Sore throats that are associated with colds are generally mild. The following may be helpful:

Cough drops, throat sprays, or gargling warm salt water may help relieve sore throat and reduce coughing.
Throat sprays that contain phenol (for example, Vicks Chloraseptic) may be particularly helpful. Phenol has antibacterial properties. In one study, patients with sore throat who used the spray experienced faster resolution of the cold itself, including fever, headache, and other symptoms compared to a placebo. The patients were not taking antibiotics.
Cough drops that contain menthol and mild anesthetics, such as benzocaine, hexylrescorincol, phenol, and dyclonine (the most potent), may soothe a mild sore throat.
People with sore throats from postnasal drip might try taking a teaspoon of liquid antacid. They shouldn't drink anything afterward, since the intention is to coat the throat and help neutralize the acid in the mucus that might be causing pain.

If soreness in the throat is very severe and does not respond to mild treatments, the patient or parent should check with the physician to see if a strep throat is present, which would require antibiotics. [See What is Strep Throat? in the Diagnosis section.]

Dozens of remedies are available that combine ingredients aimed at more than one cold or flu symptom. In general, they do no harm, but they have the following problems:

Some ingredients may produce side effects without even helping a cold.
In some cases, the ingredients conflict (such as a cough expectorant and a cough suppressant).
In other cases, a patient may wish to increase the dosage to improve one symptom, which serves to increase other ingredients that do no good and, in higher doses, may cause side effects.

Note on Antihistamines. Many combination remedies contain antihistamines. Antihistamines are used for allergies and are not generally recommended to relieve the symptoms of the common cold. Some evidence suggests, however, that they may have some value.

First-generation antihistamines may reduce cold symptoms. Their benefits for the cold are likely to be due to the drowsiness they cause. Such antihistamines include Benadryl, Tavist, and Chlor-Trimeton. The newer, second-generation antihistamines (Claritin, Allegra, Zyrtec) do not have these effects and also appear to have no benefits against colds.

Herbal remedies and dietary supplements are not regulated by the FDA. This means that manufacturers and distributors do not need FDA approval to sell their products. In addition, any substance that affects the body's chemistry can, like any drug, produce side effects that may be harmful. There have been numerous reported cases of serious and even deadly side effects from herbal products.

The following are special concerns for people taking natural remedies for colds or influenza:

Echinacea is commonly taken to prevent onset and ease symptoms of cold or flu. A rigorous study, published in 2005 in the New England Journal of Medicine, determined that this herb does not help to prevent or treat colds. In addition, some people are allergic to echinacea. People who have autoimmune diseases or plant allergies should avoid it. There have been a few reports of people experiencing a skin reaction called erythema nodosum, which is characterized by tender, red nodules under the skin.
Chinese herbal cold and allergy products can contain trace amounts of aristolochic acid, a chemical that causes kidney damage and cancer. Many herbal remedies imported from Asia may contain potent pharmaceuticals, such as phenacetin and steroids, as well as toxic metals.

Medications

Vaccines are available to prevent influenza (See section on Viral Influenza Vaccines).

For mild influenza, symptom relief is similar to that for colds.

Two classes of antiviral agents have been developed to treat influenza: neuraminidase inhibitors and M2 inhibitors.

Brands and Benefits. Zanamivir (Relenza) and oseltamivir (Tamiflu) are neuraminidase inhibitors. They are newer agents that have been designed to block a key viral enzyme, neuraminidase, which is involved with viral replication. According to a major review of over 50 studies published in 2006, these drugs are effective against the flu in about 60% of cases.

Important points about the use of these drugs:

Neuraminidase inhibitors are effective for treating both A and B strains of influenza. (M2 inhibitors are effective only against type A.) However, their main benefit has been to reduce the length of symptoms by about one day, and only when started within 48 hours after symptoms become evident.
They may help reduce transmission of the virus.
They have a lower risk than M2 inhibitors for emerging viral strains that are resistant to their effects. However, The World Health Organization reports that viral resistance to oseltamivir (Tamiflu) can develop with extensive use. The level of resistance averaged 0.3% over 3 flu seasons surveyed in Japan (2003 - 2006). During that time, 35 million Japanese patients used the drug.
They have fewer serious side effects than the M2 inhibitors.
Both show some benefits for preventing influenza. Only oseltamivir has been approved for this purpose, however, and only in people over 13.
They may reduce complications of influenza, although this needs to be confirmed. It is not yet known if they have any effect on overall survival rates.
Oseltamivir is the only drug studied in avian flu cases. Although it is active in lab experiments, it has not been successful clinically. Experience is very limited, however, and it is not clear whether people infected with avian flu received the drug in time for it to be useful.

Limitations and Side Effects. Although they have many advantages compared to the M2 inhibitors, neuraminidase inhibitors are much more expensive. They also need to be taken within 2 days of the start of symptoms to be effective. Neither neuraminidase inhibitor is effective against influenza-like illness (one that is not caused by an influenza virus). There are also some differences between the two drugs that could be significant for some individuals:

Zanamivir is administered as a nasal spray or inhaler. People with asthma or other lung disorders may experience airway spasms and should use this drug with caution. Side effects are generally minor in most patients. It is important to make sure that elderly patients are able to properly use the zanamivir inhaler device.
Oseltamivir comes in capsule and liquid form. Side effects are also minor, but about 10 - 15% of patients experience nausea and vomiting. Patients with kidney dysfunction should take lower doses.

The current use of neuraminidase inhibitors in different age and patient groups is as follows:

Adults: Both drugs are approved for treatment in adult patients.
Children: Oseltamivir is approved for use in children age one and older. Studies report significant reduction in symptoms and in the incidence of ear infections in this population. However, studies from Japan point to the possibility of psychiatric side effects in children under 16 using oseltamivir. Zanamivir is approved for children over age 7, and studies are currently underway to determine its safety in younger children.
High-Risk Patients. Recent studies indicate neuraminidase inhibitors are safe and effective in patients with serious medical problems or other conditions that put them at risk for complications of flu.

Brands and Benefits. Amantadine (Symmetrel) and rimantadine (Flumadine) are M2 inhibitors. The following benefits may apply to the minority of strains of influenza A that remain sensitive to the drugs:

Both offer protection against influenza A and prevent severe illness if a person contracts the infection. (To be effective it must be administered within 2 days of onset.)
They may shorten the duration and lessen the severity of the flu if given within 48 hours of onset of symptoms.

Limitations. Drawbacks of M2 inhibitors include:

Viral resistance to these agents is rapidly emerging. For this reason, the Centers for Disease Control and Prevention Does not recommends M2 inhibitors for use during the 2007 - 2008 flu season in the United States.
M2 inhibitors are not effective against influenza B.
Neither drug has proven to reduce the risk for complications of the flu, including pneumonia and bronchitis.

Side Effects. Both M2 inhibitors occasionally cause nausea, vomiting, indigestion, insomnia, and hallucinations. Amantadine affects the nervous system and about 10% of people experience nervousness, depression, anxiety, difficulty concentrating, and lightheadedness. Rimantadine is less likely to do so. Rarely, amantadine can cause seizures, usually in elderly people already at risk for psychiatric symptoms.

Note: Amantadine is a standard treatment for Parkinson's disease and should be continued for that condition.

Flu Shots. These vaccines use inactivated (not live) viruses. They are designed to provoke the immune system to attack antigens contained on the surface of the virus. (Antigens are foreign molecules that the immune system specifically recognizes as alien and targets for attack.)

Unfortunately, the antigens in these influenza viruses undergo genetic changes (called antigenic drift) over time, so they are likely to become resistant to a vaccine that worked in the previous year. Vaccines are then redesigned annually to match the current strain.

Influenza A. The influenza A virus is further categorized by primary molecular antigens (hemagglutinin and neuraminidase), which serve as the targets for the vaccines. Influenza A is a particular problem, because it can infect other species, such as pigs or chicken, and undergo major genetic changes.
Influenza B viruses tend to be more stable than influenza A viruses, but they too vary. Although influenza B has been far less common than A, a vaccine for type B is important because experts are concerned that small children will not have developed any immunity to the virus, and will experience severe flu if they are exposed to type B viruses.

Intranasal (inside the nose) vaccine. A live but weakened intranasal vaccine (FluMist) is proving to be effective and safe in healthy, non-pregnant people aged 2 - 49 years and has been approved by the FDA. It is known as a live, attenuated, intranasal influenza vaccine (LAIV). The vaccine is engineered to grow only in the cooler temperatures of the nasal passages, not in the warmer lungs and lower airways. It boosts the specific immune factors in the mucous membranes of the nose that fight off the actual viral infections. FluMist is given using a nasal spray.

Timing and Effectiveness of the Vaccine. Ideally, people should be vaccinated every October or November. However, it may take longer for a full supply of the vaccine to reach certain locations. In such cases, the high-risk groups should be served first.

Antibodies to the influenza virus usually develop within 2 weeks of vaccination, and immunity peaks within 4 - 6 weeks, then gradually wanes.

Because children under age 8 do not develop strong immune responses to one dose, the CDC recommends two vaccinations given 1 month apart on the first year they receive the vaccine. If children under 8 received only 1 dose of the vaccine on their first immunization year, they should receive 2 doses the following year. Children under 8 who have received single doses for 3 or more years should continue to receive single doses.
It should be noted that if an individual develops influenza symptoms and is accurately diagnosed in time, vaccination of the other members of the household within 36 - 48 hours affords effective protection to those individuals.

In healthy adults, immunization typically reduces the chance of illness by about 70 - 90%. The current flu vaccines may be slightly less effective in certain patients, such as the elderly and those with certain chronic diseases. Even in people with a weaker response, however, the vaccine is usually protective against serious flu complications, particularly pneumonia. In fact, among the elderly, interesting studies are now suggesting that influenza vaccination may help protect against stroke, adverse heart events, and death from all causes.

Children Who Should Be Vaccinated. The following children over 6 months should be vaccinated against influenza:

The American Academy of Pediatrics (AAP) and the CDC recommend influenza vaccination in all healthy children between 6 and 59 months old.
In addition, any child over the age of 2 years with a condition that requires regular medical care or who has been hospitalized for a serious illness (particularly lung or kidney disease, diabetes, sickle-cell, or immune deficiencies). If parents are concerned about vaccines that contain the mercury preservative thimerosal, they can ask their doctor about reduced-thimerosal flu vaccine.
Children who come in direct contact with a person vulnerable to complications from influenza should also be vaccinated.
Children who are receiving long-term aspirin therapy should also be immunized against the flu because they are at higher risk for Reye syndrome, a life-threatening disease, if they get the flu.
Some experts now advocate flu shots for all school-age children. Emerging research indicates that children are responsible for transmitting the vast majority of cases of seasonal flu, and that routine vaccination of school-age children would considerably reduce transmission rates throughout communities.

Older Children and Adults Who Should Be Vaccinated. The following, in order of priority, are the population groups who should be vaccinated each year. The first two groups have the highest need for influenza vaccinations and are given top priority:

All adults 50 years and older. Vaccinated older adults have lower hospitalization rates than unvaccinated peers. Evidence now suggests that vaccination may help protect against adverse heart events (including those after heart surgeries), stroke, and death from all causes in the elderly. Still, studies suggest that only two thirds of the people in this group are vaccinated, mostly because of unwarranted fears of ineffectiveness or adverse effects.
People of any age at high risk for serious complications from influenza. Such people include those with heart disease, lung problems, immune deficiencies, diabetes, kidney disease, or chronic blood disease. Those with any condition that may compromise respiratory function or the handling of respiratory secretions, including people with cognitive dysfunction, spinal cord injuries, seizure disorders, or other neuromuscular disorders, are included in this group. (There have been concerns about the safety of the vaccinations in certain high-risk patients such as those with HIV or asthma. Studies now suggest that the vaccine is generally safe in these patient groups. Furthermore, their risk for serious complications from influenza outweighs any potential adverse effects from the vaccines.)
All health care workers should be vaccinated, according to the ACIP's recommendations.
Household members in contact with individuals who are at high-risk for complications from influenza should be vaccinated.

Other adults who should consider influenza vaccinations include:

People at risk for complications for influenza and who are traveling to the tropics at any time or to the Southern Hemisphere between April and September.
Pregnant women who are at risk for complications of influenza, and who will be in their second or third trimester during flu season. (Vaccinations should usually be given after the first trimester. Exceptions may be women who are in their first trimester during flu season and their risk from complications of the flu is higher than any theoretical risk to the baby from the vaccine.)
Police officers, firefighters, and other public safety officials.

Negative Effects. Possible negative responses to the vaccines include:

Allergic Reaction. Newer vaccines contain very little egg protein, but an allergic reaction still may occur in people with strong allergies to eggs.
Soreness at the Injection Site. Up to two thirds of people who receive the influenza vaccine develop redness or soreness at the injection site for 1 - 2 days afterward.
Flu-like Symptoms. Some people actually experience flu-like symptoms, called oculo-respiratory syndrome, which include cough, wheezing, tightness in the chest, sore throat, or a combination. Such symptoms tend to occur 2 - 24 hours after the vaccination and generally last up to 2 days. These symptoms are not influenza itself but an immune response to the virus proteins in the vaccine. (Anyone with a fever at the time the vaccination is scheduled, however, should wait to be immunized until the ailment has subsided.)
Guillain-Barre Syndrome. Although iIsolated cases of a paralytic illness known as Guillain-Barre syndrome occurred in about one of every 100,000 people vaccinated with the swine-flu vaccine in 1976, it has not been a problem with subsequent vaccines.
There has been some question concerning influenza vaccinations because of some reports that vaccines may worsen asthma. Recent and major studies have been reporting, however, that the vaccination is safe for children with asthma. It is also very important for these patients to reduce their risk for respiratory diseases.

The FDA approved the first vaccine for humans against H5NI influenza virus in April 2007. The vaccine, which is made from a human strain of the virus, could be used in people ages 18 - 64 to prevent the spread of the virus from human to human. The vaccine requires two shots, given about a month apart. It will not be sold commercially, but instead is being purchased by the U.S. government to be stockpiled and distributed to public health officials in the event of an outbreak of avian flu.

In a study, 103 healthy adults received two g shots of the virus, 28 days apart. An additional group of 300 adults received the vaccine at a lower dose, while 48 people received placebo injections. The study showed that 45% of those who received the higher dose developed antibodies that may reduce their risk of getting the avian flu. The most common side effects reported were pain at the injection site, headache, and muscle pain. Research on the vaccine is continuing.

The intense and widespread use of antibiotics is leading to a serious global problem of antibiotic resistance. The inappropriate use of powerful newer antibiotics for conditions such as colds or sore throats poses a particular risk for resistant strains of bacteria. For example, the number of cases of methicillin-resistant Staphylococcus aureus (MRSA) is increasing in people who have no known risk factors. (MRSA causes sometimes-fatal skin infections.) In 2006, rates of Neisseria gonorrhoeae resistance to the fluoroquinolone antibiotics family exceeded 10%. The CDC no longer recommends treating gonorrhea infections with fluoroquinolone first.

When Antibiotics Are Needed for Upper Respiratory Infections.

Antibiotics do not affect viruses and, in healthy individuals, these drugs are almost never necessary or helpful for influenza or colds, even with persistent cough and thick, green mucus. In one disturbing study, antibiotics were prescribed for nearly half of children who went to the doctor for a common cold.

Antibiotics may be required for upper respiratory tract infections only under certain situations, such as the following:

Patients, particularly small children or elderly people, who have medical conditions that put them at high risk for complications from any respiratory tract infections, should usually be given antibiotics.
Patients with severe sinusitis that does not clear up within 7 days (some experts say 10 days) and whose symptoms include one or more of the following: green and thick nasal discharge, facial pain, or tooth pain or tenderness.
Some children with middle ear infections, although experts differ on who will benefit. Some experts recommend that only children under the age of 2 years should be treated with antibiotics, and children over 2 should be treated on a case-by-case basis.
Patients with strep throat or severe sore throat that involves fever, swollen lymph nodes, and absence of cough. (Strep throat makes up only 10 - 15% of all sore throat cases.)
Patients who have an acute cough that is caused by pneumonia (but in few other cases, regardless of the duration of the cough). Experts estimate that, outside the hospital setting, less than 20% of prescriptions for persistent coughing are necessary.

Patients at Highest Risk for Infection with Resistant Bacteria Strains. Some patients are at greater risk for developing an infection resistant to common antibiotics. At this time, the average person is not endangered by this problem. Risk factors include:

Very old or very young age
Exposure to patients with drug-resistant infection
Hospitalization in intensive care
History of an invasive surgical procedure
Staying in the hospital
Prolonged course of antibiotics, particularly within the past 4 - 6 weeks
Serious wounds
Tubes down the throat, catheters, or intravenous (I.V.) lines
Immunosuppression

Children at higher risk for antibiotic resistance are those who attend day care, who are exposed to cigarette smoke, who were bottle-fed, and who had siblings with recurrent ear infections.

What the Health Care Community Is Doing. Prescribing antibiotics only when necessary is the most important step in restoring bacterial strains that are susceptible to antibiotics. Encouraging studies are reporting that inappropriate antibiotic prescriptions are on the decline. Prescriptions for other common respiratory infections, such as otitis media, sore throat, acute bronchitis, and colds and flus have been decreasing.

What Patients and Parents Can Do. Patients and parents can also help with the following tips:

Use home or over-the-counter remedies to relieve symptoms of mild upper respiratory tract infections.
Realize that antibiotics will not shorten the course of a viral infection. It is important for patients and parents to understand that although antibiotics may bring a sense of security, they provide no significant benefit for a person with viral infection, and overuse can contribute to the growing problem of resistant bacteria.
Don't pressure a doctor into prescribing an antibiotic if it is clearly inappropriate. The doctor very often will give in.
If a child needs an antibiotic, ask the doctor whether it is appropriate to use high-dose short-term antibiotics, which may lower the risk for developing resistant strains.
If an antibiotic is prescribed, take the full course, even if you feel better before finishing it.

Resources

www.cdc.gov/flu -- U.S. Centers for Disease Control and Prevention
www.niaid.nih.gov -- National Institute for Allergy and Infectious Diseases
www.who.int/csr/disease/influenza/en -- World Health Organization
www.cdc.gov/vaccines -- National Immunization Program
www.immunize.org -- Immunization Action Coalition
www.entnet.org -- American Academy of Otolaryngology -- Head and Neck Surgery
www.cdc.gov/flu/avian -- Avian Influenza Information

References

American Academy of Pediatrics Committee on Infectious Diseases. Recommended childhood and adolescent immunization schedule: United States, 2005. Pediatrics. 2005 Jan;115(1):182.

Caruso TJ, Prober CG, Gwaltney JM Jr. Treatment of naturally acquired common colds with zinc: a structured review. Clin Infect Dis. 2007;45(5):569-74.

Centers for Disease Control and Prevention. Key Facts About Seasonal Influenza (Flu). Available online.

Centers for Disease Control and Prevention. 2007-08 Influenza Prevention & Control Recommendations: Vaccination of Specific Populations. Available online.

Centers for Disease Control and Prevention. Acute Respiratory Disease Associated with Adenovirus Serotype 14 -- Four States, 2006-2007. MMWR. 2007;56(45):1181-84.

Centers for Disease Control and Prevention. FDA Approves New Laboratory Test To Detect Human Infections With Avian Influenza A/H5 Viruses. February 3, 2006.

Harper SA, Fukuda K, Uyeki TM, Cox NJ, Bridges CB. Prevention and Control of Influenza: Recommendations of the Advisory Committee on Immunization Practices (ACIP). MMWR Recomm Rep. 2005 Jul 29;54(RR-8):1-40.

Hayden GF, Turner RB. Acute Pharyngitis. In: Behrman RE, Kliegman RM, Jenson HB, eds. Behrman: Nelson Textbook of Pediatrics, 17th ed. Philadelphia, Pa: Saunders; 2004.

Interagency Task Force on Antimicrobial Resistance. Executive Summary: 2006 Annual Report on Progress on "A Public Health Action Plan to Combat Antimicrobial Resistance." Draft release, June 2007. Available online.

Jefferson T, Demichelli V, Rivetti D, Jones M, Di Pietrantonj C, Rivetti A. Antivirals for influenza in healthy adults: systematic review. Lancet 2006 Jan 28;367(9507):303-13.

Morantz CA. ACIP Updates Guidelines on Prevention and Control of Influenza. Am Fam Physician. 2005; 72(6); 1119-1127.

Reveiz L, Cardona AF, Ospina EG. Antibiotics for acute laryngitis in adults. Cochrane Database Syst Rev. 2007 Apr 18;(2):CD004783.

Sasazuki S, Sasaki S, Tsubono Y, Okubo S, Hayashi M, Tsugane S. Effect of vitamin C on common cold: randomized controlled trial. Eur J Clin Nutr. 2006;60(1):9 - 17.

Shah SA, Sander S, White CM, Rinaldi M, Coleman CI. Evaluation of echinacea for the prevention and treatment of the common cold: a meta-analysis. Lancet Infect Dis. 2007;7(7):473-80.

Simasek M, Blandino DA. Treatment of the common cold. Am Fam Physician. 2007;75(4):515-20.

Taverner D, Latte J. Nasal decongestants for the common cold. Cochrane Database Syst Rev. 2007 Jan 24;(1):CD001953.

U.S. Food and Drug Administration: Nonprescription Drugs and Pediatric Advisory Committee Meeting. Joint Meeting of the Nonprescription Drugs Advisory Committee and the Pediatric Advisory Committee October 18-19, 2007. Available online.

World Health Organization: Neuraminidase Inhibitor Susceptibility Network. Monitoring of neuraminidase inhibitor resistance among clinical influenza virus isolates in Japan during the 2003-2006 influenza seasons. Weekly epidemiological record. 2007;82(17):149-50.

World Health Organization. Cumulative Number of Confirmed Human Cases of Avian Influenza A/(H5N1) Reported to WHO. January 15, 2008. Available online.

Review Date:
1/18/2008
Reviewed By:
Harvey Simon, MD, Editor-in-Chief, Associate Professor of Medicine, Harvard Medical School; Physician, Massachusetts General Hospital. Also reviewed by David Zieve, MD, MHA, Medical Director, A.D.A.M., Inc.

A.D.A.M. Copyright

adam.com

Periodontal disease

FitSugar — Wed, 08 Oct 2008 17:35:31 -0700

In This Report

Highlights
Introduction
Symptoms
Causes
Risk Factors
Complications
Prevention
Diagnosis
Treatment
Medications
Other Treatments
Resources
References

HEALTH GUIDE REFERENCE FROM A.D.A.M

Highlights

Symptoms of Periodontal Disease

Symptoms of periodontal disease include red and swollen gums, persistent bad breath, and gum recession and loose teeth. Smoking, certain types of illnesses (diabetes), older age, and other factors increase the risk for periodontal disease. If you have periodontal disease, your dentist may refer you to a periodontist, a dentist who specializes in treating this condition.

Practice Good Dental Hygiene

Consistent good dental hygiene can help prevent gingivitis and periodontitis. The American Dental Association recommends that everyone:

Brush twice daily with a fluoride toothpaste (be sure to replace toothbrushes every 3 - 4 months).
Clean between the teeth with floss or an interdental cleaner.
Eat a well-balanced diet and limit between meal snacks.
Have regular visits with a dentist for teeth cleaning and oral examinations.

Mouthwashes

In 2007, the American Dental Association stated that antimicrobial mouthwashes may provide additional oral health benefits for preventing and reducing gingivitis and plaque. However, they are not a substitute for daily brushing and flossing.

Research

Intensive treatment of periodontal disease may help reduce inflammation and improve blood flow throughout the body, according to a small study published in 2007 in the New England Journal of Medicine. In the study of patients with severe periodontitis, intensive treatment ultimately resulted in improved endothelial function. Poor endothelial function is associated with increased risk for atherosclerosis and heart disease. Researchers are investigating the connection between periodontal disease and heart disease, and whether treatment of periodontal disease can reduce heart disease risk.

Introduction

Periodontal disease refers to a group of problems that arise in the sulcus, the gap between the gum and the tooth.

The part of the mouth that consists of the gum and supporting structures is called the periodontium. It is made up of the following parts:

Gum (gingiva). When healthy, the gingiva is pale pink, firm, and does not move. It has a smooth or speckled texture. The gingival tissue between teeth is shaped like a wedge.
The space between the gum and tooth, called the sulcus
Root surface (the cementum)
Connective tissue
Bone. The crest of the supporting bone, which can be viewed on x-rays, is normally 2 mm below the point where the crown of the tooth meets the root (the cementoenamel junction).

The structure of the tooth includes dentin, pulp and other tissues, blood vessels, and nerves imbedded in the bony jaw. Above the gum line, the tooth is protected by the hard enamel covering.

Periodontal diseases are generally divided into two groups:

Gingivitis, which causes lesions (wounds) that affect the gums
Periodontitis, which damages the bone and connective tissue that supports the teeth

The process starts with bacteria. Even in healthy mouths, the sulcus is teeming with bacteria, but they tend to be harmless varieties. Periodontal disease develops usually because of two events in the oral cavity: an increase in bacteria quantity and a change in balance of bacterial types from harmless to disease-causing bacteria. These harmful bacteria increase in mass and thickness until they form a film called plaque.

Click the icon to see an image of plaque and damaged gum tissue.

In healthy mouths, plaque itself actually provides some barrier against outside bacterial invasion. When it accumulates to excessive levels, however, plaque sticks to the surfaces of the teeth and adjacent gums and causes cellular injury, with subsequent swelling, redness, and heat.

When plaque is allowed to remain in the periodontal area, it transforms into calculus (commonly known as tartar ). This material has a rock-like consistency and grabs onto the tooth surface. It is much more difficult to remove than plaque, which is a soft mass.

The most important component leading to the disease process, however, is the body's persistent immune response to the bacterial plaque. Specific immune factors are released that cause inflammation and damage that eventually destroys the support structures and bone and can lead to tooth loss.

Gingivitis is an inflammation of the gingiva, or gums. Is nearly always chronic, but an acute form infrequently occurs.

Chronic Gingivitis. Ordinary chronic gingivitis affects over 90% of the population. It is characterized by tender, red, swollen gums that bleed easily and may be responsible for bad breath (halitosis) in some cases. Treatment is very effective if initiated early in the course of gingivitis. Without good management, however, the problem can progress.

Periodontitis is characterized by the following:

Gum inflammation, with redness and bleeding.
Deep pockets (greater than 3 mm in depth) form between the gum and the tooth.
Loose teeth, caused by loss of connective tissue structures and bone.

Gingivitis precedes periodontitis, although it doesn't always lead to this more severe condition. In fact, some experts believe it is an entirely different disease. There are different categories of periodontal disease, including:

Chronic Periodontitis. Chronic periodontitis (also referred to as adult periodontitis) may begin in adolescence as a slowly progressing disease that becomes clinically significant in the mid-30s and continues throughout life. Some experts question whether it is a chronic, unrelenting condition and instead suggest that it waxes and wanes depending on the response of the immune system.

Aggressive Periodontitis. Aggressive periodontitis (also referred to as early onset periodontitis) often occurs in young people. It is subdivided according to whether it begins before or after puberty. Immune deficiencies and a genetic link have been shown to be possible factors for all types of aggressive periodontitis. If the condition is localized and treated, the outlook is positive. People with severe and widespread aggressive periodontitis are at high risk for tooth loss.

Periodontitis that occurs before puberty is very rare. It begins with the eruption of primary teeth in the first year and causes severe inflammation and bone and tooth loss.
Juvenile periodontitis begins at puberty and is defined by severe bone loss around the first molars and incisors. It is more common in girls than in boys. The clinical signs -- such as inflammation, bleeding, and heavy plaque accumulation -- are not present in this relatively rare disease. The treatment is the same as in chronic periodontitis.
Rapidly progressive periodontitis occurs in the early 20s to mid-30s. Severe inflammation and rapid bone and connective tissue loss occur, and tooth loss is possible within a year of onset.

Disease-Related Periodontitis. Periodontitis can also be associated with a number of systemic diseases, including type 1 diabetes, Down syndrome, AIDS, and several rare disorders of white blood cells.

Acute Necrotizing Periodontal Disease. Acute necrotizing periodontal disease is an acute infection in the gums. It is characterized by:

Black, dead tissue (necrosis)
Spontaneous bleeding
Rapid onset of pain
Bad odor
Blunted gum tissue (tissue is normally cone-shaped)

Stress, poor diet, smoking, and viral infections are predisposing factors for this acute necrotizing periodontal disease.

Symptoms

In general, symptoms progress over time and include:

Red and Swollen Gums
Gum Bleeding. Bleeding of the gums, even during brushing, is a sign of inflammation and the major marker of periodontal disease. One exception is juvenile periodontitis, in which symptoms are mild or even absent. It should be noted that the gums of smokers with periodontal disease tend to bleed less than nonsmokers.
Bad Breath. Debris and bacteria can cause a bad taste in the mouth and persistent bad breath.
Gum Recession and Loose Teeth. As the disease advances the gums recede, and supporting structure of bone is lost. Teeth loosen, sometimes causing a change in the way the upper and lower teeth fit together when biting down or a change in the fit of partial dentures.

Abnormally bulging, protruding, or swollen gums are a possible sign of disease.

Click the icon to see an image of recessed gums.

Abscesses. Deepening periodontal pockets between the gums and bone can become blocked by tartar or food particles. Infection-fighting white blood cells become trapped and die. Pus forms, and an abscess develops. Abscesses can destroy both gum and tooth tissue, cause nearby teeth to become loose and painful, and may cause fever and swollen lymph nodes.

Click the icon to see an image of a tooth abscess.

Pain is usually not a symptom, which partly explains why the disease may become advanced before treatment is sought and why some patients avoid treatment even after periodontitis is diagnosed.

Causes

Periodontal disease is marked by bacterial overgrowth. However, a persistent immune response to chronic infections in the mouth is believed to play a major role in gum destruction.

In the healthy mouth, more than 350 species of microorganisms have been found. Periodontal infections are linked to fewer than 5% of these species. Healthy and disease-causing bacteria can generally be grouped into two categories:

The harmless or helpful bacteria are usually known as gram positive aerobic bacteria.
In periodontal disease, the bacterial balance shifts over to gram negative anaerobic bacteria. Inflammatory disease and injury cannot develop without these bacteria.

Following are some of the bacteria most implicated in periodontal disease and bone loss:

Actinobacillus actinomycetemcomitans and Porphyromonas gingivalis. These two bacteria appear to be particularly likely to cause aggressive periodontal disease. Both P. gingivalis and A. actinomycetemcomitans, along with multiple deep pockets in the gum, are associated with resistance to standard treatments for gum disease. P. gingivalis may double the risk for serious gum disease. P. gingivalis produces enzymes, such as one called arginine-specific cysteine proteinase, which may be the specific destructive factors that disrupt the immune system and lead to subsequent periodontal connective tissue destruction.
Bacteroides forsythus is also strongly linked to periodontal disease.
Other bacteria associated with periodontal disease are Treponema denticola, T. socranskii, and P. intermedia. These bacteria, together with P. gingivalis, are frequently present at the same sites, and are associated with deep periodontal pockets.

Some bacteria are related to gingivitis, but not plaque development. They include various streptococcal species.

Evidence now suggests that periodontal disease is an autoimmune disorder, in which immune factors in the body attack the person's own cells and tissue -- in this case, those in the gum. It appears to work as follows:

The bacteria that form plaque and tartar release toxins that stimulate the immune system to overproduce powerful infection-fighting factors called cytokines.
Ordinarily, cytokines are important for healing. In excess, however, they can cause inflammation and severe damage. Cytokines of particular importance in periodontal disease are known as tumor necrosis factor-alpha (TNF-alpha) and interleukin-1beta, which are very active in the mouth, and are important in causing destructive inflammation.
In addition, white blood cells produced by the immune response to bacteria also release a family of enzymes called matrix metalloproteinases (MMPs), which break down connective tissue.

Studies suggest that this inflammatory response may have damaging effects not only in the gums but also in organs throughout the body, including the heart.

Certain herpes viruses (herpes simplex and varicella-zoster virus, the cause of chickenpox and shingles) are known causes of gingivitis. Other herpes viruses (cytomegalovirus and Epstein-Barr) may also play a role in the onset or progression of some types of periodontal disease, including aggressive and severe chronic periodontal disease. All herpes viruses go through an active phase followed by a latent phase and possibly reactivation.

Some experts theorize that these viruses may cause periodontal disease in different ways, including release of tissue-destructive cytokines, overgrowth of periodontal bacteria, suppressing immune factors, and initiation of other disease processes that lead to cell death.

Risk Factors

More than 75% of American adults have some form of gum disease, but according to a major survey, only 60% have any significant knowledge about the problem. Gum inflammation and ulcers are common, and not all people with these problems develop periodontal disease. Still, about 30% of people are genetically susceptible to periodontal disease. Other factors also put individuals at higher risk.

Lack of Oral Hygiene. Lack of oral hygiene encourages bacterial buildup and plaque formation.

Sugar and Acid. The bacteria that cause periodontal disease thrive in acidic environments. Therefore, eating sugars and other foods that increase the acidity in the mouth increase bacterial counts.

Poorly Contoured Restorations. Poorly contoured restorations (fillings or crowns) that provide traps for debris and plaque can also contribute to its formation.

Anatomical Tooth Abnormalities. Abnormal tooth structure can increase the risk.

Wisdom Teeth. Wisdom teeth, also called third molars, can be a major breeding ground for the bacteria that cause periodontal disease. In fact, for patients in their 20s, periodontal disease is most likely to occur around the wisdom teeth. Research suggests that periodontitis can occur in wisdom teeth that have broken through the gum as well as teeth that are impacted (buried). Periodontal disease can also be present even in patients with wisdom teeth who do not have any symptoms. Experts recommend that adolescents and young adults with wisdom teeth should have a dentist check for signs of periodontal disease

Children and Adolescents. Gingivitis, in varying degrees, is nearly a universal finding in children and adolescents. In rare genetic cases, children and adolescents are subject to destructive forms of the disease. Researchers have also observed some of the organisms seen in periodontal disease in young children without signs of gum problems. Healthy children, however, do not generally harbor two primary periodontal bacteria, P. gingivalis and T. denticola. The disease is also uncommon in teenagers.

Adults. One survey reported that 3.6% of adults between the ages of 18 - 34 had periodontal disease. As people age, the risk for periodontal disease increases. Over half of American adults have gingivitis surrounding 3 - 4 teeth, and 30% have significant periodontal disease surrounding 3 - 4 teeth. In a study of people over 70 years old, 86% had at least moderate periodontitis and over a quarter of them had lost their teeth.

About three-quarters of periodontal office visits are made by women, even though women tend to take better care of their teeth than men. Female hormones affect the gums, and women are particularly susceptible to periodontal problems. Hormone-influenced gingivitis appears in some adolescents, in some pregnant women, and is occasionally a side effect of birth control medication.

Before Menstruation. Gingivitis may flare up in some women a few days before they menstruate, when progesterone levels are high. Gum inflammation may also occur during ovulation. Progesterone dilates blood vessels causing inflammation, and blocks the repair of collagen, the structural protein that supports the gums.

Pregnancy. Hormonal changes during pregnancy can aggravate existing gingivitis, which typically worsens around the second month and reaches a peak in the eighth month. Pregnancy does not cause gum disease, and simple preventive oral hygiene can help maintain healthy gums. Any pregnancy-related gingivitis usually resolves within a few months of delivery. Because periodontal disease can increase the risk for low-weight infants and cause other complications, it is important for pregnant women to see a dentist.

Oral Contraceptives. Some studies report that oral contraceptives containing the synthetic progesterone desogestrel (but not dienogest, another common progesterone) increase the risk for periodontal disease.

Menopause. Estrogen deficiency after menopause reduces bone mineral density, which can lead to bone loss. Bone loss is associated with both periodontal disease and osteoporosis. Bone loss in the alveolar bone (which holds the tooth in place) may be a major predictor of tooth loss in postmenopausal women. Periodontal disease is the main cause of alveolar bone loss. During menopause, some women may also develop a rare condition called menopausal gingivostomatitis, in which the gums are dry, shiny, and bleed easily. Women may also experience abnormal tastes and sensations (such as salty, spicy, acidic, burning) in the mouth.

Periodontal disease often occurs in members of the same family. Genetics, intimacy, hygiene, or a mixture of factors may be responsible. Studies have found that children of parents with periodontitis are 12 times more likely to have the bacteria thought to be responsible for causing plaque and, eventually, periodontal disease.

Genetic Factors. Genetic factors may play the critical role in half the cases of periodontal disease. Up to 30% of the population may have some genetic susceptibility to periodontal disease. For example, some people with severe periodontal disease have genetic factors that affect the immune factor interleukin-1 (IL-1), a cytokine involved in the inflammatory response. Such individuals are up to 20 times more likely to develop advanced periodontitis than those without these genetic factors. Early onset and rapidly progressive periodontal disease also have strong genetic components.

Intimacy. Intimate partners and spouses of people with periodontal disease may also be at risk. Researchers have found that the bacteria P. gingivalis may be contagious after exposure to an infected person over a long period of time. There is no risk from short exposure such as after a fast kiss or when sharing an eating utensil.

Smoking is the single major preventable risk factor for periodontal disease. The habit can cause bone loss and gum recession even in the absence of periodontal disease. A number of studies indicate that smoking and nicotine increase inflammation by reducing oxygen in gum tissue and triggering an over-production of immune factors called cytokines (specifically ones called interleukins). In excess, cytokines are harmful to cells and tissue.

Furthermore, when nicotine combines with oral bacteria, such as P. gingivalis, the effect produces even greater levels of cytokines and eventually leads to periodontal connective tissue breakdown. Studies suggest that smokers are 11 times more likely than nonsmokers to harbor the bacteria that cause periodontal disease and four times more likely to have advanced periodontal disease. In one study more than 40% of smokers lost their teeth by the end of their lives.

The risk of periodontal disease increases with the number of cigarettes smoked per day. Smoking cigars and pipes carries the same risks as smoking cigarettes. Exposure to secondhand smoke is also associated with a 50 - 60% increased risk for developing periodontal disease, according to one study. Fortunately, when smokers quit, their periodontal health gradually recovers to a state comparable to that of nonsmokers.

Diabetes. Much evidence exists on the link between type 1 and 2 diabetes and periodontal disease. Diabetes causes changes in blood vessels, and high levels of specific inflammatory chemicals such as interleukins, that significantly increase the chances of periodontal disease. High levels of triglycerides (which are common in type 2 diabetes) also appear to impair periodontal health. Obesity, common in people with type 2 diabetes, may also predispose a person to gum disease. Controlling both type 1 and 2 diabetes may help reduce periodontal problems. For children with diabetes, good oral hygiene should begin at a young age. A 2006 study suggested that gum problems can start as early as 6 years of age in children with diabetes.

Osteoporosis and Osteonecrosis. Osteoporosis (loss of bone density) has been associated with periodontal disease in postmenopausal women. There have also been a few reports of osteonecrosis (bone decay) of the jaw in patients who take oral bisphosphonate drugs such as alendronate (Fosamax). Symptoms of osteonecrosis of the jaw include loose teeth, exposed jawbone, pain or swelling in the jaw, gum infections, and poor healing of the gums. As a precaution, the American Dental Association (ADA) recommends that patients who are prescribed bisphosphonate drugs get a thorough dental exam before beginning drug therapy, or as soon as possible after beginning therapy. The ADA also recommends that patients who take oral bisphosphonate drugs should discuss with their dentists any potential risks from dental procedures (such as extractions and implants) that involve the jawbone. In any case, be sure to inform your dentist if you are taking a bisphosphonate drug.

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

Giving intravenous bisphosphonates to patients being treated for bone cancer, or other cancers that have spread to the bone, increases their risk for developing osteonecrosis by 1 - 10%. Patients who take oral bisphosphonate drugs also have a slight risk, but 94% of osteonecrosis of the jaw cases involve patients who received bisphosphonates intravenously. If possible, see a dentist for a complete oral exam before beginning bisphosphonate therapy. In any case, be sure to inform your dentist if you are receiving intravenous bisphosphonates. Your dentist or oral surgeon may need to take special precautions when performing dental surgery

Herpes-Related Gingivitis. Herpes virus is a common cause of gingivitis in children and has become increasingly common in adults. It typically starts out with a purplish color and "boggy" sensation in the gums. Multiple blisters may form across the mucus membranes in the mouth and gums, followed by ulcers. They usually resolve in 7 - 14 days.

HIV-Associated Gingivitis. HIV-associated gingivitis has been reported in 15 - 50% of patients with HIV or AIDS. HIV-positive individuals harbor larger numbers of periodontal bacteria (candida albicans, P. gingivalis, black-pigmented anaerobic rods, and A. actinomycetemcomitans) than people without HIV. Severe pain is characteristic, along with odor, spontaneous bleeding, ulcers, and swollen, bright red gums. The inflammation never recedes, but halitosis and acute episodes can be managed by conventional cleaning treatments. Its severest form, known as necrotizing stomatitis, can be diagnostic for AIDS. In addition to bleeding, the gums in the front of the mouth are a yellowish-gray color, and bone thrusts out.

Autoimmune Diseases. Autoimmune conditions (Crohn's disease, multiple sclerosis, rheumatoid arthritis, lupus erythematosus, CREST syndrome) have been associated with a higher incidence of periodontal disease. Some research suggests that periodontal disease may even play some causal role. For example, one study suggested that P. gingivalis, one of the major bacteria in periodontal disease, was associated with destructive processes in the brain leading to multiple sclerosis. Still, more research is needed to determine a definitive association between these diseases.

Other Diseases. People with tuberculosis, syphilis, Wegener's granulomatosis, amyloidosis, and many genetic disorders are also at higher risk for periodontitis.

Vitamin C helps the body repair and maintain connective tissue, and its antioxidant effects are important in the presence of tissue-destroying oxidants in periodontal disease. Research indicates that vitamin C deficiency contributes to periodontal disease. A study of more than 12,000 adults found that people who consumed less than the recommended daily allowance of vitamin C, 60 mg (about one orange) were 1.5 times more likely to develop severe gingivitis than those who consumed more than 180 mg each day. Vitamin C levels are especially depleted in smokers. Eating citrus fruits high in vitamin C (such as grapefruit) may be helpful for patients with periodontitis.

Click the icon to see an image of the benefits of vitamin C.

Click the icon to see an image of the sources of vitamin C.

Dental disease is most likely to affect the poor. Children and the elderly suffer the worst oral care, and ethnic minorities follow. In the United States, the lack of access to dental insurance is a contributing factor. In a survey of residents of five states (Arizona, California, Hawaii, Oregon, and Wisconsin), the rate of total tooth loss was less than 20%. In three states (Kentucky, Louisiana, and West Virginia) it was greater than 40%.

Gingival overgrowth can be a side effect of nearly 20 different drugs, most commonly phenytoin (Dilantin), cyclosporine (Sandimmune), and a short-acting form of the calcium channel blocker nifedipine (Procardia).

Several other conditions can also cause gum inflammation, and some have been associated with periodontal disease. They include:

Mouth breathing
Psychologic stress. Stress can affect the immune system. Some studies suggest that stress can influence the development of chronic inflammatory diseases, like periodontitis.
Alcohol abuse. One study reported a higher incidence of periodontal disease, tooth decay, and possibly precancerous areas in patients who abuse alcohol.
Canker sores (aphthous ulcers)

Click the icon to see an image of a canker sore.

Self-injury in psychologically disturbed patients
Hereditary gingival fibromatosis. A rare genetic disease associated with both gum overgrowth and hairiness. It is often associated with gingivitis and periodontal disease.
Desquamative gingivitis. With this condition the outer layer of the gum tissue desquamates (peels away), exposing an acutely red surface. It usually occurs as a result of an allergic reaction or of skin diseases such as lichen planus, benign mucous membrane pemphigoid, bullous pemphigoid, and pemphigus vulgaris. (Bacteria may also play a role in this gum disease.) This condition generally resolves when the underlying problem is treated. It is fairly common in middle-aged women.

Complications

The ultimate outcome of uncontrolled periodontal disease is tooth loss. As the destructive factors cause the breakdown of bone and connective tissue, teeth lose their anchor.

A much less severe but nevertheless distressing problem caused by periodontal disease is bad breath, although coatings on the tongue may contribute more to bad breath than periodontal disease.

Studies have reported that people who have heart disease have a 1.5 - 4 times increased risk for periodontal disease. (The risk is highest for patients with extensive gum disease, bleeding from every tooth.) Acute coronary syndrome, high blood pressure (hypertension), and high cholesterol have also been associated with periodontal disease.

Periodontal disease has also been linked to stroke and coronary artery disease (CAD). The more severe the periodontitis, the greater the risk for heart problems. Many experts, however, are still not sure whether periodontal disease is a risk factor for stroke or a marker that reflects various risk factors common to both conditions.

A stroke is caused by a loss of blood circulation to areas of the brain. The blockage usually occurs when a clot or piece of atherosclerotic plaque breaks away from another area of the body and lodges within the blood vessels of the brain.

Recent evidence suggests that the inflammatory response may be the common element. This is an over-reaction of the immune system that causes injury to tissues in the body. A common link between patients with heart conditions and periodontal disease may be elevated levels of C-reactive protein (CRP), a marker for the inflammatory response. Some experts believe that immune factors causing this response are released into the bloodstream during periodontal disease and cause injury in the arteries supplying blood to the heart.

Other evidence suggests that the periodontal disease bacteria themselves -- particularly P. gingivalis, T. denticola, T. forsythia, and streptococci species -- may be the main culprit. In 2005, results from the NIH-sponsored Oral Infections and Vascular Disease Epidemiology Study (INVEST) determined an association between cardiovascular disease and the bacteria that cause periodontal disease. In this study, higher levels of periodontal bacteria were associated with thicker carotid arteries (a predictor of heart attack and stroke), regardless of C-reactive protein levels. While this study's findings are an important advance in understanding the relationship between periodontal and heart disease, it is still not clear if periodontal disease actually causes heart disease. Researchers hope that future results from INVEST will clarify this issue.

Experts are still not sure if treating gum disease can reduce the risks of heart disease and improve health outcomes for patients with periodontal disease and vascular heart problems. Studies have been mixed, but research is ongoing.

Diabetes is not only a risk factor for periodontal disease -- periodontal disease itself can worsen diabetes. Some evidence suggests that the bacteria that causes periodontal disease may enter the bloodstream and activate cytokines (damaging immune system factors), which then destroy cells in the pancreas where insulin is produced. Some studies indicate that treating periodontal disease can reduce the need for insulin and improve blood sugar control in some people with diabetes.

Bacteria that reproduce in the mouth can also be carried into the airways in the throat and lungs, increasing the risks for respiratory diseases and worsening chronic lung conditions, such as emphysema.

Click the icon to see an image of emphysema.

Many studies strongly indicate that bacterial infections that cause moderate-to-severe periodontal disease in pregnant women can increase the risk for premature delivery and low birth weight infants. The more severe the infection, the greater the risk to the baby. Research indicates that bacteria from gum disease and tooth decay may trigger the same factors in the immune system as genital and urinary tract infections. These biologic substances, called prostaglandins and tumor necrosis factor, produce inflammation in the cervix and uterus that can cause premature dilation and contractions. Research also suggests that periodontal disease increases the risk for preeclampsia, a life-threatening disorder that occurs in mid- to late pregnancy and is characterized by high blood pressure.

Experts recommend that women have a periodontal examination before becoming pregnant or as soon as possible thereafter. Because women with diabetes are at higher risk for periodontal disease, it is especially important that they see a dentist early in pregnancy. Experts are still not sure if treating periodontal disease can improve birth outcomes. A 2006 study in the New England Journal of Medicine indicated that the treatment does not affect pre-term birth or birth weight. However, the researchers reported that periodontal treatment is definitely safe for pregnant women.

Prevention

Healthy habits and good oral hygiene are critical in preventing gum disease. Regular and effective tooth brushing and mouth washing, however, are effective only above and slightly below the gum line. Once periodontal disease develops, more intensive treatments are needed.

It is important to reduce both the quantity and, in particular, the frequency of sugar intake. Avoid snacks and drinks with sugar (other than natural sugars found in fruits and vegetables). Eat sugar-containing foods with meals, ideally followed by brushing. Since fruit juices can also cause tooth erosion in children, parents should emphasize milk and water.

Smoking may play a significant role in over half the cases of chronic periodontal disease, according to research published in 2000. For smokers, quitting is one of the most important steps toward regaining periodontal health.

Fluoride treatment in children has helped to account for the decline in periodontal disease in adults. Because fluoride prevents decay, back molars, which keep the teeth in place, are spared, and are thus less vulnerable to bacteria. Even before teeth first erupt, babies' gums should be wiped clean with a bit of gauze bearing a dab of fluoride toothpaste. Supplementation with fluoride tablets or drops may be recommended for children 6 months or older who drink unfluoridated water or who are at risk for dental problems. A prescription from the child's pediatrician or dentist is required.

Some dentists recommend a fluoride gel for adult patients who are still at risk for tooth decay or sensitivity, but extra fluoride is generally not necessary for adults who use fluoride toothpaste.

Periodontitis is a silent disease. People with the disease rarely experience pain and may not be aware of the problem. A periodontal examination by a general dentist once or twice a year should reveal any incipient or progressive problems. A full mouth series of x-rays is advised every 2 - 3 years. This will alert the dentist to early bone loss and other disorders of the oral cavity.

Dentists now often perform Periodontal Screening and Recording (PSR) using a probe to measure gum pockets. Previously performed only by periodontists, this procedure is now encouraged as part of a regular dental examination. The dentist will identify any areas where deep pocketing has occurred, where the health of the gingiva appears compromised, and where there is undue mobility of teeth. It is the general dentist's responsibility to identify periodontal disease and inform the patient. If the condition is severe, the dentist may want to refer the patient to a periodontist.

Correct tooth brushing, mouth cleansing, and flossing should be everyone's defense against periodontal disease. (However, good hygiene is probably not sufficient to prevent periodontal disease in many people. Regular visits to a dentist are extremely important, especially for high-risk individuals.)

Brushing Guidelines. The following are some recommendations for brushing:

Use a dry brush. One study reported that when people brushed their teeth without toothpaste first, using a soft dry brush, their plaque deposits were reduced by 67%, and gum bleeding dropped by 50%.
No brush of any size, shape, or gimmick is effective if it is incorrectly positioned in the mouth. Place the brush where the gum meets the tooth, with bristles resting along each tooth at a 45-degree angle.
Begin by dry brushing the inside the bottom row of teeth, then the inner top teeth, and last the outer surfaces.
Wiggle the brush back and forth so the bristles extend under the gum line.
Scrub the broad, biting surfaces of the back teeth.
Dry brushing should take about a minute and a half.
A paste is then applied, and the teeth should again be brushed in the same way.
The tongue should be scrubbed for a total of about 30 seconds. A tongue scraper used with an anti-bacterial mouthwash (such as Listerine) is more effective than a toothbrush in removing bacteria.
Rinse the toothbrush thoroughly and then tap it on the edge of the sink at least five times to get rid of debris.
Flossing should finish the process. A mouthwash may also be used.

If brushing after each meal is not possible, rinsing the mouth with water after eating can reduce bacteria by 30%.

Toothbrushes. A vast assortment of brushes of varying sizes and shapes are available, and each manufacturer makes its claim for the benefits of a particular brush. Look for the American Dental Association (ADA) seal on both electric and regular brushes.

In spite of the wide variety of nonelectric toothbrushes, both in shape and bristle design, a study of eight brands found no significant differences in effectiveness among them.

Electric toothbrushes, particularly those with a stationary grip and revolving tufts of bristles, can be advantageous for some people with physical disabilities. Electric toothbrushes with heads that move back and forth up to 4,200 times a minute remove significantly more plaque than ordinary brushes. Even more high-tech brushes are now available that use sound waves to remove plaque.

In general, studies have reported no differences between electric and manual toothbrushes in their ability to remove plaque. (One study showed considerable improvement in groups using sonic toothbrushes, particularly in those with moderate periodontal disease.) Experts recommend, however, that if a regular toothbrush works, it isn't necessary to buy an expensive electric one.

For individuals with average dexterity, a four- or five-rowed, soft, nylon-bristled toothbrush is sufficient. The most important factor in buying any toothbrush, electric or manual, is to choose one with a soft head. Soft bristles get into crevices easier and do not irritate the gums, thereby reducing the risk of exposing teeth below the gum line compared to hard brushes.

Experts generally recommend replacing toothbrushes every 1 - 3 months. Not only do they become breeding grounds for bacteria, but the worn bristles are less effective at removing plaque.

Toothpaste. The object of a good toothpaste is to reduce the development of plaque and eliminate periodontal-causing microorganisms without destroying the organisms that are important for a healthy mouth. All brands should show ADA approval. Even a good toothpaste, however, cannot be delivered past 3 mm below the gum line, where periodontitis develops.

Toothpastes are a combination of abrasives, binders, colors, detergents, flavors, fluoride, humectants, preservatives, and artificial sweeteners. Avoid highly abrasive toothpastes, especially for individuals whose gums have receded.

Ingredients contained in toothpastes may include:

Fluoride. Most commercial toothpastes contain fluoride, which both strengthens tooth enamel against decay and enhances remineralization of the enamel. Fluoride also inhibits acid-loving bacteria, especially after eating, when the mouth is more acidic. This antibacterial activity may help control plaque.
Triclosan. Triclosan is an anti-bacterial substance that may help reduce mild gingivitis.
Metal salts. Metal salts, such as stannous and zinc, serve mostly as anti-bacterial substances in toothpastes. Stannous fluoride gel toothpastes do not reduce plaque, however, even though they have some effect against the bacteria that cause it, but slightly reduce gingivitis.
Peroxide and baking soda. Toothpastes with these ingredients claim to have a whitening action, but while they may help remove stains there is little evidence they whiten the actual color of the teeth. In addition, these substances appear to offer no benefits against gum disease.
Antibacterial sugar substitutes (xylitol), and detergents (delmopinol)

Mouthwashes. The American Dental Association recommends (in addition to daily brushing and flossing) antimicrobial mouthwash to help prevent and reduce plaque and gingivitis, and fluoride mouthwashes to help provide additional protection against tooth decay.

Chlorhexidine (Peridex or PerioGard) is an antimicrobial mouthwash available by prescription only. It reduces plaque by 55% and gingivitis by 30 - 45%. Patients should rinse for 1 minute twice daily. They should wait at least 30 minutes (and preferably 2 hours) between brushing and rinsing since chlorhexidine can be inactivated by certain compounds in toothpastes. It has a bitter taste. It also binds to tannins, which are in tea, coffee, and red wine, so it has tendency to stain teeth in people who drink these beverages. Studies are mixed as to its effectiveness for preventing or reducing periodontal disease.
Listerine is another antimicrobial mouthwash. It is composed of essential oils and is available over the counter. It reduces plaque and gingivitis, when used for 30 seconds twice a day. It leaves a burning sensation in the mouth that most people better tolerate after a few days of use. The usual regimen is to rinse twice a day. (Listerine PocketPaks, which are strips that dissolve on the tongue, have no proven effects on plague and gingivitis.)
Mouthwashes containing cetylpyridinium (Scope, Cepacol) have moderate antimicrobial effect on plaque, but only if they are used an hour after brushing. None are as effective as Listerine or chlorhexidine, but they may still have some value for people who cannot tolerate the other mouthwashes.
Mouthwashes containing stannous fluoride and amine fluoride (Meridol) are moderately effective, but are also not as effective as effective as Listerine or chlorhexidine.
Fluoride mouthwashes (Act) are helpful in preventing cavities.
Mouthwashes that contain alcohol are dangerous for children and should be kept away from them.

Flossing. The use of dental floss, either waxed or unwaxed, is critical in cleaning between the teeth where the toothbrush bristles cannot reach. In spite of this, nearly two-thirds of people do not floss.

To floss correctly, the following steps may be helpful:

Break off about 18 inches of floss and wind most of it around the middle finger of one hand and the rest around the other middle finger.
Hold the floss between the thumbs and forefingers and gently guide and rub it back and forth between the teeth.
When it reaches the gum line, the floss should be curved around each tooth and slid gently back and forth against the gum.
Finally, rub gently up and down against the tooth. Repeat with each tooth, including the outside of the back teeth.
If, on repeated flossing attempts, the floss becomes shredded or cannot be removed easily from between the teeth, a rough crown or overhanging filling may be the cause. In such cases, the restoration should be redone. Such areas create spaces for the collection of food debris, plaque, and calculus.

Here are some tips in choosing the right floss or flossing device:

Use a floss that does not shred or break.
Avoid a very thin floss, which can cut the gum if brought down with too much force or not guided along the side of the tooth.
A floss threader is an invaluable aid for the person who has bridgework. Made of plastic, it looks like a needle with a huge eye, or loop. A piece of floss is threaded into the loop, which can then be inserted between the bridge and the gum. The floss that is carried through with it can then be used to clean underneath the false tooth or teeth and along the sides of the abutting teeth.
Another handy device for cleaning under bridges is a Proxabrush, which is an interdental cleaner. This is a tiny narrow brush that can be worked in between the natural teeth and around the attached false tooth or teeth.
Special toothpicks such as Stim-U-Dent may be effective for wide spaces between teeth but should never replace flossing. Standard toothpicks should never be used for regular hygiene.
Electronic products, such as water piks, are also helpful. These devices are expensive but may improve flossing compliance.

Producing Saliva and Drinking Water. Saliva is important for diluting the toxins created by plaque. Drinking at least 7 glasses of water a day helps reduce inflammation in the mouth by producing more saliva. Increasing water intake is particularly important as one ages, when less saliva is produced.

Diagnosis

The dental practitioner typically performs a number of procedures to determine a diagnosis of periodontal disease.

The dentist will first take a medical history to reveal any past or present periodontal problems, any underlying diseases that might be contributing to the problem, and any medications the patient is taking. After noting the general state of oral hygiene, the dentist may ask about the quality of home dental care.

Inspection of the Gum Area. The dentist inspects the color and shape of gingival tissue on the cheek (buccal) side and the tongue (lingual) side of every tooth and compares these qualities to the healthy ideal. Redness, puffiness, and bleeding upon probing indicate inflammation. If the gum formation between teeth is blunt and not pointed, acute necrotizing periodontal disease may be indicated.

Periodontal Screening and Recording (PSR). PSR is a painless procedure used to measure and determine the severity of periodontal disease:

The dentist uses a mirror and a periodontal probe, a fine instrument calibrated in millimeters (mm), which is used to measure pocket depth. (A new automatic probing device may prove to be even more sensitive and accurate than the standard manual probe that most dentists use.)
The probe is held along the length of the tooth with the tip placed in the pocket. The tip of the probe will then touch the point where the connective tissue attaches to the tooth.
The dentist will "walk" the probe to six specified points on each tooth, three on the buccal (cheek) and three on the lingual (tongue) sides. The dentist measures the depth of the probe at each point.
Pocket depths greater than 3 mm indicate disease.

These measurements help determine the condition of the connective tissue and amount of gingival overgrowth or recession. PSR appears to be even more reliable than x-rays in diagnosing gum disease.

Testing Tooth Movement. Tooth mobility is determined by pushing each tooth between two instrument handles and observing any movement. Mobility is a strong indicator of bone support loss.

X-rays. X-rays are taken to show any loss of bone structure supporting the teeth. Eighteen x-rays make up the full mouth series necessary for diagnosis.

Treatment

Studies support the effectiveness of active treatment combined with a strict maintenance program for patients with periodontal disease. In one study, for example, people with periodontal disease who were inconsistent in caring for their gums after treatment had 5.6 times the risk for tooth loss as those who were very vigilant.

Some dentists have reported a success rate of 85% when professional treatment and good home maintenance are combined. Treatment helps nonsmokers more than smokers, particularly when pockets are deep and persistent. Some studies suggest that periodontal treatment in people with type 2 diabetes helps improve blood sugar levels. Whether treatment will help reduce other health risks, including heart attack and stroke, is unknown.

Treatment Goals. Once periodontal disease has been identified, the goals of treatment are:

To arrest and control the progress of the disease
To leave the periodontal tissues in an easily maintainable state
If possible, to restore the supporting structures, which include bone, gum tissue, and ligaments

Treatment Phases. To achieve these goals, there are various approaches:

Initial cleaning, scaling, and curettage
Surgery -- if needed for reducing deep pockets that remain underneath the gum after extensive cleaning sessions
Low-dose oral or topical antibiotics
Maintenance

After the active treatment is completed and the mouth is in a relative state of health, the patient should have regular cleanings lasting 45 minutes to 1 hour, approximately every 3 months. These may be done by the dental hygienist, the periodontist, or the general dentist. The patient may alternate between them. Home care, of course, must be continued.

Antibiotics Before Treatment. In cases where the individual has a mitral valve prolapse or history of rheumatic heart disease, pretreatment with an appropriate antibiotic is required before any dental work, including cleaning. This is necessary to prevent the possibility of bacterial endocarditis, which can be life threatening.

Scaling, polishing, and sometimes curettage are used to manage periodontal disease. They are usually accomplished in a series of three to four visits spaced about a week apart. (Patients might ask their dentist about the gas nitrous oxide, which is helpful for many patients and may reduce the visits to a single one.) The dental hygienist or practitioner generally uses both ultrasonic and manual instruments to remove calculus.

Calculus above the gum is easily seen. The dental professional usually detects calculus below the gum by careful probing with an instrument.
The hygienist or dentist may use an ultrasonic instrument for removal of the more accessible calculus. This probe-like device vibrates at a frequency range higher than is audible to the human ear. Some people with low tolerance for the ultrasonic probe may wish to request nitrous oxide.
A spray of water is used with ultrasound to prevent overheating and to flush out the debris that is dislodged.
The dental professional will scrape the plaque from above and below the gum line (called scaling). When the probe contacts the rock-like calculus, deposits fracture off the tooth fairly efficiently.
The hygienist or dentist will then smooth the rough spots on the tooth. Smoothing the surface helps remove bacteria that collect there (root planing) and also helps the gums reattach.
Polishing is the finishing procedure. It uses a rubber cup with an abrasive paste to remove plaque and stains on the crown portion of the tooth. It produces a smooth surface, making it temporarily harder for plaque to adhere.

After the cleaning procedure, the dentist will check the pocket depths around the teeth after the cleaning process has been completed. Further treatment needs are determined by the results of these initial sessions:

If the cleaning processes have reduced inflammation, observation only is needed.
If an abscess is present, surgery may be required.

Finally, the dental hygienist or practitioner should offer thorough instructions on home care to insure the removal of bacteria on a daily basis. This includes proper use of the toothbrush, paste, mouth rinses, floss, floss threaders, and proxabrushes. Home care can effectively eliminate the plaque above the gums and down to 2 mm below the gums.

Gingival curettage removes the soft tissue lining of the periodontal pockets in order to completely eliminate bacteria and diseased tissue. It may be used along with scaling and root planing, but achieves a deeper and more complete cleaning. Evidence indicates, however, that it does not contribute any additional benefits beyond simple scaling and planing.

Surgery allows access for deep cleaning of the root surface, removal of diseased tissue, and repositioning and shaping of the bones, gum, and tissues supporting the teeth. Surgical procedures vary depending on the individual diagnosis and needs of the patient. The basic procedure is known as open flap curettage. It involves:

The periodontal surgeon lifts, or flaps, the gums away from the tooth and surrounding bone.
The diseased root surfaces are cleaned and curetted (scraped) to remove deposits.
Gum tissue is replaced into positions to minimize pocket depth.
The periodontist may also contour the remaining bone and attempt to regenerate lost bone and gingival attachment through bone grafts and guided tissue regeneration or the use of enamel matrix protein derivatives.

There is some debate about whether this procedure is any more effective in preventing disease progression than non-surgical therapies, such as low-dose doxycycline, short-term antibiotics, or antibiotic gels. Some studies have reported that although surgical treatment reduced pocket depth more than non-surgical therapies for at least a year after the procedure, benefits from surgery do not persist beyond 5 years, except in very deep pockets.

Postsurgery Pain and Discomfort. Post-surgery discomfort is usually managed easily with over-the-counter medications such as ibuprofen. If discomfort is severe, stronger analgesics may be prescribed. Some patients experience sensitivity to hot or cold temperatures from exposed roots. These problems can be managed with topical fluoride treatments or, in severe cases, with dental restoration.

Guided Tissue Regeneration. A more advanced technique, called guided tissue regeneration, is used to stimulate bone and gum tissue growth:

First, the root surfaces and diseased bone are meticulously cleaned out. Preventing bacterial contamination is very important. The more residual bacteria, the greater the chance that the treatment will fail.
A specialized piece of fabric is sewn around the tooth to cover the crater in the bone left after the cleaning. It is either absorbable or nonabsorbable. (Some studies report highly beneficial results with new absorbable materials, including those coated with the antibiotic doxycycline.)
The gum is then sewn over the fabric. The fabric prevents the gum tissue from growing down into the bone defect and allows the bone and the attachment to the root to regenerate.
After 4 - 6 weeks, the nonabsorbable fabric must be removed using a minor surgical procedure. The absorbable membrane may be left in. In general, there is little difference in outcome between absorbable and nonabsorbable procedures. The absorbable fabric may not be as effective as standard grafts if gum tissue is thin, although newer materials may prove to produce better results.

Bone Grafting. In some cases of severe bone loss, the surgeon may attempt to encourage regrowth and restoration of bone tissue that has been lost through the disease process. This involves bone grafting:

The surgeon places bone graft material into the defect.
The material may be either bone from the same patient or a substance called decalcified freeze-dried bone allografts (DFDBA) which is obtained from a donor.
This material then stimulates new bone growth in the area.

Enamel Matrix Protein Derivative. Amelogenin is a derivative of a major protein in the structure (the matrix) of enamel that helps stimulate gum tissue growth. A gel containing amelogenin (Emdogain) is applied during surgery and forms a coat over the roots of the teeth. The gel itself dissolves after 2 days, leaving the active substance behind. Studies report that it is safe and may significantly reduce the effects of periodontal disease. One study suggested that the benefits, as indicated by bone attachment, can persist for at least 4 years. (Results were similar to guided tissue regeneration.)

Gum grafting techniques can also be very useful for improving the looks of the gum as well as adding support to the teeth. During this procedure, the periodontist takes gum tissue from the palate or another donor source to cover the exposed root in order to even the gum line and reduce sensitivity. Other procedures are available to improve the look of the gums and teeth. The gum line can be sculpted to improve uneven or excess gums and to cover exposed roots as gums recede.

Periodontists report that they are achieving great success with tooth implants in patients who have lost teeth due to periodontal disease. The average cost for a single implant is high, however, and one implant requires 5 - 7 months for completion.

Medications

Antibiotics are often used in combination with surgery, curettage, or alone to eliminate or prevent disease-causing bacteria after periodontal procedures. They are being investigated in oral forms as well as in topical forms that are applied directly to the gum. Increasingly, dental professionals are finding that local application of antibiotics is more effective than periodontal surgery alone. They may even prove to be an alternative to surgery.

Some experts are concerned, however, that long-term use of antibiotics increases the risk of bacterial resistance to these drugs, which is a growing health problem in general. Of some encouragement was a 2000 review, which indicated that low-dose antibiotics do not increase the risk of bacterial resistance. However, long-term studies are still needed

Antibiotics given orally and at standard doses have some limited applications for periodontal disease. They are typically given for an acute infection. Long-term use of antibiotics is advised for the control of juvenile periodontitis, refractory periodontitis, rapidly progressing periodontitis, and prepubertal periodontitis. Specific antibiotics used in periodontal disease include:

Tetracycline antibiotics -- which include tetracycline hydrochloride, doxycycline, and minocycline -- are the primary drugs used. They not only have anti-bacterial actions but also reduce inflammation and help block collagenase, the protein that destroys connective tissue and bone, even in low doses. In fact, these two actions seem to contribute most to periodontal protection, rather than their antibacterial properties. Short-term use of standard-dose doxycycline (a 10-day treatment) is used for treating acute periodontal infections and for eliminating inflammation. Topical application and long-term use of these antibiotics are showing particular promise.
Some macrolide antibiotics (roxithromycin) may have actions against inflammation and growth involved in periodontal disease.
Some quinolone antibiotics (moxifloxacin, ciprofloxacin) may specifically target A. actinomycetemcomitans, an important bacteria in periodontal disease.
Metronidazole (Flagyl) in combination with tetracycline or amoxicillin (a penicillin) may be used for severe and chronic periodontal disease.

There is growing bacterial resistance to many of these antibiotics, such as roxithromycin and metronidazole, therefore limiting their use in periodontal disease. One study indicated, however, that 3 months after antibiotic administration, the percentage of bacteria that could be eliminated with standard antibiotics returned to normal.

Topical application of antibiotics to the gum surface does not affect the entire body like oral antibiotics do, and they are preferred whenever possible. Studies suggest that, in combination with scaling and planing, any of these approaches are very effective for periodontal health.

Several different topical applications are showing promise, including:

Atridox is a doxycycline gel that conforms to the gum surface and then solidifies. Over the next few days, it releases the antibiotics.
Elyzol is a gel or strip applied to the gum that is composed of metronidazole. It has unique actions that are effective against parasites as well as bacteria. Studies suggest that Atridox, which contains doxycycline, may be more effective than Elyzol. (In one study, however, the doxycycline gel worked faster, but metronidazole achieved a greater bacterial reduction.)
PerioChip is a chip that is placed into the gum pocket after scaling. Over time, it slowly releases chlorhexidine, a powerful bacteria-killing antiseptic. Early studies report benefits in reducing pocket depths, but it is still not known whether these improvements are sustained.
Minocycline microspheres (Arestin) contain antibiotics in tiny capsules, which are applied to the gums after scaling and planing. Studies report that they are more effective in reducing pocket depth and bone loss than standard periodontal maintenance. Patients obtain these benefits regardless of their smoking status, age gender, or extent of the periodontal disease.
Actisite is a thin strip similar to dental floss, which is treated with tetracycline hydrochloride. The treated thread is temporarily inserted between the tooth and gum. (Using multiple strips may be more beneficial than using a single strip.) This was one of the first topical applications of antibiotics. Other topical approaches are being increasingly used.

Subantimicrobial Dose Doxycycline (Periostat). Subantimicrobial dose doxycycline (SDD) is a term used for a treatment that uses very low doses (20 mg) of doxycycline (Periostat). Although doxycycline is a tetracycline antibiotic, the doses used are too low to affect bacteria. However, at these dose levels, the drug blocks matrix metalloproteinases (MMPs) -- enzymes that destroy the connective tissues holding the teeth. Periostat is taken twice a day for months. There is some concern that such long-term use may pose a risk for the development of antibiotic-resistant bacteria or other, still unknown, adverse effects. The doses used in this treatment, however, are too low to have any effect on bacteria, so some experts believe this risk is very low. In fact, several 12-month studies report significant improvements in tooth attachment and pocket depth with no increased incidence of side effects. [Taking a common nonsteroidal anti-inflammatory drug, such as aspirin or ibuprofen (Advil) along with doxycycline, may enhance the effectiveness of this treatment.]

Chemically Modified Tetracyclines. Other tetracyclines are being developed that inhibit MMPs but have no antibiotic properties, which would, theoretically, avoid possible long-term problems with antibiotic resistance.

Other Treatments

Nonsteroidal Anti-inflammatory Drugs (NSAIDs). NSAIDs are drugs that block factors that cause inflammation and pain.

Over-the-counter NSAIDs include aspirin, ibuprofen (Motrin IB, Advil, Nuprin, Rufen), naproxen (Aleve), ketoprofen (Actron, Orudis KT).
Prescription NSAIDs include naproxen (Naprosyn, Anaprox), diclofenac (Voltaren), tolmetin (Tolectin), ketoprofen (Orudis, Oruvail), indomethacin (Indocin).

These drugs are used not only for relieving pain in periodontal disease but also for slowing the disease process. NSAIDs block inflammatory enzymes triggered by cytokines, which are important immune factors in periodontal disease. A number of NSAIDs have been investigated and have been shown to reduce gingivitis and slow progression of periodontal disease.

In one study, long-term use of oral flurbiprofen (Ansaid) resulted in significantly lower bone loss, although disease progression returned when the drug was stopped.

Investigators are also studying rinses, creams, and other topical forms of NSAIDs. For example, a cream containing ketoprofen appears to reduce bone loss. (Ketoprofen is of particular interest because it blocks not only COX-2 but also another pathway involved in the disease process.)

Warning about NSAIDs: Although NSAIDs work well, long-term use 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.

Gels containing growth factors -- including substances called recombinant human (rh), platelet-derived growth factor-BB (PDGF-BB), and (rh) insulin-like growth factor-I (IGF-I) -- are showing promise for restoring bone.

Research is underway to find a vaccine against periodontal disease. To date, animal studies show promise, but an effective vaccine for people is years away.

Researchers are investigating the use of photodynamic therapy (PDT) as an alternative to antibiotic drugs. PDT destroys periodontal bacteria by applying photosensitive drugs to oral regions and exposing the drug-treated area to a light or laser. Research appears promising but is still in its preliminary stages.

Resources

www.nidcr.nih.gov -- National Institute of Dental and Craniofacial Research
www.perio.org -- American Academy of Periodontology
www.ada.org -- American Dental Association
www.aaoms.org -- American Association of Oral and Maxillofacial Surgeons

References

Amaliya , Timmerman MF, Abbas F, Loos BG, Van der Weijden GA, Van Winkelhoff AJ, et al. Java project on periodontal diseases: the relationship between vitamin C and the severity of periodontitis. J Clin Periodontol. 2007 Apr;34(4):299-304.

de Oliveira RR, Schwartz-Filho HO, Novaes AB Jr, Taba M Jr. Antimicrobial photodynamic therapy in the non-surgical treatment of aggressive periodontitis: a preliminary randomized controlled clinical study. J Periodontol. 2007 Jun;78(6):965-73.

Kolahi J, Soolari A. Rinsing with chlorhexidine gluconate solution after brushing and flossing teeth: a systematic review of effectiveness. Quintessence Int. 2006 Sep;37(:605-12.

Persson GR, Yeates J, Persson RE, Hirschi-Imfeld R, Weibel M, Kiyak HA. The impact of a low-frequency chlorhexidine rinsing schedule on the subgingival microbiota (the TEETH clinical trial). J Periodontol. 2007 Sep;78(9):1751-8.

Staudte H, Sigusch BW, Glockmann E. Grapefruit consumption improves vitamin C status in periodontitis patients. Br Dent J. 2005 Aug 27;199(4):213-7, discussion 210.

Review Date:
1/26/2008
Reviewed By:
Harvey Simon, MD, Editor-in-Chief, Associate Professor of Medicine, Harvard Medical School; Physician, Massachusetts General Hospital. Also reviewed by David Zieve, MD, MHA, Medical Director, A.D.A.M., Inc.

A.D.A.M. Copyright

adam.com

Heart failure

FitSugar — Wed, 08 Oct 2008 17:35:10 -0700

In This Report

Highlights
Introduction
Causes
Symptoms
Risk Factors
Complications
Diagnosis
Treatment
Medications
Surgery and Devices
Lifestyle Changes
Resources
References

HEALTH GUIDE REFERENCE FROM A.D.A.M

Highlights

Permanent Implantable Heart Approved

In 2006, the FDA approved the first permanent artificial heart. The AbiCor is intended for patients who are not eligible for heart transplants and who are only expected to survive about a month without medical treatment. Patients who received the AbiCor have survived, on average, about 5 months.

Statin Drug Approved for Heart Failure

In 2006, the FDA approved the cholesterol drug atorvastatin (Lipitor) to reduce the risks of hospitalization for heart failure in patients with heart disease.

Drug Research

The investigational drug tolvaptan improved symptoms in patients hospitalized with severe heart failure and fluid build-up in the lungs, according to several 2007 Journal of the American Medical Association (JAMA) studies. However, the drug did not reduce the risks of re-hospitalization and death.

Preserved Versus Reduced Ejection Fraction

Heart failure with preserved left-ventricular ejection fraction (LVEF) is becoming more common, suggests several 2006 studies published in JAMA and the New England Journal of Medicine. Unfortunately, this type of heart failure is less well studied than reduced LVEF. Experts are urging that more studies be conducted to determine better treatment options for preserved LVEF. Both types of heart failure have high mortality rates.

Systolic Blood Pressure Predictor of Mortality

Patients who are admitted to the hospital with heart failure and low systolic blood pressure have a poorer chance of survival than patients admitted with high blood pressure, indicates a 2006 JAMA study.

Diet and Lifestyle Factors

Daily consumption of whole-grain breakfast cereals may reduce the risk for heart failure, suggests research presented at a 2007 American Heart Association conference on heart disease prevention.
A drink or two a day is associated with lower risk of heart failure, indicates a 2006 Journal of the American College of Cardiology study. However, heavy alcohol consumption can increase the risk for heart failure.

Introduction

To understand what occurs in heart failure, it is useful to be familiar with the anatomy of the heart and how it works. The heart is composed of two independent pumping systems, one on the right side, and the other on the left. Each has two chambers, an atrium and a ventricle. The ventricles are the major pumps in the heart.

The external structures of the heart include the ventricles, atria, arteries, and veins. Arteries carry blood away from the heart while veins carry blood into the heart. The vessels colored blue indicate the transport of blood with relatively low content of oxygen and high content of carbon dioxide. The vessels colored red indicate the transport of blood with relatively high content of oxygen and low content of carbon dioxide.

The Right Side of the Heart. The right system receives blood from the veins of the whole body. This is "used" blood, which is poor in oxygen and rich in carbon dioxide.

The right atrium is the first chamber that receives blood.
The chamber expands as its muscles relax to fill with blood that has returned from the body.
The blood enters a second muscular chamber called the right ventricle.
The right ventricle is one of the heart's two major pumps. Its function is to pump the blood into the lungs.
The lungs restore oxygen to the blood and exchange it with carbon dioxide, which is exhaled.

The Left Side of the Heart. The left system receives blood from the lungs. This blood is now oxygen rich.

The oxygen-rich blood returns through veins coming from the lungs (pulmonary veins) to the heart.
It is received from the lungs in the left atrium, the first chamber on the left side.
Here, it moves to the left ventricle, a powerful muscular chamber that pumps the blood back out to the body.
The left ventricle is the strongest of the heart's pumps. Its thicker muscles need to perform contractions powerful enough to force the blood to all parts of the body.
This strong contraction produces systolic blood pressure (the first and higher number in blood pressure measurement). The lower number ( diastolic blood pressure) is measured when the left ventricle relaxes to refill with blood between beats.
Blood leaves the heart through the ascending aorta, the major artery that feeds blood to the entire body.

The Valves. Valves are muscular flaps that open and close so blood will flow in the right direction. There are four valves in the heart:

The tricuspid regulates blood flow between the right atrium and the right ventricle.
The pulmonary valve opens to allow blood to flow from the right ventricle to the lungs.
The mitral valve regulates blood flow between the left atrium and the left ventricle.
The aortic valve allows blood to flow from the left ventricle to the ascending aorta.

Click the icon to see an image of the internal structures of the heart.

The Heart's Electrical System. The heartbeats are triggered and regulated by the conducting system, a network of specialized muscle cells that form an independent electrical system in the heart muscles. These cells are connected by channels that pass chemically caused electrical impulses.

Click the icon to see an image of the conduction system of the heart.

Heart failure is not a disease. It is a condition or process in which the heart is unable to pump enough blood to meet the needs of the body's tissues. The heart doesn't "fail" in the sense of ceasing to beat (as occurs during a heart attack). Rather, it weakens, usually over the course of months or years, so that it is unable to pump out all the blood that enters its chambers. As a result, fluids tend to build up in the lungs and tissues, causing congestion. This condition used to be called "congestive heart failure," but the name was officially changed to heart failure in 2005.

Ways the Heart Can Fail. Heart failure can occur in several ways:

The muscles of the heart pumps (ventricles) become thin and weakened. They stretch (dilate) to the extent that they cannot pump the blood with enough force to reach all the body's tissues.
The heart muscles stiffen or thicken. Here, they lose elasticity and cannot relax. Insufficient blood enters the chamber, so not enough blood is pumped out into the body to serve its needs.
Sometimes the valves of the heart are abnormal. (Valves open or close to control the flow of blood entering or leaving the heart). They may narrow, such as in aortic stenosis, causing a back up of blood, or they may close improperly so that blood leaks back into the heart. The mitral valve (which regulates blood flow between the two chambers on the left side of the heart) often becomes leaky in severe heart failure -- a condition called mitral regurgitation.

Click the icon to see an image of the valves of the heart.

The very mechanisms that the body uses to compensate for inefficient heart pumping can, over time, change the architecture of the heart (called remodeling) and finally lead to irreversible problems.

The specific effects of heart failure on the body depend on whether it occurs on the left or right side. Over time, however, in either form of heart failure, the organs in the body do not receive enough oxygen and nutrients, and the body's wastes are removed slowly. Eventually, vital systems break down.

Failure on the Left Side (Left-Ventricular Heart Failure). Failure on the left side of the heart is more common than failure on the right side. The failure can be a result of abnormal systolic (contraction) or diastolic (relaxation) action:

Systolic. Systolic heart failure is a pumping problem. In systolic failure, the heart muscles weaken and cannot pump enough blood throughout the body. The left ventricle is usually stretched (dilated). Fluid backs up and accumulates in the lungs (pulmonary edema). Systolic heart failure typically occurs in men between the ages of 50 - 70 years who have had a heart attack.
Diastolic. Diastolic heart failure is a filling problem. When the left ventricle muscle becomes stiff and cannot relax properly between heartbeats, the heart cannot fill fully with blood. When this happens, fluid entering the heart backs up. This causes the veins in the body and tissues surrounding the heart to swell and become congested. Patients with diastolic failure are typically women, overweight, and elderly, and have high blood pressure and diabetes.

Failure on the Right Side (Right-Ventricular Heart Failure). Failure on the right side of the heart is most often a result of failure on the left. Because the right ventricle receives blood from the veins, failure here causes the blood to back up. As a result, the veins in the body and tissues surrounding the heart to swell. This causes swelling in the feet, ankles, legs, and abdomen.

Ejection Fraction. To help determine the severity of left-sided heart failure, doctors use an ejection fraction (EF) calculation, also called a left-ventricular ejection fraction (LVEF). This is the percentage of the blood pumped out from the left ventricle during each heartbeat. An ejection fraction of 50 - 75% is considered normal. Patients with left-ventricular heart failure are classified as either having a preserved ejection fraction (greater than 50%) or a reduced ejection fraction (less than 50%).

In general, systolic heart failure has been thought to be associated with a reduced ejection fraction, whereas diastolic heart failure was associated with a preserved (normal) ejection fraction. However, several 2006 studies indicated that diastolic heart failure can occur regardless of the ejection fraction, although it is more common in patients with a preserved ejection fraction. Mortality rates among patients with reduced LVEF and preserved LVEF are similar.

Although reduced LVEF heart failure is better studied, and its treatment goals more clearly defined, several important 2006 studies suggest that preserved LVEF heart failure is becoming increasingly common. The studies, published in the Journal of the American Medical Association and the New England Journal of Medicine, indicated that patients with preserved LVEF heart failure are more likely to be female and older, and have a history of high blood pressure and atrial fibrillation (a disturbance in heart rhythm). Experts are now urging that more studies focus on patients with preserved LVEF so that better treatment options can be established.

Causes

Heart failure has many causes and can evolve in different ways.

It can be a direct, last-stage result of heart damage from one or more of several heart or circulation diseases.
It can occur over time as the heart tries to compensate for abnormalities caused by these conditions, a condition called remodeling.

In all cases, the weaker pumping action of the heart means that less blood is sent to the kidneys. The kidneys respond by retaining water and salt. This in turn increases edema (fluid buildup) in the body, which causes widespread damage.

Uncontrolled high blood pressure (hypertension) is also a major cause of heart failure even in the absence of a heart attack. In fact, about 75% of cases of heart failure start with hypertension. It generally develops as follows:

The heart muscles thicken to make up for increased blood pressure.
The force of the heart muscle contractions weaken over time, and the muscles have difficulty relaxing. This prevents the normal filling of the heart with blood.

[See In-Depth Report #14:High blood pressure.]

Hypertension is a disorder characterized by consistently high blood pressure. Generally, high blood pressure consists of systolic blood pressure (the "top" number, which represents the pressure generated when the heart beats) higher than 140, or diastolic blood pressure (the "bottom" number, which represents the pressure in the vessels when the heart is at rest) over 90.

Coronary artery disease is the end result of a complex process called atherosclerosis (commonly called "hardening of the arteries"). It is the most common cause of heart attack and involves the build-up of unhealthy cholesterol in the arteries, with inflammation and injury in the cells of the blood vessels. The arteries narrow and become brittle. Heart failure in such cases most often results from a pumping defect in the left side of the heart. [See In-Depth Report #3: Coronary artery disease and angina ; and In-Depth Report #23: Cholesterol.]

Click the icon to see an image of atherosclerosis.

People now often survive heart attacks, but eventually many develop heart failure from the physical damage done to the heart muscles by the attack. Ironically, heart attack recovery is probably one of the major factors in the dramatic increase in heart failure cases over the past decade. On an encouraging note, however, new therapies that are reducing the severity of heart attacks may help stabilize heart failure rates. [See In-Depth Report #12: Heart attack.]

The valves of the heart control the flow of blood leaving and entering the heart. Abnormalities can cause blood to back up or leak back into the heart.

Click the icon to see an image of the heart valves.

In the past, rheumatic fever, which scars the heart valves and prevents them from closing, was a major cause of death from heart failure. Fortunately, antibiotics have relegated this disease to a minor cause of heart failure. Birth defects may also cause abnormal valvular development. Although more children born with heart defects are now living to adulthood, they still face a higher than average risk for heart failure as they age.

Cardiomyopathy is disease that damages the heart muscles and leads to heart failure. There are several different types. Injury to the heart muscles may cause the heart muscles to thin out (dilate) or become too thick (become hypertrophic). In either case, the heart doesn't pump correctly.

Dilated Cardiomyopathy. Dilated cardiomyopathy involves an enlarged heart ventricle. The muscles thin out, reducing the pumping action, usually on the left side. Although this condition is associated with genetic factors, the direct cause often is not known. (This is called idiopathic dilated cardiomyopathy.) Research strongly indicates that viruses, such as Coxsackie virus, or other infections may be at the base of this condition. Experts think that an autoimmune response occurs in which infection-fighting antibodies attack a person's own proteins in the heart, mistaking them for foreign substances.

Click the icon to see an image of dilated cardiomyopathy.

Hypertrophic Cardiomyopathy. In hypertrophic cardiomyopathy, the heart muscles become thick and contract with difficulty. Some research indicates that this occurs because of a genetic defect that causes a loss of power in heart muscle cells and, subsequently, lower pumping strength. To compensate for this power loss, the heart muscle cells grow. This condition, rare in the general population, is often the cause of sudden death in young athletes.

Click the icon to see an image of hypertrophic cardiomyopathy.

High blood pressure, heart attacks, or other initial processes that impair the pumping actions of the heart trigger a number of hormonal and neurochemical mechanisms to correct imbalances in pressure and blood flow. Unfortunately, while these corrective responses help in the short term, they increase the work of the heart. The mechanisms are now viewed as major contributors to the end stages of heart failure. Some are described briefly in the following sections.

Remodeling. The heart responds to high blood pressure and overload by enlarging in order to increase blood input. This leads to structural damage called remodeling:

In order to accommodate the increased blood input, the heart muscle cells elongate. The muscular walls of the heart that they form become thinner and inefficient.
The muscle cells undergo other changes that result in calcium loss. Calcium is a mineral that is crucial for healthy heart contractions.
The thinner heart muscles and the impaired heart contractions further weaken the heart's pump.
Mitral valve regurgitation is a possible outcome of remodeling. The mitral valve regulates blood flow between the two chambers on the left side of the heart. In response to remodeling, the structural changes in the heart may distort the mitral valve so that the blood leaks backward into the left atrium of the heart instead of flowing out into the body's circulation.
These changes are generally irreversible, although heart pacemakers and certain drugs, including beta-blockers and ACE inhibitors, may reverse some of the remodeling in some patients.

Activation of the Sympathetic Nervous System. The sympathetic nervous system consists of the nerve cells that automatically govern and regulate the beating heart.

This nervous system responds to the failing heart pump by signaling the release of stress hormones, in particular a powerful one called norepinephrine.
These hormones flood the heart, causing it to beat even faster.
These rapid heart beats, although intended to accommodate the weakened pumping actions, only accelerate the damage.

The Renin-Angiotensin-Aldosterone System (RAAS). The renin-angiotensin-aldosterone system (RAAS) is a group of hormones that are responsible for the opening and narrowing of blood vessels and retention of fluids. They also affect cell development in the heart.

The RAAS hormones are called into action by the failing heart.
They respond to the lower blood volume of the weakened heart by constricting the blood vessels and retaining fluids and sodium.
The heart then works harder to pump blood through these narrowed vessels. Blood pressure, then, is forced to increase, which creates a vicious cycle.

Immune System Response. The immune system may also compound the damage. In response to injury in the heart muscle cells or in other parts of the body that occurs as the heart fails, the immune system releases factors intended to protect these areas.

In excess, however, they can cause inflammation and damage.

The most important of these factors are called cytokines. Active cytokines include tumor necrosis factor (TNF) and possibly interleukins 1 and 6.
High levels of these cytokines have been observed in patients with the most severe classes of heart failure.
They may play an important role in the process leading to remodeling. High levels of these cytokines may actually trigger muscle cell growth and enlargement of the heart.

Other Players. Other molecules or compounds have been identified that might play a positive or negative role in the process of the failing heart.

Natriuretic peptides are a family of compounds released to counterbalance the effects of RAAS. Atrial natriuretic peptide (ANP) is a specific member of this family that opens blood vessels and counteracts the sodium-retaining properties of aldosterone (one of the RAAS hormones). It is of particular interest to researchers looking for new treatments.
Endothelin is a powerful protein involved in blood vessel constriction, cell proliferation and build-up, and other negative effects on the heart.
Nitric oxide is important for blood vessel dilation and elasticity.

Symptoms

Many symptoms of heart failure result from the congestion that develops as fluid backs up into the lungs and leaks into the tissues. Other symptoms result from inadequate delivery of oxygen-rich blood to the body's tissues. Since heart failure can progress rapidly, it is essential to consult a doctor immediately if any of the following symptoms are detected.

Fatigue and shortness of breath (dyspnea) are the first symptoms. They are caused by fluid in the lungs. Patients typically report that they feel out of breath after mild exertion. It is unlike the breathlessness of angina, which feels like a heavy weight pressing on the chest.

Fluid retention. Patients may complain of leg or abdominal swelling.
Wheezing or cough. Patients may have asthma-like wheezing or a dry hacking cough that occurs a few hours after lying down, but then stops after the patient sits up.
Central sleep apnea. This disorder results when the brain fails to signal the muscles to breathe during sleep. It occurs in up to half of people with heart failure. Sleep apnea causes disordered breathing at night. If heart failure progresses, the apnea may be so acute that a person, unable to breathe, may awaken from sleep in panic.
Loss of muscle mass. Over time, patients may lose muscle weight due to low cardiac output.

Ultimately, fluid in the lungs may build up. This is called pulmonary edema. When this happens, symptoms become more severe.

In addition to shortness of breath, patients sometimes have a cough that produces a pinkish froth.
Patients may experience a bubbling sensation in the lungs and feel as if they are drowning.
Typically, the skin is clammy and pale, sometimes nearly blue. This is a life-threatening situation, and the patient must go immediately to an emergency room.

Fatigue. As with left-side heart failure, an early symptom of right-side (right-ventricular) failure is extreme tiredness.
Fluid accumulation. This first occurs in the feet, then the ankles and legs, and finally in the abdomen. The liver may also be enlarged.
Weight gain. Although appetites are often depressed, patients with heart failure gain weight because they retain salt and water.
Loss of muscle mass.

Risk Factors

Nearly 5 million Americans currently suffer from heart failure. About 550,000 new cases of heart failure are now diagnosed each year. In 1970 there were only 250,000 new cases, so the annual numbers have risen dramatically. Such numbers represent an increasingly older population. Although there has been a dramatic increase over the last several decades in the number of people who suffer from heart failure, survival rates have been improving greatly.

Coronary artery disease and high blood pressure are the main causes of heart failure. Other diseases that damage or weaken the heart muscle or heart valves can also cause heart failure. Heart failure is most common in people over age 65, African-Americans, and women.

Heart failure is the most common reason for hospitalization in the elderly, and as the population ages, the incidence of heart failure is rising dramatically. According to one report, it occurs at a rate of about 10 in 1,000 people after age 65. The positive implication is, however, that people are living longer with heart failure.

Men are at higher risk for heart failure than women, although the difference narrows with age. Women also have a better survival rate than men do when heart failure is caused by valvular heart disease, high blood pressure, or alcohol abuse. (Some studies indicate that this is because men may be more susceptible to the process of heart muscle-cell remodeling, a damaging effect of hypertension.)

The survival rates of women and men are more similar, however, when heart failure evolves from coronary artery disease or heart attack. Women are much more likely to develop heart failure after a heart attack than men. In such cases, some evidence suggests that the reasons for this may include less aggressive approach to treatment for the initial heart conditions.

African-Americans are at higher risk for heart failure than Caucasians, and studies have reported that they tend to do much worse. In a 2003 study, however, in which Caucasians and African-Americans had comparable treatment, African-Americans actually had lower 1-year mortality rates (with slightly higher rates of rehospitalizations). Some evidence suggests that African-Americans are more often likely than Caucasians to develop diastolic heart failure (a failure of the heart muscle to relax normally), which is often a precursor to systolic heart failure (impaired ability to pump blood). Caucasians tend to develop systolic heart failure first.

According to a 2006 New England Journal of Medicine study, people whose parents had heart failure have a greatly increased risk of developing heart failure, particularly left-ventricular systolic heart failure. Earlier studies have suggested that a family history of early heart failure caused by cardiomyopathies (diseases that damage the heart muscle) may also predispose people to the disease. Researchers are looking for changes in specific genes that might regulate systems involved in heart failure and so increase susceptibility in certain populations.

Chronic alcohol abuse can damage the heart muscles, can cause hypertension, and may prove to be one cause of idiopathic dilated cardiomyopathy. Moderate alcohol consumption, on the other hand (generally defined as 2 drinks a day for men and 1 drink for women), may protect against heart failure. Non-drinkers, though, are not advised to begin drinking.

Coronary artery disease. More than 60% of heart failure cases may be due to coronary artery disease and its risk factors (smoking, sedentary living, obesity).
Heart attack. The injured heart after an attack is at high risk for failure. The improved survival rates from heart attack over the past decades have actually been responsible for the dramatic increase in heart failure rates.
High blood pressure. Hypertension is a significant risk factor and is present in 75% of patients with heart failure.
Diabetes. People with diabetes are at high risk for heart failure, particularly if they also have coronary artery disease. Even blood sugar abnormalities that precede diabetes increase the risk.
Obesity. Obesity is associated with both hypertension and type 2 diabetes, conditions that place people at risk for heart failure. Evidence strongly suggests that obesity itself is a major risk factor for heart failure, particularly in women. In a major 2002 study, about 14% of heart failure cases in women and 11% in men could be attributed to obesity. Both overweight and obese women had a significantly higher than normal risk for heart failure. Only obesity led to a significant risk in men.
Valvular heart disease. Specific valvular conditions that are common in patients with heart failure include aortic stenosis and mitral regurgitation.
Severe emphysema. Chronic obstructive pulmonary disease is a major risk factor for right-side heart failure.

Emphysema is a lung disease involving damage to the air sacs (alveoli).There is progressive destruction of alveoli and the surrounding tissue that supports them. As the disease gets worse, large air cysts take the place of normal lung tissue. Air is trapped in the lungs.

Cardiomyopathies due to various causes, including birth defects, HIV infection, and other infections.
In rare cases, heart failure can occur in women around the time of childbirth, a condition called peripartum cardiomyopathy.

Click the icon to see an image of peripartum cardiomyopathy.

An overactive thyroid (hyperthyroidism) or underactive thyroid (hypothyroidism) can have severe effects on the heart and increase the risk for heart failure.
Amyloidosis. A starchy protein (amyloid) that builds up in tissues and organs can lead to heart failure.
Surviving childhood cancers. Survivors face a risk for developing heart failure in later years, particularly those treated with chemotherapies such as doxorubicin. Newer cancer advances may reduce this risk.
Acute myocarditis. This rare viral infection involves the heart muscle and can produce temporary but potentially life-threatening heart failure.

Long-term use of anabolic steroids (male hormones used to build muscle mass) increases the risk for heart failure. The drug itraconazole (Sporanox), used to treat skin, nail, or other fungal infections, has been linked to heart failure. In 2006, the FDA warned that the cancer drug imatinib (Gleevec) has been associated with heart failure cases. Most patients who took imatinib and developed heart failure had a history of diabetes, high blood pressure, or heart disease.

Complications

At least 20% of hospitalizations in older adults are due to heart failure. For people over age 65, it is the number one cause of death, with nearly 290,000 people dying from this disease each year. Nevertheless, although heart failure produces very high mortality rates, treatment advances in hypertension, heart surgeries, and heart pacemakers are improving survival rates.

The most serious and life-threatening complications of heart failure are:

Arrhythmias (irregular beatings of the heart)
Acute pulmonary edema (fluid in the lungs)

Left-side heart failure tends to be more severe than right-side heart failure, particularly when it is associated with the following conditions:

Coronary artery disease
HIV infection
Amyloidosis (a metabolic disorder than can lead to organ failure)
Chemotherapy that uses the drug doxorubicin

The outlook is better in patients with left-side heart failure associated with:

Idiopathic cardiomyopathy (the cause is unknown)
Heart failure due to childbirth

Weight Issues. If patients with heart failure are overweight to begin with, their condition tends to be more severe. Once heart failure develops, however, an important indicator of a worsening condition is the occurrence of cardiac cachexia, which is unintentional rapid weight loss (a loss of at least 7.5% of normal weight within 6 months).

Impaired Kidney Function. Heart failure weakens the heart’s ability to pump blood. This can affect other parts of the body including the kidneys (which in turn can lead to fluid build-up). Decreased kidney function is common in patients with heart failure, both as a complication of heart failure and as a complication of other diseases associated with heart failure (such as diabetes). Studies suggest that in patients with heart failure, impaired kidney function increases the risks for heart complications including hospitalization and death.

Congestion (Fluid Buildup). In left-sided heart failure, fluid builds up first in the lungs. Later, as right-sided heart failure develops, fluid builds up in the legs, feet, and abdomen. According to one study, patients with severe symptoms who had congestion (fluid buildup) had poorer survival rates than those without fluid build up. Two-year survival rates were 87% in those who were congestion-free compared to 41 - 67% in patients with various signs of congestion (such as swelling, difficulty breathing when lying down, and weight gain from fluid buildup). Fluid buildup is treated with lifestyle measures, such as reducing salt in the diet, as well as drugs, such as diuretics. Sometimes, for hospitalized patients, an ultrafiltration device is used to remove excess water and salt from the body (see Surgery and Devices).

Atrial Fibrillation. This abnormal rhythm is a rapid quivering beat in the upper chambers of the heart. It is a major cause of stroke and very dangerous in people with heart failure.

Left Bundle Branch Block. Left bundle-branch block is an abnormality in electrical conduction in the heart. It develops in about 30% of patients with heart failure and is a major risk factor for serious adverse heart events.

Systolic Blood Pressure. An important 2006 study indicated that patients who arrive at the hospital with heart failure and low systolic blood pressure have a poorer prognosis than those who arrive with high systolic blood pressure. Researchers think that high systolic blood pressure may be a signal for unique clinical characteristics.

Sleep Apnea. With this disorder, a person stops breathing during the night, perhaps hundreds of times, usually for periods of 10 seconds or longer. It is a very strong risk factor for heart failure, and patients with apnea have a higher mortality rate than those who do not.

Depression. The presence of depression indicates a poorer outlook for the heart. Studies indicate that depression may have adverse biologic effects on the immune and nervous systems, blood clotting, blood pressure, blood vessels, and heart rhythms.

Seasonal and Daily Patterns. Studies have shown that more emergency room visits and higher mortality rates occur during winter months and on Mondays in patients with heart failure. One factor in this higher risk may be sudden and strenuous exertion, particularly snow-shoveling, which is associated with a risk for heart attack in people with heart problems.

Diagnosis

Doctors can often make a preliminary diagnosis of heart failure by medical history and careful physical examination.

The medical history risks for heart failure include:

High blood pressure
Diabetes
Poor cholesterol levels
Heart or peripheral vascular disease
Sleep apnea
Thyroid problems
Obesity
Lifestyle factors (smoking, alcohol use)

The following physical signs, along with medical history, strongly suggest heart failure:

Enlarged heart
Irregular heart sounds
Abnormal sounds in the lungs
Swelling or tenderness of the liver
Fluid retention in legs and abdomen
Elevation of pressure in the veins of the neck

Both blood and urine tests are used to check for problems with the liver and kidneys and to detect signs of diabetes. Lab tests can measure:

Cholesterol and lipid levels
Blood sugar (glucose)
Red blood cell count (to rule out anemia)
Blood sugar levels
Thyroid function

Urine tests can be used to assess the presence of a protein called albumin. Albumin in the urine is usually a sign of kidney disease, but even tiny amounts (microalbumin) signal an increased risk for heart failure in people with and without diabetes.

The exercise stress test measures heart rate, blood pressure, and oxygen consumption while a patient is performing physically, usually walking on a treadmill. It is an important diagnostic component in determining heart failure symptoms. Doctors also use exercise tests to gauge long-term outlook and the effects of particular treatments.

An electrocardiogram (ECG) cannot diagnose heart failure, but it can indicate underlying heart problems. It is sometimes called an EKG. The test is simple and painless to perform. It may be used to diagnose:

Enlargement of the heart muscle, which may help to determine long-term outlook
The presence of coronary artery disease
Abnormal cardiac rhythms. A rhythm pattern called a prolonged QT interval, for example, might predict people with heart failure who are at risk for severe complications and would need more aggressive therapies.

The major benefit of an ECG is that it can help determine which patients do not need an echocardiogram, a more accurate (but more expensive) diagnostic test.

The electrocardiogram (ECG, EKG) is used extensively to diagnose heart disease, from congenital heart disease in infants to myocardial infarction and myocarditis in adults. There are several different types of electrocardiograms.

The best diagnostic test for heart failure is echocardiography. Echocardiography is a noninvasive, entirely safe test that uses ultrasound to image the heart as it is beating. Cardiac ultrasounds provide the following information:

Accurate indications of valve function
The amount of blood flow through the heart's chambers
The location of the failure and where it has occurred

Doctors use information from the echocardiogram for calculating the ejection fraction (how much blood is pumped out during each heartbeat), which is important for determining the severity of heart failure.

Radionuclide Ventriculography. Radionuclide ventriculography is an imaging technique that uses a tiny amount of radioactive material (called a trace element). The substance is injected into a patient. As it passes through the bloodstream it is picked up on x-rays. This is a very important imaging technique for patients with heart failure. It is very sensitive in revealing heart enlargement or evidence of fluid accumulation around the heart and lungs. It is typically used in concert with angiography.

Magnetic Resonance Imaging. Magnetic resonance imaging (MRI) scans that use contrast dyes to improve resolution are proving helpful for identifying patients with irreversible heart damage. Damage appears as very bright areas on the scan.

Doctors may recommend angiography if they suspect that blockage of the arteries is contributing to heart failure. This procedure is invasive.

A thin tube called a catheter is inserted into one of the large arteries in the arm or leg.
It is gently guided through the artery until it reaches the heart.
The catheter measures internal blood pressure at various locations, giving the doctor a comprehensive picture of the extent and nature of the heart failure.
Dye is then injected through the tube into the heart.
X-rays called angiograms are taken as the dye moves through the heart and arteries.
These images help locate problems in the heart's pumping action or blockage in the arteries.

Major complications of angiography are rare (about 0.1%) but can occur. They include stroke, heart attacks, and kidney damage. The more experienced the medical center in this procedure, the lower the risk.

Click the icon to see an image of cardiac catheterization.

Researchers are looking for biologic factors (called biomarkers) that will confirm a diagnosis or suggest a better or worse prognosis. Many are under investigation.

Tumor Necrosis Factor. Elevated levels of tumor necrosis factor (TNF) may be a very strong and accurate predictor of a poor outlook. This immune substance is known to be a potent substance in the inflammatory process.

Natriuretic Peptides. Natriuretic peptides are substances that help regulate salt and water balance in the body. Levels of these peptides increase as heart failure symptoms worsen. Blood tests for brain natriuretic peptide (BNP) are now used to help diagnose heart failure. There are two types of BNP tests: The enzyme-linked immunosorbent assay (ELISA) and the radioimmunosorbent assay (RIA). Research from 2006 suggested that the ELISA test may be more accurate, but it is also more expensive.

BNP testing can be very helpful in correctly diagnosing heart failure in patients who come to the emergency room complaining of shortness of breath (dyspnea). A 2006 study indicated that this test can also help predict which patients with dyspnea are at greatest risk of dying within a year from heart failure.

Brain Metabolites. High levels of a compound called N-acetylaspartate, generated as a byproduct of chemical processes in the brain, may indicate a poor outlook.

Treatment

Guidelines for evaluating the severity of heart failure and determining treatments use a staging system that is similar to the one used for major cancers:

Stage A: Patients are at high risk for heart failure, but there is no evidence of structural damage to the heart. Risk factors include high blood pressure, heart diseases, diabetes, obesity, metabolic syndrome, and previous use of medications that damage the heart (such as some chemotherapy).
Stage B: Patients have a structural heart abnormality but no symptoms of heart failure. Abnormalities include left ventricular hypertrophy and low ejection fraction, asymptomatic valvular heart disease, and a previous heart attack.
Stage C: Patients have a structural abnormality and current or previous symptoms of heart failure, including shortness of breath, fatigue, and difficulty exercising.
Stage D: Patients have end-stage symptoms that do not respond to standard treatments.

According to expert guidelines, the first step in managing heart failure is to treat the primary conditions causing or complicating heart failure. These include:

Coronary artery disease. Treatment includes a healthy diet, exercise, smoking cessation, medications, and, possibly, bypass or angioplasty. [See In-Depth Report #3: Coronary artery disease and angina.]
Cholesterol and lipid problems. Treatments include lifestyle management and medications, especially statins. [See In-Depth Report #23: Cholesterol.]
High blood pressure. A normal systolic blood pressure is considered below 120 mm Hg, and a normal diastolic blood pressure is below 80 mm Hg. Patients with diabetes or chronic kidney disease should maintain blood pressure readings of 130/80 or less, while other patients with high blood pressure should aim for readings no higher than 140/90. Effective reduction of blood pressure reduces the risk of heart failure by 30 - 50%. [See In-Depth Report #14: High blood pressure.]
Diabetes. Treating diabetes is extremely important for reducing the risk for heart disease. ACE inhibitors are especially beneficial, particularly for people with diabetes. Recent research suggests that metformin, a drug used to treat diabetes, may also help prevent heart failure. [See In-Depth Report #60: Diabetes - type 2; and In-Depth Report #9: Diabetes - type 1.]
Valvular abnormalities such as aortic stenosis and mitral regurgitation. Surgery may be required.
Abnormal health rhythms (arrhythmias). Ventricular assisted devices, notably biventricular pacers (BVPs), are proving to be important in preventing hospitalizations for patients with these conditions.
Anemia. Giving erythropoietin (EPO) and iron injections to patients with heart failure and underlying anemia not only reverses the anemia, but may markedly improve heart symptoms as well. [See In-Depth Report #57: Anemia.]
Thyroid function. Various medications are used to treat overactive thyroid (hyperthyroidism) or underactive thyroid (hypothyroidism). [See In-Depth Report #38: Hypothyroidism.]
Sleep apnea. Continuous positive airway pressure (CPAP) is an effective treatment for sleep apnea. CPAP may help reduce systolic blood pressure and improve left ventricular systolic function. [See In-Depth Report#65:Sleep apnea.]

Click the icon to see an image of CPAP treatment.

Treatments for patients with Stage B risk for heart failure include all of the treatments recommended in Stage A. In addition, the following types of drugs and devices may be recommended for some patients. These include:

Angiotensin-converting enzyme (ACE) inhibitors for patients with a recent or past history of heart attack. Also for patients who have not had a heart attack if they have a low left ventricular ejection fraction (LVEF) and no heart failure symptoms. A reduced LVEF indicates that the heart’s left ventricle is not pumping blood efficiently.
Beta blockers for patients with a recent or past history of heart attack. Also for patients who have not had a heart attack but who do have reduced LVEF without heart failure symptoms.
Angiotensin-receptor blockers (ARBs) for patients who have had a heart attack or have low LVEF, but who cannot take ACE inhibitors.
Implantable defibrillators for patients who have weakened heart pumps (ischemic cardiomyopathy), who had a heart attack more than 40 days prior, and who have low LVEF.

Treat conditions as recommended in Stage A plus:

Restrict dietary salt. Lowering salt in the diet can help diuretics work better.
ACE inhibitors, beta blockers, and diuretics are recommended for most patients.
ARBs are recommended for patients who cannot tolerate ACE inhibitors.
Aldosterone inhibitors or digitalis may be used for some patients.
A hydralazine and nitrate combination (BiDil) may be used for African-American patients who are taking an ACE inhibitor and beta blocker and who still have heart failure symptoms.
Avoid drugs that can worsen heart failure symptoms. These include nonsteroidal anti-inflammatory drugs (NSAIDs), most calcium channel blockers, and most drugs used to treat irregular heart rhythms (arrhythmia).
Exercise training for appropriate patients.
Biventricular pacemakers and implantable defibrillators for some patients.

Treatment includes appropriate measures used for Stages A, B, and C plus:

Heart transplantation referral for appropriate patients.
Left-ventricular assist devices (LVADs) as permanent therapy for patients who are not candidates for heart transplants. LVADs are surgically implanted to help pump blood through the body.
Hospice and end-of-life care information for patients and families.

Medications

Many different medications are used in the treatment of heart failure. They include:

Angiotensin-converting enzyme (ACE) inhibitors
Angiotensin-receptor blockers (ARBs)
Beta blockers
Diuretics
Aldosterone blockers
Digitalis
Hydralazine and nitrates
Statins
Nesiritide (Natrecor)
Aspirin

Angiotensin-converting enzyme (ACE) inhibitors are among the most important drugs for treating patients with heart failure. ACE inhibitors open blood vessels and decrease the workload of the heart. They are used to treat high blood pressure but can also help improve heart and lung muscle function. Major studies suggest that ACE inhibitors may reduce the risk of death, heart attack, and hospital admissions by 28% in patients with existing heart failure.

ACE inhibitors are particularly important for patients with diabetes. A large study reported that patients with diabetes who took these drugs had fewer heart attacks and lower overall mortality rates than patients who took other types of high blood pressure medications. ACE inhibitors may also help slow progression of kidney disease, in addition to controlling blood pressure.

Doctors sometimes avoid giving aspirin to patients who are taking ACE inhibitors due to concerns that this drug combination can cause kidney problems. A 2005 study of patients with both coronary artery disease and heart failure indicated that an aspirin and ACE inhibitor combination is not harmful, and that aspirin can significantly reduce mortality risk for these patients.

Choosing an ACE inhibitor. ACE inhibitors treat Stage A high-risk conditions such as high blood pressure, heart disease, and diabetic nerve disorders (neuropathy). They also treat Stage B patients who have had a heart attack or who have left ventricular systolic disorder, and Stage C patients with heart failure. Specific brands and stages include:

Benazepril (Lotrel) -- (Stage A)
Captopril (Capoten) -- (Stages A, B, C)
Enalapril (Vasotec) -- (Stages A, B, C)
Fosinopril (Monopril) -- (Stages A, C)
Lisinopril (Prinivil, Zestril) -- (Stages A, B, C)
Moexipril (Univasc) -- (Stage A)
Perindopril (Aceon) -- (Stage A)
Quinapril (Accupril) -- (Stages A, C)
Ramipril (Altace) -- (Stages A, B, C)
Trandolapril (Mavik) -- (Stages A, B, C)

Side Effects of ACE Inhibitors:

Low blood pressure is the main side effect of ACE inhibitors. This can be severe in some patients, especially at the start of therapy.
Irritating cough is a common side effect, which some people find intolerable. Although all ACE inhibitors can have this side effect, sometimes switching to another brand will reduce this symptom.
Although ACE inhibitors can protect against kidney disease, they also increase potassium retention in the kidneys. This increases the risk for cardiac arrest if potassium levels become too high. Because of this action, they are not generally given with potassium-sparing diuretics or potassium supplements.
A rare but severe side effect is granulocytopenia, which is an extreme reduction in infection-fighting white blood cells.
In very rare cases, patients suffer a sudden and severe allergic reaction called angioedema that causes swelling in the eyes and mouth and may close off the throat.

Patients who have difficulty tolerating ACE inhibitor side effects are usually switched to an angiotensin-receptor blocker (ARB).

ARBs, also known as angiotensin II receptor antagonists, are similar to ACE inhibitors in their ability to open blood vessels and lower blood pressure. They may have fewer or less-severe side effects than ACE inhibitors, especially coughing, and are sometimes prescribed as an alternative to ACE inhibitors. Some patients with heart failure take an ACE inhibitor along with an ARB.

Brands and Indications. ARBs are used to treat Stage A high-risk conditions such as high blood pressure and diabetic nerve disorders (neuropathy). They are also used to treat Stage B patients who have had a heart attack or who have left ventricular systolic disorder, and Stage C patients with heart failure. Specific brands, and the stage of heart failure they are used for, are listed below.

Candesartan (Atacand) -- (Stages A, C)
Eprosartan (Teveten) -- (Stage A)
Irbesartan (Avapro) -- (Stage A)
Losartan (Cozaar) -- (Stages A, B)
Olmesartan (Benicar) -- (Stage A)
Telmisartan (Micardis) -- (Stage A)
Valsartan (Diovan) -- (Stages A, B, C)

Common Side Effects

Low blood pressure
Dizziness and lightheadedness
Raised potassium levels
Drowsiness

Beta blockers are almost always used in combination with other drugs, such as ACE inhibitors and diuretics. They help slow heart rate and lower blood pressure. Research presented at the 2006 American College of Cardiology meeting indicated that beta-blockers are an important treatment for most patients with left ventricular heart failure. Data from the study found that the beta blocker carvedilol (Coreg) significantly lowered the risk of death or rehospitalization within 3 - 6 months after hospital discharge.

Beta blockers can help patients with heart failure by:

Treating high blood pressure, angina, arrhythmias, and preventing heart attack in high-risk patients.
Preventing left ventricular remodeling in patients with enlarged heart chambers and weakened heart muscles (dilated cardiomyopathy), and in those who have suffered a first heart attack.
Blocking inflammatory immune factors called cytokines, including tumor necrosis factor (TNF). TNF may play a key role in the process leading to heart failure.
Preventing norepinephrine (adrenaline) from binding to heart cells. Elevated levels of norepinephrine, a stress hormone, can overstimulate the failing heart and are associated with severe heart failure.

Brands and Indications. Beta blockers treat Stage A high blood pressure. They are also treat Stage B patients (both those who have had a heart attack and those who have not had a heart attack but who have heart damage). Recent guidelines identify three drugs best for treating Stage C patients with heart failure. Specific brands and stages include:

Acebutolol (Sectral) -- (Stage A)
Atenolol (Tenormin) -- (Stages A, B)
Betaxolol (Kerlone) -- (Stage A)
Bisoprolol (Zebeta) -- (Stages A, C)
Cartelol (Cartrol) -- (Stage A)
Carvedilol (Coreg) -- (Stages A, B, C)
Labetalol (Trandate) -- (Stage A)
Metoprolol succinate (Toprol XL) -- (Stages A, C)
Metoprolol tartrate (Lopressor) -- (Stages A, B)
Nadolol (Corgard) -- (Stage A)
Penbutolol (Levatol) -- (Stage A)
Pindolol (Visken) -- (Stage A)
Propranolol (Inderal) -- (Stages A, B)
Timolol (Blocadren, Timolide) -- (Stages A, B)

Beta Blocker Concerns

Do not abruptly stop taking these drugs. The sudden withdrawal of beta blockers can rapidly increase heart rate and blood pressure. Your doctor may want you to slowly decrease the dose before stopping completely.
Beta blockers are categorized as non-selective or selective. Non-selective beta blockers such as carvedilol and propranolol can narrow bronchial airways. Patients with asthma, emphysema, or chronic bronchitis should not use these beta blockers.
Beta blockers can lower HDL (“good”) cholesterol.
These drugs can hide warning signs of low blood sugar (hypoglycemia) in patients with diabetes.
Beta blockers are usually used in combination with ACE inhibitors, but the two drugs are not started at the same time. Research presented at the 2005 European Society of Cardiology meeting indicates that either a beta blocker or an ACE inhibitor can be prescribed at first, and the other drug added on later.

Common Side Effects

Fatigue and lethargy
Vivid dreams and nightmares
Depression
Memory loss
Dizziness and lightheadedness
Reduced ability to exercise
Coldness in extremities (legs, toes, arms, hands)

Check with your doctor about any side effects. Do not stop taking these drugs on your own.

Diuretics cause the kidneys to rid the body of excess salt and water. Fluid retention is a major symptom of heart failure. Aggressive use of diuretics can help eliminate excess body fluids, while reducing hospitalizations and improving exercise capacity. These drugs are also important to help prevent heart failure in patients with high blood pressure. In addition, certain diuretics, notably spironolactone (Aldactone), block aldosterone, a hormone involved in heart failure. This drug class is beneficial for patients in late stages of heart failure (Stages C and D).

Diuretic Types and Brands. Diuretics come in many brands and are generally inexpensive. Some need to be taken once a day, some twice a day. Treatment is usually started at a low dose and gradually increased. Diuretics are virtually always used in combination with other drugs, especially ACE inhibitors and beta blockers. There are three main types of diuretics:

Potassium-sparing diuretics. These include amiloride (Midamor), spironolactone (Aldactone), and triamterene (Dyrenium).
Thiazide diuretics. These include chlorothiazide (Diuril), chlorthalidone (Hygroton), indapamide (Lozol), hydrochlorothiazide (Esidrix, HydroDiuril), and metolazone (Mykrox, Zaroxolyn).
Loop diuretics. Because loop diuretics act faster than other diuretics it is important to avoid dehydration and potassium loss. Loop diuretics include bumentanide (Bumex), furosemide (Lasix), and torsemide (Demadex).

Problems with Diuretics. Loop and thiazide diuretics deplete the body's supply of potassium, which, if left untreated, increases the risk for arrhythmias. Arrhythmias are heart rhythm disturbances that can, in rare instances, lead to cardiac arrest. In such cases, doctors will prescribe lower doses of the current diuretic, recommend potassium supplements, or use potassium-sparing diuretics either alone or in combination with a thiazide. Potassium-sparing drugs have their own risks, which include dangerously high levels of potassium in people with existing elevated levels of potassium or in those with damaged kidneys. However, all diuretics are generally more beneficial than harmful.

Common Side Effects

Fatigue
Depression and irritability
Urinary incontinence
Reduced sexual drive

Aldosterone is a hormone that is critical in controlling the body's balance of salt and water. Excessive levels may play important roles in hypertension and heart failure. Drugs that block aldosterone are prescribed for some patients with Stage C heart failure.

Spironolactone (Aldactone, Spirinol) is both a potassium-sparing diuretic and an aldosterone blocker. A major study of patients with heart failure found that spironolactone reduced death rate by 30%. Like all medications for heart failure, it must be used with care; elevated potassium levels are a potential risk of therapy.
Eplerenone (Inspra), a newer aldosterone blocker, has been specifically approved for treatment of heart failure. It is prescribed for patients who have heart failure following a heart attack. Its actions are similar to potassium-sparing diuretics and, like these drugs, it poses some risk for high potassium levels.

Digitalis is derived from the foxglove plant. It has been used to treat heart disease since the 1700s. Digoxin (Lanoxin) is the most commonly prescribed digitalis preparation. Digoxin decreases heart size and reduces certain heart rhythm disturbances (arrhythmias).

Unfortunately, digitalis does not reduce mortality rates, although it does reduce hospitalizations and worsening of heart failure. Controversy has been ongoing for more than 100 years over whether the benefits of digitalis outweigh its risks and adverse effects.

Digitalis may be useful for patients with left-ventricular systolic dysfunction who do not respond to other drugs (diuretics, ACE inhibitors). It is also used for patients who have atrial fibrillation.

Digitalis does not appear to help patients with left-ventricular diastolic heart failure. It may be harmful in patients with right-ventricular heart failure and those who stop taking digoxin after using it in combination with ACE inhibitors.

Side Effects and Problems. While digitalis is generally a safe drug, it can have toxic side effects due to overdose or other accompanying conditions. The most serious side effects are arrhythmias (abnormal heart rhythms that can be life-threatening). Early signs of toxicity may be irregular heartbeat, nausea and vomiting, stomach pain, fatigue, visual disturbances (such as yellow vision, seeing halos around lights, flickering or flashing of lights), and emotional and mental disturbances.

Many factors increase the chance for side effects.

Advanced age
Low blood potassium levels (which may be caused by diuretics)
Hypothyroidism
Anemia
Valvular heart disease
Impaired kidney function

Digitalis also interacts with many other drugs, including quinidine, amiodarone, verapamil, flecainide, amiloride, and propafenone.

A blood test that monitors drug levels in patients taking the drug can limit the rate of toxicity to about 2%. For most patients with mild-to-moderate heart failure, low-dose digoxin may be as effective as higher doses. If side effects are mild, patients should still consider continuing with digitalis if they experience other benefits.

Hydralazine and nitrates are two older drugs that help relax arteries and veins, thereby reducing the heart's workload and allowing more blood to reach the tissues. In 2005, the FDA approved BiDil, a drug that combines isosorbide dinitrate and hydralazine. BiDil is approved to specifically treat heart failure in African-Americans. African-Americans have a particularly high risk for heart failure. BiDil is the first drug approved for a specific racial group. The Food and Drug Administration (FDA) based its approval on a landmark 2004 study published in the New England Journal of Medicine, which showed that African-Americans who took the drug were 43% more likely to survive heart failure than patients who took placebo. Some experts suggest that BiDil could also benefit other racial groups.

Statins are important drugs used to lower cholesterol and to prevent heart disease leading to heart failure. These drugs include lovastatin (Mevacor), pravastatin (Pravachol), simvastatin (Zocor), fluvastatin (Lescol), atorvastatin (Lipitor), and rosuvastatin (Crestor). In 2007, the FDA approved atorvastatin to reduce the risks for hospitalization for heart failure in patients with heart disease.

In a 2006 Journal of the American Medical Association study, patients with heart failure who began taking a statin drug had a 24% lower relative risk of death and a 21% lower relative risk of hospitalization for heart failure than patient who did not take a statin. Statins appeared to help these patients regardless of whether or not they had co-existing coronary heart disease.

Aspirin is a type of non-steroid anti-inflammatory (NSAID). A 2005 study in the Journal of the American College of Cardiology indicated that aspirin is important for preventing heart failure death in patients with heart disease, and can safely be used with ACE inhibitors. However, some research has suggested that NSAIDs may increase the risk of heart failure for patients with a history of heart disease, especially when used in combination with ACE inhibitors or diuretics. Patients with heart disease should ask their doctor which NSAIDs are right for them.

Nesiritide treats patients who have arrived at a hospital with decompensated heart failure. Decompensated heart failure is a life-threatening condition in which the heart fails over the course of minutes or a few days, often as the result of a heart attack or sudden and severe heart valve problems. However, nesiritide may cause serious kidney damage.

In 2005, the FDA released recommendations from an expert panel concerning the appropriate and inappropriate use of nesiritide. The panel emphasized that nesiritide should be used to treat only patients with decompensated heart failure who have shortness of breath (dyspnea) and trouble breathing. The drug should not be a replacement for diuretics.

Despite these warnings, some doctors have prescribed nesiritide “off-label” to treat patients with severe heart failure outside of a hospital setting. Research presented at the 2007 American College of Cardiology annual conference criticized this practice by demonstrating that nesiritide plus standard treatment does not reduce the risk of heart- or kidney-related death or hospitalization. In addition, the research suggested some concerns about nesiritide’s overall safety.

Tolvaptan. Tolvaptan is an investigational drug that is being studied in combination with standard therapy for treatment of heart failure. It is especially being investigated for acute decompensated heart failure, a type of heart failure categorized by fluid build-up in the lungs (pulmonary edema) for which there are few available treatments. In patients hospitalized with heart failure, tolvaptan plus standard drugs improved breathing problems (dyspnea) and reduced fluid accumulation (edema) and body weight, according to two studies published in 2007 in the Journal of the American Medical Association. However, the drug did not appear to reduce the risk of re-hospitalization or death.

Levosimendan. Levosimendan is an experimental inotropic drug that is being investigated as a treatment for severely ill patients with heart failure. It belongs to a new class of drugs called calcium sensitizers that may help improve heart contractions and blood flow. Clinical trials suggest that levosimendan may improve survival in patients hospitalized for heart failure. The drug also appears to reduce levels of BNP (brain natriuretic peptide), a chemical marker for heart failure severity.

Prograf. Tacrolimus (Prograf) was approved in 2006 to help prevent organ rejection in patients who have received a heart transplant. The drug suppresses the immune system. Patients who receive this drug are at increased risk of developing lymphoma (a cancer of the immune system).

Surgery and Devices

Revascularization surgery helps to restore blood flow to the heart. It can treat blocked arteries in patients with coronary artery disease and may help selected patients with heart failure. Surgery types include coronary artery bypass graft (CABG) and percutaneous coronary intervention (PCI). CABG is a traditional type of open heart surgery. PCI, also called angioplasty, uses a catheter to inflate a balloon inside the artery. A metal stent may also be inserted during a PCI procedure. [See In-Depth Report#03:Coronary artery disease.]

A 2006 study suggested that early treatment with revascularization surgery may be particularly important for patients with systolic heart failure, a condition that occurs when the heart does not pump out enough blood. This condition has a very high death rate. Researchers found that CABG or PCI surgery halved the risk of dying compared to standard drug therapy. Patients in the study first underwent a positron emission tomography (PET) test to determine if they would be good candidates for surgery.

Click the icon to see an illustrated series detailing coronary artery balloon angioplasty.

Click the icon to see an illustrated series detailing heart bypass surgery.

In appropriate patients, mitral valve surgery may significantly reduce the severity of heart failure. In a study of 92 patients with late-stage heart failure and faulty valves, reconstruction of the heart's mitral valve drastically improved heart function.

An experimental mesh "heart sock" is being investigated as an adjunct to mitral valve repair surgery. Research presented at the 2004 American Heart Association Scientific Sessions suggested that the device reduced the progression of heart failure and halved the need for transplant surgery. The "sock" helps realign the shape of the heart and improve heart function. To date, it has been tested in patients with dilated cardiomyopathy.

Ventricular Remodeling. Ventricular remodeling (also called partial left ventriculectomy or the Batista procedure, after its inventor) may allow some patients with dilated cardiomyopathy to avoid a heart transplant.

The procedure involves the following:

The surgeon first performs ventriculectomy, which is the removal of a section of healthy heart muscle weighing about 3 ounces.
The surgeon then reshapes the heart to a more normal size and form.
Any faulty heart valves are repaired.

Ventricular remodeling is still relatively new, and mortality rates are very high. Studies on long-term improvement are mixed. More research is needed to target the patients who would most benefit.

Patients who suffer from severe heart failure and whose symptoms do not improve with drug therapy or mechanical assistance may be candidates for heart transplantation. Some 3,600 people are awaiting a transplant, although only about 2,000 operations are performed each year.

The most important factor for heart transplant eligibility is overall health. Chronological age is less important. Most heart transplant candidates are between the ages of 50 – 64 years. About 72% of transplant patients are male, and 70% are white.

While the risks of this procedure are high, the 1-year survival rate is about 86% for men and 84% for women. The 3-year survival rate is 78% for men and 75% for women. Five years after a heart transplant, about 71% of men and 67% of women remain alive. In general, the highest risk factors for death 3 or more years after a transplant operation are coronary artery disease and the adverse effects (infection and certain cancers) of immunosuppressive drugs used in the procedure. The rejection rates in older people appear to be similar to those of younger patients.

In 2004, the FDA approved a temporary artificial heart (Syncardia) intended to keep patients alive in the hospital while they waited for a heart transplant. In 2006, the FDA approved the first permanent implantable artificial heart (AbiCor). The AbiCor is available only for patients who are not eligible for a heart transplant and who are not expected to live more than a month without medical treatment. The device requires a large chest cavity, which means that most women will not be eligible for it. Of the 14 men who have received the AbiCor, the average survival was less than 5 months after surgery. Only one patient was discharged from the hospital. The device’s manufacturer is working on a new model that it hopes will extend survival by as long as 5 years.

A growing array of heart devices and machines are changing the face of heart failure treatment. They have gained widespread acceptance for use as a bridge to transplant in patients who are on medications but still have severe symptoms and are awaiting a donor heart. Increasingly, though, doctors are exploring the possibility that such devices may be satisfactory treatments themselves, forestalling the need for a transplant altogether in some patients.

Ventricular Assist Devices (VADs). Ventricular assist devices are machines that help improve pumping actions. Several models with slightly different features are in use or under investigation. Some include the following:

Left ventricular assist device (LVAD) are used for patients whose heartbeat has slowed dangerously (a condition called bradycardia) to help take over the pumping action of the failing heart. Studies suggest that in some people the use of an LVAD may allow some of the damaged heart muscle to heal, perhaps even helping some patients avoid heart transplants. These devices are also being studied in combination with drug therapy to help recover heart function and improve patients’ chances for survival. Until recently, these machines required remaining in the hospital. Smaller battery-powered LVAD units, however, are allowing many patients to leave the hospital and are proving to be effective bridges to heart transplants in adults. The HeartMate, for example, a portable LVAD about the size of a portable CD player (2 in. by 4 in.), is implanted in the upper abdomen. The implanted device plugs into an external power base, which is used when the patient is at rest to recharge the battery and provide continuous power.
Fully implanted miniature artificial pumps that assist the heart (not replace it) are also being tested. The DeBakey ventricular assist device (VAD) for example, is a tiny heart pump that weighs less than 4 ounces. It has been approved in Europe and is being tested in the United States. The Jarvik 2000 heart pump is also showing promise.
The intra-aortic balloon pump (IABP) is helpful for maintaining heart function in people with left-side failure waiting for transplants and in those who develop a sudden and severe deterioration of heart function. The IABP is an implanted thin balloon that is usually inserted into the artery in the leg and threaded up to the aorta leading from the heart. Its pumping action is generated by inflating and deflating the balloon at certain rates. Usually, it is used only for short periods, but some studies indicate that patients may be able to use it safely for somewhat longer periods (an average duration of 23 days in one study).

There are risks involved with many of these devices, including bleeding, blood clots, and right-side heart failure. Infections are a particular hazard.

Pacers (Pacemakers). Pacers, or pacemakers, help regulate the heart’s beating action, especially when the heart beats too slowly. Biventricular pacers (BVPs) are a special type of pacemaker used for patients with heart failure. Because BVPs help the heart’s left and right chambers beat together, this treatment is called cardiac resynchronization therapy (CST). BVPs may particularly help heart failure patients who have left bundle branch block, a condition in which the electrical impulses in the heart do not follow their normal pattern. In general, BVPs are recommended for patients with moderate-to-severe heart failure. A small 2006 study suggested that a defibrillator may be better suited for patients with moderate heart failure, while indicating a BVP might be best for patients with severe heart failure.

Implantable Cardioverter-Defibrillators. Devices called implantable cardioverter-defibrillators (ICDs), which are sometimes combined with pacemakers, work well for preventing arrhythmias (abnormal heart rhythms) in heart failure patients. Studies have also found them effective in preventing sudden death from severe rhythm disturbances in patients with weakened hearts from previous arrhythmias and in patients with genetic hypertrophic cardiomyopathy. Patients who have an ICD should avoid taking fish oil supplements. A 2005 Journal of the American Medical Association study found that omega-3 fatty acid supplements may increase the risk of rapid heart beat (ventricular tachycardia) or irregular heart rhythm (ventricular fibrillation) in some of these patients.

ICDs have many benefits, and recent expert guidelines recommend that they be used in more patients with heart failure. However, in June 2005, certain ICD models and biventricular pacemaker-defibrillators were recalled by the manufacturer because of a circuitry flaw that prevents the devices from delivering therapeutic electrical shocks when needed. The problem may result in patient death. Although the FDA did not make any specific recommendations, the agency encourages patients who may have such a device to ask their doctor if they should have it removed or replaced.

In April 2006, two studies published in the Journal of the American Medical Association evaluated data concerning the safety and reliability of implantable pacemakers and defibrillators. The studies found that from 1990 – 2002, pacemakers became increasingly reliable. From 1998 – 2002, ICDs had a significantly higher rate of malfunction than pacemakers, although the reliability of ICDs appeared to improve from 2003 – 2004.

In October 2006, the U.S. Heart Rhythm Society issued recommendations for doctors, manufacturers, and the FDA to help improve communication concerning performance and recalls of ICDs and pacemakers. Experts stress that the chance of an ICD or pacemaker saving a person’s life far outweigh the possible risks of these devices failing.

Ultrafiltration devices are used in hospitals to pump excess water and salt from the body. Catheters are inserted into several of the patient’s veins. The catheters are connected to a blood filter device. Blood is withdrawn through one of the catheters and filtered in the device to remove excess fluid. The filtered blood is then returned to the patient through another catheter. A 2006 study reported that ultrafiltration devices may work better than diuretic drugs for patients with acute decompensated heart failure (ADHF). ADHF is heart failure that has rapidly deteriorated so that patients require immediate hospitalization.

Lifestyle Changes

Between 30 - 47% of patients who require hospitalization for heart failure are back in the hospital within 6 months. Many people return because of lifestyle factors such as poor diet, failure to comply with medications, and social isolation.

In one study, elderly people who had no emotional support at home had triple the risk of a heart attack after hospitalization for heart failure than those who did have such support. (Women had eight times the risk.) In another study, the greatest risk factor for death and readmission to the hospital after a first hospitalization was being single, regardless of the health of the patient at discharge. A third study confirmed that a strong marriage predicted long-term survival. Evidence continues to mount that programs that offer intensive follow-up to ensure that the patient complies with lifestyle changes and medication regimens at home are reducing rehospitalization rates and improving survival. Patients without available rehabilitation programs should seek support from local and national heart associations and groups.

Patients should weigh themselves each morning and keep a record. Any changes are important:

A sudden increase in weight of more than 2 - 3 pounds may indicate fluid accumulation and should prompt an immediate call to the doctor.
Rapid wasting weight loss over a few months is a very serious sign and may indicate the need for surgical intervention.

Whole Grains. Evidence suggests that daily consumption of whole grain foods may help prevent heart failure. In research presented at a 2007 American Heart Association conference, people who ate whole-grain breakfast cereals seven or more times a week had a 28% lower risk of developing heart failure than those who never ate these cereals.

Mediterranean Diet. Evidence suggests that the Mediterranean diet helps protect the heart and may even reduce the risk for heart failure after a first heart attack. The diet emphasizes whole grains, fish, olive oil, garlic, and moderate daily intake of wine. There are several variations to the Mediterranean diet but general recommendations include:

Limit red meats.
Limit dairy products.
Eat moderate amounts of fish and poultry. Fish is the diet’s main protein source. Some studies suggest that fish is the primary heart-protective ingredient in this diet. However, patients who have an implantable defibrillator should not take fish oil supplements. A 2005 study suggested that these supplements may worsen heart rhythm problems in some patients.
Eat plenty of fresh fruits and vegetables, nuts, legumes, beans, and whole grains.
Daily glass or two of wine. Light-to-moderate alcohol use may reduce the risk for heart failure, (but heavy alcohol consumption is a risk factor).
Plenty of fresh fruits and vegetables, as well as nuts, legumes, beans, and whole grains.

DASH Diet. The Dietary Approaches to Stop Hypertension (DASH) diet is an important lifestyle step in managing blood pressure. It may also be useful for many patients with heart failure. This diet is not only rich in important nutrients and fiber but also includes foods that contain two and a half times the amounts of electrolytes, potassium, calcium, and magnesium found in the average American diet.

Potassium-rich foods, which are important for patients with heart failure, include bananas, oranges, prunes, cantaloupes, carrots, spinach, celery, alfalfa, mushrooms, lima beans, potatoes, avocados, and broccoli. However, patients who take potassium-sparing diuretics or ACE inhibitors, and those with kidney dysfunction, may have to restrict their potassium intake.

The DASH diet is rich in whole grains and fresh fruits and vegetables. It stresses avoiding saturated fats, as any healthy diet does, although it includes calcium-rich dairy products that are non- or low-fat. When choosing fats, the diet recommends monounsaturated oils such as olive or canola oil.

Salt Restriction. People with high blood pressure are generally urged to restrict salt, although certain people may be more susceptible to its effects. For example, a high intake of salt may be an independent risk factor for the development of heart failure in people who are overweight. All patients with heart failure should limit their salt intake, and in severe cases, very stringent salt restriction may be necessary. Patients should not add salt to their cooking and their meals. They should also avoid foods high in sodium. These salty foods include ham, bacon, hot dogs, lunch meats, prepared snack foods, dry cereal, cheese, canned soups, soy sauce, and condiments. Some patients may need to reduce their water intake as well. People with high cholesterol levels or diabetes require additional dietary precautions. [See In-Depth Report #43: Heart-healthy diet. ]

People with heart failure used to be discouraged from exercising. Now, experts think that exercise, when performed under medical supervision, is extremely important for many patients with stable conditions. Studies have reported that patients with stable conditions who engage in regular moderate exercise (three times a week) experience a better quality of life and lower mortality rates than those who do not exercise.

The following guidelines are critical:

Experts warn that exercise is not appropriate for all patients with heart failure. If you have heart failure, always consult your doctor before starting an exercise program.
People who are approved for, but not used to, exercise should start with 5 - 15 minutes of easy exercise with frequent breaks. Although the goal is to build up to 30 - 45 minutes of walking, swimming, or low-impact aerobic exercises three to five times every week, even shorter times spent exercising are useful.

Studies report benefits from specific exercises:

Progressive strength training may be particularly useful for patients with heart failure since it strengthens muscles, which commonly deteriorate in this disorder. Strength training typically uses light weights, weight machines, or even the body's weight (leg raises or sit-ups, for example). Even performing daily handgrip exercises can improve blood flow through the arteries.
Patients who exercise regularly using supervised treadmill and stationary-bicycle exercises can increase their exercise capacity by 14 - 36%. In one study, patients as old as 91 years increased their oxygen consumption significantly after 6 months of supervised treadmill and stationary bicycle exercises. Exercising the legs may help correct problems in heart muscles. In one study, patients who did leg extension exercises for 8 weeks had higher levels of an enzyme involved in forming new blood vessels. Exercise has also been associated with reduced inflammation in blood vessels.
Dancing may be a fun and beneficial alternative to standard aerobic exercise, according to research presented at the 2006 annual meeting of the American Heart Association. In a study of patients with stable chronic heart failure, dancing helped improve cardiopulmonary fitness, arterial elasticity, and quality of life. Patients in the study danced fast and slow waltzes for 21 minutes, three times a week.

Bed rest may be required in cases of severe heart failure. To reduce congestion in the lungs, the patient's upper body should be elevated. For most patients, resting in an armchair is better than lying in bed. Relaxing and contracting leg muscles is important to prevent clots. As the patient improves, a doctor will progressively recommend more activity.

Experts have traditionally recommended that people with heart failure avoid warm baths, which can increase the heart rate. Some studies now report that carefully controlled bathing for short periods may not be harmful and may actually be beneficial, reducing irregular heart beats and increasing cardiac output and ejection fraction. Warm water may behave like a vasodilating drug, opening up the vessels gently and improving circulation. In clinical trials, patients sat in warm water or a dry sauna for 10 minutes, with their bodies tilted at a 45 degree angle.

Warning Note: Prolonged periods in hot or even warm conditions can be dangerous. Any patient with heart failure should consult their doctor first, not bathe unaccompanied, and be sure that the temperature does not go above 106° Fahrenheit for water bathing or 140° Fahrenheit for dry saunas.

Stress reduction techniques, such as meditation and relaxation response methods, may have direct physical benefits for lowering stress hormones. These hormones include cortisol, which suppresses the immune system, and norepinephrine (also known as adrenaline), the chemical messenger associated with heart dysfunction.

Patients with heart failure may resort to alternative remedies. Such remedies are often ineffective and may have severe or toxic effects. Of particular note for patients with heart failure is an interaction between St. John's wort (an herbal medicine used for depression) and digoxin (a heart drug). St. John's wort can significantly interfere with this drug.

Arginine. Some evidence suggests that arginine (also called L-arginine) may have some benefit. This amino acid appears to reduce endothelin, a protein that causes blood vessel constriction and is found in high amounts in patients with heart failure. It can have adverse effects, however, including gastrointestinal problems. It can also lower blood pressure and change levels of certain chemicals and electrolytes in the body. It may increase the risk for bleeding. Some people have an allergic reaction to it, which in same cases may be severe. It may worsen asthma.

Coenzyme Q10 and Vitamin E. Small studies have suggested that coenzyme Q10 (CoQ10) may help patients with heart failure, particularly when combined with vitamin E. CoQ10 is a vitamin-like substance found in organ meats and soybean oil. More recent studies, however, have found that CoQ10 and vitamin E do not help the heart or prevent heart disease. According to a 2005 Journal of the American Medical Association study, vitamin E supplements can actually increase the risk of heart failure, especially for patients with diabetes or vascular diseases.

Crataegus Extract. An herbal remedy, Crataegus Extract WS1442, which is made from the leaves of the Crataegus tree, may have antioxidant properties that can help patients with heart failure. In a study presented at the 2007 American College of Cardiology annual meeting, over 2,000 patients with severe heart failure were randomized to receive either Crataegus Extract or placebo (plus standard drug treatment) for 2 years. The researchers noted a 20% reduction in heart-related deaths among patients who received the extract, and suggested that the herb extended patients’ lives by 4 months during the first 18 months of the study.

Other Vitamins and Supplements. A wide variety of other vitamins (thiamin, B6, and C), minerals (calcium, magnesium, zinc, manganese, copper, selenium), nutritional supplements (carnitine, creatine), and herbal remedies (hawthorn) have been proposed as treatments for heart failure. None have been adequately tested. There is no evidence that a particular vitamin or supplement can cure heart failure. In any case, vitamins are best consumed through the food sources contained in a healthy diet.

Generally, manufacturers of herbal remedies and dietary supplements do not need FDA approval to sell their products. Just like a drug, herbs and supplements can affect the body's chemistry, and therefore have the potential to produce side effects that may be harmful. There have been several reported cases of serious and even lethal side effects from herbal products. Always check with your doctor before using any herbal remedies or dietary supplements.

Resources

www.nhlbi.nih.gov -- National Heart, Lung, and Blood Institute
www.americanheart.org -- American Heart Association
www.acc.org -- American College of Cardiology
www.hfsa.org -- Heart Failure Society of America
www.heartfailure.org -- Heart Failure Online
www.unos.org -- United Network for Organ Sharing
www.organdonor.org -- National Transplant Society
www.organdonor.gov -- US government organ donor site

References

Ahmed A, Rich MW, Fleg JL, Zile MR, Young JB, Kitzman DW, et al. Effects of digoxin on morbidity and mortality in diastolic heart failure: the ancillary digitalis investigation group trial. Circulation. 2006 Aug 1;114(5):397-403.

Battaglia M, Pewsner D, Juni P, Egger M, Bucher HC, Bachmann LM. Accuracy of B-type natriuretic peptide tests to exclude congestive heart failure: systematic review of test accuracy studies. Arch Intern Med. 2006 May 22;166(10):1073-80.

Bhatia RS, Tu JV, Lee DS, Austin PC, Fang J, Haouzi A, et al. Outcome of heart failure with preserved ejection fraction in a population-based study. N Engl J Med. 2006 Jul 20;355(3):260-9.

Birks EJ, Tansley PD, Hardy J, George RS, Bowles CT, Burke M, et al. Left ventricular assist device and drug therapy for the reversal of heart failure. N Engl J Med. 2006 Nov 2;355(18):1873-84.

Bryson CL, Mukamal KJ, Mittleman MA, Fried LP, Hirsch CH, Kitzman DW, et al. The association of alcohol consumption and incident heart failure: the Cardiovascular Health Study. J Am Coll Cardiol. 2006 Jul 18;48(2):305-11.

Bursi F, Weston SA, Redfield MM, Jacobsen SJ, Pakhomov S, Nkomo VT, et al. Systolic and diastolic heart failure in the community. JAMA. 2006 Nov 8;296(18):2209-16.

Carlson MD, Wilkoff BL, Maisel WH, Carlson MD, Ellenbogen KA, Saxon LA, et al. Recommendations from the Heart Rhythm Society Task Force on Device Performance Policies and Guidelines Endorsed by the American College of Cardiology Foundation (ACCF) and the American Heart Association (AHA) and the International Coalition of Pacing and Electrophysiology Organizations (COPE). Heart Rhythm. 2006 Oct;3(10):1250-73.

Davis BR, Piller LB, Cutler JA, Furberg C, Dunn K, Franklin S, et al. Role of diuretics in the prevention of heart failure: the Antihypertensive andLipid-Lowering Treatment to Prevent Heart Attack Trial. Circulation. 2006 May 9;113(18):2201-10. Epub 2006 May 1.

Gheorghiade M, Abraham WT, Albert NM, Greenberg BH, O'Connor CM, She L, et al. Systolic blood pressure at admission, clinical characteristics, and outcomes inpatients hospitalized with acute heart failure. JAMA. 2006 Nov 8;296(18):2217-26.

Gheorghiade M, Konstam MA, Burnett JC Jr, Grinfeld L, Maggioni AP, Swedberg K, et al. Short-term clinical effects of tolvaptan, an oral vasopressin antagonist, in patients hospitalized for heartfFailure: the EVEREST clinical status trials. JAMA. 2007 Mar 25; [Epub ahead of print]

Go AS, Lee WY, Yang J, Lo JC, Gurwitz JH. Statin therapy and risks for death and hospitalization in chronic heart failure. JAMA. 2006 Nov 1;296(17):2105-11.

Hildebrandt P. Systolic and nonsystolic heart failure: equally serious threats. JAMA. 2006 Nov 8;296(18):2259-60.

Konstam MA, Gheorghiade M, Burnett JC Jr, Grinfeld L, Maggioni AP, Swedberg K, et al. Effects of oral tolvaptan in patients hospitalized for worsening heart failure: the EVEREST Outcome Trial. JAMA. 2007 Mar 25; [Epub ahead of print]

Lee DS, Pencina MJ, Benjamin EJ, Wang TJ, Levy D, O'Donnell CJ, et al. Association of parental heart failure with risk of heart failure in offspring. N Engl J Med. 2006 Jul 13;355(2):138-47.Maisel WH. Pacemaker and ICD generator reliability: meta-analysis of device registries. JAMA. 2006 Apr 26;295(16):1929-34.

Maisel WH, Moynahan M, Zuckerman BD, Gross TP, Tovar OH, Tillman DB, et al. Pacemaker and ICD generator malfunctions: analysis of Food and Drug Administration annual reports. JAMA. 2006 Apr 26;295(16):1901-6.

Mueller C, Laule-Kilian K, Schindler C, Klima T, Frana B, Rodriguez D, et al. Cost-effectiveness of B-type natriuretic peptide testing in patients with acute dyspnea. Arch Intern Med. 2006 May 22;166(10):1081-7.

Owan TE, Hodge DO, Herges RM, Jacobsen SJ, Roger VL, Redfield MM. Trends in prevalence and outcome of heart failure with preserved ejection fraction. N Engl J Med. 2006 Jul 20;355(3):251-9.

Review Date:
4/11/2007
Reviewed By:
Harvey Simon, MD, Associate Professor of Medicine, Harvard Medical School; Physician, Massachusetts General Hospital.

A.D.A.M. Copyright

adam.com

Anxiety disorders

FitSugar — Wed, 08 Oct 2008 17:34:56 -0700

In This Report

Highlights
Introduction
Causes
Risk Factors
Complications
Diagnosis
Treatment
Medications
Other Treatments
Resources
References

HEALTH GUIDE REFERENCE FROM A.D.A.M

Highlights

Drug Approval

In 2007, duloxetine (Cymbalta) was approved for treatment of generalized anxiety disorder. Duloxetine is a dual inhibitor antidepressant.

Anxiety Disorders Under-Recognized and Under-Treated

About 41% of patients with an anxiety disorder do not receive any treatment, indicates a 2007 study in the Annals of Internal Medicine. Anxiety disorders can interfere with daily functioning, and problems worsen when people have more than one type of anxiety disorder. The study’s researchers recommend that screening for anxiety become a regular part of office visits in the same way that primary care doctors screen patients for depression.

Antidepressants and Children

The benefits of antidepressants for treating pediatric anxiety disorders appear to outweigh the risks for suicide, according to a 2007 review in the Journal of the American Medical Association. Researchers also found that antidepressants did not work as well for treating obsessive compulsive disorder compared to other types of anxiety disorders. This review was the largest to date of antidepressant use in children and adolescents. Most doctors recommend cognitive behavioral therapy as the first treatment approach for childhood anxiety disorders.

Psychological Therapies for Post-Traumatic Stress Disorder

Specially designed psychotherapies -- such as trauma-focused cognitive behavioral therapy, eye movement desensitization and reprocessing, and stress management -- are the most effective therapies for patients with post-traumatic stress disorder, according to a 2007 review in the Cochrane Database.

Introduction

Fear and stress reactions are essential for human survival. They enable people to pursue important goals and to respond appropriately to danger. In a healthy individual, the stress response (fight, fright, or flight) is provoked by a genuine threat or challenge and is used as a spur for appropriate action.

An anxiety disorder, however, involves an excessive or inappropriate state of arousal characterized by feelings of apprehension, uncertainty, or fear. The word is derived from the Latin, angere, which means to choke or strangle. The anxiety response is often not attributable to a real threat. Nevertheless it can still paralyze the individual into inaction or withdrawal. An anxiety disorder persists, while a healthy response to a threat resolves, once the threat is removed.

Anxiety disorders have been classified according to the severity and duration of their symptoms and specific behavioral characteristics. Categories include:

Generalized anxiety disorder (GAD), which is long lasting and low-grade
Panic disorder, which has more dramatic symptoms
Phobias
Obsessive-compulsive disorder (OCD)
Post-traumatic stress disorder (PTSD)
Separation anxiety disorder (which is almost always seen in children)

GAD and panic disorder are the most common. Anxiety disorders are usually caused by a combination of psychological, physical, and genetic factors, and treatment is, in general, very effective.

Generalized anxiety disorder (GAD) is the most common anxiety disorder. It affects about 5% of Americans over the course of their lifetimes. It is characterized by the following:

A more-or-less constant state of worry and anxiety, which is out of proportion to the level of actual stress or threat in their lives.
This state occurs on most days for more than 6 months despite the lack of an obvious or specific stressor. (It worsens with stress, however.)
It is very difficult to control worry. For a clear diagnosis of GAD, the specific worries should be differentiated from those that would define other anxiety disorders, such as fear of panic attacks or appearing in public. Moreover, they are not obsessive like people with obsessive-compulsive disorder. (It should be noted, however, that over half of those with GAD also have another anxiety disorder or depression.)
Patients with anxiety may experience physical symptoms (such as gastrointestinal complaints) in addition to, or even in place of, mental worries. (This latter case may be more common in people from non-Western cultures such as those with Asian backgrounds.)
People with GAD tend to be unsure of themselves, overly perfectionist, and conforming.

Given these conditions, a diagnosis of GAD is confirmed if three or more of the following symptoms are present (only one for children) on most days for 6 months:

Being on edge or very restless
Feeling tired
Having difficulty with concentration
Being irritable
Having muscle tension
Experiencing disturbed sleep

Symptoms should cause significant distress and impair normal functioning and not be due to a medical condition, another mood disorder, or psychosis. It should be noted that pure GAD is uncommon. It typically occurs with other mood disorders (anxiety or depression) or substance use.

Panic disorder is characterized by periodic attacks of anxiety or terror (panic attacks). They usually last 15 - 30 minutes, although residual effects can persist much longer. The frequency and severity of acute states of anxiety determine the diagnosis. (It should be noted that panic attacks can occur in nearly every anxiety disorder, not just panic disorder. In other anxiety disorders, however, there is always a cue or specific trigger for the attack.) A diagnosis of panic disorder is made under the following conditions:

A person experiences at least two recurrent, unexpected panic attacks.
For at least a month following the attacks, the person fears that another will occur.

Symptoms of a Panic Attack. During a panic attack a person feels intense fear or discomfort with at least four or more of the following symptoms:

Rapid heart beat
Sweating
Shakiness
Shortness of breath
A choking feeling or a feeling of being smothered
Dizziness
Nausea
Feelings of unreality
Numbness
Either hot flashes or chills
Chest pain
A fear of dying
A fear of going insane

Women may be more likely than men to experience shortness of breath, nausea, and feelings of being smothered. More men than women have sweating and abdominal pain. Panic attacks that include only one or two symptoms, such as dizziness and heart pounding, are known as limited-symptom attacks. These may be either residual symptoms after a major panic attack or precursors to full-blown attacks. (It should be noted that panic attacks can also accompany other anxiety disorders, such as phobias and post-traumatic stress disorder. In such cases, however, additional characteristics differentiate these disorders from panic disorder.)

Frequency of Panic Attacks. Frequency of attacks can vary widely. Some people have frequent attacks (for example, every week) that occur for months; others may have clusters of daily attacks followed by weeks or months of remission.

Triggers of Panic Attacks. Panic attacks may occur spontaneously or in response to a particular situation. Recalling or re-experiencing even harmless circumstances surrounding an original attack may trigger subsequent panic attacks.

Phobias, manifested by overwhelming and irrational fears, are common. In most cases, people can avoid or at least endure phobic situations, but in some cases, as with agoraphobia, the anxiety associated with the feared object or situation can be incapacitating.

Agoraphobia. Agoraphobia has been somewhat misleadingly described as fear of open spaces, the term having been derived from the Greek word agora, meaning outdoor marketplace. In its severest form, agoraphobia is characterized by a paralyzing terror of being in places or situations from which the patient feels there is neither escape nor accessible help in case of an attack. (One patient described the terror of going outside as opening a door onto a landscape filled with snakes.) Consequently, people with agoraphobia confine themselves to places in which they feel safe, usually at home. The patient with agoraphobia often makes complicated plans in order to avoid confronting feared situations and places.

Social Phobia. Social phobia, also known as social anxiety disorder, is the fear of being publicly scrutinized and humiliated and is manifested by extreme shyness and discomfort in social settings. This phobia often leads people to avoid social situations and is not due to a physical or mental problem (such as stuttering, acne, or personality disorders). The incidence of social phobia is about 13% and has been termed "the neglected anxiety disorder" because it is often not properly diagnosed.

The associated symptoms vary in intensity, ranging from mild and tolerable anxiety to a full-blown panic attack. (Unlike a panic attack, however, social phobia is always directly related to a social situation.) Symptoms include sweating, shortness of breath, pounding heart, dry mouth, and tremor.

The disorder may be further categorized as generalized or specific social phobia:

Generalized social phobia is the fear of being humiliated in front of other people during nearly all social situations. People with this subtype are the most socially impaired and also the most likely to seek treatment.
Specific social phobia usually involves a phobic response to a specific event. Performance anxiety ("stage fright") is the most common specific social phobia and occurs when a person must perform in public. These patients usually feel comfortable in informal social situations.

Children with social anxiety develop symptoms in settings that include their peers, not just adults, and they may include tantrums, blushing, or not being able to speak to unfamiliar people. These children should be able to have normal social relationships with familiar people, however.

Specific Phobias. Specific phobias (formerly simple phobias) are an irrational fear of specific objects or situations. Specific phobias are among the most common medical disorders. Most cases are mild and not significant enough to require treatment.

The most common phobias are fear of animals (usually spiders, snakes, or mice), flying (pterygophobia), heights (acrophobia), water, injections, public transportation, confined spaces (claustrophobia), dentists (odontiatophobia), storms, tunnels, and bridges.

When confronting the object or situation, the phobic person experiences panicky feelings, sweating, avoidance behavior, difficulty breathing, and a rapid heartbeat. Most phobic adults are aware of the irrationality of their fear, and many endure intense anxiety rather than disclose their disorder.

Obsessive-compulsive disorder (OCD) has been described as hiccups of the mind. OCD is time-consuming, distressing, and can disrupt normal functioning. Much research suggests that a critical feature in this disorder is an overinflated sense of responsibility, in which the patient's thoughts center around possible dangers and an urgent need to do something about it.

Obsessions are recurrent or persistent mental images, thoughts, or ideas. The obsessive thoughts or images can range from mundane worries about whether one has locked a door to bizarre and frightening fantasies of behaving violently toward a loved one.
Compulsive behaviors are repetitive, rigid, and self-directed routines that are intended to prevent the manifestation of an associated obsession. Such compulsive acts might include repetitive checking for locked doors or unlit stove burners or calls to loved ones at frequent intervals to be sure they are safe. Some people are compelled to wash their hands every few minutes or to spend inordinate amounts of time cleaning their surroundings in order to subdue the fear of contagion.

Over half of OCD-sufferers have obsessive thoughts without the ritualistic compulsive behavior. Although individuals recognize that the obsessive thoughts and ritualized behavior patterns are senseless and excessive, they cannot stop them in spite of strenuous efforts to ignore or suppress the thoughts or actions. OCD often accompanies depression or other anxiety disorders. There is some evidence that the symptoms improve over time and that nearly half will eventually recover completely or have only minor symptoms.

Symptoms in children may be mistaken for behavioral problems (taking too long to do homework because of perfectionism, refusing to perform a chore because of fear of germs). Children do not usually recognize that their obsessions or compulsions are excessive.

Associated Obsessive Disorders. Certain other disorders that may be part of, or strongly associated with, the OCD spectrum include the following:

Body dysmorphic disorder (BDD). In BDD, people are obsessed with the belief that they are ugly, or part of their body is abnormally shaped.
Hypochondriasis. People who have hypochondiasis have an excessive fear of having a serious disease.
Anorexia nervosa. OCD frequently accompanies this eating disorder, where the compulsive behavior focuses on food restriction and thinness.
Trichotillomania. People with trichotillomania continually pull their hair, leaving bald patches.
Tourette syndrome. Symptoms of Tourette syndrome include jerky movements, tics, and uncontrollably uttering obscene words.

Obsessive-Compulsive Personality. OCD should not be confused with obsessive-compulsive personality, which defines certain character traits (being a perfectionist, excessively conscientious, morally rigid, or preoccupied with rules and order). These traits do not necessarily occur in people with obsessive-compulsive disorder.

Post-traumatic stress disorder (PTSD) is a severe, persistent emotional reaction to a traumatic event that severely impairs one’s life. It is classified as an anxiety disorder because of its symptoms. Not every traumatic event leads to PTSD, however. There are two criteria that must be present to qualify for a diagnosis of PTSD:

The patient must have directly experienced, witnessed, or learned of a life-threatening or seriously injurious event.
The patients' response is intense fear, helplessness, or horror. Children may behave with agitation or with disorganized behavior.

Triggering Events. PTSD is triggered by violent or traumatic events that are usually outside the normal range of human experience. There is some evidence that events most likely to trigger PTSD are those that involve deliberate and destructive behavior (murder, rape) and those that are prolonged or physically challenging. Such events include, but are not limited to, experiencing or witnessing sexual assaults, accidents, military combat, natural disasters (such as earthquakes), or unexpected deaths of loved ones. PTSD may also occur in people who have serious illness and receive aggressive treatments or who have close family members or friends with such conditions.

Symptoms of PTSD. There are three basic sets of symptoms associated with PTSD. They may begin immediately after the event or can develop up to a year afterward:

Re-experiencing. In such cases, patients persistently re-experience the trauma in at least one of the following ways: in recurrent images, thoughts, flashbacks, dreams, or feelings of distress at situations that remind them of the traumatic event. Children may engage in play, in which traumatic events are enacted repeatedly.
Avoidance. Patients may avoid reminders of the event, such as thoughts, people, or any other factors that trigger recollection. They tend to have an emotional numbness, a sense of being in a daze or of losing contact with their own identity or even external reality. They may be unable to remember important aspects of the event.
Increased Arousal. This includes symptoms of anxiety or heightened awareness of danger (sleeplessness, irritability, being easily startled, or becoming overly vigilant to unknown dangers).

To further qualify for a diagnosis of PTSD, patients must have at least one symptom in the re-experiencing category, three avoidance symptoms, and two arousal symptoms. Symptoms are chronic (3 months or more). Symptoms should also not be associated with alcohol, medications, or drugs and should not be intensifications of a pre-existing psychological disorder.

Acute Stress Disorder. Experts have identified a syndrome called acute stress disorder, in which symptoms of PTSD occur within 2 days to 4 weeks after the traumatic event. Acute stress disorder can accurately identify up to 94% of victims at risk for PTSD. Between 50 - 80% of these patients actually develop the more chronic and serious disorder. In other words, it is very sensitive for identification of those at highest danger for PTSD but less successful in determining specifically who will or will not recover emotionally.

Long-Term Outlook. The long-term impact of a traumatic event is uncertain. In one study of people who survived a mass killing spree in Texas, less than half of those who suffered PTSD (28% of all survivors) had recovered after a year. In another study, PTSD became chronic in 46% of the subjects. In fact, PTSD may cause physical changes in the brain, and in some cases the disorder can last a lifetime.

Separation anxiety disorder almost always occurs in children. It is suspected in children who are excessively anxious about separation from important family members or from home. For a diagnosis of separation anxiety disorder, the child should also exhibit at least three of the following symptoms for at least 4 weeks:

Extreme distress from either anticipating or actually being away from home or being separated from a parent or other loved one
Extreme worry about losing or about possible harm befalling a loved one
Intense worry about getting lost, being kidnapped, or otherwise separated from loved ones
Frequent refusal to go to school or to sleep away from home
Physical symptoms such as headache, stomach ache, or even vomiting, when faced with separation from loved ones

Separation anxiety often disappears as the child grows older, but if not addressed, it may lead to panic disorder, agoraphobia, or combinations of anxiety disorders.

Studies suggest that an imbalance of certain substances called neurotransmitters (chemical messengers in the brain) may contribute to anxiety disorders. The neurotransmitters targeted in anxiety disorders are gamma-aminobutyric acid (GABA), serotonin, dopamine, and epinephrine. Serotonin appears to be specifically important in feelings of well-being, and deficiencies are highly related to anxiety and depression.

Examples of study findings on some neurotransmitters are:

Abnormalities in the neurotransmitters gamma-aminobutyric acid (GABA) and serotonin may have a particular role in susceptibility to generalized anxiety disorder. GABA helps prevent nerve cells from over-firing and serotonin is a brain chemical important in feelings of well-being.
Serotonin is a major player in OCD.
Changes in serotonin and dopamine have been observed in social phobia.
People with post-traumatic stress disorder have abnormalities in stress hormones (cortisol) and neurotransmitters associated with stress (epinephrine and norepinephrine). Such imbalances could account for the higher anxiety levels and a tendency to startle easily after a threat in people with PTSD.
Corticotropin-releasing factor (CRF), which is believed to be a stress hormone and a neurotransmitter, is thought to be involved in depression and anxiety by causing changes in serotonin levels.

The best way to envision the brain's response to a threat is to imagine a primal situation, such as being chased by a bear.

The Brain's Response to Acute Stress. In response to seeing the bear, a part of the brain called the hypothalamic-pituitary-adrenal (HPA) system is activated.

Release of Steroid Hormones and the Stress Hormone Cortisol. The HPA systems trigger the production and release of steroid hormones (glucocorticoids), including the primary stress hormone cortisol. Cortisol is very important in marshaling systems throughout the body (including the heart, lungs, circulation, metabolism, immune systems, and skin) to deal quickly with the bear.

Release of Catecholamines and Activation of the Amygdala. The HPA system also releases certain neurotransmitters (chemical messengers) called catecholamines, particularly those known as dopamine, norepinephrine, and epinephrine (also called adrenaline).

Catecholamines activate the amygdala, a small structure deep in the brain, which regulates control of major emotional activities, including anxiety, depression, aggression, and affection. In fact, the amygdala is sometimes known as the "fear" center.

Effects on Long- and Short-Term Memory. During the stressful event, catecholamines also suppress activity in areas at the front of the brain concerned with short-term memory, concentration, inhibition, and rational thought. This sequence of mental events allows a person to react quickly to the bear, either to fight or to flee from it. (It also hinders the ability to handle complex social or intellectual tasks and behaviors during that time.)

On the other hand, neurotransmitters at the same time signal the hippocampus (a nearby area in the brain) to store the emotionally loaded experience in long-term memory. In primitive times, this brain action would have been essential for survival, since long-lasting memories of dangerous stimuli (the large bear) would be critical for avoiding such threats in the future.

Response by the Heart, Lungs, and Circulation to Acute Stress. The stress response also affects the heart, lungs, and circulation:

As the bear comes closer, the heart rate and blood pressure increase instantaneously.
Breathing becomes rapid and the lungs take in more oxygen.
The spleen discharges red and white blood cells, allowing the blood to transport more oxygen throughout the body. Blood flow may actually increase 300 - 400%, priming the muscles, lungs, and brain for added demands.

The Immune System's Response to Acute Stress. The effect on the immune system from confrontation with the bear is similar to marshaling a defensive line of soldiers to potentially critical areas. The steroid hormones dampen parts of the immune system, so that specific infection fighters (including important white blood cells) or other immune molecules can be redistributed. These immune-boosting troops are sent to the body’s front lines where injury or infection is most likely, such as the skin, the bone marrow, and the lymph nodes.

The Acute Response in the Mouth and Throat. As the bear gets closer, fluids are diverted from nonessential locations, including the mouth. This causes dryness and difficulty in talking. In addition, stress can cause spasms of the throat muscles, making it difficult to swallow.

The Skin's Response to Acute Stress. The stress effect diverts blood flow away from the skin to support the heart and muscle tissues. (This also reduces blood loss in the event that the bear catches up.) The physical effect is a cool, clammy, sweaty skin. The scalp also tightens so that the hair seems to stand up.

Metabolic Response to Acute Stress. Stress shuts down digestive activity, a nonessential body function during short-term periods of physical exertion or crisis.

The Relaxation Response: the Resolution of Acute Stress. Once the threat has passed and the effect has not been harmful (the bear has not eaten or seriously wounded the human), the stress hormones return to normal. This is known as the relaxation response. In turn, the body's systems also normalize.

Causes

A person's genetics, biochemistry, environment, history, and psychological profile all seem to contribute to the development of anxiety disorders. Most people with these disorders seem to have a biological vulnerability to stress, making them more susceptible to environmental stimuli than the rest of the population.

Abnormalities in the Brain. Scientists are using imaging techniques, particularly magnetic resonance imaging (MRI), to identify different areas of the brain associated with anxiety responses.

An MRI (magnetic resonance imaging) of the brain creates a detailed image of the complex structures in the brain. An MRI can give a three-dimensional depiction of the brain, making location of problems such as tumors or aneurysms more precise.

Important research in anxiety disorders is focusing on changes in the amygdala, which is sometimes referred to as the "fear center." This part of the brain regulates fear, memory, and emotion and coordinates these resources with heart rate, blood pressure, and other physical responses to stressful events. Some evidence suggests that the amygdala in people with anxiety disorders is highly sensitive to novel or unfamiliar situations and reacts with a high stress response.

Obsessive-compulsive disorder (OCD) is the anxiety disorder most strongly associated with specific brain dysfunction. For example, abnormalities in a specific pathway of nerves have been linked to OCD, attention deficit disorder, and Tourette syndrome. The symptoms of the three disorders are similar and they often coexist.

A number of imaging studies have reported less volume in the hippocampus in people with post-traumatic stress disorder. This important region is related to emotion and memory storage.

The influence of the family on anxiety is complicated by both genetic and psychological factors.

Panic Disorder and Family Influence. Certain psychodynamic theories suggest, and a few studies support the idea, that some people may develop panic disorder if they cannot resolve the early childhood conflict of dependence vs. independence. In one study, for example, young adults who had experienced childhood anxiety were more likely to live with their parents until their early to mid-twenties. Many people with panic disorder perceive their parents as being extremely controlling and overly protective while showing little actual affection.

Phobias and Family Influence. Several studies show a strong correlation between a parent's fears and those of the offspring. Although an inherited trait may be present, some researchers believe that many children can "learn" fears and phobias, just by observing a parent or loved one's phobic or fearful reaction to an event. People who have social phobias and severe agoraphobia generally report less parental affection and more strictness, overprotection, and encouragement of dependence than those without these disorders.

Obsessive-Compulsive Disorder and Family Influence. One study found that parental influence played no part in obsessive-compulsive disorder if the OCD patient was also not suffering from depression. However, depression coexists in two-thirds of OCD patients, and in the study patients who had both OCD and depression reported lower levels of parental care and overprotectiveness.

Traumatic events generally trigger anxiety disorders in individuals who are susceptible to them because of psychological, genetic, or biochemical factors. The clearest example is post-traumatic stress disorder. Specific traumatic events in childhood, particularly those that threaten family integrity, such as spousal or child abuse, can also lead to other anxiety and emotional disorders. Some individuals may even have a biological propensity for specific phobias, for instance of spiders or snakes, that have been triggered and perpetuated after a single exposure.

The acronym PANDAS (Pediatric Autoimmune Neuropsychiatric Disorders Associated with Streptococcus) is a term for an autoimmune condition associated with group A streptococcal infection in children (the cause of "strep throat" and rheumatic fever). Children with PANDAS develop tic-related disorders, including OCD and Tourette syndrome. In such cases, the OCD symptoms develop abruptly soon after the infection. It is unlikely to be an important cause of OCD.

Risk Factors

As many as 25% of all American adults experience intense anxiety sometime in their lives. The prevalence of true anxiety disorders is much lower, although they are still the most common psychiatric conditions in the United States and affect more than 20 million Americans.

Gender. With the exception of obsessive-compulsive disorder (OCD), women have twice the risk for most anxiety disorders as men. A number of factors may increase the reported risk in women, including cultural pressures to meet everyone else's needs except their own, and fewer self-restrictions on reporting anxiety to doctors.

Age. In general, phobias, OCD and separation anxiety show up early in childhood, while social phobia and panic disorder are often diagnosed during the teen years. Studies suggest that 3 - 5% of children and adolescents have some anxiety disorder. Children and adolescents who have an anxiety disorder are at risk of later developing other anxiety disorders, depression, and substance abuse.

Personality Factors. Children's personalities may indicate higher or lower risk for future anxiety disorders. For example, research suggests that extremely shy children and those likely to be the target of bullies are at higher risk for developing anxiety disorders later in life. Children who cannot tolerate uncertainty tend to be worriers, a major predictor of generalized anxiety. In fact, such traits may be biologically based and due to a hypersensitive amygdala -- the "fear center" in the brain.

Family History and Dynamics. Anxiety disorders tend to run in families. Genetic factors may play a role in some cases, but family dynamics and psychological influences are also often at work.

Social Factors. Several studies have reported a significant increase in anxiety levels in children and college students in the past two decades compared to children in the 1950s. In several studies, anxiety was associated with a lack of social connections and a sense of a more threatening environment. It also appears that more socially alienated populations have higher levels of anxiety. For example, a study of Mexican adults living in California reported that native-born Mexican Americans were three times more likely to have anxiety disorders (and even more likely to be depressed) as those who had recently immigrated to the U.S. The longer the immigrants lived in the U.S., the greater their risk for psychiatric problems. Traditional Mexican cultural and social ties seemed to protect recently arrived immigrants from mental illness.

Genetic Factors. Up to 50% of people with panic disorder and 40% of patients with generalized anxiety (GAD) have close relatives with the disorder. (About half of GAD patients also have family members with panic disorder, and about 30% have relatives with simple phobias.)

Obsessive-compulsive disorder (OCD) is also strongly related to a family history of the disorder. Close relatives of people with OCD are up to 9 times more likely to develop OCD themselves. Researchers are making progress in identifying specific genetic factors that might contribute to an inherited risk. Of particular interest are genes that regulate specific neurotransmitters (brain chemical messengers), including serotonin and glutamate. Recent research has suggested that the SLC1A1 gene, which is associated with glutamate regulation, may play an important role in early-onset OCD in boys. Research is also beginning to pinpoint regions on specific chromosomes (1, 3, 7, 6, 9, 15) that may contain genes linked to OCD.

However, there are no genetic tests to date that can identify patients at risk for anxiety disorders.

Medical Conditions. Although no causal relationships have been established, certain medical conditions have been associated with panic disorder. They include migraines, obstructive sleep apnea, mitral valve prolapse, irritable bowel syndrome, chronic fatigue syndrome, and premenstrual syndrome.

GAD affects about 1 - 5% of Americans in the course of their lives and is more common in women than in men. Some experts believe that it is underdiagnosed and more common than any other anxiety disorder. It is certainly the most common anxiety disorder among the elderly. GAD usually begins in childhood and often becomes a chronic ailment, particularly when left untreated. Depression in adolescence may be a strong predictor of GAD in adulthood. Depression commonly accompanies this anxiety disorder in any case.

Age and Panic Disorder. Studies indicate that the prevalence of panic disorder among adults is between 1.6 - 2% and is much higher in adolescence, 3.5 - 9%. Panic disorder usually first occurs either in late adolescence or in the mid-30s.

Gender and Panic Disorder. Women have about twice the risk for panic disorder as men. Panic attacks are very common after menopause. In one study, nearly 18% of older women reported panic attacks within a 6-month period, with over half of these attacks being full-blown. They tended to be associated with stressful life events and poor health. The effects of pregnancy on panic disorder appear to be mixed. It seems to improve the condition in some women and worsen it in others.

Obsessive-compulsive disorder occurs equally in men and women, and it affects about 2 - 3% of people over a lifespan. Most cases of OCD first develop in childhood or adolescence, although the disorder can occur throughout the life span.

Social anxiety disorder is currently estimated to be the third most common psychiatric disorder in the U.S. Studies have reported a prevalence of 7 - 12% in Western nations.

Age and Phobias. The onset of social anxiety disorder is usually during the early teenage years.

Gender and Phobias. Women are more likely to develop social anxiety disorder than men, although equal numbers of men and women seek treatment for it. Most people seeking treatment have had symptoms for at least 10 years.

Studies estimate a lifetime risk for PTSD in the U.S. of up to 8%. People exposed to traumatic events, of course, are at highest risk, but many people can go through such events and not experience PTSD. Studies estimate that 6 - 30% or more of trauma survivors develop PTSD, with children and young people being among those at the high end of the range. Women have the twice the risk of PTSD as men.

Furthermore, PTSD can occur in people not directly involved with a traumatic event. For example, 17% of the U.S. population outside New York City reported some symptoms of post-traumatic stress 2 months after the September 11 attack on the World Trade Towers. (In the city itself, where the attack occurred, an estimated 7.5% of New York's population reported PTSD within the month of the event, which declined to 0.6% at 6 months.)

Researchers are trying to determine factors that might increase vulnerability to catastrophic events and put people at risk for develop PTSD. Some studies report the following may be risk factors:

Pre-existing emotional disorder. People who have a history of an emotional disorder, particularly depression, before the traumatic event are at higher risk for PTSD.
Drug or alcohol abuse
A family history of anxiety
A history of abuse, particularly that which threatens family integrity, such as spousal or child abuse. Studies of individuals who had suffered physical or sexual abuse or neglect as children suggest that up to one-third develop PTSD.
An early separation from parents
Lack of social support and poverty
Sleep disorders. Insomnia and excessive daytime sleepiness even within a month after a traumatic event are important predictors for the development of PTSD. One specific sleep disorder -- sleep apnea -- may even intensify symptoms of PTSD, including sleeplessness and nightmares. Sleep apnea occurs when tissues in the upper throat (or airway) collapse at intervals during sleep, thereby blocking the passage of air. In one study, 91% of crime victims with PTSD had either sleep apnea or a lesser condition that partially blocked the airways during sleep. In fact, in one study treatment of sleep apnea eased PTSD. Sleep apnea has also been associated with a risk for panic disorder. [For more information, see In-Depth Report #65: Sleep apnea.]

Complications

Studies consistently report that all types of anxiety disorders can be very debilitating and seriously affect a person’s quality of life.

Depression. Depression is very common in people with an anxiety disorder, and it is sometimes difficult to distinguish one from the other because either or both can be accompanied by anxious feelings, agitation, insomnia, and problems with concentration.

Depression and nearly every anxiety disorder often go hand in hand, in both the young and old. In fact, the lifetime risk for depression in people with anxiety disorders may be higher than 70%. Furthermore, the combination of depression and anxiety is a major risk factor for both substance abuse and suicide. The following are examples of depression in specific anxiety disorders:

Between 50 - 65% of people with panic disorder also have major depression. Some studies have suggested that treating panic disorder early enough may help prevent major depression later on.
More than two-thirds of OCD patients suffer from depression.
Most patients with GAD will experience at least one episode of significant depression and many develop recurrent episodes. In patients with both disorders, GAD usually precedes the onset of depression.
Social anxiety during adolescence or young adulthood has been associated with a higher risk for depression, and the presence of both increases the chances for severe depression.
People with PTSD are four to seven times as likely to be depressed as are people without PTSD.

Bipolar Disorder. Symptoms of panic disorder are very common in people with bipolar disorder (manic-depression). In fact, people with bipolar have 26 times the rate of panic disorder as in the general population. Furthermore, anxiety worsens bipolar disorder. According to one study, anxiety disorders in teenagers were associated with bipolar disorder in adulthood, while manic behavior in adolescence was linked to later anxiety disorders.

Evidence now strongly supports an association between panic disorder and a risk for suicidal thoughts. Studies report that up to 18% of people with panic disorder attempt suicide and up to 38.5% regularly harbor suicidal thoughts, with the risks being higher in people with both panic disorder and depression. One study reported suicide attempts in about 12% of people with social phobias or OCD. If a person has an anxiety disorder and a mood disorders (such as depression), the risk for suicide is even higher.

Suicide is the third most common cause of death among adolescents, and is one of the most devastating events than can happen to a family. Suicide is most commonly associated with depression in young people, but it is also commonly associated with anxiety, psychosis, substance abuse, or impulsivity. More girls attempt suicide but more boys succeed, most often because they choose guns or violent methods while girls tend to overdose, which is more treatable. Nevertheless, unsuccessful attempts are major risk factors for a later suicide. Any expression of suicidal intent should be treated very seriously.

The following are danger signs in young people:

Withdrawal from friends
Sudden decrease in school performance
Loss of interest in activities that were previously pleasurable
Unusual irritability
Unusual changes in sleep or eating habits

Risk factors for suicide include a history of neglect or abuse, history of deliberate self-harm, a family member who committed suicide (nearly always one who shared a common mood disorder), access to firearms, and living in communities where there have been recent outbreaks of suicide in young people. A romantic break-up is often the trigger for a suicidal attempt in teenagers. Feeling connected with parents and family protected young people with depression in one study, regardless of gender or ethnicity.

In one study, adolescents failed to seek help for suicidal thoughts for the following reasons:

They believed nothing would help.
They were reluctant to tell anyone they had problems.
They thought it was a sign of weakness to seek help.
They did not know where to go.

Parents should not hesitate to seek professional help for their children if they suspect they are thinking about killing themselves. This is a medical emergency and requires immediate treatment.

[For more information on suicide, see In-Depth Report #8: Depression.]

Severely depressed or anxious people are at high risk for alcoholism, smoking, and other forms of addiction. Anxiety disorders are highly prevalent among people with alcoholism. Moreover, long-term alcohol use can itself cause biologic changes that may actually produce anxiety and depression.

Risk for Substance Abuse in Specific Anxiety Disorders. The following are some observations on specific anxiety disorders and substance abuse:

Some people with GAD and panic disorders may use alcohol or drugs to self-medicate.
Social phobia appears to pose a particular risk for alcohol abuse. People with this disorder are likely to drink in order to boost confidence. Alcohol itself has no direct beneficial effect on anxiety, but studies suggest that the belief in its effect appears to relieve anxious feelings. (Alcohol or substance abuse is not associated with specific phobias -- such as a fear of flying or spiders.)
Heavy smoking and substance abuse are common in people with PTSD. In adolescents, the disorder not only increases the risk for drug and alcohol use but also for eating disorders.

Studies consistently report that anxiety disorders have negative effects on work and relationships. Some examples:

In one study, more than 10% of patients with GAD missed at least 6 days of work within the previous month.
In a survey of OCD sufferers, 40% reported that they had to stop working because of the disorder. Only 40% worked full-time, while only half were married.
A 2006 study indicated that children with OCD are more likely to be bullied than other children.
Studies report that people with social phobias are less likely to get married, to leave home, and to finish school than those without this disorder. Their outlook worsens if they have other emotional disorders.

Anxiety disorders are associated with many different physical illnesses. Research suggests that people who have both an anxiety disorder and a physical illness have a worse quality of life and greater risk for disability than those who have only a physical illness. Anxiety disorders often tend to occur before the development of physical disorders.

Heart Disease. Anxiety has been associated with several heart problems, including unhealthy cholesterol levels, thicker blood vessels, and high blood pressure. Both anxiety and depression have been associated with a poorer response to treatment in heart patients, including a worse outcome after heart surgery.

Cholesterol is a soft, waxy substance that is present in all parts of the body including the nervous system, skin, muscle, liver, intestines, and heart. It is made by the body and obtained from animal products in the diet. Cholesterol is manufactured in the liver and is needed for normal body functions including the production of hormones, bile acid, and vitamin D. Excessive cholesterol in the blood contributes to atherosclerosis and subsequent heart disease. The risk of developing heart disease or atherosclerosis increases as the level of blood cholesterol increases.

Some researchers speculate that intense anxiety might trigger abnormal and dangerous heart rhythms in people with existing heart problems. In other studies, panic disorders, post-traumatic stress disorder, and phobias have been associated with a higher rate of sudden death from cardiac events, including heart attack.

Gastrointestinal Disorders. Anxiety frequently accompanies gastrointestinal conditions. Of note, half the cases of irritable bowel syndrome are associated with anxiety.

Headache. Both tension and migraine headaches are associated with anxiety disorders. One study reported that 32% of people with chronic tension headaches met criteria for anxiety. Similarly, another study reported that young girls with anxiety disorders were three times more likely to have chronic headaches than those without the disorder. (Headaches in both studies were also strongly associated with depression.)

Respiratory Problems. Studies report an association between anxiety in patients with obstructive lung conditions (asthma, emphysema, and chronic bronchitis) and more frequent relapses.

Obesity. Anxiety disorders may lead to obesity, and the reverse may also be true. A 2006 study suggested that anxiety disorders and depression in childhood may lead to higher body mass index (BMI) in adult women (but not men). Another 2006 study indicated that obesity is associated with a 25% increased risk of developing anxiety and mood disorders.

Allergic Conditions. Anxiety disorders are associated with numerous allergic conditions including hay fever, eczema, hives, food allergies, and conjunctivitis.

Other Conditions. Other physical conditions associated with anxiety disorders include thyroid problems and arthritis.

People with obsessive-compulsive disorders can experience skin problems from excessive washing, injuries from repetitive physical acts, and hair loss from repeated hair pulling (behavior known as trichotillomania).

Effect of PTSD on the Brain. Studies are reporting that PTSD is associated with shrinkage in the hippocampus, the part of the brain important for memory and learning. Some animal studies indicate that such damage may result from long-term exposure to cortisol, the major stress hormone. In one study, people who had suffered severe trauma scored 40% lower in tests of verbal memory than did the general population. There was no difference in IQ or in scores of other types of memory. Some studies suggest that exposure to chronic stress, common in PTSD patients, may even compromise the function of the brain’s receptors for anti-anxiety medication. On the other hand, a small hippocampal volume may itself increase stress hormone levels, so people with genetically smaller hippocampi may be susceptible to PTSD.

Effects of PTSD on Health. Studies of military veterans who have endured major traumatic events have found a higher risk for health problems. One study of Vietnam veterans reported that PTSD was associated with greater physical limitations, poorer physical health, and a lower quality of life than was found in the general population, regardless of other accompanying emotional or medical disorders. In another study of these veterans, PTSD sufferers had twice the risk for abnormal heart rhythms and four times the risk of a heart attack compared to men without PTSD.

Evidence suggests an association between anxiety in children and recurrent stomach aches. Anxiety has been associated with a higher risk for sleep disorders in children, such as frequent nightmares, restless legs syndrome, and bruxism (grinding and gnashing of the teeth during sleep).

Diagnosis

A physical examination and medical and personal history is essential. Because anxiety accompanies so many medical conditions, some serious, it is extremely important for the doctor to uncover any medical problems or medications that might underlie or be masked by an anxiety attack.

The patient should describe any occurrence of anxiety disorders or depression in the family and mention any other contributing factors, such as excessive caffeine use, recent life changes, or stressful events.

It is very important to be honest with your doctor about all conditions, including excessive drinking, substance abuse, or other psychological or mood states that might contribute to, or result from, the anxiety disorder.

Diagnosing children with an anxiety disorder can be very difficult, since anxiety often results in disruptive behaviors that overlap with attention-deficit hyperactivity or oppositional disorder. Other conditions with symptoms similar to anxiety disorders include pervasive developmental disorders such Asperger syndrome, learning disabilities, bipolar disorder, and depression. Many children have anxiety disorder and a co-occurring condition, which should be treated along with anxiety.

People with anxiety disorders are more likely to see a family doctor before a mental health specialist, since their symptoms are often physical. Symptoms can include muscle tension, trembling, twitching, aching, soreness, cold and clammy hands, dry mouth, sweating, nausea or diarrhea, or urinary frequency. Anxiety attacks can mimic or accompany nearly every acute disorder of the heart or lungs, including heart attacks and angina (chest pain). In fact, nearly all individuals with panic disorders are convinced that their symptoms are physical and possibly life-threatening.

Heart Problems. Studies suggest that up to a third of patients entering the emergency room with chest pain and who are low-to-moderate risk for a heart attack are actually suffering from panic attacks. It is often difficult even for specialists to distinguish between heart conditions and a panic attack:

Women who are having an actual heart attack or acute heart problem are much more likely to be misdiagnosed as having an anxiety attack than are men with similar symptoms.
Mitral valve prolapse, a common and usually mild heart problem, may have symptoms that are nearly identical to those of panic disorder. The two conditions, in fact, frequently occur together.

Mitral valve prolapse is a disorder in which the mitral valve does not close properly when the heart contracts. When the valve does not close properly it allows blood to backflow into the left atrium. Some symptoms can include palpitations, chest pain, difficulty breathing after exertion, fatigue, cough, and shortness of breath while lying down.

People with a heart-rhythm disturbance called paroxysmal supraventricular tachycardia have many of the same symptoms as those with panic attacks.

Asthma. Asthma attacks and panic attacks have similar symptoms and can also coexist.

Hyperthyroidism. Hyperthyroidism can cause many of the same symptoms of generalized anxiety disorder and must be ruled out.

Click the icon to see an image of hyperthyroidism.

Epilepsy. The symptoms of partial seizures and panic attacks often overlap.

Other Medical Conditions. In addition, anxiety-like symptoms are seen in many other medical problems, including hypoglycemia, recurrent pulmonary emboli, and adrenal-gland tumors. Women can also experience intense anxiety attacks with hot flashes during menopause.

Medication Side Effects. Many drugs, including some for high blood pressure, diabetes, and thyroid disorders, can produce symptoms of anxiety. Withdrawal from certain drugs, often those used to treat sleep disorders or anxiety, can also precipitate anxiety reactions.

Substance Abuse. People with anxiety disorders often drink alcohol or abuse drugs in order to conceal or eliminate symptoms, but substance abuse and dependency can also cause anxiety. In addition, withdrawal from alcohol can produce physiologic symptoms similar to panic attacks. Clinicians often have difficulty determining whether alcoholism or anxiety is the primary disorder. Overuse of caffeine or abuse of amphetamines can cause symptoms resembling a panic attack.

Clinicians use various screening tests to determine the causes, type, severity, and frequency of anxiety. Such tests include the Hamilton Anxiety Rating Scale, the Beck Anxiety Inventory, the Penn State Worry Questionnaire, and the Yale-Brown Obsessive Compulsive Scale.

Treatment

Anxiety disorders require treatment. Simply trying to talk oneself out of anxiety is as futile as trying to talk oneself out of a heart or stomach problem. Most anxiety disorders, especially phobias, respond well to treatment. They may, however, require long-term treatment. Many patients have a recurrence and may require additional medications. Nevertheless, most patients do not receive appropriate care for anxiety disorders. Many patients do not receive any treatment at all.

The standard current approach to most anxiety disorders is a combination of cognitive-behavioral therapy (CBT) and an antidepressant medication. A selective serotonin reuptake inhibitor (SSRI) is typically the first choice, with the serotonin-norepinephrine reuptake inhibitor (SNRI) venlafaxine (Effexor) an alternative. If patients do not respond to these drugs, tricyclic antidepressants or monoamine oxidase inhibitors (MAOIs) may be helpful. Benzodiazepines may be recommended for patients who are not helped by antidepressants. A healthy lifestyle that includes exercise, adequate rest, and good nutrition can also help to reduce the impact of anxiety.


Anxiety Disorder	Medications	Cognitive-Behavioral Therapy (CBT) and other Non-Drug Therapies
Generalized Anxiety Disorder	Antidepressants, benzodiazepines, and buspirone are helpful but have varying side effects. Investigational drugs include pregabalin and other anticonvulsants.	Cognitive-behavioral therapy or anxiety management therapy. Anxiety management therapy involves education, relaxation training, and exposure to anxiety-provoking stimuli but does not include cognitive restructuring.
Panic Attacks	SSRIs are treatment of choice. If patients do not respond to SSRIs, short-term treatment with a benzodiazepine may be used, or patients may switch to another type of antidepressant such as venlafaxine or tricyclics.	Cognitive-behavioral therapy, provided in 12 - 16 sessions over 3 - 4 months, focuses on recreating fear symptoms and helping patients change their response to them.
Social Anxiety Disorder	SSRIs or venlafaxine are first-line drug treatments. Benzodiazepines may help patients who do not respond to these antidepressants. In severe cases, an MAOI antidepressant may be prescribed. Anticonvulsants such as gabapentin (Neurontin) and pregabalin (Lyrica) are being investigated.	Cognitive-behavioral therapy can help improve symptoms after 6 - 12 weeks.
Obsessive-Compulsive Disorder	SSRIs are the first choice for adults. Clomipramine (a tricyclic antidepressant) is an alternative for adult patients who do not respond to SSRIs. For children, SSRIs do not seem to work as well for OCD as for other types of anxiety disorders.	Cognitive-behavioral therapy is the first treatment choice for children. For adults, either CBT or drug therapy may be offered as initial treatment. CBT techniques focus on exposure and response prevention (ERP).
Post-Traumatic Stress Disorder	Antidepressants, particularly SSRIs (sertraline and paroxetine approved for PTSD). The atypical antipsychotic olanzapine may be added to an antidepressant for patients who do not respond to a SSRI alone.	Trauma-focused psychological treatments include exposure therapy, trauma-focused cognitive therapy, and eye movement desensitization and reprocessing.
Note: For anxiety disorders in adults, the most effective treatments are usually combinations of drugs and CBT techniques. For children, CBT is usually the first treatment.

Medications

Selective serotonin-reuptake inhibitors (SSRIs), or the serotonin-norepinephrine reuptake inhibitor (SNRI) venlafaxine (Effexor), are the primary first-line treatment for anxiety disorders. For patients who are not helped by these drugs, benzodiazepines, either alone or in combination with an antidepressant, may be prescribed. Other types of antidepressants, including tricyclic antidepressants and monoamine oxidase inhibitors (MAOIs), may also be used to treat patients with severe or chronic forms of anxiety disorders.

Drug therapies for anxiety disorders work best in combination with cognitive behavioral therapy.

Selective Serotonin Reuptake Inhibitors (SSRIs). SSRIs include fluoxetine (Prozac), sertraline (Zoloft), paroxetine (Paxil), fluvoxamine (Luvox), citalopram (Celexa), and escitalopram (Lexapro).

SSRIs can cause agitation, nausea, and diarrhea. Sexual function side effects include low sex drive, inability to have an orgasm, and impotence. Over time, many SSRI-treated patients gain weight, although the degree of weight gain varies depending on the drug. Elderly people taking these drugs should take the lowest effective dose possible, and those with heart problems should be monitored closely.

There have been many concerns about SSRIs and increased risk for suicidal behavior. Both adults and children who are treated with SSRIs should be carefully monitored for any worsening of depressive symptoms or changes in behavior. This is especially important during the first few months of antidepressant treatment.

Paroxetine has been linked to heart-related birth defects when women took this drug during the first trimester of pregnancy. Experts are also advising caution in prescribing other types of SSRIs to pregnant women. While certain SSRIs may carry increased risks for some specific type of rare birth defects, research suggests that the overall risks are minimal. Still, women who are pregnant or who are considering becoming pregnant should discuss the potential risks of these drugs with their doctors.

Serotonin-norepinephrine reuptake inhibitors (SNRIs). SNRIs are known as dual inhibitors because they work on two neurotransmitters -- norepinephrine and serotonin. Venlafaxine (Effexor) is an SNRI that is approved for treatment of generalized anxiety disorder, social anxiety disorder, and panic disorder in adults. (It is not approved for children.) As with many SSRIs, venlafaxine impairs sexual function. Venlafaxine can increase blood pressure and heart rate and should be used with caution in patients with high blood pressure or heart disease. Some patients report severe withdrawal symptoms, including dizziness and nausea. This drug has a serious risk for overdose. Venlafaxine should not be taken during the last trimester of pregnancy because the drug can cause complications in newborn infants.

Duloxetine (Cymbalta) also acts on both serotonin and norepinephrine. In 2007, it was approved for treatment of generalized anxiety disorder. Side effects are generally mild and include dry mouth, nausea, and sleepiness. Patients with narrow-angle glaucoma or patients with liver or kidney diseases should not take duloxetine. Because duloxetine can cause liver damage, patients who drink large quantities of alcoholic beverages should not take it.

Mitrazapine (Remeron) is another type of SNRI that is sometimes used for treatment of post-traumatic stress disorder and social anxiety disorder.

Tricyclic Antidepressants. Tricyclics are an older type of antidepressant. Tricyclics used for treatment of anxiety disorder include imipramine (Tofranil, for generalized anxiety disorder, panic disorder), nortriptyline (Pamelor, for panic disorder), desipramine (Norpramin, for panic disorder), and clomipramine (Anafranil, for obsessive compulsive disorder). Clomipramine is approved specifically for OCD, but because of its severe side effects it is usually used only if SSRIs have failed to help.

Side effects of TCAs include sleep disturbance, abrupt reduction in blood pressure upon standing, weight gain, sexual dysfunction, and mental disturbance. Elderly patients and those with a history of seizures, cardiac problems, closed-angle glaucoma, and urinary retention or obstruction should be closely supervised when taking tricyclics.

Monoamine Oxidase Inhibitors. Monoamine oxidase inhibitors (MAOIs) are the oldest type of antidepressant. The MAOI phenelzine (Nardil) is sometimes used to treat social anxiety disorder or post-traumatic stress disorder that has not responded to other treatments.

MAOIs commonly cause weight gain, drowsiness, dizziness, sexual dysfunction, and insomnia. Dietary restrictions are the main problem with these drugs. Severe high blood pressure (hypertension) can be brought on by eating certain foods that have a high tyramine content, including cheese, red wine, and processed meats. High blood pressure can also occur when MAOIs are taken with certain drugs, including some common over-the-counter cough medications and decongestants. MAOIs can cause birth defects and should not be taken by pregnant women.

Most serious, fatal reactions can occur when MAOIs and SSRIs or venlafaxine are taken at the same time. There should be at least a 2- to 5-week break if a patient is changing from one type of antidepressant to the other.

Benzodiazepines are safe and effective medications for most anxiety disorders and have been the standard of treatment for years. However, their on-going use has been associated with a high risk for dependency and abuse. Therefore, they have been supplanted in most cases by SSRIs and other newer antidepressants. For anxiety disorders, benzodiazepines are most often used to treat panic disorder, and are sometimes used for social anxiety disorder and generalized anxiety disorder. These drugs include alprazolam (Xanax), clonazepam (Klonopin), and lorazepam (Ativan).

Benzodiazepines have many side effects, generally associated with chronic use. The most common are daytime drowsiness and a hung-over feeling. In rare cases, they can cause agitation. They may worsen respiratory problems. Benzodiazepines are potentially dangerous when used in combination with alcohol. Overdoses can be serious, although they are very rarely fatal.

The elderly are more susceptible to side effects and should usually start at half the dose prescribed for younger people. These drugs increase the risk of falling, which can increase the risk for hip fracture in older people. Also of concern are studies showing a high risk of automobile accidents in people who take benzodiazepines. Benzodiazepines taken during pregnancy are associated with birth defects, and they should not be used by pregnant women or by nursing mothers.

Loss of Effectiveness and Dependence. Eventually these drugs can lose their effectiveness with continued use at the same dosage. As a result, patients may want to increase their dosage to prevent anxiety. This causes dependency, which can occur after taking these drugs for several weeks.

Withdrawal and its Treatments. Withdrawal symptoms can be very severe, even in people who rapidly discontinue benzodiazepines after taking them for only 4 weeks. Symptoms include sleep disturbance and anxiety, which can develop within hours or days after stopping the medication. Some patients experience stomach distress, sweating, and insomnia, which can last 1 - 3 weeks. The longer the drugs are taken and the higher their dose, the more severe these symptoms can become. Simply tapering off gradually helps about 60% of people stop taking these drugs. Certain medications (anti-seizure drugs, antidepressants, buspirone) may also help with withdrawal.

Azapirones, such as buspirone (BuSpar), act on serotonin receptors called 5-HT(1A). Buspirone appears to work as well as a benzodiazepine for treating generalized anxiety disorder. It usually takes several days to weeks for the drug to be fully effective. It is not useful against panic attacks.

Buspirone does not produce any immediate euphoria or change in sensation, so some people believe, erroneously, that the drug doesn't work. Such qualities result in a very low potential for abuse. In fact, unlike the benzodiazepines, buspirone is not addictive, even with long-term use, so it may be particularly useful for the patient whose anxiety disorder coexists with alcoholism or drug abuse.

Buspirone also seems to have less pronounced side effects than benzodiazepines and no withdrawal effects, even when the drug is discontinued quickly. Common side effects include dizziness, drowsiness, and nausea. Buspirone should not be used with monoamine oxidase inhibitors (MAOIs).

Beta-blockers, including propranolol (Inderal) and atenolol (Tenormin), block the nerves that stimulate the heart to beat faster. They affect only the physiologic symptoms of anxiety (particularly rapid heart rate) and are most helpful for phobias, particularly performance anxiety. They may be taken before entering a situation where anxiety symptoms tend to occur. Beta-blockers are less effective for other forms of anxiety.

Atypical antipsychotics are mostly used for treating schizophrenia, bipolar disorder, and major depressive disorder. Doctors sometimes use the atypical antipsychotic olanzapine (Zyprexa) for treating severe cases of post-traumatic stress disorder. However, olanzapine has severe side effects, including weight gain and increased high blood sugar levels, which can increase the risk for diabetes. [For more information, see In-Depth Report #47: Schizophrenia.]

Pregabalin (Lyrica) and gabapentin (Neurontin) are drugs used to treat seizures and other conditions. Researchers are investigating whether these drugs may be useful for certain anxiety disorders, such as social anxiety disorder and general anxiety disorder. Their exact role in the treatment of anxiety disorders is not clear, however.

Studies indicate that the dietary supplement inositol may have benefits for panic disorder and, possibly, obsessive compulsive disorder. Inositol is part of the vitamin B complex.

Some patients use aromatherapy as a relaxation aid. Aromatherapy is in general safe, but some plant extracts in these formulas have been linked to skin allergies.

There is no evidence supporting the efficacy of valerian, St. John’s wort, or passionflower for treatment of anxiety. The herbal remedy kava has been associated with liver problems and should not be avoided, especially by patients with liver disease or those who use alcohol. Kava can also interact dangerously with medications that are metabolized by the liver.

Other Treatments

The goal of cognitive-behavioral therapy (CBT) is to regain control of reactions to stress and stimuli, thus reducing the feeling of helplessness that often accompanies anxiety disorders. CBT works on the principle that the thoughts that produce and maintain anxiety can be recognized and altered using various techniques that change behavioral responses and eliminate the anxiety reaction. Many studies have shown that a combination of CBT and medication works best for treating anxiety disorders.

A number of CBT approaches work well for treating many types of anxiety disorders. Studies suggest that CBT is also helpful for patients who have additional conditions, such as depression, a second anxiety disorder, or alcohol dependency. (It may take longer to achieve a successful outcome in such cases, however.) CBT is often given along with drug treatment. A study in the Journal of the American Medical Association found that children and adolescents with OCD responded better to CBT alone than the antidepressant setraline (Zoloft) alone, but most patients did best when they were treated with a combination of CBT and sertraline.

Both individual and group treatments work well. (However, people with social phobia may do better in individual sessions.) Several recent studies also indicate that telephone-based behavioral therapy works well for people with OCD, generalized anxiety disorder, and panic disorders.

Anxiety disorders are chronic, however, and recurrence is common. Some studies indicate that 30 - 82% of people with panic disorder and phobias have a recurrence of attacks at an average of 9 months, even after successful short-term therapy. Medications, then, are also generally recommended for most patients.

Basic Cognitive Therapy Techniques. Treatment usually takes about 12 - 20 weeks. The essential goal of cognitive therapy is to understand the realities of an anxiety-provoking situation and to respond to reality with new actions based on reasonable expectations.

First, the patient must learn how to recognize anxious reactions and thoughts as they occur. One way of accomplishing this is by keeping a daily diary that reports the occurrences of anxiety attacks and any thoughts and events associated with them. A patient with OCD, for instance, may record repetitive thoughts.
These entrenched and automatic reactions and thoughts must be challenged and understood. Again, using the OCD example, one approach is to record and play back the words of the repetitive thoughts, over exposing the patient to the thoughts and reducing their effect. One effective approach for patients with generalized anxiety disorder targets their intolerance of uncertainty and helps them develop methods to cope with it.
Patients are usually given behavioral homework assignments to help them change their behavior. For example, a person with generalized social phobia may be asked to buy an item and then return it the next day. As the patient performs this action, they observe any unrealistic fears and thoughts triggered by such an event.
As the patient continues with self-observation, they begin to perceive the false assumptions that underlie the anxiety. For example, OCD patients may learn to recognize that their heightened sense of responsibility for preventing harm in non-threatening situations is not necessary or even useful.
At that point, the patient can begin substituting new ways of coping with the feared objects and situations.

Systematic Desensitization. Systematic desensitization is a specific technique that breaks the link between the anxiety-provoking stimulus and the anxiety response. This treatment requires the patient to gradually confront the object of fear. There are three main elements to the process:

Relaxation training
A list composed by the patient that prioritizes anxiety-inducing situations by degree of fear
The desensitization procedure itself, confronting each item on the list, starting with the least stressful

This treatment is especially effective for simple phobias, social phobias, agoraphobia, and post-traumatic stress syndrome.

Exposure and Response Treatment. Exposure treatment purposefully generates anxiety by exposing the patient repeatedly to the feared object or situation, either literally or using imagination and visualization. It uses the most fearful stimulus first. (This differs from the desensitization process because it does not involve relaxation or a gradual approach to the source of anxiety.)

Exposure treatments are usually known as either flooding or graduated exposure:

Flooding exposes the person to the anxiety-producing stimulus for as long as 1 - 2 hours.
Graduated exposure gives the patient a greater degree of control over the length and frequency of exposures.

In both cases, the patient experiences the anxiety over and over until the stimulating event eventually loses its effect. Combining exposure with standard cognitive therapy may be particularly beneficial. This approach has helped certain patients in most anxiety disorder categories, including post-traumatic stress disorder.

Modeling Treatment. Phobias can often be treated successfully with modeling treatment:

The therapy typically uses an actor who approaches an anxiety-producing object or engages in a fear-provoking activity that is similar to the patient's specific problem. Either a live or videotaped situation may be used, although the live model is considered to be more effective.
The patient observes this event and tries to learn how to behave in a comparable manner.

Other forms of psychotherapy, commonly called emotion-based psychotherapy (EBT), psychodynamic therapy, or "talk" therapy, deal more with childhood roots of anxiety and usually, although not always, require longer treatments. They include interpersonal therapy, supportive psychotherapy, attention intervention, and psychoanalysis. All work is done during the sessions. Some research indicates that such therapies might be more useful for generalized anxiety, which may require more sustained work to process and recover from early traumas and fears. Studies suggest that although emotion-based psychotherapies are not as effective as cognitive-behavioral therapy (CBT) in treating panic disorders, patients tend to stay longer in EBT than in CBT. Some doctors suggest adding elements of EBT to the usual CBT and medication treatments.

Anxiety Management Therapy. Anxiety management therapy is sometimes used as an alternative to CBT for generalized anxiety disorder. It involves patient education, relaxation training, and exposure to anxiety-provoking stimuli but does not include exercises in cognitive retraining.

Relaxation Training. Relaxation techniques use muscle relaxation and mental visualization to help focus attention towards a calming feeling. Some people find meditation helpful.

Breathing Retraining. Breathing retraining techniques may help reduce the physical effects of anxiety. For example, hyperventilation is one of the primary physical manifestations of panic disorders. This involves rapid, tense breathing, resulting in chest pain, dizziness, tingling of the mouth and fingers, muscle cramps, and even fainting. By practicing measured, controlled breathing at the onset of a panic attack, patients may be able to prevent full attacks.

Biofeedback. Biofeedback uses special sensors that allow patients to recognize anxiety states by changes in specific physical functions, such as changes in pulse rate, skin temperatures, and muscle tone. Eventually they learn to modify these changes, which in turn helps relieve anxiety. While commonly used, there are not many rigorous studies showing that biofeedback helps patients reduce or eliminate their symptoms over the long term.

Several types of psychological treatments have been designed specifically for treating patients with PTSD. These approaches include a special type of CBT known as trauma-focused cognitive behavioral therapy (TFCBT), and a psychotherapy treatment called eye movement desensitization and reprocessing (EMDR).

With TFCBT, patients are taught stress management skills. The therapist helps the patient develop a narrative (verbal, written, or artistic) about the traumatic event. Patients may be exposed to reminders about the trauma and are taught how to cope with future reminders. Through the process, the patient learns how to reprocess their thoughts, feelings, and behaviors.

With EMDR, the patient focuses on remembering the traumatic experience while visually following the rhythmic movement of the therapist’s fingers. The patient recounts to the therapist what memories have been provoked during the exercise. EMDR may help patients recall details and sensations that they had blocked out. Through this breakthrough, patients learn how to regain emotional control.

Transcranial magnetic stimulation (TMS) uses high frequency magnetic pulses to target and stimulate specific areas of the brain. Research has particularly focused on possible benefits for obsessive-compulsive behavior. Some studies have found some improvement in mood, but more research is needed to determine its value for reducing anxiety and obsessions.

In 2006, the U.S. National Institutes of Health funded a large study to examine whether deep brain stimulation (DBS) can help patients with OCD. DBS involves implanting tiny stimulators into the brain to block abnormal nerve signals that cause obsessive symptoms. These “brain pacemakers” are approved to treat epilepsy and Parkinson’s disease. Researchers hope that DBS may eventually provide a new treatment option for patients with severe OCD.

A surgical technique called cingulotomy involves interrupting the cingulate gyrus, a bundle of nerve fibers in the front of the brain. It is sometimes used as a last resort for patients with severe OCD. A variation of this procedure using magnetic resonance imaging (MRI) to guide the surgeon has resulted in long-term improvement in about 25 - 33% of OCD patients in whom it is performed. The procedure is generally safe with few serious complications and does not affect intellect or memory.

Resources

www.nimh.nih.gov -- National Institute of Mental Health
www.adaa.org -- Anxiety Disorders Association of America
www.nami.org -- National Alliance on Mental Illness
www.psych.org -- The American Psychiatric Association
www.apa.org -- The American Psychological Association
www.istss.org -- International Society for Traumatic Stress Studies
www.ncvc.org -- National Center for Victims of Crime
www.ncptsd.va.gov -- National Center for Post-Traumatic Stress Disorders
www.rainn.org -- Rape, Abuse, and Incest National Network
www.aacap.org -- American Academy of Child and Adolescent Psychiatry
www.aabt.org -- Association for Behavioral and Cognitive Therapies
www.ocfoundation.org -- Obsessive Compulsive Foundation

References

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Review Date:
12/25/2007
Reviewed By:
Harvey Simon, MD, Editor-in-Chief, Associate Professor of Medicine, Harvard Medical School; Physician, Massachusetts General Hospital. Also reviewed by David Zieve, MD, MHA, Medical Director, A.D.A.M., Inc.

A.D.A.M. Copyright

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