FitSugar

The Skinny on Zinc

FitSugar — Thu, 04 Oct 2007 02:00:00 -0700

Zinc is one of those essential minerals that often flies under the radar, mostly because deficiencies of zinc are rare here in the U.S. It is, however, present in almost every cell of your body. It stimulates almost 100 enzymes, which are responsible for many biomechanical reactions in the body. This busy mineral supports a healthy immune system, is needed for wound healing and helps maintain your sense of taste and smell.

The recommended daily intake of zinc is 9 milligrams for an adult woman, and it is always better to get your RDI in the form of whole foods. That being the case, here are some foods high in zinc include: oysters (6 oz = 75 mg), crab (3 oz = 7), beef (3 oz = 6), and beans (1/2 cup = 1.8 mg).

Zinc has been getting a lot attention lately for its ability to fight colds. Some studies indicate that it can decrease the length of a common cold, while others show no real benefits to using zinc lozenges. The debate continues, and it seems like the form of zinc you take matters. Look for zinc supplements that use zinc gluconate, since it seems to be the most effective form of the mineral. If you are fighting a cold with zinc, do be aware that the upper tolerance is 40 mg for adults and high doses of zinc can interfere with iron and copper absorption.

Source

Colds and the flu

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

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.

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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

Urinary tract infection

FitSugar — Wed, 08 Oct 2008 17:35:27 -0700

In This Report

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

HEALTH GUIDE REFERENCE FROM A.D.A.M

Highlights

Urinary Tract Infections (UTIs) in the United States

According to Urologic Diseases in America, a report published in 2007 by the U.S. National Institutes of Health:

UTIs are the most expensive of all urologic diseases, accounting for about $3.5 billion a year in medical costs, including $96.4 million in prescriptions.
Over 60% of women will experience a UTI at least once in their lifetime. At least a third of women experience a UTI by the time they are 24 years old.
Only 20% of UTIs occur in men. However, men are far more likely than women to be hospitalized for an infection.
Childhood risk for UTIs is 2% for boys and 8% for girls. Vesicouretereal reflux, a condition in which urine backs up into the kidneys, affects about 10% of all children.

Circumcision Prevents UTIs

Baby boys who are uncircumcised are 10 - 12 times more likely than circumcised boys to develop UTIs during their first year of life, indicates the Urologic Diseases in America report.

High Doses of Zinc Increase UTI Risk

People who take very high daily doses of zinc supplements may face an increased risk for UTIs and other urologic problems, suggests a 2007 study in the Journal of Urology. Patients in the study who took 80 mg/day of zinc were more likely to be hospitalized for urinary complications than those who did not take zinc.
In general, the upper limit for zinc supplements should not exceed 40 mg/day. Eight mg/day for women and 11 mg/day for men are the recommended average doses. However, very high doses of zinc are sometimes prescribed for certain medical conditions, such as age-related macular degeneration.

Introduction

A urinary tract infection (UTI) is a condition where one or more structures in the urinary tract become infected after bacteria overcome its strong natural defenses. In spite of these defenses, UTIs are the most common of all infections and can occur at any time in the life of an individual. Almost 95% of cases of UTIs are caused by bacteria that typically multiply at the opening of the urethra and travel up to the bladder (known as the ascending route). Much less often, bacteria spread to the kidney from the bloodstream.

The male and female urinary tracts are relatively the same except for the length of the urethra.

Different classifications have been devised to help doctors choose treatments and determine the causes of UTIs.

Primary or Recurrent UTIs. UTIs are classified as primary or recurrent, depending on whether they are the first infection or whether they are repeat events.

Community- or Hospital-Acquired. UTIs are also sometimes grouped according to where they are acquired:

Community-Acquired Infections. Most UTIs are thought to develop in the community at large. It is unclear how primary community-acquired infections occur or how they are spread. Although most cases have been thought to arise sporadically, a rare outbreak in 1996 - 2000 caused by drug-resistant bacteria suggests epidemic spread of community-acquired infections could be more common than previously thought and may be spread via contaminated food. Most community-acquired infections are not serious and probably develop when the intestines become colonized with bacteria that are also predisposed to infecting the urinary tract.
Hospital-Acquired Infections. UTIs are also commonly acquired in the hospital, often due to contaminated urinary catheters. Hospital-acquired infections (known as nosocomial infections) tend to be more serious because the bacteria that cause them are often resistant to drug treatment and patients are often in poor general health.

Uncomplicated and Complicated. UTIs are also sometimes further defined as either being uncomplicated or complicated depending on the factors that trigger the infections.

Uncomplicated infections are only associated with bacterial infection, most often Escherichia coli (E. coli). They affect women much more often than men.
Complicated infections, which occur nearly as often in men as women, are also caused by bacteria but they occur as a result of some anatomical or structural abnormality. Often they are associated with catheter use in the hospital setting, bladder and kidney dysfunction, or kidney transplant (especially in the first three months after transplant). Recurrences occur in up to 50 - 60% of patients with complicated UTI if the underlying structural or anatomical abnormalities are not corrected.

Classifications Based on Symptoms and Levels of Infection. UTIs can also occur without symptoms and with symptoms but very low bacterial levels.

When bacteria are present and there are no symptoms it is called asymptomatic UTI or also bacteriuria.
Some patients can also have symptoms of infection with very low bacterial counts. In such cases, the condition is called acute urethral syndrome.

Cystitis. Cystitis is the most common urinary tract infection and is sometimes referred to as acute uncomplicated UTI. It occurs in the lower urinary tract (the bladder and urethra) and nearly always in women. In most cases, the infection is brief and acute and only the surface of the bladder is infected. Deeper layers of the bladder may be harmed if the infection becomes persistent, or chronic, or if the urinary tract is structurally abnormal.

Pyelonephritis (Kidney Infection). When infection spreads to the upper tract (the ureters and kidneys) it is called pyelonephritis, or more commonly, kidney infection. As many as half of all women with cystitis may have infections of the upper urinary tract at the same time as cystitis.

Click the icon to see an image of the kidney.

Urethritis. When infection is limited only to the urethra, the infection is known as urethritis. This is a common sexually transmitted disease in men.

Complicated UTIs may develop because of any one of a number of physical problems and affect any gender and age group. The common feature in most complicated UTIs is the inability of the urinary tract to clear out bacteria because of a physical condition that causes obstruction to the flow of urine or problems that hinder treatment success.

Most women who have had an uncomplicated UTI have occasional recurrences. About 25 - 50% of these women can expect another infection within a year of the previous one. Between 3 - 5% of women have ongoing, recurrent urinary tract infections, which follow the resolution of a previous treated or untreated episode.

Recurrence is often categorized as either reinfection or relapse:

Reinfection. About 80% of recurring UTIs are reinfections. A reinfection occurs several weeks after antibiotic treatment has cleared up the initial episode and can be caused by the same bacterial strain that caused the original episode or a different one. The infecting organism is usually introduced through the rectal region from fecal matter and moves up through the urinary tract.
Relapse. Relapse is the less common form of recurrent urinary tract infection. It is diagnosed when a UTI recurs within 2 weeks of treatment of the first episode and is due to treatment failure. Relapse usually occurs in kidney infection (pyelonephritis) or is associated with obstructions such as kidney stones, structural abnormalities or, in men, chronic prostatitis.

When a person has no symptoms of infection but significant numbers of bacteria have colonized the urinary tract, the condition is called asymptomatic UTI (also called asymptomatic bacteriuria). (In general, there must be at least 100,000 bacteria per milliliter of urine.) The condition is harmless in most people and rarely persists, although it does increase the risk for developing symptomatic UTIs.

Screening for asymptomatic bacteriuria is not necessary during most routine medical examinations, with the following exceptions:

Pregnant women. Pregnant women with asymptomatic bacteriuria have a 30% risk for acute pyelonephritis in their second or third trimester. Therefore, they need screening and treatment for this condition.
People undergoing urologic surgery (such as prostate surgery in men). The presence of an infection during surgery can lead to serious consequences.

Some groups recommend screening women with diabetes for asymptomatic bacteriuria. However, a 2003 study suggested that treating women who test positive for this condition does not reduce their risk of complications from UTIs. Asymptomatic bacteriuria may be an indicator for serious health problems in the elderly, but screening for the condition is not warranted in this group.

Some people have symptoms of cystitis but have a bacterial count lower than that ordinarily found in UTI. Such patients are sometimes diagnosed with acute urethral syndrome. This condition is usually caused by E. coli or other bacteria that cause cystitis, but in lower numbers, or by a sexually transmitted disease such as Chlamydia or gonorrhea.

Interstitial cystitis (IC) is an inflammation of the bladder wall that occurs almost exclusively in women. The average age of patients with IC is 40 years, but 25% of cases occur in women under age 30. Symptoms are very similar to cystitis, but no bacteria are present. These women often complain of experiencing pain during sex. Pelvic pain, depression, and stress may intensify symptoms. Women with IC also frequently suffer from other conditions, including allergies, urinary incontinence, sinusitis, and irritable bowel syndrome (IBS). Some doctors think that IC may be related to autoimmune diseases such as fibromyalgia and lupus.

IC is difficult to diagnose and treat. Pentosan (Elmiron) is the most frequent drug treatment, but doctors prescribe other medications as well (see Medications section). Some evidence suggests that diet can worsen IC symptoms. For instance, patients should avoid coffee (both caffeinated and decaf), alcohol, cola, vinegar, citrus fruits, tomatoes, chili, strawberries, pineapple, onions, pizza, chocolate, and apples, according to research presented at the 2006 American Urological Association scientific meeting.

The Urinary System. The urinary system helps maintain proper water and salt balance throughout the body and also expels urine from the body. It is made up of the following organs and structures:

The two kidneys, located on each side below the ribs and toward the middle-back, play the major role in this process. They filter waste products, water, and salts from the blood to form urine.
Urine passes from each kidney to the bladder through thin tubes called ureters.
Ureters empty into the bladder, which rests on top of the pelvic floor. This is a muscular structure similar to a sling running between the pubic bone in front to the base of the spine.
The bladder stores the urine, which is then eliminated from the body via another tube called the urethra, which is the lowest part of the urinary tract. (In men it is enclosed in the penis. In women it leads directly out.)

Defense Systems Against Bacteria. Infection does not always occur when bacteria are introduced into the bladder. A number of defense systems protect the urinary tract against infection-causing bacteria:

Urine itself functions as an antiseptic, washing potentially harmful bacteria out of the body during normal urination. (Urine is normally sterile, that is, free of bacteria, viruses, and fungi.)
The ureters are structurally designed to prevent urine from backing up into the kidney.
The prostate gland in men secretes infection-fighting substances.
The immune system in both sexes continuously fights bacteria and other harmful micro-invaders. In addition, immune system defenses and antibacterial substances in the mucous lining of the bladder eliminate many organisms.
In normal fertile women, the vagina is colonized by lactobacilli, beneficial microorganisms that maintain a highly acidic environment (low pH). Acid is hostile to other bacteria. Lactobacilli also produce hydrogen peroxide, which helps eliminate bacteria and reduces the ability of E. coli to adhere to vaginal cells. (E. coli is the major bacterial culprit in urinary tract infections.)
Some interesting research suggests that when bacteria infect the bladder, the cells that line the bladder literally sacrifice themselves and self-destruct (a process called apoptosis). In so doing, they fall away from the lining, carrying the bacteria with them. This eliminates about 90% of the E. coli.
Some researchers have identified a possible natural antibiotic called human beta-defensin-1 (HBD-1), which fights E. coli within the female urinary and reproductive tracts.

Click the icon to see an image of the prostate gland.

Causes

The bacterial strains that cause UTIs include:

Escherichia (E.) coli is responsible for 75 - 90% of uncomplicated cystitis cases in younger women and in more than half the cases in older women (over age 50). In most cases of UTI, E. coli, which originates as a harmless microorganism in the intestines, spreads to the vaginal passage, where it invades and colonizes the urinary tract. Some bacteria may be able to invade into deeper tissue in the bladder, where they survive to reinfect the patient after resolution of the previous infection.
Staphylococcus saprophyticus accounts for 5 - 15% of UTIs, mostly in younger women. Infections caused by this bacterium tend to have a seasonal variation, with a higher incidence in the summer and fall than in the winter and spring.
Klebsiella, Enterococci bacteria, and Proteus mirabilis account for most of remaining bacterial organisms that cause UTIs. They are generally found in UTIs in older women.
Rare bacterial causes of UTIs include ureaplasma urealyticum and Mycoplasma hominis, which are generally harmless organisms.

The bacteria that cause kidney infections (pyelonephritis) are generally the same bacteria that cause cystitis. There is some evidence, however, the E. coli strains in pyelonephritis are more virulent (able to spread and cause illness).
Complicated UTIs that are related to physical or structural conditions are apt to be caused by a wider range of organism. E. coli is still the most common organism, but others have also been detected, including Klebsiella, P. mirabilis, and Citrobacter.
Fungal organisms, particularly Candida species. (Candida albicans, for example, causes the so-called "yeast infections" that also occur in the mouth, digestive tract, and vagina.)
Other bacteria associated with complicated or severe infection include Pseudomonas aeruginosa, Enterobacter, and Serratia species, gram-positive organisms (including Enterococcus species), and S. saprophyticus.

Recurring infections are often caused by different bacteria than those that caused a previous or first infection.

Even if the reinfecting bacterium is still E. coli, it may be a variant of the original infecting E. coli strain. Such strains produce substances, such as one called P fimbriae, which tend to make the bacteria more infectious. Uncommon causes of reinfection include Ureaplasma and Mycoplasma hominis, which are sometimes associated with acute urethral syndrome.

The bacteria that cause most UTIs are very common. Nearly everyone harbors them. It is not clear how they proliferate and break down the natural defenses of the body. Among the possible ways this occurs are:

Changes in the Acid-Alkaline Balance of the Urinary Tract. Changes in the amount or type of acid within the genital and urinary tracts are major contributors to lowering the resistance to infection. For example, beneficial organisms called lactobacilli increase the acidic environment in the urinary tract. Reductions in their number (which, for example, occurs with estrogen loss after menopause), increases pH and therefore the risk of infection.

Biofilm. One theory, called the biofilm mode of growth, suggests that sometimes bacteria form capsules that adhere to the urinary tract, protecting them from many of the body's normal defenses.

Symptoms

Symptoms of lower urinary tract infections usually begin suddenly and may include one or more of the following signs:

The urge to urinate frequently, which may recur immediately after the bladder is emptied.
A painful burning sensation. (If this is the only symptom, then the infection is most likely urethritis.)
Discomfort or pressure in the lower abdomen. The abdomen can feel bloated.
Cramping in the pelvic area or back.
The urine often has a strong smell, looks cloudy, or contains blood. This is a sign of pyuria, or a high white blood cell count in the urine, and is a very reliable indicator of urinary tract infections.
Occasionally, fever develops.

Symptoms of kidney infections tend to affect the whole body and be more severe than those of cystitis. They may include:

Symptoms of lower UTIs that persist longer than a week. (Sometimes lower UTI symptoms may be the only signs of kidney infection. People at highest risk for such "silent" upper urinary tract infections include patients with diabetes, impaired immune systems, or a history of relapsing or recurring UTIs.)
An increased need to urinate at night.
Chills and persistent fever (typically lasting more than 2 days).
Pain in the flank (pain that runs along the back at about waist level).
Vomiting and nausea.

UTIs in infants and preschool children tend to be more serious than those that occur in young women, in part because they are more likely to occur in the kidneys and upper urinary tract. (Older children are more likely to have lower urinary tract infections and standard symptoms.) Infants and young children should always be checked for UTIs if the following symptoms are present:

A persistent high fever of otherwise unknown cause, particularly if it is accompanied by signs of feeding problems and debility, such as listlessness and fatigue. (Studies have reported that up to 5% of infants and toddlers who are brought to the emergency room with fevers have UTIs. Scarring is a risk so very young children with UTIs need to be screened.)
Painful, frequent, and foul smelling urine. (Parents are generally unable to identify a UTI just by the smell of their child's urine. Medical tests are needed.)
Cloudy urine. (If the urine is clear, the child most likely has some other ailment, although it is not absolute proof that the child is UTI-free.)
Abdominal and low back pain may be present.
Vomiting and abdominal pain (usually in infants).
Jaundice (yellowing of the skin and the whites of the eyes) in infants, particularly if it develops after 8 days of age.

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 the skin and whites of the eyes to have a yellowish appearance. 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 classic lower UTI symptoms of pain, frequency, or urgency and upper tract symptoms of flank pain, chills, and tenderness may be absent or altered in older patients with UTIs. In one study, only 20% of these patients had new urinary complaints, and many have no symptoms at all.

Symptoms of UTIs that may occur in seniors but not in younger adults may include mental changes or confusion, nausea or vomiting, abdominal pain, or cough and shortness of breath. Concomitant illness may further confuse the picture and make diagnosis difficult.

Risk Factors

After the flu and common cold, urinary tract infections (UTIs) are the most common medical complaint among women in their reproductive years. Women are 30 times more likely to have UTIs than men. At least a third of American women are diagnosed with a UTI by the time they are 24 years old. Every year, 11% of American women have at least one such infection, and up to 60% of all women will develop a UTI at some time in their lives. A third of these women will have a recurrence within a year. Furthermore, each year about 250,000 women develop kidney infections (pyelonephritis) and 100,000 are hospitalized for treatment.

According to a 2007 report from the U.S. National Institutes of Health, urinary tract infections in both women and men are the most expensive of all urologic problems. Nationally, UTIs account for about $3.5 billion a year in medical costs.

Structure of the Female Urinary Tract. In general, the higher risk in women is mostly due to the shortness of the female urethra, which is 1.5 inches compared to 8 inches in men. Bacteria from fecal matter can be easily transferred to the vagina or the urethra.

The female and male urinary tracts are relatively the same except for the length of the urethra.

Sexual Behavior. Frequent or recent sexual activity is the most important risk factor for urinary tract infection in young women. Nearly 80% of all urinary tract infections occur within 24 hours of intercourse. (Sexual activity is less associated with cystitis in women after menopause.)

UTIs are very rare in celibate women. It is important to stress, however, that UTIs are NOT sexually transmitted infections, although these infections ( Chlamydia trachomatis, gonorrhea, or herpes simplex virus) may increase the risk for UTIs.

In general, however, it is the physical act of intercourse itself that produces conditions that increase susceptibility to the UTI bacteria, with some factors increasing the risk:

Women having sex for the first time or who have intense and frequent sex after a period of abstinence are at risk for a condition called "honeymoon cystitis."
A sudden increase in the frequency of sexual intercourse poses a significant risk for UTI, particularly if a diaphragm is used.
Sexual position (such as the woman on top) can contribute to the risk.

Click the icon to see an image of a diaphragm.

Contraceptives may also contribute to risk in a number of ways:

The spring-rim of the diaphragm may bruise the area near the bladder neck, making it susceptible to bacteria.
Unlubricated condoms may injure vaginal tissue and make it vulnerable to infections. (Using a sterile water-based lubricant, such as KY jelly, may help reduce this risk. Petroleum-based lubricants should be avoided because they weaken latex condoms.)
Some women experience UTI as an allergic reaction to latex in condoms or to oral contraceptives.
Use of spermicide, such as nonoxynol-9, doubles or triples a women's risk for UTI, regardless of whether it is used with a condom or diaphragm. Spermicides also pose a risk for sexually transmitted infections, and experts warn against their use.

Pregnancy. Although pregnancy does not increase the rates of asymptomatic bacteriuria, it does increase the risk that it will progress to a full-blown infection. About 2 - 11% of pregnant women have asymptomatic bacteriuria and, of those, 13 - 27% will develop a kidney infection late in their term. (However in early pregnancy, frequent urination -- a common symptom of UTI -- is most likely due to pressure on the bladder.)

Although all pregnant women should be tested for UTIs, women at highest risk have the following conditions or situations:

Diabetes
Sickle cell trait
Low-income
Have had many children
History of childhood UTIs
Have undergone a cesarean section with catheterization of the bladder
Have received epidural anesthesia

Women who have had a UTI before or during pregnancy also have a higher risk of developing recurrent urinary tract infections after delivery. About 25 - 33% of women who experience bacteriuria during pregnancy will have another urinary tract infection, sometimes as many as 10 - 14 years later.

Menopause. The risk for UTIs, both symptomatic and asymptomatic, is highest in women after menopause. Studies indicate that between 20 - 25% of women over 65 years old have UTIs, and 10 - 15% have asymptomatic bacteriuria (compared to 2 - 5% of young women). Sexual activity plays a lesser role in UTIs in older women than in younger women. In general, biologic changes due to menopause put older women at particular risk for primary and recurring UTIs:

With estrogen loss, the walls of the urinary tract thin, weakening the mucous membrane and reducing its ability to resist bacteria. The bladder may lose elasticity and fail to empty completely.
Estrogen loss has also been associated with reduction in certain immune factors in the vagina that help block E. coli from adhering to vaginal cells.
Levels of lactobacilli (protective bacteria) decline after menopause, perhaps also due to drops in estrogen.

Some women carry the blood group P1, which, as they get older, is associated with high levels of specific cells in the vagina and urethra that bind to a specific strain of E. coli that is resistant to normal infection-fighting mechanisms.

Other Risk Factors in Women. Women who have skin allergies to ingredients in soaps, vaginal creams, bubble baths, or other chemicals that are used in the genital area are at high risk for UTIs. In such cases, the allergies may cause small injuries that can introduce bacteria.

Most women who have had one UTI have occasional recurrences. About 25 - 50% of these women can expect another infection within a year of the previous one.

Between 3 - 5% of women, however, have ongoing, recurrent urinary tract infections, which follow the resolution of a previous treated or untreated episode. The major groups of women who are at highest risk for recurrent infections are young highly sexually active women and postmenopausal women. It might be argued that nearly all women who have a urinary tract infection are at risk for another, particularly if they are not treated for the first one.

Lifestyle Factors Increasing the Risk for Recurrence. Why urinary tract infections become chronic and recurring in many women is not entirely clear, but researchers are identifying certain lifestyle factors that may increase the risk in specific women:

Engaging in sexual intercourse more than four times a month.
Recent changes in sexual partners.
Having a mother with a history of UTIs.
Having a first UTI before age 15.
Use of spermicides.
Smoking and taking tub baths may also increase the risk for recurrent urinary tract infections, but they are less significant than other risk factors.

Biologic and Physical Factors. Some women may also have certain biologic or anatomical factors that increase the risk for recurring UTIs:

Having a shorter than average distance between the urethra and the anus.
Certain women may carry a compound called sialosyl galactosyl globoside (SGG) on the surface of kidney cells, which is a highly powerful receptor for E. coli bacteria.
Certain women have a genetic susceptibility to becoming infected in the vaginal area with greater numbers of disease-causing organisms that adhere to the lining.
Certain women may be deficient in human beta-defensin-1 (HBD-1), believed to be a naturally occurring antibiotic.

Risk Factors for Recurrence in the Aging Woman. In addition to menopause, other very strong risk factors for recurrences in older women include urinary incontinence and previous operations on the genital or urinary tracts. Additional risk factors for UTIs in older women include diabetes, vaginal itching or dryness, having had children, and poor overall health.

Each year, about 3% of American children develop urinary tract infections. During the first few months of life, UTIs are more common in boys than in girls. Boys who are uncircumcised are about 10 - 12 times more likely than circumcised boys to develop UTIs by the time they are 1 year old. After the age of 2 years, UTIs are far more common in girls. Throughout childhood, the risk of UTIs is about 2% for boys and 8% for girls. As with adults, Escherichia coli (E. coli) is the most common cause of UTIs in children.

Vesicoureteral Reflux (VUR). Vesicoureteral reflux (VUR) affects about 10% of all children. It is the source of urinary tract infections in 30 - 50% of childhood cases. This is a structural defect of the valve-like mechanism between the ureter and bladder that allows urine to flow backward, carrying infection from the bladder up into the kidneys. VUR also puts children at risk for recurrence. Such recurrences nearly always occur within the first 6 months after the first UTI.

Click the icon to see an image of vesicoureteral reflux.

Men become more susceptible to UTIs after 50 years of age, when they begin to develop prostate problems. Benign prostatic hyperplasia (BPH), enlargement of the prostate gland, can produce obstruction in the urinary tract and increase the risk for infection. In men, recurrent urinary tract infections are also associated with prostatitis, an infection of the prostate gland that is caused by E. coli. Although only about 20% of UTIs occur in men, these infections can cause more serious problems than they do in women. Men with UTIs are far more likely to be hospitalized than women. [See In-Depth Report #71: Benign prostatic hyperplasia.]

Hospitalizations and Catheters. About 40% of all infections that develop in hospitalized patients are in the urinary tract. The organisms that cause infections in hospitals (called nosocomial infections) are usually different from those that commonly cause UTIs. They are also more likely to be resistant to standard antibiotics. Hospitalized patients at highest risk for such infections are those with in-dwelling urinary catheters, patients undergoing urinary procedures, long-stay elderly men, and patients with severe medical conditions.

About 80% of UTIs in the hospital are due to catheters. Nearly all patients who need urinary catheters develop high levels of bacteria in their urine, and the longer the catheter is in place, the higher the risk for infection. Catheterized patients who develop diarrhea are nine times more likely to develop UTIs than are patients without diarrhea. In most cases of catheter-induced UTIs, the infection produces no symptoms. Because of the risk for wider infection, however, anyone requiring a catheter should be screened for infection. Catheters should be used only when necessary and should be removed as soon as possible.

Nursing Homes. All older adults who are immobilized, catheterized, or dehydrated are at increased risk for UTIs. Nursing home residents, particularly those who are incontinent and demented, are at very high risk. Up to 40% of elderly patients who live in nursing homes will contract a urinary tract infection.

Some people have structural abnormalities of the urinary tract that cause urine to stagnate or flow backward into the upper urinary tract. Such conditions include:

A prolapsed bladder (cystocele) can result in incomplete urination so that urine collects, creating a breeding ground for bacteria.
Tiny pockets called diverticula sometimes develop inside the urethral wall and can collect urine and debris, further increasing the risk for infection.

Click the icon to see an image of a cystocele.

Antibiotics often eliminate lactobacilli, the protective bacteria, along with harmful bacteria. This causes an overgrowth of E. coli in the vagina. In one study, the risk for UTI increased during the 15 - 28 days that women were taking antibiotics. In fact, some research suggests that taking antibiotics for a urinary tract infection increases the risk for a subsequent infection.

Diabetes. Diabetes puts women at significantly higher risk for asymptomatic bacteriuria. The longer a woman has diabetes, the higher the risk. (Control of blood sugar has no effect on this condition.) The risk for UTI complications is also higher in people with diabetes. In fact, certain UTI-related abscesses are reported only in patients with diabetes. These patients are also at higher risk for fungal-related UTIs.

Kidney Problems. Nearly any kidney disorder increases the risk for complicated UTIs.

AIDS and Immunosuppressed Patients. Any infection is dangerous in people whose immune systems are damaged, and UTIs are no exception, particularly pyelonephritis.

Sickle-Cell Anemia. Patients with sickle-cell anemia are particularly susceptible to kidney damage from their disease, and UTIs put them at even greater risk.

Kidney Stones. In some cases, kidney stones can cause urinary tract obstruction that leads to infection, particularly pyelonephritis. Symptoms of severe urinary tract infection in people with a history of kidney stones may indicate obstruction, which is a serious condition.

Click the icon to see an image of kidney stones.

Zinc. High doses of zinc supplements may increase the risk for urinary tract infections and other urologic problems, according to a 2007 study. Researchers found that hospitalizations for urinary complications were far more common among patients who took high doses of zinc than those who did not take this mineral supplement. Patients in the study took 80 mg of zinc daily. In general, the recommended daily amount for zinc is 8 mg/day for women and 11 mg/day for men. Higher doses of zinc are sometimes prescribed for people with certain medical conditions, such as age-related macular degeneration (an eye disease). However, no one should take more than 40 mg/day of zinc without talking to a doctor.

Complications

Urinary discomfort and emotional distress are the primary concerns in most women with recurrent UTIs. One study reported significant impairment of a woman's quality of life during symptom periods, which affected social function, vitality, and emotional well-being.

Nearly all urinary tract infections are mild, treatable, and have no long-term consequences. Serious physical complications can occur in some cases, however, most often in hospitalized patients.

Obstruction and Widespread Infection. Very severe upper urinary tract infections may cause obstruction that results in widespread and even life-threatening infection. Patients who develop UTIs in the hospital are at higher risk for such infections than those outside the hospital. In one particularly dangerous form of kidney infection that obstructs the ureter, mortality rates exceed 40%. This specific condition should be suspected in people with diabetes who have severe UTIs.

Kidney Damage. In high-risk adults, recurrent UTIs may cause scarring in the kidneys, which over time can lead to hypertension and eventual kidney failure. People with UTIs who develop serious kidney disease from UTIs are likely to have other predisposing diseases or structural abnormalities. (Recurrent urinary tract infections, even in the kidney, almost never lead to progressive kidney damage in otherwise healthy women.)

Urge Incontinence. Recurrent UTIs may increase the risk for urge incontinence after menopause. (People with urge incontinence experience leakage and the need to urinate frequently.) [See In-Depth Report #50: Urinary incontinence.]

Kidney Stones. Kidney stones can be caused by urinary tract infections (as well as increase the risk for UTIs in the first place). Those known as struvite stones are almost always caused by urinary tract infections due to bacteria that secrete certain enzymes. These enzymes raise urine concentrations of ammonia, which composes the crystals forming struvite stones. The stone-promoting bacterium is usually Proteus, but others include Pseudomonas, Klebsiella, Providencia, Serratia, and staphylococci.

Urinary tract infections during pregnancy pose particular risks for both mother and child:

If asymptomatic bacteriuria is not detected and treated promptly in pregnant women, as many as 25% develop kidney infection (pyelonephritis), which in turn increases the risk for premature birth, infant mortality, and later chronic kidney disease.
Even if kidney infection does not develop, untreated UTIs occurring in the first and third trimester of pregnancy slightly increase the risk for mental retardation and developmental delay in the infant.
Certain strains of E. coli can increase the risk for complications during pregnancy, including miscarriage or premature delivery, even if pyelonephritis does not develop.
Infants of women who harbor Ureaplasma urealyticum also have an increased risk for respiratory infections.

Urinary tract infections are a major cause of hospitalization in children. Untreated, they can be very serious, particularly in children under 4 years old. Fortunately, with prompt treatment, childhood cases of upper urinary tract infections rarely cause any serious consequences.

Spread of Infection. Widespread infection is a major complication of a primary infection. Although laboratory tests in some infants with UTI may suggest the presence of meningitis (inflammation of the spinal column), in most of these UTI cases the outcome is good with treatment, and there appear to be no neurological symptoms afterward.

Kidney Scarring. Kidney scarring is the major concern in children who develop serious or recurrent UTIs. Scarring in young growing kidneys is much more serious than in the mature kidney. Over the years, it increases the risk for hypertension and kidney failure. In one study, evidence of scarring developed in 6% of children who had been hospitalized for a urinary tract infection. Children most at risk for this complication include:

Children with vesicoureteral reflux (VUR). (Carefully managed vesicoureteral reflux without scarring is not associated with serious complications.)
Abnormally structured urinary tracts
Recurrent kidney infections
A delay in treating an acute UTI

One encouraging study followed children with evidence of kidney scarring for 16 - 26 years. On average, their total kidney function was well preserved, although the scarred kidney had signs of lower function and patients with scarring in both kidneys were at higher risk for future problems. Earlier studies have shown poorer results, which suggests that outcomes are now improving with early detection and better follow-up.

Women with diabetes have more frequent and more severe UTIs than women without the disease. They also are more frequently hospitalized for kidney infections. In fact, the most serious, but rare, complications of urinary tract infections (pyelonephritis, widespread infections, abscesses, inflammation of the bladder wall) occur mostly in patients with diabetes.

Diagnosis

In younger women, UTI symptoms plus positive results on an over-the-counter dipstick test are often enough to make a diagnosis. Symptoms include frequent urination and vaginal burning, without other complications such as fever, chills, and pain in the kidney. In such cases, young women can usually receive treatment by calling a health professional (usually a nurse) who will prescribe antibiotics. A good response to antibiotic therapy usually eliminates the need for further tests.

This course is recommended only for nonpregnant women at low risk for recurrent infection who do not have symptoms suggesting other problems, such as vaginitis. In some centers, women who are treated over the phone have to be younger than 55 years old; other patients need to see a doctor for evaluation. Pregnant women should be screened for E. coli because of the risk of complications, including miscarriage, from certain strains of these bacteria.

About half of women with symptoms of a UTI actually have some other condition, such as irritation of the urethra, vaginitis, interstitial cystitis, or sexually transmitted diseases (STDs). Some of these problems may also accompany or lead to UTIs.

Vaginitis. Vaginitis is a common vaginal infection that can be caused by a fungus (candidiasis) or bacteria. Occasionally, the infection causes frequent urination, mimicking cystitis. The typical symptoms of vaginitis are itching and an abnormal discharge.

Sexually Transmitted Diseases. Women with painful urination whose urine does not exhibit signs of bacterial growth in culture may have a sexually transmitted disease. The most common culprit is the organism Chlamydia trachomatis. Other STDs that may be responsible include gonorrhea and genital herpes.

Interstitial Cystitis. Interstitial cystitis (IC) is an inflammation of the bladder wall that occurs almost predominantly in women. The average age of patients with IC is 40 years old, but 25% of cases occur in women under age 30. Symptoms are very similar to cystitis, but no bacteria are present. Pain during sex is a very common complaint in these patients, and stress may intensify symptoms.

Bladder Cancer. Bladder cancer is a rare cause of painful urination and is more common in men than in women.

Kidney Stones. The pain of kidney stones along with blood in the urine can resemble the symptoms of pyelonephritis. There are no bacteria present with kidney stones, however.

Thinning Urethral and Vaginal Walls. After menopause, the vaginal and urethral walls become dry and fragile, causing pain and irritation that can mimic a UTI.

Disorders in Children that Mimic UTIs. Problems that might cause painful urination in children include reactions to chemicals in bubble bath, diaper rashes, and infection from the pinworm parasite.

Prostate Conditions in Men. Prostate conditions, including prostatitis (inflammation of the prostate) and benign prostatic hyperplasia, can cause symptoms similar to urinary tract infections.

Click the icon to see an image of benign prostatic hypertrophy.

During an exam, the doctor should examine the pelvic and vaginal area in women. Men require a digital rectal examination to determine if prostate enlargement is present. The doctor will also examine the male genitals for signs of infection. In both men and women, the doctor should also check the abdomen and areas around the kidneys for swelling and tenderness.

With the exception of skin cancer, prostate cancer is the most common type of cancer among men in the United States. Early detection may result from a blood test called a PSA (prostate-specific antigen) or a digital rectal exam. The digital rectal exam checks the rear surface of the prostate gland for any abnormalities. A lump or hardness found during the exam might be a sign of prostate cancer.

Dipstick tests, available over the counter, are quite reliable in making a reasonable diagnosis of UTIs in women with symptoms. Dipstick tests may also be useful for identifying UTIs in children and infants. The test uses a chemical on a stick that when dipped in urine reacts to nitrites, substances produced by many of the bacteria that cause UTIs. A positive test (which indicates that an infection is present) often eliminates the need for urine cultures, a more expensive test used to detect bacteria. A negative dipstick test helps to avoid unnecessary antibiotics, which are contributing to the growing problem of antibiotic resistance. These tests are not entirely accurate, however, and studies report that they may miss up to 25% of actual UTIs. If a woman has persistent UTI symptoms, and the dipstick test is negative, she should check with her doctor to see if more accurate tests are needed.

A urine sample is needed for most extensive testing. In most cases, the doctor requests a clean-catch sample. There are also other methods for collecting urine, depending on the patient's condition.

Clean-Catch Sample. A clean-catch sample for UTI depends on a sample free of contaminants normally present at the opening of the urethra (white blood cells and bacteria unrelated to UTIs). To obtain an untainted urine sample, doctors usually request a so-called midstream, or clean-catch, urine sample. To provide this, the following steps are taken:

Patients must first wash their hands thoroughly, then wash the penis or vulva and surrounding area four times, with front-to-back strokes, using a new soapy sponge each time.
The patient must then begin urinating into the toilet and stop after a few drops.
The patient then positions the container to catch the middle portion of the stream. Ideally, this urine will contain only the bacteria and other evidence of the urinary tract infection.
The patient then urinates the remainder into the toilet.
The patient securely screws the container cap in place without touching the inside of the rim.

The sample is generally given to the doctor or sent to the laboratory for analysis.

Incontinence Pads. Testing and diagnosing UTIs in elderly patients who are incontinent is especially difficult, because of the similarities in symptoms. Researchers have found that pressing a dipstick into an incontinence pad is an effective way to screen for urinary tract infections in incontinent patients.

Collection with a Catheter. Some patients (small children, elderly people, or hospitalized patients) cannot provide a urine sample. In such cases, a catheter may be inserted into the bladder to collect urine. This is the best method for providing a contaminant-free sample.

A urinalysis involves a physical and chemical examination of urine. In addition, the urine is spun in a centrifuge to allow sediments containing blood cells, bacteria, and other particles to collect. This sediment is then examined under a microscope. A urinalysis offers a number of valuable clues for an accurate diagnosis:

Color and cloudiness of urine
Acidity
White blood cells (leukocytes). A high count of white cells in the urine is referred to as pyuria. (A leukocyte count over 10 per microliter is considered to indicate pyuria.) Pyuria is usually sufficient for a diagnosis of UTI in nonhospitalized patients if other standard symptoms (or just fever in small children) are also present.

Treatment can be started without the need for further tests if the following urinalysis results are present in patients with symptoms and signs of UTIs:

A high white cell count
Cloudy urine

A urine culture uses a urine specimen that is placed on an agar plate, then incubated in the laboratory for 24 - 48 hours. It is then examined for the presence of bacterial growth. Urinary tract infection is nearly always caused by a single species of bacteria, notably E. coli. Cultures have limitations, however. If a mix of different species is found, the test is considered contaminated and is redone. In addition, even if E. coli is identified, researchers are also looking for variants of these bacteria. Certain types may indicate a higher risk for a second infection, while others may even be protective against recurring infections. Furthermore, some organisms, such as Chlamydia, which is a sexually transmitted organism, may not be detected.

A urine culture is usually performed if the dipstick results are positive, but even if the results are negative, a culture may still be helpful under certain circumstances:

If urinalysis or dipstick is negative but the patient has UTI symptoms, particularly if the patient has recurring infections or is in a high-risk group.
If the doctor suspects complications.
In girls less than 2 years of age with a high fever of unknown origin that lasts 2 days or more.

Even if bacteria are present in the culture, a diagnosis of UTI depends on symptoms and gender:

The presence in a culture of at least 100,000 bacteria per milliliter of urine usually provides conclusive evidence of infection in women with symptoms.
A count of 100,000 bacteria per milliliter in a woman without symptoms indicates asymptomatic bacteriuria. The decision to treat depends on the woman's risk factors for complications.
In young women with symptoms of cystitis, a diagnosis of infection can reasonably be made with counts as low as 1,000 bacteria per milliliter.
Men are considered to have an infection with a count of only 1,000.

If doctors suspect that bacteria other than E. coli may be present, a Gram stain is used to help predict the species. This is a staining procedure used to make bacteria visible through a microscope. Many bacteria are categorized by the terms Gram-positive and Gram-negative.

Bacteria that turn pink from staining are called Gram-negative
Those that turn blue are called Gram-positive

Escherichia coli bacteria are Gram-negative and the most common cause of UTIs. If doctors suspect that bacteria other than E. coli are causing a UTI, a Gram stain is useful for identifying other species.

Because of the expense and the limited accuracy of imaging procedures, these techniques are used only for the following:

Serious and recurrent cases of pyelonephritis
When structural abnormalities are suspected
If infections do not respond to treatment
If a doctor suspects obstruction or an abscess
After a first urinary tract infection in children age 2 - 24 months to detect possible obstruction or vesicoureteral reflux. Tests include ultrasound and a voiding cystourethrogram and possibly scans. Some evidence suggests that ultrasound is probably not necessary, but at this time it is recommended by major medical groups.

Ultrasound. Ultrasound is a noninvasive, risk-free imaging test that can be used to screen for hydronephrosis (obstructions of the flow of urine), kidney stones that predispose to infection, and kidney abscesses. In men, ultrasound can detect enlargement or abscesses of the prostate and, when combined with x-rays, is an accurate method for detecting incomplete emptying of the bladder, a common cause of UTI in men over age 50. In children with urinary tract infections, it also can be used to detect vesicoureteral reflux, the defect of the valve-like mechanism between the ureter and bladder. Ultrasounds are not as accurate as voiding cystourethrograms.

Nuclear Scans. Imaging techniques called nuclear scans may be useful in certain complicated cases, such as detecting kidney scarring after pyelonephritis in children. They produce better images and expose the patient to far less radiation than x-rays. One such scan called dimercaptosuccinic acid (DMSA) scintigraphy uses injections of tiny amounts of radioactive tracers. A scanning machine (scintillation or gamma camera) is then used to detect pictures of the tracer in the kidney. This information is recorded on a computer screen or on film.

Magnetic Resonance Imaging (MRI) or Computed Tomography (CT). Magnetic resonance imaging (MRI) and computed tomography (CT) scans are noninvasive advanced imaging techniques that are sometimes used when nuclear scans are inconclusive. A CT scan is useful for ruling out kidney stones or obstructions in women with recurrent UTIs.

X-Rays. Special x-rays can be used to screen for structural abnormalities, urethral narrowing, or incomplete emptying of the bladder, which can cause stagnation of urine and predispose to infection.

Voiding cystourethrogram is an x-ray of the bladder and urethra. To obtain a cystourethrogram, a dye, called contrast material, is injected through a catheter inserted into the urethra and passed through the bladder.
An intravenous pyelogram (IVP) is an x-ray of the kidney. For a pyelogram, the contrast matter is injected into a vein and eliminated by the kidneys. In both cases, the dye passes through the urinary tract and reveals any obstructions or abnormalities on x-ray images. Due to the possible risks to the fetus, x-rays are not performed on pregnant women.

Click the icon to see an image of a voiding cystourethrogram.

Click the icon to see an image of an intravenous pyelogram.

Cystoscopy. Cystoscopy is used to detect structural abnormalities, interstitial cystitis, or masses that might not show up on x-rays during an IVP. The patient is given a light anesthetic, and the bladder is filled with water. The procedure uses a cystoscope, a flexible, tube-like instrument that the urologist inserts through the urethra into the bladder.

Click the icon to see an image of cystoscopy.

No noninvasive test will differentiate between upper and lower urinary tract infections. This is a particular problem because of the high percentage of women whose cystitis symptoms mask infections that also exist in the upper tract.

Antibiotic Trial. The best current test for pyelonephritis is the short-term antibiotic therapy given for cystitis. If the infection returns within 2 weeks after treatment, upper urinary tract infection is usually present.

Blood Cultures. If symptoms are severe, blood cultures will be taken to determine if the infection is in the bloodstream and threatening other parts of the body.

Treatment

Although antibiotics should be used as a cure for most urinary tract infections, severe symptoms can persist for several days until treatment effectively eliminates the bacteria. A number of options are available for relieving symptoms until the antibiotics take action.

Important Note. All of the drugs discussed below treat only symptoms and are not cures. They should never be used to replace antibiotics.

Phenazopyridine (Pyridium, Uristat, Barodium, Eridium, AZO Standard) relieves pain and burning caused by the infection. It should not be taken for more than 2 days and should be discontinued when symptoms are relieved.

Side effects include headache and stomach distress. The drug turns urine a red or orange color, which can stain fabric and be difficult to remove. In rare cases, it can cause serious side effects, including shortness of breath, a bluish skin, a sudden reduction in urine output, shortness of breath, and confusion. In such cases, patients should immediately call the doctor.

Methenamine (Atrosept, Prosed, Urised) or flavoxate (Urispas) reduce bladder spasms, which may occur with some UTIs. These drugs can have severe side effects, however, that the patient should discuss with the doctor.

Medications

Antibiotics are the mainstay treatment for all UTIs. A variety of antibiotics are available, and choices depend on many factors, including whether the infection is complicated or uncomplicated or primary or recurrent. Treatment decisions are also based on the type of patient (man or woman, a pregnant or nonpregnant woman, child, hospitalized or nonhospitalized patient, person with diabetes). Treatment should not necessarily be based on the actual bacteria count. For example, if a woman has symptoms, even if bacterial count is low or normal, infection is probably present and antibiotic treatment should be considered.

Bacterial Resistance to Antibiotics. Antibiotic-resistant strains of E. coli, the most common cause of UTIs, are increasing. The prevalence of such bacteria has dramatically increased worldwide, in large part due to widespread use of antibiotics in humans and animal feed. In a 2003 report, 42% of E. coli were resistant to one or more of the 12 antibiotics that researchers investigated. As more bacteria have become resistant to the standard UTI treatment trimethoprim-sulfamethoxazole (TMP-SMX), more doctors have been prescribing quinolone antibiotics to treat UTIs. A 2006 study found that quinolones have now overtaken TMP-SMX as the most commonly prescribed antibiotic for UTIs. Experts are concerned that resistance may develop to these drugs as well.

Beta-Lactams

The beta-lactam antibiotics share common chemical features and include penicillins, cephalosporins, and some newer similar drugs. Their primary actions to interfere with bacterial cell walls. Many have been important in the treatment of urinary tract infections.

Penicillins (Amoxicillin). Until recent years, the standard treatment for a UTI was 10 days of amoxicillin, a penicillin antibiotic, but it is now ineffective against E. coli bacteria in up to 25% of cases. A combination of amoxicillin-clavulanate (Augmentin) is sometimes given for drug-resistant infections. Amoxicillin or Augmentin may be useful for UTIs caused by Gram-positive organisms, including Enterococcus species and S. saprophyticus.

Cephalosporins. Antibiotics known as cephalosporins are also alternatives for infections that do not respond to standard treatments or for special populations. They are often classed as:

First generation, including cephalexin (Keflex), cefadroxil (Duricef, Ultracef), and cephradine (Velosef).
Second generation, including cefaclor (Ceclor), cefuroxime (Ceftin), cefprozil (Cefzil), and loracarbef (Lorabid).
Third generation, including cefpodoxime (Vantin), cefdinir (Omnicef) cefditoren (Sprectracef), cefixime (Suprax), and ceftibuten (Cedex). Ceftriaxone (Rocephin) is an injected cephalosporin. These are effective against a wide range of Gram-negative bacteria.

Other Beta-Lactam Drugs. Other beta-lactam antibiotics have been developed. For example, pivmecillinam (a form of mecillinam), is commonly used in Europe for UTIs. It appears to be safe during pregnancy.

Trimethoprim-Sulfamethoxazole (TMP-SMX)

The typical treatment is a 3-day course of the combination drug trimethoprim-sulfamethoxazole, commonly called TMP-SMX (Bactrim, Cotrim, Septra). A 1-day course is somewhat less effective but poses a lower risk for side effects. Longer courses (7 - 10 days) work no better than the 3-day course and have a higher rate of side effects. TMP-SMX should not be used in patients whose infections occurred after dental work or in patients allergic to sulfa drugs. Allergic reactions can be very serious. Trimethoprim (Proloprim, Trimpex) is sometimes used alone in those allergic to sulfa drugs. TMP-SMX can interfere with the effectiveness of oral contraceptives. High rates of bacterial resistance to TMP-SMX exist in many parts of the United States. Still, even when regional rates approach 30%, cure rates with TMP-SMX reach 80 - 85%.

Fluoroquinolones (Quinolones)

Fluoroquinolones (also simply called quinolones) are now becoming as widely used as TMP-SMX. These drugs interfere with the bacteria's genetic material so they cannot reproduce. They are the standard alternatives to TMP-SMX. Examples of quinolones include ofloxacin (Floxacin), ciprofloxacin (Cipro), norfloxacin (Noroxin), levofloxacin (Levaquin), gatifloxacin (Tequin), and sparfloxacin (Zagam). These antibiotics are effective against a wide range of organisms but are expensive and, in general, used in the following circumstances:

In patients with complicated or catheter-induced UTIs
In patients who do not respond or who are allergic to TMP-SMX
In communities where there are high rates of bacteria resistant to TMP-SMX
In elderly patients. A 2001 study of older women with UTIs (mean age 80), about half of whom were living in nursing homes, found that 96% responded to ciprofloxacin, compared with 87% to TMP-SMX.

Pregnant women should not take fluoroquinolone antibiotics. They also have more adverse effects in children than other antibiotics and should not be the first-line option in most situations.

Antibiotics Used Specifically for UTIs

Nitrofurantoin. Nitrofurantoin (Furadantin, Macrodantin) is a relatively inexpensive antibiotic that is used specifically for urinary tract infections. It is an effective alternative to TMP-SMX or a quinolone. Unlike many of the other drugs, however, it must be given 7 - 10 days, even in cases of simple cystitis. (Shorter course treatments are being investigated.) It is not useful for treating kidney infections. Nitrofurantoin frequently causes stomach upset and interacts with many drugs. Other chronic or serious medical conditions may also affect its use. It should not be used in pregnant women within 1 - 2 weeks of delivery, in nursing mothers, or in those with kidney disease.

Fosfomycin. The antibiotic fosfomycin (Monurol), which comes in an orange-flavored, soluble powder, is proving to be another good alternative. It can be an effective 1-dose treatment for many women, including those who are pregnant. To date, bacterial resistance rates to this antibiotic are very low.

Tetracyclines

Tetracyclines inhibit bacterial growth. They include doxycycline, tetracycline, and minocycline. Long-term treatment with tetracycline or doxycycline may be used for infections that are caused by Mycoplasma or Chlamydia. Tetracyclines have unique side effects among antibiotics, including skin reactions to sunlight, possible burning in the throat, and tooth discoloration.

Aminoglycosides

Aminoglycosides (gentamicin, kanamycin, tobramycin, amikacin) are given by injection for very serious bacterial infections. They can be given only in combination with other antibiotics. Gentamicin is the most commonly used aminoglycoside for serious UTIs. They can have very serious side effects, including damage to hearing, sense of balance, and kidneys.

UTIs in low-risk women can often be successfully treated over the phone. In such cases, a health professional provides the patients with 3-day antibiotic regimens without even requiring an office urine test. This course is recommended only for women at low risk for recurrent infection and who do not have symptoms suggesting other problems, such as vaginitis.

Antibiotic Regimen. Oral antibiotic treatment cures 94% of uncomplicated urinary tract infections, although the rate of recurrence remains high. The following antibiotics are commonly used for uncomplicated UTIs:

The standard regimen has traditionally been a 3-day course of trimethoprim-sulfamethoxazole, commonly called TMP-SMX (Bactrim, Cotrim, Septra). TMP-SMX combines an antibiotic with a sulfa drug. A single dose of TMP-SMX is sometimes prescribed in mild cases, but cure rates are generally lower than with the 3-day regimens.
Fluoroquinolone antibiotics, also called quinolones, have usually been a second choice. However, in geographic areas that have a high resistance to TMP-SMX, quinolones are now the first-line treatment for UTIs. Ciprofloxacin (Cipro) is the quinolone antibiotic most commonly prescribed. Quinolones are usually given over a 3–day period. Pregnant women should not take these drugs.
Nitrofurantoin (Furadantin, Macrodantin) is a third option. This drug must be given for longer than 3 days.
Fosfomycin (Monurol) is not as effective as other antibiotics but may be used during pregnancy. Resistance rates to this drug are very low.
Many other effective antibiotics are available, including amoxicillin (with or without clavulanate) and cephalosporins. Doxycycline is often effective but cannot be given to children or pregnant women.

After a week of antibiotic treatment, most patients are free of infection. If the symptoms do not clear up within the first few days of therapy, doctors generally suggest that women discontinue their antibiotic and provide a urine sample for culturing in order to identify the specific organism causing the condition.

Treatment for Relapsing Infection. A relapsing infection (caused by treatment failure) occurs within 3 weeks in about 10% of women. Relapse is treated similarly to a first infection, but the antibiotics are continued for at least 2 weeks. (Relapsing infections may be due to structural abnormalities, abscesses, or other problems that may require surgery, and such conditions should be ruled out.)

Preventive antibiotics may be required for women who experience two or more symptomatic UTIs within 6 months or three or more over the course of a year. A woman's own perception of discomfort can generally guide her decisions on whether to use preventive antibiotics or not. All women should use lifestyle measures to prevent recurrences.

Intermittent Self Treatment. Many, if not most, women with recurrent UTIs can effectively self-treat recurrent UTIs without going to a doctor. In general, this requires the following steps:

As soon as the patient develops symptoms, she takes the antibiotic. Infections that occur less than twice a year are usually treated as if they were an initial attack, with single-dose or three-day antibiotic regimens.
At that time, she also performs a clean-catch urine test and sends it to the doctor for culturing to confirm the infection.

A doctor should be consulted under the following circumstances:

If symptoms have not completely resolved within 48 hours
If there is a change in symptoms
If the patient suspects that she is pregnant
If the patient has more than four infections a year

Women who are not good candidates for self-treatment are those with impaired immune systems, previous kidney infections, structural abnormalities of the urinary tract, or a history of infection with antibiotic-resistant bacteria.

Postcoital Antibiotics. If recurrent infections are clearly related to sexual activity and episodes recur more than two times within a 6-month period, a single preventive dose taken immediately after intercourse is very effective. Antibiotics for such cases include TMP-SMX, nitrofurantoin, cephalexin, or a fluoroquinolone (such as ciprofloxacin). (Fluoroquinolones are not appropriate during pregnancy.)

Continuous Preventive Antibiotics (Prophylaxis). Continuous preventive (prophylactic) antibiotics are an option for some women who do not respond to other measures. With this approach, low-dose antibiotics are taken continuously for 6 months or longer.

Typical prophylactic regimens include one dose of nitrofurantoin (50 mg), 1/2 tablet of TMP-SMX, or cephalexin (250 mg) daily. Taking the antibiotic at bedtime may be most effective. Studies suggest that continuous prophylactic antibiotics reduces recurrences by up to 95% and may prevent kidney infection.

Adverse effects mostly include gastrointestinal problems and yeast infections. (Taking probiotic supplements or eating yogurt may help prevent yeast infections.) Although there is concern that continuous risk increases the risk for bacteria that are resistant to the antibiotics, studies to date have not reported any significant risk even up to 5 years of use.

Treating Uncomplicated Kidney Infections. Patients with uncomplicated kidney infections (pyelonephritis) may be treated at home with oral antibiotics. Such patients are healthy and nonpregnant. They typically are experiencing fever, chills, and flank pain. However, they are not nauseous or vomiting and show no symptoms or signs of kidney involvement or complicated infection.

The standard treatment for uncomplicated pyelonephritis is a 14-day course of oral antibiotics, usually trimethoprim-sulfamethoxazole (TMP-SMX) or a fluoroquinolone. Sometimes patients with uncomplicated pyelonephritis are first given an antibiotic injection, if indicated.

Oral amoxicillin or amoxicillin-clavulanate (Augmentin) may be prescribed for women with bacteria (Gram-positive organisms, including Enterococcus species and S. saprophyticus) that do not respond to standard regimens.

A urine culture may be obtained within 1 week of completion of therapy and again 4 weeks later.

Treating Moderate-to-Severe Kidney Infections. Patients with moderate-to-severe acute kidney infection and those with severe symptoms or other complications may need to be hospitalized. In such cases, antibiotics (ceftriaxone and gentamicin) are usually given intravenously for 3 - 5 days or until symptoms are relieved and patients have not shown any signs of fever for 24 - 48 hours.

If fever and back pain persist after 72 hours of antibiotic administration, the doctor will usually order imaging tests to see if abscesses, obstructions, or other abnormalities are present.

Treating Chronic Kidney Infections. Patients with chronic pyelonephritis are often treated with long-term antibiotics, even during periods when they have no symptoms.

The two approved treatments for interstitial cystitis are pentosan polysulfate (Elmiron), and dimethyl sulfoxide (DMSO). Patients generally prefer Elmiron because it can be taken by mouth. A DMSO solution is instilled into the bladder through a catheter. Elmiron is a type of blood thinner that helps to coat the bladder lining and prevent infections. It may take several months before having an effect on symptoms, but the benefits increase the longer the drug is used.

Doctors sometimes also prescribe other types of medications to help interstitial cystitis symptoms. These drugs include antihistamines, such as hydroxyzine (Atarax), and low doses of the tricyclic antidepressant amitriptyline (Elavil). Drugs that reduce bladder spasms (hyoscine, oxybutynin) are also sometimes used. Other treatments are being investigated, including hyperbaric oxygen therapy. This treatment involves having a patient breathe pure oxygen inside a sealed pressurized chamber.

Some doctors think that interstitial cystitis may be related to immune disorders. Researchers are investigating various drugs that block immune and inflammatory responses.

Treating the Pregnant Woman. Pregnant women should be screened for UTIs, since they are at high risk for UTIs and their complications. The antibiotics used during pregnancy are amoxicillin, ampicillin, nitrofurantoin, or an oral cephalosporin. Fosfomycin (Monurol) is not as effective as others but may be used during pregnancy. Pregnant women should not take fluoroquinolones.

Pregnant women with even asymptomatic bacteriuria (evidence of infection but no symptoms) have a 30% risk for acute pyelonephritis in their second or third trimester. They need screening and treatment for this condition. In such cases, they should be treated with a short course of antibiotics (3 - 5 days). For an uncomplicated UTI, pregnant women may need longer-term antibiotics (7 - 10 days).

Treating Women with Diabetes. Women with diabetes have more frequent and more severe UTIs than women without the disease. Many experts recommend that patients with diabetes and UTI, even an uncomplicated infection, be treated with antibiotics for 7 - 14 days. People with diabetes have higher than average rates of asymptomatic bacteriuria, but it is unclear whether they should be screened and treated for this condition. A 2003 study indicated that treating this condition had little value in these women and did not prevent complications.

Treating Urethritis in Men. Urethritis in men has typically been treated with a 7-day regimen of doxycycline. Some research suggests that a single dose of azithromycin may be just as effective while causing fewer side effects. One-dose treatment also improves compliance, so cure rates may even be better than with a long-term regimen. However, once an infection spreads to the prostate gland it is harder to treat, so most doctors still prefer the longer regimen. Patients with urethritis should also be tested for an accompanying sexually transmitted disease such as gonorrhea.

Treating Children with UTIs. Children with UTIs are generally treated with TMP-SMX or cephalexin (Keflex). These drugs are usually taken by mouth in either liquid or pill form. Doctors sometimes give them as a shot or IV. Children usually respond to treatment within a few days. Antibiotic resistance to cephalosporin antibiotics such as cephalexin is increasing, and some doctors prefer to prescribe an aminoglycoside antibiotic. Gentamicin (Garamycin) is the aminoglycoside antibiotic that is most commonly used. It is given intravenously.

Vesicoureteral reflux (VUR) is a concern for children with UTIs. About a third of children with UTIs develop this condition, in which urine backs up into the kidneys. VUR can lead to kidney infection (pyelonephritis), which can cause kidney damage. Either long-term antibiotics or surgery are options to correct vesicoureteral reflux (VUR) and prevent infection. Many experts recommend surgery over antibiotics, especially due to concerns of antibiotic resistance. Antibiotic treatment usually continues for years with the idea that the condition will resolve when the child has grown. However, a 2006 study suggested that long-term antibiotics are not useful for preventing VUR. Furthermore, the study found that mild-to-moderate VUR does not increase the likelihood of UTIs or pyelonephritis.

Children with acute kidney infection are treated with oral cefixime (Suprax) or a short course (2 - 4 days) of an intravenous (IV) antibiotic (typically gentamicin, given in one daily dose). An oral antibiotic then follows the IV.

Preventing Catheter-Induced Infections

Catheter-induced urinary tract infections are very common, and preventive measures are extremely important. Catheters should not be used unless absolutely necessary, and they should be removed as soon as possible. Reducing the risk for infections during long-term catheter use, however, remains problematic.

Catheter Coatings. Catheter coatings, such as silver nitrate, antibiotics, and other substances, are being tested and are showing some benefits, but the problem is still not resolved. One promising catheter (LoFric) uses a so-called hydrophilic coating consisting of PVP (polyvinyl pyrrolidone) and salt. It attracts water to the catheter surface, putting up a water barrier to reduce friction. In a 2003 study, it was associated with significantly fewer UTIs.

Intermittent Use of Catheters. If a catheter is required for long periods, it is best to use it intermittently if possible (as opposed to an indwelling catheter). Some doctors recommend replacing it every 2 weeks to reduce the risk of infection and irrigating the bladder with antibiotics between replacements.

Daily Hygiene. A typical catheter is one that has been preconnected and sealed and uses a drainage bag system. To prevent infection, some of the following tips may be helpful:

Drink plenty of fluids, including 3 glasses of cranberry juice a day.
The catheter tube should be free of any knots or kinks.
Clean the catheter and the area around the urethra with soap and water daily and after each bowel movement. (Women should be sure to clean front to back.)
Wash hands before touching the catheter or surrounding area.
Never disconnect the catheter from the drainage bag without careful instructions from a health professional on strict methods for preventing infection.
Keep the drainage bag off the floor.
Stabilize the bag against the leg using tape or some other system.

Antibiotics for Catheter-Induced Infections

Patients using catheters who develop UTIs with symptoms should be treated for each episode with antibiotics and the catheter should be removed, if possible. A major problem in treating catheter-related UTIs is that the organisms involved are constantly changing. Because there are likely to be multiple species of bacteria, experts generally recommend an antibiotic that is effective against a wide variety of microorganisms. These medications include those in the fluoroquinolone group and drug combinations such as ampicillin plus gentamicin or imipenem plus cilastatin.

Although high bacteria counts in the urine (bacteriuria) occur in most catheterized patients, administering antibiotics to prevent a UTI is rarely recommended. Many catheterized patients do not develop symptomatic urinary tract infections even with high bacteria counts. If bacteriuria occurs without symptoms, antibiotic therapy has little benefit if the catheter is to remain in place for a long period.

Catheterization is accomplished by inserting a catheter (a hollow tube, often with an inflatable balloon tip) into the urinary bladder. This procedure is performed for urinary obstruction, following surgical procedures to the urethra, in unconscious patients (due to surgical anesthesia, coma, etc.), or for any other problem in which the bladder needs to be kept empty (decompressed) and urinary flow assured. Catheterization in males is slightly more difficult and uncomfortable than in females because of the longer urethra.

Other Treatments

The following are hygiene tips. Although there is no evidence that good hygiene makes a real difference in preventing UTIs, it is always a wise practice.

Clean the genital and urinary areas from front to back with soap and water after each bowel movement.
Keep the genital and anal areas clean before and after sex. Urinate before and after intercourse to empty the bladder and cleanse the urethra of bacteria.
Avoid tight-fitting pants.
Wear cotton-crotch underwear and panty hose, changing both at least once a day. (Mild detergents are best for washing underwear.)
Take showers rather than baths.
Avoid bath oils, feminine hygiene sprays, douches, and powders. As a general rule, do not use any product containing perfumes or other possible allergens near the genital area. Douching in is never recommended. It may destroy the natural antiviral organisms normally present in the vagina, making women more susceptible to human papillomavirus (HPV), a risk factor for cervical cancer.
Choose sanitary napkins instead of tampons (which some doctors believe encourage infection). Napkins and tampons, in any case, should be changed after each urination.
Urinate frequently.

Appropriate hygiene and cleanliness of the genital area may help reduce the chances of introducing bacteria through the urethra. Females are especially vulnerable to this, because the urethra is in close proximity to the rectum. The genitals should be cleaned and wiped from front to back to reduce the chance of dragging E. coli bacteria from the rectal area to the urethra.

The following recommendations may reduce the risks from sexual activity:

In women using contraceptives, consider alternatives, particularly if exposed to spermicides from condoms or diaphragms. Discuss the best contraceptive choice with a doctor.
Avoid sex with multiple partners. This can cause many health problems, including sexually transmitted diseases and UTIs.

Postmenopausal women with recurrent UTIs may consider the use of an estrogen vaginal cream or estrogen-releasing vaginal ring (Estring). Estrogen may resist infection by increasing the number of lactobacilli, the microorganism that fights infection by lowering the vaginal pH levels and preventing E. coli from adhering to vaginal cells. Estrogen creams and estrogen-releasing rings may help reduce the risk of recurring urinary tract infections. Oral hormone replacement therapies that contain estrogen do not seem to provide the same benefit as the topical forms. Estrogen HRT carries many health risks, including an increased risk for breast cancer and heart disease. It is not clear if vaginal forms of estrogen are associated with these risks.

Many doctors believe that emptying the bladder frequently will help prevent bladder irritation and therefore recommend drinking plenty of water daily and urinating often.

Cranberries, blueberries, and lignonberry, a European relative of the cranberry, are three fruits that may have protective properties. Researchers are finding that red pigments in these closely related fruits called tannins (or proanthocyanadins) prevent E. coli bacteria from adhering to cells in the urinary tract, thereby inhibiting infection. Fructose, which is commonly used to sweeten fruit juices, may also interfere with bacterial adhesion.

Cranberry juice offers well-known protection against urinary tract infections. In one study, only 15% of elderly women who drank cranberry juice daily for 6 months experienced UTIs, compared with 28% of women who did not drink the juice. Its effects were stronger in helping the body rid itself of infections than in preventing them in the first place, but it showed benefits in both situations.

Studies suggest that for protection, it is necessary to drink at least one to two cups of 30% cranberry or lignonberry juice daily, or to take at least 300 - 400 mg in tablet form twice daily.

Important research has targeted probiotics (essentially friendly organisms), which may protect against infections in the genital and urinary tracts. They may have other health benefits as well. The best-known probiotics are the lactobacilli strains, such as acidophilus, which is found in yogurt and other fermented milk products (kefir). The probiotics bifidobacteria and GG lactobacilli may prove to be even more important. Other probiotics include the lactobacilli rhamnosus, casel, plantarium, bulgaricus, and salivarius, and also Enterococcus faecium and Streptococcus thermophilus.

Lactobacilli have the potential to help protect women from UTIs in a number of ways:

Maintain a low pH environment
Hinder E. coli growth
Produce hydrogen peroxide, which produces an environment hostile for bacteria

In a 2003 study, drinking fermented milk reduced the risk for UTIs. Not all studies show benefits from drinks containing lactobacilli, but more research is warranted.

Researchers are studying several different herbal treatments for urinary tract infections. Studies on these herbs have only been conducted on animals and cell samples -- not in humans:

Forskolin, an extract from the Indian coleus plant, may help flush out bacteria hiding in the lining of the bladder.
Green tea contains compounds that may help prevent inflammation in bladder cells.
St. John’s wort, a popular herbal remedy for depression, may help relieve pain associated with interstitial cystitis.

It is important to inform your doctor of any herbs, dietary supplements, or vitamins and minerals that you take or are considering taking. Some of these remedies may actually increase your chance of developing urinary tract infections. For example, high doses of zinc have been associated with increased risk of UTIs.

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.

Biofeedback is a technique that provides visual and auditory clues in response to specific exercises. Some research indicates that biofeedback teaches children who are prone to UTIs to relax and control their pelvic muscles, resulting in fewer recurrences of infection.

Resources

http://kidney.niddk.nih.gov -- National Kidney and Urologic Diseases Clearinghouse
www.urologyhealth.org -- American Urological Association
www.acog.org -- American College of Obstetricians and Gynecologists
www.ichelp.com -- Interstitial Cystitis Association

References

Bishop BL, Duncan MJ, Song J, Li G, Zaas D, Abraham SN. Cyclic AMP-regulated exocytosis of Escherichia coli from infected bladder epithelial cells. Nat Med. 2007 May;13(5):625-30. Epub 2007 Apr 8.

Johnson AR, Munoz A, Gottlieb JL, Jarrard DF. High dose zinc increases hospital admissions due to genitourinary complications. J Urol. 2007 Feb;177(2):639-43.

Litwin MS, Saigal CS, editors. Urologic Diseases in America. US Department of Health and Human Services, Public Health Service, National Institutes of Health, National Institute of Diabetes and Digestive and Kidney Diseases. Washington, DC: US Government Printing Office, 2007; NIH Publication No. 07–5512.

Review Date:
6/15/2007
Reviewed By:
Harvey Simon, MD, Associate Professor of Medicine, Harvard Medical School; Physician, Massachusetts General Hospital.

A.D.A.M. Copyright

adam.com

Sinusitis

FitSugar — Wed, 08 Oct 2008 17:35:28 -0700

In This Report

Highlights
Introduction
Causes
Risk Factors
Symptoms
Complications
Diagnosis
Prevention
Treatment for Acute Sinusit...
Treatment for Chronic Sinus...
Surgery
Resources
References

HEALTH GUIDE REFERENCE FROM A.D.A.M

Highlights

Drug Restriction

In February 2007, the FDA announced that the antibiotic telithromycin (Ketek) should no longer be used for treatment of acute bacterial sinusitis. In June 2006, the FDA reported that several people had died of liver damage after taking this drug. Telithromycin is now only approved for treatment of community-acquired pneumonia.

Acute Sinusitis Treatment

Antibiotics are widely over-prescribed for acute sinusitis, according to a 2007 study. Researchers also reported that inhaled corticosteroids are frequently prescribed for acute sinusitis, despite little evidence for their efficacy. Most cases of acute sinusitis resolve on their own and do not require antibiotic treatment.

Allergic Fungal Sinusitis

Allergic fungal sinusitis should be considered a distinct form of chronic sinusitis, according to research presented at the 2007 annual meeting of the American Academy of Allergy, Asthma, & Immunolology. Researchers found that patients with allergic fungal sinusitis have an increased allergic and inflammatory response to fungi compared to patients with other types of chronic sinusitis.

Anti-Fungal Drugs

Allergic fungal sinusitis is currently treated with oral corticosteroids such as prednisone, but researchers are investigating whether anti-fungal drugs may help. The anti-fungal drug Amphotericin B (SinuNase) is currently in Phase III trials for patients with chronic sinusitis who have had sinus surgery but are still experiencing sinusitis symptoms. However, several 2006 studies indicated disappointing results.

Balloon Sinuplasty

Balloon sinuplasty is a relatively new procedure that uses a catheter-inserted balloon to gently open and drain nasal passages. In a study of 115 patients with chronic sinusitis, balloon sinuplasty achieved promising results, according to research presented at the 2007 meeting of the American Academy of Otolaryngology–Head and Neck Surgery Foundation. However, some experts believe that it is still too early to recommend this procedure for wide-scale use, especially until further large-scale clinical trials are conducted.

Introduction

The skull contains a number of air-filled spaces called sinuses. They perform the following functions:

Reduce the weight of the skull
Provide insulation for the skull
Provide resonance for the voice

Four pairs of sinuses, known as the paranasal air sinuses, connect to the nasal passages (the two airways running through the nose) and are those that are involved in sinusitis. These sinuses are the following:

Frontal sinuses (behind the forehead)
Maxillary sinuses (behind the cheekbones)
Ethmoid sinuses (between the eyes)
Sphenoid sinuses (behind the eyes)

Healthy sinuses are sterile and contain no bacteria. (The nasal passage, on the other hand, normally contains many bacteria that enter through the nostrils.) Maintaining sinus health depends on a cycle that involves a number of important factors and processes:

The sinuses are lined with a membrane that secretes mucus. Mucus drains down into the nasal passage from a small channel in each sinus. The mucous membranes must be intact and free of injury.
The mucus must be fluid in order to flow freely while being sticky enough to absorb pollutants and entrap bacteria.
The mucus must also contain sufficient amounts of bacteria-fighting substances, including immune factors called antibodies.
Small, hair-like projections called cilia must beat in unison to propel mucus outward, expelling bacteria and other particles.
The sinus passages must be open to allow mucus drainage and the circulation of air through the nasal passage.

Click the icon to see an image of an antibody.

The Disease Process. Sinusitis is an infection that occurs if one or more of the defense processes or factors are amiss, causing obstruction, and bacterial growth occurs in the paranasal sinuses. Among the many causes of such obstruction or congestion are the common cold, allergies, certain medical conditions, abnormalities in the nasal passage, and change in atmosphere. In any of these cases, sinusitis can develop as follows:

Mucus drainage and airflow are blocked.
Secretions build up, encouraging the growth of certain bacteria.
The resulting infection, swelling, and inflammation create further blockage, which may cause the sinuses to close up completely.

Forms of Sinusitis. Sinusitis is classified as acute, subacute, or chronic, or recurrent. The classification is based on how long symptoms last:

Acute: Less than 4 weeks
Subacute: 4 - 8 weeks
Chronic: 8 weeks or longer
Recurrent: 3 or more acute episodes in 1 year

Causes

Bacteria are the most common direct cause of acute sinusitis. (Other organisms might be the infecting cause in less common cases.) The ability of bacteria or other organisms to infect the sinuses, however, must first be set up by conditions that create a favorable environment in the sinus cavities. Sinusitis is most often an acute condition, which is self-limiting and treatable. In some cases, however, the inflammation in the sinuses persists or is chronic do begin with. The causes for such chronic sinusitis cases are sometimes unclear.

The typical process leading to acute sinusitis starts with a flu or cold virus. Viruses themselves do not usually cause sinusitis directly and are implicated in only about 10% of sinusitis cases. Instead, they set the stage by causing inflammation and congestion in the nasal passages (called rhinitis) that leads to obstruction in the sinuses. This creates a hospitable environment for bacterial growth, which is the direct cause of sinus infection. In fact, rhinitis is the precursor to sinusitis in so many cases that expert groups now refer to most cases of sinusitis as rhinosinusitis.

Rhinosinusitis tends to involve the following sinuses:

The maxillary sinuses (behind the cheekbones) are the most common sites.
The ethmoid sinuses (between the eyes) are the second most common sites affected by colds.
The frontal (behind the forehead) and sphenoid (behind the eyes) sinuses are involved in about a third of cold-related cases.

Nearly everyone with colds has inflamed sinuses. These inflammations are typically brief and mild, however, and most people with colds do not develop true sinusitis.

Chronic or recurrent acute sinusitis typically results from one of the following conditions:

Untreated acute sinusitis that results in damage to the mucous membranes
Chronic medical disorders that cause inflammation in the airways or persistent thickened stagnant mucus (such as diabetes, AIDS or other disorders of the immune system, hypothyroidism, cystic fibrosis, Kartagener's syndrome, and Wegener's granulomatosis)
Structural abnormalities
Allergic reaction to fungi

Chronic or recurrent acute sinusitis can be a lifelong condition.

The Role of Bacteria. The role of bacteria or other infectious organisms is complicated in chronic sinusitis. They may play a direct, an indirect, or, in some patients, no role at all. For example, one study reported the following for patients with chronic sinusitis who had not responded to antibiotics:

30% had no evidence of bacteria in their passageways.
20% had bacteria unrelated to infection.

Inflammatory Response, Allergies, and Asthma. The absence of bacterial organisms as a causal factor in many cases suggests that some instances of chronic sinusitis may be due to a continuing inflammatory condition. Such on-going inflammation may have been triggered immune factors that were produced in response to injuries from acute sinusitis. Many of the immune factors observed in people with chronic sinusitis resemble those that appear in allergic rhinitis, suggesting that sinusitis in some individuals is due to an allergic response.

Allergies, asthma, and sinusitis often overlap. Those with allergic rhinitis (so-called hay fever and rose fever) often have symptoms of sinusitis, and true sinusitis can develop as a result of the mucus blockage it causes. A causal association, however, has not been proved, and many experts believe allergies themselves rarely predispose to sinusitis. People with chronic sinusitis may also have an allergic reaction to fungal organisms.

Severe asthma (which is often associated with allergies) and chronic sinusitis often overlap, although the relationship is unclear. Between 53 - 75% of children with asthma caused by allergies have sinus abnormalities, and various studies have shown that between 17 - 30% of asthmatic patients develop true sinusitis. In fact, chronic sinusitis may actually be the cause of asthma in some cases.

Abnormalities of the Nasal Passage. Abnormalities in the nasal passage can cause blockage and thereby increase the risk for chronic sinusitis. Some abnormalities include:

Polyps (small benign growths) in the nasal passage block mucus drainage and restrict airflow. Polyps themselves may be consequences of previous sinus infections that caused overgrowth of the nasal membrane.
Enlarged adenoids can lead to sinusitis.

Adenoids are masses of tissue located high on the posterior wall of the pharynx. They are made up of lymphatic tissue, which trap and destroy pathogens in the air that enter the nasopharynx.

Cleft palate
Tumors
Deviated septum (a common structural abnormality in which the septum, the center section of the nose, is shifted to one side, usually the left)

Click the icon to see an image of a deviated septum.

The bacteria most commonly implicated in sinusitis include:

Streptococcus pneumoniae (also called pneumococcal pneumonia or pneumococci). This bacterium is found in between 20 - 43% of adults and children with sinusitis.
H. influenzae (a common bacterium associated with many upper respiratory infections). This bacterium colonizes nearly half of all children by age 2, and causes about 25% of sinusitis cases in this group. Studies have reported the presence of this bacterium in 22 - 35% of adult sinusitis patients.
Moraxella catarrhalis. Over 75% of all children harbor this bacterium, which causes about 25% of sinusitis cases.

Other possible bacterial culprits include:

Other streptococcal strains
Staphylococcus aureus

While fungi are an uncommon cause of sinusitis, the incidence of such infections is increasing. At least 5 - 10% of chronic rhinosinusitis patients may actually have allergic fungal sinusitis. At the 2007 meeting of the American Academy of Allergy, Asthma, & Immunology (AAAAI), experts presented evidence suggesting that allergic fungal sinusitis is a distinct form of chronic rhinosinusitis. Research indicates that allergic fungal sinusitis may provoke a distinct immune response. In the AAAAI study, patients with allergic fungal sinusitis showed increased antibody levels of immunoglobulin E (IgE) and immunoglobulin G (IgG) compared to patients with other types of chronic rhinosinusitis.

In earlier research from 2004, scientists from the U.S. National Institute of Allergy and Infectious Diseases exposed immune cells from patients with chronic sinusitis and healthy volunteers to four common types of fungi: Alternaria, Aspergillus, Penicillium, and Cladosporium. The study’s findings suggested that some people who suffer from chronic sinusitis have an extreme immune and inflammatory response to fungi and may benefit from anti-fungal treatment.

Fungi involved in sinusitis include:

Aspergillus is the most common cause of all forms of fungal sinusitis.
Other fungi include Curvularia, Bipolaris, Alternaria, Dreschslera, Cryptococcus, Candida, Sporothrix,Exserohilum, and Mucormycosis.
There have been a few reports of fungal sinusitis caused by Metarrhizium anisopliae, which is used in biological insect control.

There are four categories of fungal sinusitis:

Acute or invasive fungal sinusitis - This infection is most likely to affect people with diabetes and compromised immune systems.
Chronic or indolent fungal sinusitis - This form is generally found outside the U.S., most commonly in the Sudan and northern India.
Fungus ball (mycetoma) - This fungal sinusitis is noninvasive and occurs usually in one sinus, most often the maxillary sinus.
Allergic fungal sinusitis - This form typically occurs because of an allergy to the fungus Aspergillus (rather than being caused by the fungus itself). In such cases, a peanut butter-like fungal growth occurs in the sinus cavities that may cause nasal passage obstruction and the erosion of the bones.

Fungal infections can be very serious, and both chronic and acute fungal sinusitis require immediate treatment. Fungal ball is not invasive and is nearly always treatable.

Fungal infections should be suspected in people with sinusitis who also have diabetes, leukemia, AIDS, or other conditions that impair the immune system. Fungal infections can also occur in patients with healthy immune systems but they are far less common.

Risk Factors

Sinusitis is one of the most common diseases in the United States. According to the National Institute of Allergies and Infectious Diseases (NIAID), it affects an estimate 37 million Americans each year. However, a 2004 report in the Archives of Otolaryngology - Head and Neck Surgery suggests that sinusitis may not be as common as previously reported. The researchers found that accounts that rely solely on patient self-reporting may be exaggerated.

Everyone gets viral colds and flu, and most people develop symptoms in the upper respiratory tract (air passages in the head and neck) at some point. Over 85% of people with colds have inflamed sinuses. These inflammations are typically brief and mild, however, and only between 0.5 - 10% of people with colds develop true sinusitis. (One study suggested that nose blowing during a cold may transmit bacteria back into the sinuses and increase the risk for sinusitis.) Studies suggest that the following population groups have higher risks for sinusitis:

Young children and the elderly are at higher risk for more serious upper respiratory tract infections and for complications from them.
Women appear to be at higher risk than men.
People living in the Midwest and South have a higher incidence of sinusitis than those in the Northeast and West.
People in higher income and educational groups appear to have a greater risk than those in lower groups.
Caucasian and African Americans have a higher rate than Hispanic Americans.

Before the immune system matures, all infants are susceptible to respiratory infections, with a possible frequency of one cold every 1 - 2 months. Young children are prone to colds and may have 8 - 12 bouts every year. Smaller nasal and sinus passages also make children more vulnerable to upper respiratory tract infections than older children and adults. Ear infections such as otitis media are also associated with sinusitis. Nevertheless, true sinusitis is very rare in children under 9 years of age. Some experts believe it is greatly overdiagnosed in this population.

The elderly are at specific risk for sinusitis. Their nasal passages tend to dry out with age. In addition, the cartilage supporting the nasal passages weakens causing airflow changes. They also have diminished cough and gag reflexes and faltering immune systems and are at greater risk for serious respiratory infections than are young and middle-aged adults.

People with asthma, allergies or both are at higher risk for non-infectious inflammation in the sinuses. The risk for sinusitis is higher in patients with severe asthma. People with a combination of polyps in the nose, asthma, and sensitivity to aspirin (called Samter's or ASA triad) are specifically at very high risk for chronic or recurrent acute sinusitis.

Hospitalized patients are at higher risk for sinusitis, particularly those with:

Head injuries
Conditions requiring insertion of tubes through the nose
Antibiotics or steroids treatment
Breathing aided by mechanical ventilators. (Such patients may have a significantly higher risk for maxillary sinusitis. In fact, treating sinusitis in such patients may significantly reduce the risk for ventilator-associated pneumonia.)

A number of medical conditions put people at risk for chronic sinusitis. They include:

Diabetes
Gastroesophageal reflux disease
Nasal polyps or septal deviation
AIDS and other disorders of the immune system predispose the patient to sinusitis (fungal infections are especially risky)
Pregnancy -- may cause temporary congestion and symptoms of sinusitis
Hypothyroidism -- causes congestion that clears up when the condition is treated
Cystic fibrosis -- a genetic disorder in which the mucus is very thick and builds up
Kartagener's syndrome
Wegener's granulomatosis -- a serious but very rare illness that causes long-term swelling and tumor-like masses in air passages

Dental Problems. Anaerobic bacteria are associated with infections from dental problems or procedures, which precipitate about 10% of cases of sinusitis.

Changes in Atmospheric Pressure. People who experience changes in atmospheric pressure, such as while flying, climbing to high altitudes, or swimming, risk sinus blockage and therefore an increased chance of developing sinusitis. (Swimming increases the risk for sinusitis for other reasons, as well.)

Cigarette Smoke and Other Air Pollutants. Air pollution from industrial chemicals, cigarette smoke, or other pollutants can damage the cilia responsible for moving mucus through the sinuses. Whether air pollution is an important cause of sinusitis and, if so, which pollutants are critical factors is still not clear. Cigarette smoke, for example, poses a small but increased risk for sinusitis in adults. Second-hand smoke does not appear to have any significant effect on adult sinuses, although it does seem to pose a risk for sinusitis in children.

Symptoms

Symptoms Indicating a Bacterial Infection. Sinus symptoms are very common during a cold or the flu, but in most of these cases they are due to the effects of the infecting virus and resolve when the infection does. It is important to differentiate between inflamed sinuses associated with cold or flu virus and sinusitis caused by bacteria. With true acute bacterial sinusitis, the signs and symptoms typically have the following course:

Nasal congestion and discharge comes first and is typically thick with pus that is yellowish to yellow-green.
Pain in the teeth is increased by bending over. Symptoms may vary, however, depending on the sinuses involved.
Symptoms continue for 10 days or more after the start of a cold or flu.
They worsen after 5 - 7 days, or they return after initial improvement in a cold (called double sickening).

Other symptoms of acute sinusitis that usually occur in adults include:

Severe headache and pain or pressure in specific areas in the face -- eyes may be red, bulging or painful eyes if the sinus infection occurs around the eyes; in some cases, patients may also have double vision and even temporary vision loss.
A persistent cough (particularly during the day)
Fever
Fatigue (from lack of good rest)
Lack of response to decongestants or antihistamines

Sneezing, sore throat, and muscle aches may be present, but they are rarely caused by sinusitis itself. Muscle aches may be caused by fever, sore throat by post-nasal drip, and sneezing from cold or allergies.

Rare complications of sinusitis can produce additional symptoms, which may be severe or even life threatening.

Symptoms in Children. Children are most likely to develop infection in the ethmoid sinuses, located between the eyes. Children with sinusitis are also less likely to experience facial pain over the affected sinus and headache, which are the primary signs in adults. Symptoms of bacterial sinusitis may be less specific than in adults and include:

Persistent nasal discharge (of any type) and day time cough for more than 10 days, or
Severe symptoms last for at least 3 - 4 days in a row and include thick, greenish nasal discharge plus a fever of at least 102° F.

Other symptoms in children may include:

Irritability
Vomiting
Gagging on mucus
Cough

Recurrent acute and chronic sinusitis tend to take the following course:

Symptoms are more vague and generalized than acute sinusitis.
They last longer than 4 weeks. (Subacute sinusitis lasts longer than 4 weeks but less than 8 weeks. Chronic sinusitis lasts 8 weeks or longer.)
They occur throughout the year, even during nonallergy seasons.

Specifically symptoms may include:

Nasal congestion and obstruction
Chronic cough (day and night) -- research suggests that sinusitis is one of the main causes of chronic cough
Bad breath
Postnasal drip (which can cause repeated throat clearing)
Facial tenderness or pressure --patients do not usually experience facial pain unless the infection is in the frontal sinuses

Specific symptoms depend on the location of the infection:

Frontal sinusitis causes pain across the lower forehead.
The pain in maxillary sinusitis occurs over the cheeks and may travel to the teeth, and the hard palate in the mouth sometimes becomes swollen.
Ethmoid sinusitis causes pain behind the eyes and sometimes redness and tenderness in the area across the top of the nose.
Sphenoid sinusitis rarely occurs by itself; when it does, the pain may be experienced behind the eyes, across the forehead, or in the face.



ETHMOID SINUSITIS
Ethmoid sinuses are located between the eyes. They resemble a honeycomb and are vulnerable to obstruction. This is a common location for sinusitis in children.	Nasal congestion. Nasal discharge or postnasal drip. Pain or pressure around the inner corner of the eye or down one side of the nose. Headache in the temple or surrounding the eye. Symptoms worse when coughing, straining, or lying on the back and better when the head is upright. Fever. Symptoms of maxillary sinusitis often occur. Symptoms indicating medical emergency: Increasing severity of symptoms. Fever, swelling and drooping eyelid, loss of eye movement (possible orbital infection, which is in the eye socket). Fever, vision changes, pupil fixed or dilated. Symptoms spreading to both sides of face (may indicate blood clot).	Chronic nasal discharge, obstruction, and low-grade discomfort usually across the bridge of the nose. Symptoms worse in the late morning or when wearing glasses. Chronic sore throat and bad breath. Sinusitis also can recur in other sites.
ACUTE MAXILLARY SINUSITIS
Maxillary sinuses are located behind the cheek bones. They are present at birth and continue to develop as long as teeth erupt. Tooth roots, in some cases, can penetrate the floor of these sinuses.	Pain across the cheekbone, under or around the eye, or around the upper teeth; may occur on one or both sides of the face. Area over the cheekbone is tender and may be red or swollen. Possibly tooth pain. Symptoms are worse when the head is upright and improve when patient reclines. Nasal discharge or postnasal drip. Fever.	Discomfort or pressure below the eye. Chronic toothache. Symptoms become worse with colds, flu, or allergies. Discomfort increases during the day. Coughing increases at night.
FRONTAL SINUSITIS
Frontal sinuses are located on both sides of the forehead. These sinuses are late in developing, so infection here is uncommon in children.	Severe headache in the forehead. Fever (common but not always present). Symptoms are worse when lying on the back and when pressing against the area over the eye on the side closest to the nose. Symptoms are better when the head is upright. Nasal discharge or postnasal drip. Symptoms indicating medical emergency: Increasing severity of symptoms, particularly severe headache, altered vision, mild personality or mental changes (may indicate spread of infection to brain). Fever, vision changes, fixed or dilated pupil. Symptoms spreading to both sides of face (may indicate blood clot). Headache, fever, along with a soft swelling over the bone (may indicate bone infection).	Persistent, low-grade headache in the forehead. History of physical injury or other damage to the sinus area.
SPHENOID SINUSITIS
Sphenoid sinuses are located behind the eyes. They usually are present by age 3 and are fully developed by age 12.	Deep headache with pain in many places, including the back and top of the head, across the forehead, and behind the eye. Fever. Symptoms are worse when lying on the back or bending forward. Nasal discharge or postnasal drip. Symptoms indicating medical emergency: Increasing severity of symptoms, particularly severe headache, altered vision, mild personality or mental changes (may indicate spread of infection to brain).	Low grade, general headache (although not always present).

Complications

Bacterial sinusitis is nearly always harmless (although uncomfortable and sometimes even very painful). If an episode becomes severe, antibiotics generally eliminate further problems. In rare cases, however, sinusitis can be very serious.

Osteomyelitis. Adolescent males with acute frontal sinusitis are at particular risk for severe problems. One important complication is infection of the bones (osteomyelitis) of the forehead. In such cases, the patient usually experiences headache, fever, and a soft swelling over the bone known as Pott's puffy tumor.

Infection of the Eye Socket. Infection of the eye socket, or orbital infection, which causes swelling and subsequent drooping of the eyelid, is a rare but serious complication of ethmoid sinusitis. In these cases, the patient loses movement in the eye, and pressure on the optic nerve can lead to vision loss, which is sometimes permanent. Fever and severe illness are usually present.

Blood Clot. Another danger, although rare, from ethmoid or frontal sinusitis are blood clots. If a blood clot forms in the sinus area around the front and top of the face, symptoms are similar to orbital infection. In addition, the pupil may be fixed and dilated. Although symptoms usually begin on one side of the head, the process usually spreads to both sides.

Widespread Infection. The most dangerous complication of sinusitis, particularly frontal and sphenoid sinusitis, is the spread of infection by anaerobic bacteria to the brain, either through the bones or blood vessels. Abscesses, meningitis, and other life-threatening conditions may result. In such cases, the patient may experience mild personality changes, headache, altered consciousness, visual problems, and, finally, seizures, coma, and death.

Chronic and acute fungal sinusitis caused by the fungi Aspergillus and mucormycosis is difficult to treat and potentially lethal, particularly in people with diabetes and compromised immune systems. Mucormycosis is particularly dangerous if it is not treated quickly. Fungal ball (mycetoma) is not invasive and is nearly always treatable with surgery. Recurrence is rare.

The relationship between sinusitis and asthma is unclear. A number of theories have been proposed for a causal or shared association between sinusitis and asthma. Some include the following:

Stimulation of nerve pathways, inflammation, and overproduction of mucus in the nasal passages and sinus cavities may eventually affect the airways in the lung, causing them to hyperreact.
Breathing through the mouth when the sinuses are blocked allows in large particles that would other wise be filtered by the nasal defense system. Such particles could trigger allergic responses in the lungs that can trigger asthma in susceptible people.
Air breathed through the mouth is colder than air warmed in the nasal passages. Cold air is a known trigger of asthma.
Both may share similar immune abnormalities that cause inflammation in the airways in the lungs and sinuses.

Successful treatment of both allergic rhinitis and chronic sinusitis in children who also have asthma may reduce symptoms of asthma. It is particularly important to treat any coexisting bacterial sinusitis in people with asthma. They might not respond to asthma treatments unless the infection is cleared up first.

Pain and other symptoms of chronic sinusitis can have significant effects on the quality of life. This condition can cause emotional distress, impair normal activity, and reduce attendance at work or school. According to the American Academy of Allergy, Asthma, and Immunology, the average sinusitis patient misses about 4 work days a year. In fact, a 2003 study placed sinusitis in the top 10 medical conditions that most adversely affect American employers. In addition, some people may lose their sense of smell. Surgery or medical treatments can help restore this sense.

Diagnosis

Patients who have sinusitis symptoms that do not clear up within a few days, are severe, or are accompanied by high fever or acute illness should see a doctor. However, that only one-half to two-thirds of patients with such symptoms actually have sinusitis. Some experts complain that too many patients are diagnosed with true sinusitis and given unnecessary antibiotics when their symptoms would actually resolve easily in days with over-the-counter medications or no drugs at all. Others believe that true sinusitis is often mistakenly diagnosed as an allergy and not treated, which could lead to serious illness.

The first goal in diagnosing sinusitis is to rule out other possible causes of symptoms, and then determine:

The site where the infection has occurred
Whether the condition is acute or chronic
The organism causing the infection (if possible)

Ruling Out Sinus Symptoms Due to Cold or Flu Viruses. It is often difficult to tell when a viral infection converts to a bacterial infection. Studies have found that between 40 - 85% of patients with the common cold show signs of inflamed sinuses on x-rays or CT scans. A cold, however, unlike sinusitis, typically clears up without treatment within a week. (Only about 0.5 - 2% of adults with viral colds or flus actually develop bacterial infections.) In general, the doctor should suspect a bacterial infection under the following circumstances:

If sinus symptoms persist for 10 days or longer after a cold or flu, or
If symptoms become worse after 5 - 7 days

Ruling Out Allergies. Symptoms of both sinusitis and allergic rhinitis include nasal obstruction and congestion. The conditions often occur together. People with allergies and no sinus infection may have:

Thin, clear, and runny nasal discharge
Itchy nose, eyes, or throat (do not occur with bacterial sinusitis)
Recurrent sneezing
Symptoms of allergies appear only during exposure to allergens

Ruling Out Migraine and Other Headaches. Many primary headaches, particularly migraine or cluster, may closely resemble sinus headache. In fact, results presented at a 2004 meeting of the American Headache Society suggest that 90% of people who thought they had a sinus headache actually had migraines. Migraine and sinus headaches may even coexist in many cases. Sinus headaches are usually more generalized than migraines, but it is often difficult to tell them apart, particularly if headache is the only symptom of sinusitis. The following symptoms suggest a migraine rather than a sinus headache:

The headache is recurrent
It has a significant impact on daily activities
The headache does not get worse over time

Ruling Out Neuralgia. In some cases, headache that persists after successful treatment of chronic sinusitis may be due to neuralgia (nerve-related pain) in the face. This condition requires specific drugs, such as tricyclic antidepressants or carbamazepine. Trials using such drugs may identify patients with neuralgia and help avoid unnecessary invasive treatments for chronic sinusitis.

Ruling Out Other Conditions. A number of other conditions can mimic sinusitis. They include:

Dental problems
A foreign object in the nasal passage
Temporal arteritis (headache caused by inflamed arteries in the head and neck)
Persistent upper respiratory tract infections
Chronic fatigue syndrome (CFS) or fibromyalgia. However, researchers reported in the Archives of Internal Medicine that there may be a link between CFS and sinusitis. In the study, patients with unexplained chronic fatigue were nine times more likely to suffer sinus problems than those without fatigue.
Temporomandibular disorders (problems in the joints and muscles of the jaw hinges)
Vasomotor rhinitis, a condition in which the nasal passages become congested in response to irritants or stress. It often occurs in pregnant women.

Medical History. The patient should describe all symptoms such as nasal discharge and specific pain in the face and head, including eye and tooth pain.

After assessing symptoms, the doctor should take a thorough medical history of the patient:

Any history of allergies or headaches
Recent upper respiratory infection (colds, flus, infection)
History of sinusitis episodes that is unresponsive to antibiotic treatment. (In such cases, the doctor will usually diagnose chronic or recurrent acute sinusitis and refer the patient to a specialist for more advanced testing.)
Exposure to cigarette smoke or other environmental pollutants
Recent travel
Recent dental procedures, particularly if there is pain toward the back of the mouth
Medications being taken (particularly decongestants)
Any known structural abnormalities in the nose and face
Injury to the head or face
History of medical conditions, such as chronic fatigue syndrome or fibromyalgia, which can produce tender areas in the face or sinus regions and nonspecific symptoms of ill health
Any family history of allergies, immune disorders, cystic fibrosis, or immotile cilia syndrome
In small children with sinusitis, whether they attend a day care center or nursery school

The doctor will press the forehead and cheekbones to check for tenderness and check for other signs of sinusitis, including yellow to yellow-green nasal discharge. The doctor will also check the inside of the nasal passages using a device with a bright light to check the mucus and look for any structural abnormalities.

In some cases, tests may be used to detect that presence of immune factors in sinus tissues that would suggest persistent inflammation. Such findings would strongly suggest a chronic or allergic condition. In 2005, a new laboratory test became available for diagnosing chronic sinusitis. The CRS Fungal Profile tests mucus samples for eosinophil major basic protein (a protein involved in allergic and inflammatory reactions) and a type of fungi.

Nasal endoscopy, or rhinoscopy, is now used for diagnosing chronic and recurrent acute sinusitis and for differentiating between allergies and true acute sinusitis. It involves the insertion of a flexible tube into the nasal passage and the use of a fiberoptic light that enables the doctor to see inside the sinuses. Endoscopy allows detection of even very small abnormalities in the sinuses. It can determine whether surgery is necessary and if medications are having any effect. Bacterial cultures can also be taken from samples removed using endoscopy. (Endoscopy is also used for treating sinusitis.)

Computer Tomography. Computed tomography (CT) scanning is the best method for viewing the paranasal sinuses. There is little relationship, however, between symptoms in most patients and findings of abnormalities on a CT scan. CT scans are recommended for acute sinusitis only if there is a severe infection, complications, or a high risk for complications. CT scans are useful for diagnosing chronic or recurrent acute sinusitis and for surgeons as a guide during surgery. They show inflammation and swelling and the extent of the infection, including that in deep hidden air chambers missed by x-rays and nasal endoscopy. Often, they can detect the presence of fungal infections.

X-Rays. Until the availability of endoscopy and CT scans, x-rays were commonly used. They are not as accurate, however as these procedure in identifying abnormalities in the sinuses. For example, more than one x-ray is needed for diagnosing frontal and sphenoid sinusitis. X-rays do not detect ethmoid sinusitis at all, which can be the primary site of an infection that has spread to the maxillary or frontal sinuses.

Magnetic Resonance Imaging. MRI is not as effective as CT in defining the paranasal anatomy and therefore is not typically used to image the sinuses for suspected sinusitis. MRI is also more expensive than CT. However, it can help rule out fungal sinusitis and may help differentiate between inflammatory disease, malignant tumors, and complications within the skull. It may also be useful for showing soft tissue involvement.

Transillumination is a procedure aimed at visualizing maxillary and frontal sinuses. First the doctor shines a bright light against the patient's cheek or forehead in a completely darkened room. If the sinuses are clear, the doctor will observe a glow on the hard palate of the open mouth or in the areas of the cheek where the sinus passages are located. It is fast, safe, and inexpensive, but it is useful only in adults and only to rule out any problems. It has largely been supplanted by more accurate diagnostic techniques.

Sinus puncture with bacterial culture is the gold standard for diagnosing a bacterial sinus infection. It is invasive, however, and is performed only when antibiotics have not worked. Sinus puncture involves using a needle to withdraw a small amount of fluid from the sinuses. It requires a local anesthetic and is performed by a specialist. The fluid is then cultured to determine what type of bacteria is causing sinusitis.

Prevention

The best way to prevent sinusitis is to avoid colds and influenza. If you are unable to avoid them, the next best way to prevent sinusitis is to effectively treat colds and influenza.

Colds and flu are spread primarily when an infected person coughs or sneezes near someone else. A very common method for transmitting a cold is by shaking hands. 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. A 2002 study reported, however, that in older adults cold temperatures can thicken the blood and may increase the risk for respiratory infections and even circulatory and heart problems.

Foods Containing Lactobacilli (Good Bacteria). Researchers are 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 study, milk containing the strain lactobacilli GG helped reduce respiratory infections in children attending day care by 10 - 20%.

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 in 2002 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.

Studies on vitamin E specifically have been largely negative. A 2002 study, in fact, reported a higher incidence and greater severity of respiratory infections in older adults who took 200 mg of vitamin E daily.

Breastfeeding. Evidence suggests that women who breastfeed reduce the risk of respiratory infections in their children. The American Academy of Pediatrics recommends that babies be fed exclusively breastmilk for their first 6 months.

Low Stress and Active Social Life. More than one study has reported that people with low stress who also have an active social life have fewer colds than people who have high stress levels or those who have low stress and few social connections.

A nasal gel (Zicam), which contains zinc gluconate, has shown some success, possibly because the gel sticks to the nasal passages long enough for the zinc to interact with the virus. In a 2003 study, for example, the nasal gel shortened the duration and severity of the cold compared to placebo when it was started within 14 - 48 hours of the onset of symptoms. The supports earlier studies reporting that it shortened the duration of a cold by about 2 days.
Zinc lozenges are showing mixed results. One 2000 study suggested that the use of zinc acetate lozenges may be more effective and have a better taste than other formulations, such as zinc gluconate. On the other hand, a 2002 study reported that zinc gluconate reduced cold duration significantly. To further confuse matters, the two zinc lozenge preparations were directly compared in a 2000 study, and neither was effective.

In any case, no one with an adequate diet and a healthy immune system should take zinc for prolonged periods for preventing colds. Long-term use of zinc (100 mg or higher daily) has been associated with heart problems, anemia, and other conditions.

Side Effects. Side effects of zinc include:

Dry mouth
Constipation
Nausea
Bad taste (possibly only with zinc gluconate lozenges)
Overdose may cause severe vomiting, dehydration, and restlessness. Call a doctor if any of these symptoms occur.
In rare cases, an allergic response may occur.

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

Zinc 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.

The following are special concerns for people taking natural remedies for sinusitis:

Echinacea is commonly taken to prevent onset and ease symptoms of cold or flu. However, a rigorous study published in 2005 in the New England Journal of Medicine determined that echinacea does not help to prevent or treat colds. In addition, allergic reactions have been reported. People with autoimmune diseases or plant allergies should particularly avoid this herbal remedy. Echinacea has also been associated with a reaction called erythema nodosum. This involves a rash, sometimes accompanied by fever, headache, muscle and joint aches, and sore throat.
Grapeseed extract is sometimes touted as a natural antihistamine. A 2002 study, however, reported no benefits from it.
Chinese herbal products containing aristolochic acid have been associated with several reports of kidney failure in Europe. Some studies suggest that up to 30% of herbal patent remedies imported from China are laced with potent pharmaceuticals such as phenacetin and steroids. Chinese herbal remedies can also contain toxic metals such as lead.

Vaccines against influenza use inactivated (not live) viruses. Because influenza viruses change from year to year, influenza vaccines are redesigned annually to match the anticipated viral strains. Experts recommend that people receive annual influenza vaccinations in October or November. People who should definitely be vaccinated include: all adults 65 years or older; children age 6 months - 5 years; other adults or children who are at high risk for developing serious medical complications from influenza; health care workers and others who care for individuals who are at high risk for influenza complications. [See In-Depth Report #94: Colds and influenza.]

The pneumococcal vaccine protects against S. pneumoniae (also called pneumococcal) bacteria, the most common cause of respiratory infections. There are two effective vaccines available, one called a 23-valent polysaccharide vaccine (Pneumovax, Pnu-Immune) for adults and a 7-valent conjugate vaccine (Prevnar or PCV7) for infants and young children. Experts are now recommending that more people, including healthy elderly people, be given the pneumococcal vaccine, particularly in light of the increase in antibiotic-resistant bacteria. [See In-Depth Report #64: Pneumonia.]

Treatment for Acute Sinusitis

The primary objectives for treatment of sinusitis are reduction of swelling, eradication of infection, draining of the sinuses, and ensuring that the sinuses remain open. Less than half of patients reporting symptoms of sinusitis need aggressive treatment. Home remedies can be very useful.

Home remedies that open and hydrate sinuses may, indeed, be the only treatment necessary for mild sinusitis that is not accompanied by signs of acute infection.

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 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.
Inhaling steam 2 - 4 times a day is extremely helpful, costs nothing, and requires no expensive equipment. The patient should sit comfortably and lean over a bowl of boiling hot water (no one should ever inhale steam from water as it boils) while covering the head and the bowl with a towel so the steam remains under the cloth. The steam should be inhaled continuously for 10 minutes. A mentholated or other aromatic preparation may be added to the water. Long, steamy showers, vaporizers, and facial saunas are alternatives.

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) is the pain-reliever of choice in children. Most pediatricians advise such medications for children who run fevers over 101°F.
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.

Some studies suggest that these anti-fever drugs may actually reduce the body's immune response against cold and flu viruses and prolong symptoms. A 2000 study, for example, reported a longer flu duration in people who took aspirin or acetaminophen (although people still felt better). Nevertheless, most doctors strongly recommend lowering fevers in children, since high fevers can sometimes cause seizures.

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. (Mix 1 teaspoon of table salt with a pinch of baking soda in 2 cups of warm water.) The nasal wash should be performed several times a day. Researchers have reported that daily irrigation of the nasal passages with a hypertonic saline solution relieves sinusitis symptoms and also reduces antibiotic use and the occurrence of acute exacerbations. Patients in the study had 72% fewer sinus infections, a 69% improvement in breathing, and they reduced medication usage by more than half.

A simple method for administering a nasal wash is:

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:

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.

Decongestants are drugs that help reduce nasal congestion. They are available in a pill or nasal form. However, decongestants will not cure sinusitis. Nasal decongestants can actually worsen sinusitis by increasing sinus inflammation. Due to the lack of evidence for nasal decongestants’ benefits for sinusitis, the FDA has ruled that manufacturers of over-the-counter (OTC) nasal decongestant products remove from their labeling all references to sinusitis.

Your doctor may still recommend that you take either an OTC or prescription nasal decongestant to help relieve blockage symptoms associated with sinusitis. If you think you have sinusitis, it is important that you check with your doctor before taking a decongestant. Do not try to treat sinusitis by yourself.

Nasal Decongestants. Nasal decongestants come in long-acting or short-acting forms. The effects of short-acting decongestants last about 4 hours; long-acting decongestants last 6 - 12 hours. The active ingredients in nasal decongestants include oxymetazoline, xylometazoline, and phenylephrine.

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.
Do not share droppers and inhalators with other people.
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.

Decongestants Taken by Mouth. Pseudoephedrine is the only decongestant taken by mouth that is currently available over-the-counter (OTC) in the United States. It decreases the volume of mucous in the nose, as well as within the Eustachian tubes. Many brands of OTC oral decongestants are available. A common brand is Sudafed. Oral decongestants such as Sudafed can also be helpful for relieving cough associated with postnasal drip.

Warning: Anyone with old forms of any decongestant should check the labels and discard them if they contain phenylpropanolamine. In November 2000, the FDA banned products, including decongestants, which contained phenylpropanolamine (PPA). This action was in response to a few reports of an increased risk of stroke. (Stroke tended to occur in people who took diet suppressants containing PPA rather than decongestants. In any case, serious events were still very rare.) All major brands that previously contained PPA have now substituted other active ingredients (usually pseudoephedrine) and are safe to use.

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

Agitation and nervousness
Drowsiness (particularly with decongestants taken by mouth 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

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. (Such individuals should particularly avoid high-potency short-acting nasal decongestant.)
People taking medications that increase serotonin levels, such as certain antidepressants, anti-migraine drugs, diet pills, St. John's wort, and methamphetamine. The combinations can cause blood vessels in the brain to narrow suddenly, causing severe headaches and even stroke.

Anyone with these conditions should not use either oral or nasal decongestants without a doctor's guidance. Other groups who should not use these drugs without first consulting a doctor include:

Pregnant women
Children. The American College of Chest Physicians advises against the use of over-the-counter decongestants and other cold medications in children ages 14 years or younger. 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. In 2007, the FDA began reviewing the safety and effectiveness of cough and cold remedies for children.

Older antihistamines such as diphenhydramine (Benadryl) are helpful in relieving cough when used alone or in combination with a decongestant.

Expectorants are drugs that cause mucus to be coughed up from the lungs. The most common type used is guaifenesin, which is found in many over-the-counter (OTC) cough syrups as well as prescription products. Expectorants used to be recommended for treatment of sinusitis-associated cough, but some recent guidelines advise against their use. According to the American College of Chest Physicians (ACCP), expectorants and cough suppressants do not help treat cough. The ACCP recommends that adults instead take a decongestant or antihistamine to relieve cough. The ACCP also recommends against OTC cold and cough medicine for children ages 14 years and younger. Parents should talk with their child’s pediatrician for advice on treating cough.

Overview on Antibiotics and Their Overuse. Sinusitis is the fifth most common diagnosis for antibiotic prescriptions. And, there is much evidence that antibiotics are inappropriately prescribed for many patients:

According to a 2007 study of recent treatment patterns for acute and chronic sinusitis, antibiotics are widely overused. The researchers noted that viruses (not bacteria) account for a large percentage of acute sinusitis cases and that most acute sinusitis cases clear up on their own. The study also indicated that inhaled corticosteroids are frequently prescribed for acute sinusitis despite a lack of evidence for their benefit.
A major analysis reported that antibiotics helped only 1 child in 8 who had persistent nasal discharge for at least 20 days. Even when antibiotics were helpful, benefits were modest in reducing duration of the infection. This study supports other research that has found no significant benefit from antibiotics for most children. In a 2001 study, for example, 87% of children improved regardless of their treatment.

The intense and widespread use of antibiotics -- not only for sinusitis but also for other upper respiratory tract infections -- is leading to a serious global problem, which is bacterial resistance to common antibiotics. For example, according to reports in 2002 and 2001, in Canada 15% of S. pneumoniae strains are resistant to penicillin; in the U.S. 30 - 40% are resistant; in Hong Kong 70 - 80% of strains no longer respond to penicillin. Furthermore, in the U.S. about 23% of S. pneumoniae are currently resistant to at least three antibiotics. High rates of resistance strains are even being observed in infants. In general, regions with the highest rate of resistance are those in which antibiotics are the most heavily prescribed. Encouraging studies are now reporting that inappropriate antibiotic prescriptions are on the decline.

When to Use Antibiotics. Because the majority of sinusitis cases resolve on their own, doctors generally wait 10 - 14 days before prescribing antibiotics. However, antibiotics may be prescribed sooner if severe symptoms develop. These symptoms include:

Fever
Facial pain or tenderness
Swelling around the eyes

Antibiotic Regimens

The standard first-line antibiotic treatment for acute bacterial sinusitis is a 10 - 14 day course of amoxicillin. Trimethoprim-sulfamethoxazole is an alternative choice.
If no change occurs within 3 - 5 days, the doctor may prescribe a different type of antibiotic such as amoxicillin-clavulanate, cephalosporin, or a macrolide.
If the patient does not respond after 21 - 28 days, broad-spectrum antibiotics such as amoxicillin-clavulanate, cefuroxime, or cefpodoxime may be used. Other choices include clarithromycin or azithromycin (macrolides) or levofloxacin (a fluoroquinolone).

Side Effects of Antibiotics. Most antibiotics have the following side effects (although specific antibiotics may have other side effects or fewer of the standard ones):

The most common side effect for nearly all antibiotics is gastrointestinal distress.
Antibiotics double the risk for vaginal infections in women. Taking supplements of acidophilus or eating yogurt with active cultures may help restore healthy bacteria that offset the risk for such infections.
Allergic reactions can also occur with all antibiotics but are most common with medications derived from penicillin or sulfa. These reactions can range from mild skin rashes to rare but severe, even life-threatening anaphylactic shock.
Certain drugs, including some over-the-counter medications, interact with antibiotics; patients should inform the doctor of all medications they are taking and of any drug allergies.

Beta-Lactams

The beta-lactam antibiotics share common chemical features and include penicillins and cephalosporins. Their primary action is to interfere with bacterial cell walls.

Penicillins. Amoxicillin (Amoxil, Polymox, Trimox, Wymox, or any generic formulation) has been the most widely prescribed antibiotic for acute sinusitis. This penicillin is both inexpensive and at one time was highly effective against the S. pneumoniae bacteria. Unfortunately, bacterial resistance to amoxicillin has increased significantly, both among S. pneumoniae and H. influenzae, and penicillin is no longer as reliable as it once was.

Amoxicillin-clavulanate (Augmentin) is a type of penicillin that works against a wide spectrum of bacteria. An extended release form has been approved for treating adults with sinusitis infections that have become resistant to penicillin.

Many people have a history of an allergic reaction to penicillin, but some evidence is suggesting that the allergy may not recur in a significant number of adults. Skin tests are available that could determine if some people previously allergic could use these important antibiotics.

Cephalosporins. These drugs are also effective against S. pneumoniae. They are often classed by generation:

First generation includes cephalexin (Keflex), cefadroxil (Duricef, Ultracef), and cephradine (Velosef).
Second generation include cefaclor (Ceclor), cefuroxime (Ceftin), cefprozil (Cefzil), and loracarbef (Lorabid).
Third generation include cefpodoxime (Vantin), cefdinir (Omnicef) cefditoren (Sprectracef), cefixime (Suprax), and ceftibuten (Cedex). Ceftriaxone (Rocephin) is an injected cephalosporin. These are effective against a wide range of bacteria.

The later-generation antibiotics cefpodoxime, cefdinir, and cefuroxime are good choices for penicillin-allergic patients with mild-to-moderate sinusitis who have been treated in the previous 4 - 6 weeks. Penems, a type of beta-lactam antibiotic, are also being investigated for sinusitis treatment.

Macrolides and Azalides

Macrolides are a class of antibiotics that are divided into different sub-groups. Azalides are one of those sub-groups. This type of antibiotic is often used to treat mild-to-moderate bacterial sinusitis in patients who are allergic to penicillin. Some of the most common macrolids/azalides are azithromycin (Zithromax), clarithromycin (Biaxin), and roxithromycin (Rulid). An extended-release form of azithromycin (Zmax) was approved in 2005 as a single dose treatment for mild-to-moderate acute bacterial sinusitis. These antibiotics are also effective against many strains of S. pneumoniae and M. catarrhalis, but macrolide-resistance rates doubled between 1995 - 1999 as the number of children treated with the antibiotics increased. Erythromycin is not effective against H. influenzae.

Macrolides have anti-inflammatory actions, which may have benefits for some patients with chronic sinusitis. Investigators are studying long-term low-dose macrolide treatments, which are not intended to eliminate bacteria, but to reduce inflammation. Studies suggest that this approach may be effective without increasing the risk for bacterial resistance.

Trimethoprim-Sulfamethoxazole

Trimethoprim-sulfamethoxazole (Bactrim, Cotrim, Septra) is another first-line antibiotic for sinusitis. It is less expensive than amoxicillin and particularly useful for patients with mild sinusitis who are allergic to penicillin. It is no longer effective, however against certain streptococcal strains. It should not be used in patients whose infections occurred after dental work or in patients allergic to sulfa drugs. Allergic reactions can be very serious.

Fluoroquinolones (Quinolones)

Fluoroquinolones (also simply called quinolones) interfere with the bacteria's genetic material so they cannot reproduce.

Newer generation fluoroquinolones, which include levofloxacin (Levaquin), sparfloxacin (Zagam), gatifloxacin (Tequin), and moxifloxacin (Avelox), are currently the most effective antibiotics against the common bacteria that cause sinusitis. They are recommended for adults with moderate sinusitis who have already been treated with antibiotics within 6 weeks or who are allergic to beta-lactam antibiotics.

Some of the newer fluoroquinolones only need to be taken once a day, which make compliance easier. Some, but not all, quinolones cause photosensitivity. S. pneumoniae strains resistant to the quinolones have been uncommon in the U.S. but their numbers are increasing. In fact, levofloxacin was the first drug approved specifically for penicillin-resistant S. pneumoniae. Unfortunately, studies are now finding resistance to this drug as well.

Lincosamide

Lincosamides prevent bacteria from reproducing. The most common lincosamide is clindamycin (Cleocin). This antibiotic is useful against many S. pneumoniae bacteria but not against H. influenzae.

Tetracyclines

Tetracyclines inhibit bacterial growth. They include doxycycline, tetracycline, and minocycline. They can be effective against S. pneumoniae and M. catarrhalis, but bacteria that are resistant to penicillin are also often resistant to doxycycline. Tetracyclines have unique side effects among antibiotics, including skin reactions to sunlight, possible burning in the throat, and tooth discoloration.

Ketolides

In February 2007, the FDA withdrew approval of telithromycin (Ketek) for treatment of acute bacterial sinusitis. The agency decided that the serious risks of telithromycin outweigh its benefits for sinusitis treatment. The decision followed several 2006 reports of patient deaths due to severe liver damage. Telithromycin is now approved only for treatment of community-acquired pneumonia (CAP).

In 2003, research suggested that delivering medications directly to the sinus passages (instead of the bloodstream, like a pill might) significantly increases the amount of time chronic sinusitis patients remain infection free. The treatment, called nebulized antibiotic therapy, requires that patients inhale antibiotics in mist form to topically treat their sinusitis. The study showed that nebulization therapy increased the infection free period for some patients by almost 300% when compared to other treatments.

Patients who show signs that infection has spread beyond the nasal sinuses into the bone, brain, or other parts of the skull require emergency care. High dose antibiotics are administered intravenously, and emergency surgery is almost always necessary in such cases.

Severe Fungal Sinusitis. Sinusitis caused by severe fungal infections is a medical emergency. Treatment is aggressive surgery, and high-dose antifungal chemotherapy with a drug such as amphotericin B can be life saving. The use of oxygen administered at high pressure (hyperbaric oxygen) is showing promise as additional therapy for potentially deadly fungal infections.

Treatment for Chronic Sinusitis

Determining and Treating any Underlying Conditions. A thorough diagnostic work-up should be performed to rule out any underlying conditions, including but not limited to allergies, asthma, any immune problems, gastroesophageal reflux disorder, and structural problems in the nasal passages. If a primary trigger for chronic sinusitis can be identified, it should be treated or controlled if possible.

Initial Treatment of Sinusitis. For treatment of chronic sinusitis itself, some doctors recommend:

A wide spectrum antibiotic (one that can eliminate a wide range of bacteria) taken for at least 30 days.
Alternatively, an antibiotic that attacks anaerobic pathogens.
A corticosteroid nasal spray -- some doctors also recommend oral corticosteroids (such as prednisone) for patients who do not respond to nasal corticosteroids or for those patients who have nasal polyps. Prednisone is also used for patients who have allergic fungal sinusitis.
Saline nasal washes.
The expectorant guaifenesin with a decongestant taken by mouth.
Antihistamines.

If the condition dramatically improves between 1 - 2 months, then the antibiotics are stopped. The patient should continue with both the steroid and saline nasal solutions. If there is no improvement after this time, the surgery may be considered. For some people with chronic sinusitis, however, the condition is not curable, and the goal of treatment is to improve the quality of life.

Chronic sinusitis is often the result of damage to the mucous membrane from a past, untreated acute sinus infection. The aerobic and anaerobic bacteria present in chronic sinusitis are often different from those that cause the acute form. The role of antibiotic treatment for chronic sinusitis is controversial. Special types of antibiotics may be used, and treatment may be needed for a longer time.

Intravenous antibiotic therapy may be required for some patients with chronic sinusitis, particularly those with underlying medical disorders that can worsen the condition. They are typically administered 2 weeks before surgery and continued for about month afterward.

Some studies have reported good results in using antibiotics that are sprayed into the nasal passages using a nebulizer. In one study, patients preferred this method to either oral or intravenous treatments.

Benefits of Corticosteroid Nasal Sprays. Nasal-spray corticosteroids, most commonly called steroids, are effective drugs for treating allergic rhinitis. They also are proving to be very important in the treatment of chronic sinusitis and are sometimes used for acute sinusitis. Some studies have reported that, when combined with antibiotics, they speed recovery and improve healing rates of sinusitis compared to antibiotics alone. Nasal spray steroids are proving to be safe and have the following benefits:

They reduce inflammation and mucus production.
They improve night sleep and daytime alertness in patients with perennial allergic rhinitis.
They appear to be beneficial in treating polyps in the nasal passages.

Nasal-Spray Brands. Corticosteroids available in nasal spray form include:

Triamcinolone (Nasacort). Approved for children over age 6.
Mometasone furoate (Nasonex). Approved for use in patients as young as age 3.
Fluticasone (Flonase, Flounce). Approved for children over age 4.
Beclomethasone (Beconase, Vancenase), flunisolide (Nasalide), and budesonide (Rhinocort). Approved for children over age 6.

Side Effects. Corticosteroids are powerful anti-inflammatory drugs. Although oral steroids can have many side effects, the nasal-spray form affects only local areas, and the risk for wide spread side effects is very low unless the drug is used excessively.

Dryness, burning, stinging in the nasal passage
Sneezing
Headaches and nosebleed (these side effects are uncommon but should be reported to your doctor immediately)

Possible Long-Term Complications. Corticosteroids suppress stress hormones, which are known to produce some serious long-term complications in people who take oral steroids. Researchers have found far fewer concerns with nasal administration or inhaled forms, but there may be certain problems.

Effect on growth. The major concern for children is whether nasal steroids, like other forms of steroids, will adversely affect growth. Studies report either only a temporary and slight (about half an inch) early effect on growth or no effect at all.
Effect on eyes. Glaucoma is a known side effect of oral steroids. Some ophthalmologists have observed higher pressure in the eye (a sign of glaucoma) in some patients taking nasal steroid sprays. Studies have found no increased risk for cataracts in young people who have taken intranasal steroids. All the conditions resolve after stopping the steroid, although periodic eye examinations are advised.
Use during pregnancy. Steroids are most likely safe during pregnancy, but pregnant women should discuss all options carefully before taking them.
Nasal passage injury. Steroid sprays may injure the nasal septum (the bony area that separates the nasal passage) if the spray is directed onto it. This complication is very rare.
Lower resistance to infection. People with any infectious disease or injury in the nose should not take these drugs until the disease or wound has been treated and cured. People should avoid steroids if they have not been vaccinated or have had chicken pox or measles.
In some cases, people become insensitive to the effects of corticosteroids and they stop working.

Leukotriene-antagonists are oral drugs that block leukotrienes, powerful immune system factors that are important in causing airway constriction and mucus production in allergy-related asthma. Leukotriene-antagonists include zafirlukast (Accolate), montelukast (Singulair), (Ziflo), and pranlukast (Ultair, Onon). They may also be useful in certain cases of chronic sinusitis, including sinusitis due to polyps, when allergies are the cause, or in some cases when the cause is unknown.

Scientists are investigating whether antifungal drugs may help treat chronic sinusitis. One such drug, Amphotericin B (SinuNase), is currently in Phase III trials for patients who have had sinus surgery but are still experiencing recurrent sinusitis. Results from previous clinical trials have been mixed.

Patients often have various combinations of allergies, sinusitis, and asthma. Treating each condition is important for improving them all. In addition to decongestants, pain relievers, and expectorants, other remedies are available for people who suffer from nonbacterial sinusitis during allergy season.

Anti-Inflammatory Drugs. Nasal spray corticosteroids (commonly called steroids) are important for reducing the inflammatory response in the nasal passages and airways. They are important in the treatment of asthma and are now considered to be the most effective measure for preventing allergy attacks. Leukotriene-antagonists are also useful for sinusitis symptoms.
Antihistamines. Antihistamine tablets relieve sneezing and itching and can prevent nasal congestion before an allergy attack. Many brands are available by prescription and over the counter.
Immunotherapy. Immunotherapy, commonly referred to as "allergy shots," may be considered for patients with severe seasonal allergies that do not respond to treatment. Immunotherapy is the only treatment that affects the cause of allergies. In one year-long study using immunotherapy, over half of young patients participating experienced improvement in overall sinusitis symptoms, and nearly all felt better in general. Immunotherapy also may prevent asthma and the development of new allergies in children. Newer immunotherapeutic approaches using specially designed antibodies and vaccines are also showing promise.
All drug treatments have side effects, some very unpleasant and, in rare cases, serious. Patients may need to try different drugs until they find one that relieves symptoms without producing excessively distressing side effects.

Surgery

Surgery is used to unblock the sinuses when drug therapy is not effective or if there are other complications, such as structural abnormalities or fungal sinusitis.

The simplest surgical approach is the insertion of a drainage tube into the sinuses followed by an infusion of sterile water to flush them out.

In the past few years there has been a major advance in the surgical treatment with a minimally invasive technique called functional endoscopic sinus surgery (FESS). The procedure allows correction of obstructions, including any polyp and ventilation and drainage to aid healing.

Candidates for the Procedure.

FESS may be a good choice for people with chronic sinusitis associated with structural abnormalities. In one study, the best results were seen in people with polyps (but not those associated with ASA triad, the combination of polyps in the nose, asthma, and sensitivity to aspirin).
Several studies are finding it to be safe and effective in children with chronic sinusitis or whose sinuses have not developed. It does not have an adverse effect on facial growth.
Surgery may help patients with HIV who have chronic or recurrent sinusitis.
It may benefit appropriate candidates who have both sinusitis and asthma. One study suggested that lung function may improve afterward in some patients.

Surgery may not be as effective for patients with the ASA triad, fungus infections, or severe chronic sinusitis, although endoscopy is proving to be beneficial even for these conditions with the use of more powerful instruments.

Procedure. The surgery generally proceeds as follows:

Adults require only a local anesthetic for the procedure, though a general anesthetic is needed for children.
Before the procedure, a computed tomography (CT) scan is taken for use by the surgeon in planning the procedure and as a guide to the sinuses during surgery. Some doctors are now using a device called a depth of field image (DOFI) video enhancement screen that displays a holographic 3-D image. It allows the surgeon an excellent view of the sinus cavities and may prove to significantly reduce complications.
A flexible tube, a miniature camera, and a fiberoptic light source are inserted through a single small opening.
Instruments are then used to remove diseased bone or tissue and clear obstructions. For instance, shavers are used to gently remove soft tissue. Bone cutters are sometimes employed to open the floor of the frontal sinus and restore drainage (called the modified Lothrop procedure). Lasers are also being investigated to remove bone, coagulate the passageways, or clear obstructions.

Complications. Serious complications of FESS are very rare, but the following have been reported in a few cases:

Cerebrospinal fluid leak is the most common major complication, but it occurs in only 0.2% of cases and is usually easily repaired during surgery.
Other very rare complications include meningitis, hemorrhage, infection, or vision loss.
Patients can develop infections afterward that are very difficult to treat. Interesting studies are reporting good to excellent results in these patients by spraying antibiotics into the nasal passages using a nebulizer.

Postsurgical Care. Postsurgical care involves the following:

The patient will experience a dull ache around the nose and sinus cavity that can be treated with pain medication.
Following surgery, the patient should flush the sinuses twice daily with a saline or alkaline solution.
Antibiotics may be prescribed for several weeks until postnasal drip has stopped, and corticosteroid sprays and antihistamines may be needed.

Success Rates. It may take several months for the mucous membranes to completely recover, but between 85 - 90% of patients experience good to excellent symptomatic relief after surgery. Children may require a second procedure 2 - 3 weeks after the first surgery to remove crusty matter.

A high-pressure water jet (HPWJ) treatment that flushes diseased mucus that remains after FESS surgery is being investigated for those whose symptoms do not clear. One 2000 study found the procedure an effective therapy that may even be safe for children.

A new type of surgical procedure threads a small balloon through the sinus passages. As the balloon is gently opened, the sinus passages expand and drainage occurs. Some experts think that this procedure is only appropriate for select patients with sinusitis disease in the maxillary (behind cheek bones), frontal (behind the sides of the forehead), and sphenoid (behind the eyes) sinus regions. It may not work for patients with disease in the ethmoid (between the eyes) sinuses, even though this a common sinusitis location.

Endoscopy is now used in most cases of chronic sinusitis, but in severe cases, invasive surgery using conventional scalpel techniques to remove infected areas may be required. This may be the case with acute ethmoid sinusitis in which pus breaks through the sinus and threatens the eye, with very severe frontal sinusitis, with invasive fungal sinusitis, or when cancer is present in the sinuses.

Resources

www.entnet.org -- American Academy of Otolaryngology - Head and Neck Surgery
www.aaaai.org --American Academy of Allergy, Asthma, and Immunology
www.acaai.org --American College of Allergy, Asthma, and Immunology
www.niaid.nih.gov -- National Institute of Allergy and Infectious Disease
www.american-rhinologic.org -- American Rhinologic Society
www.cdc.gov/nip -- National Immunization Program

References

Brown CL, Bolger WE. Safety and feasibility of balloon catheter dilation of paranasal sinus ostia: a preliminary investigation. Ann Otol Rhinol Laryngol. 2006 Apr;115(4):293-9.

Clay KD, Hanson JS, Pope SD, Rissmiller RW, Purdum PP 3rd, Banks PM. Brief communication: severe hepatotoxicity of telithromycin: three case reports and literature review. Ann Intern Med. 2006 Mar 21;144(6):415-20.

Ebbens FA, Scadding GK, Badia L, Hellings PW, Jorissen M, Mullol J, et al. Amphotericin B nasal lavages: not a solution for patients with chronic rhinosinusitis. J Allergy Clin Immunol. 2006 Nov;118(5):1149-56.

Sharp HF, Denman D, Puumala S, Leopold DA. Treatment of acute and chronic rhinosinusitis in the United States, 1999-2002. Arch Otolaryngol Head Neck Surg. 2007 March;133(3):260-265.

Weschta M, Rimek D, Formanek M, Podbielski A, Riechelmann H. Effect of nasal antifungal therapy on nasal cell activation markers in chronic rhinosinusitis. Arch Otolaryngol Head Neck Surg. 2006 Jul;132(7):743-7.

Review Date:
3/23/2007
Reviewed By:
Harvey Simon, MD, Associate Professor of Medicine, Harvard Medical School; Physician, Massachusetts General Hospital.

A.D.A.M. Copyright

adam.com

Influenza

FitSugar — Wed, 08 Oct 2008 17:35:25 -0700

Overview

Signs and Symptoms
Causes
Risk Factors
Diagnosis
Preventive Care
Treatment Approach
Other Considerations
Supporting Research

HEALTH GUIDE REFERENCE FROM A.D.A.M

Influenza, or "flu," is a caused by a virus infecting the respiratory system (nose, throat, bronchial tubes, lungs). Flu symptoms are usually more severe than those of the common cold and are more likely to affect other parts of your body. Flu also tends to come on suddenly, while colds can take a while to develop. Flu is very contagious, spreading easily from one person to the next. Most people with healthy immune systems will get over the flu in a week or two, but young children, senior adults, and people with chronic illnesses are more likely to develop complications such as pneumonia. About 36,000 people die of flu each year in the United States.

There are three types of flu viruses: A, B, and C. Type A viruses are the ones responsible for periodic pandemics (worldwide epidemics, such as the one in 1918 that killed as many as 50 million people worldwide). The avian or bird flu is a type A flu virus.

The best way to protect yourself from the flu is to get an annual vaccine (flu shot).

Signs and Symptoms

Fever that comes on suddenly (usually above 101 degrees Fahrenheit)
Chills and sweats
Headache
Muscle or body aches
Fatigue
Dry cough
Sore throat
Sneezing, runny nose, stuffy nose
Loss of appetite
Nausea, vomiting, or diarrhea, especially in children

Causes

Influenza is caused by viruses that are spread through the air by sneezes and coughs, or by touching a surface a person with the flu has touched and transmitting the virus to your mouth or nose. Some flu viruses cause a very mild illness, or none at all. Others cause serious, widespread illness.

Since there are many types of influenza virus, and because they change over time, a new flu vaccine is offered every fall. Getting vaccinated before the flu season starts reduces your chances of getting the flu, and helps you recover faster if you do get it. You should not take the vaccine if you have an allergy to eggs, because the viruses for the vaccines are grown in chick embryos. See Risk Factors for list of people who should get the vaccine every year.

Risk Factors

Infants and young children, as well as senior adults, are considered at highest risk of complications from flu. Other risks include:

Having a chronic illness, such as heart disease
Having a weakened immune system, from medications or HIV
Pregnant women
Peole who work in healthcare
People who work in childcare
Residents of nursing homes

If you are at risk for complications, you should get an annual flu shot (see Prevention).

Diagnosis

Your doctor will probably be able to diagnose flu from a physical exam and a description of your symptoms. He or she may take a chest X-ray if there is concern about complications such as pneumonia.

Preventive Care

The best way to prevent the flu is by getting a flu shot. Annual flu shots are recommended if you:

Are 50 or older
Have chronic heart, lung, or kidney disease
Live in an institution (such as a nursing home)
Have a weakened immune system
Have sickle cell anemia

You should not receive the vaccine if you are allergic to eggs.

You can also cut your risk of flu by washing your hands frequently during flu season.

Treatment Approach

Bed rest and drinking plenty of fluids are usually enough to treat flu. Mild over-the-counter pain relievers and fever reducers (such as acetaminophen or Tylenol, and ibuprofen or Advil), can help relieve fever and muscle aches.If you are at high risk for complications (see Risk Factors), then your doctor may prescribe antiviral medications (drugs that fight the virus). They must be started within two days to be effective. Certain herbs, supplements, and homeopathic remedies may help some of your symptoms.

Lifestyle

Drink lots of fluids
Rest to restore your energy and avoid complications like pneumonia.
Eat a diet rich in fresh fruits and vegetables. These foods provide lots of antioxidants (substances that may help boost your immune system), especially vitamins A and C.
Exercising regularly may cut your risk of flu and help your body respond better to a flu shot.
Minimize stress and your reaction to stress. Consider yoga, tai chi, or other forms of relaxation on an ongoing basis. Stress can put you at increased risk for viruses like influenza.

Medications

Pain and fever reducers - include ibuprofen (Advil, Motrin) and acetaminophen (Tylenol) for fever reduction and relief of minor aches and pain. Children under 18 should not take aspirin due to the risk of a rare but serious illness called Reye's syndrome.
Decongestants - help open your nasal passages so you can breathe easier. If decongestant nasal sprays or drops are used for more than three days, however, they can cause rebound congestion. Decongestants are often combined in cold and flu medicines with antihistamines, cough suppressants, and pain relievers. People with heart disease, high blood pressure, diabetes, or glaucoma should not take decongestants. Popular brands of decongestants include Sudafed, Afrin, and Neo-Synephrine.
Cough medicines - cough suppressants (for a dry cough) or expectorants (for a wet, productive cough that brings up mucous) are available over the counter and by prescription.
Antiviral medications - Several antiviral medications have been approved by the Food and Drug Administration to treat flu, although a number of flu viruses have developed resistance to some of the medications. In addition, using these medications may help contribute to other strains of flu becoming resistant. These drugs must be started within 48 hours of becoming sick to be effective. Medications include
- Oseltamivir (Tamiflu): The FDA requires Tamiflu to carry a warning that people who have the flu, especially children, may be at increased risk of confusion and injuring themselves after taking Tamiflu.
- Zanamavir (Relenza)
- Amantadine (Symmetrel): Recently, most flu viruses in the U.S. have been resistant to Symmetrel
- Rimantadine (Flumadine): Recently, most flu viruses in the U.S. have been resistant to Flumadine

Nutrition and Dietary Supplements

Because supplements may have side effects or interact with medications, they should be taken only under the supervision of a knowledgeable healthcare provider. Be sure to talk to your doctor about any supplements you are taking or considering taking.

Warm liquids - Chicken soup and warm liquids (broth, tea) can help soothe a sore throat and loosen mucus, which in turn helps ease congestion from the flu.
Probiotics (Lactobacillus) - So-called “good” bacteria or probiotics help prevent infections in the intestines, and there is preliminary evidence that they might help prevent colds, too, although they have not been studied for the flu. One study found that children in daycare centers who drank milk fortified with Lactobacillus had fewer and less severe colds. Several studies that examined probiotics combined with vitamins and minerals also found a reduction in the number of colds caught by adults, although it’s not possible to say whether the vitamins, minerals, or probiotics were most responsible for the benefit.
Zinc - Your body needs zinc for its immune system to function properly, so it has long been thought that zinc could help protect against catching a cold or flu. But the evidence has been decidedly mixed, with some studies finding a benefit from zinc lozenges but others showing no effect. Recently, a review of studies that compared zinc to placebo found that most of them had flaws that made any positive results unreliable. Only four studies were deemed reliable, and three found no benefit from zinc lozenges. The remaining positive study suggested that zinc nasal sprays might help reduce nasal stuffiness. If you do decide to try zinc lozenges for a cold, remember that getting too much zinc (more than 50 mg per day over a long period of time) can be dangerous.
Spirulina - In test tubes, spirulina seems to be able to stop some flu viruses from reproducing. It isn't known whether it will have the same effect in humans, however.

Herbs

The use of herbs is a time-honored approach to strengthening the body and treating disease. Herbs, however, can trigger side effects and can interact with other herbs, supplements, or medications. For these reasons, herbs should be taken with care, under the supervision of a healthcare practitioner. Before giving any herbs to a child to treat the flu, talk to your pediatrician.

Andrographis (Andrographic paniculata) - One study found that andrographis, an herb used in Ayurvedic medicine, combined with eleuthero or Siberian ginseng (Eleutherococcus senticosus) in a formula called Kan Jang, helped reduce symptoms and shorten the duration of the flu. More studies are needed to say for sure whether it is effective.
Echinacea (Echinacea purpurea, 300 mg three times per day) - Although evidence on whether echinacea works to prevent or treat colds and flu has gone back and forth, recent evidence is encouraging. An analysis of 14 scientific studies found that people who took echinacea reduced their risk of getting a cold by 58 percent and reduced the duration of a cold by an average of a day and a half. However, many of the studies used echinacea in combination with another herb or vitamin, so it’s impossible to say which one was responsible for the benefit. The analysis looked at colds, not flu, so the evidence may be more mixed as to whether Echinacea can help prevent flu. Echinacea should not be used by women who are pregnant or breastfeeding, or by anyone taking drugs that suppress the immune system (such as corticosteroids or methotrexate).
Garlic (Allium sativum) - Some studies suggest taking garlic may help reduce your risk of getting an upper respiratory infection, such as a cold or flu. More studies are needed to tell whether garlic has any true benefit for flu, however. Because garlic can increase the risk of bleeding, people who take anticoagulants (blood-thinners, such as aspirin or warfarin) should not take garlic. Women who are pregnant or breastfeeding should talk to their doctor before taking garlic supplements.
Elder or elderberry (Sambucus nigra) - By lessening congestion and possibly increasing perspiration, elder may help reduce the symptoms of colds and flu. One study suggested that using a standardized elderberry extract, Sambucol™, could shorten the duration of flu by about three days. Sambucol™ also contains other herbs plus vitamin C, so it isn’t known whether elder by itself would have the same effect. Pregnant and breast-feeding women should not take elder.
Eucalyptus (Eucalyptus globulus) - Eucalyptus is used in many remedies to treat cold and flu symptoms, particularly cough. It can be found in many lozenges, cough syrups, and vapor baths throughout the United States and Europe. Fresh leaves can be used in teas and gargles to soothe sore throats. Ointments containing eucalyptus leaves are also applied to the nose and chest to relieve congestion and loosen phlegm.
Goldenseal (Hydrastis canadensis) - Goldenseal is often combined with echinacea in herbal cold and flu remedies, although scientific evidence that it works is lacking. Women who are pregnant or breast-feeding should talk to their doctor before taking goldenseal.
Licorice (Glycyrrhiza glabra) - Licorice root is a traditional treatment for sore throat, although scientific evidence is lacking. Licorice interacts with a number of medications, so ask your doctor before taking it. People with high blood pressure or heart disease, women who are pregnant or breast-feeding, and those who take anticoagulants (blood thinners) should not take licorice.
Marshmallow (Althea officinalis) - Although there isn’t any scientific evidence that it works, marshmallow has been used traditionally to treat sore throat and cough.
Peppermint (Mentha x piperita) - Like eucalyptus, peppermint is widely used to treat cold and flu symptoms. Its main active agent, menthol, is a good decongestants. Menthol also thins mucus and works as an expectorant, meaning that it helps loosen and break up phlegm. It is soothing and calming for sore throats and dry coughs as well.
Slippery elm (Ulmus fulva) - Slippery elm may help ease sore a sore throat and has been used traditionally for this purpose, although scientific evidence is lacking.

Homeopathy

Although very few studies have examined the effectiveness of specific homeopathic therapies, professional homeopaths may consider the following remedies for the treatment of the flu based on their knowledge and experience. Before prescribing a remedy, homeopaths take into account a person's constitutional type. A constitutional type is defined as a person's physical, emotional, and psychological makeup. An experienced homeopath assesses all of these factors when determining the most appropriate treatment for each individual.

A combination remedy including Aconite, Gelsemium, Eucalyptus, Ipecacuanha, Phosphorus, Bryonia, and Eupatorium perfoliatum
A mixture of Anas barbarice hepatis and Cordis extractum
Gelsemium - for chills, weakness, lack of energy, fever, and headaches in the back and top of the head; this is one of the most common homeopathic remedies for the flu
Eupatorium perfoliatum - for deep aches, sneezing and coughing
Nux vomica - for violent vomiting, irritability, dry cough, chills, and a stuffy nose that develops into a watery, irritating discharge

Other Considerations

Warnings and Precautions

If you are in any of the high-risk groups described in the Risk Factors section, be sure to call your doctor at the earliest signs of flu symptoms. The sooner you are treated, the less likely you are to develop complications.

Prognosis and Complications

Most healthy people get over the flu in one to two weeks. For those at high risk, certain serious, even life-threatening, complications can occur including:

Pneumonia
Encephalitis (an infection of the brain)
Secondary bacterial infection elsewhere in the body

Supporting Research

Alvarez-Olmos MI. Probiotic agents and infectious diseases: a modern perspective on a traditional therapy. Clin Infect Dis. 2001;32(11):1567-1576.

Barak V, Birkenfeld S, Halperin T, Kalickman I. The effect of herbal remedies on the production of human inflammatory and anti-inflammatory cytokines. Isr Med Assoc J. 2002;4(11 Suppl):919-922.

Barak V, Halperin T, Kalickman I. The effect of Sambucol, a black elderberry-based, natural product, on the production of human cytokines: I. Inflammatory cytokines. Eur Cytokine Netw. 2001;12(2):290-296.

Barrett BP, Brown RL, Locken K, Maberry R, Bobula JA, D'Alessio D. Treatment of the common cold with unrefined Echinacea: a randomized, double-blind, placebo-controlled trial. Ann Intern Med. 2002;137:936-946.

Belongia EA, Berg R, Liu K. A randomized trial of zinc nasal spray for the treatment of upper respiratory illness in adults. Am J Med. 2001;111(2):103-108.

Blumenthal M, Goldberg A, Brinckmann J. Herbal Medicine: Expanded Commission E Monographs. Newton, MA: Integrative Medicine Communications; 2000:57-61, 233-239, 240-243, 244-248, 297-303.

Brinkeborn RM, Shah DV, Degenring FH. Echinaforce and other Echinacea fresh plant preparations in the treatment of the common cold. A randomized, placebo controlled, double-blind clinical trial. Phytomedicine. 1999;6(1):1-6.

Cohen S, Hamrick N, Rodriquez MS, Feldman PJ, Rabin BS, Manuck SB. Reactivity and vulnerability to stress-associated risk for upper respiratory illness. Psychosom Med. 2002;64(2):302-310.

Cummings S, Ullman D. Everybody's Guide to Homeopathic Medicines. 3rd ed. New York, NY: Penguin Putnam; 1997: 57, 69.

de Vrese M, Winkler P, Rautenberg P, Harder T, Noah C, Laue C, et al. Probiotic bacteria reduced duration and severity but not the incidence of common cold episodes in a double blind, randomized, controlled trial. Vaccine. 2006 Nov 10;24(44-46):6670-4.

Douglas RM, Chalker EB, Treacy B. Vitamin C for preventing and treating the common cold. Cochrane Database Syst Rev. 2000;(2):CD000980.

Eby GA. Zinc ion availability-the determinant of efficacy in zinc lozenge treatment of common colds. J Antimicrob Chemother. 1997;40:483-493.

Fiore C, Eisenhut M, Krausse R, Ragazzi E, Pellati D, Armanini D, Bielenberg J. Antiviral effects of Glycyrrhiza species. Phytother Res. 2007 Sep 20; [Epub ahead of print]

Fortes C, Forastiere F, Agabiti N, et al. The effect of zinc and vitamin A supplementation on immune response in an older population. J Am Geriatr Soc. 1998;46:19–26.

Glatthaar-Saalmuller B, Sacher F, Esperester A. Antiviral activity of an extract derived from roots of Eleutherococcus senticosus. Antiviral Res. 2001;50(3):223-8.

Gruenwald J, Brendler T, Jaenicke C, et al, eds. PDR for Herbal Medicines. 2nd ed. Montvale, NJ: Medical Economics Company Inc; 2000:283-287, 477-479.

Guo R, Pittler MH, Ernst E. Complementary medicine for treating or preventing influenza or influenza-like illness. Am J Med. 2007 Nov;120(11):923-929.e3. Review.

Guralnik M, Rosenbloom RA, Petteruti MP, Lefante C. Limitations of current prophylaxis against influenza virus infection. Am J Ther. 2007 Sep-Oct;14(5):449-54. Review.

Hatakka K, Savilahti, Ponka A, et al. Effect of long term consumption of probiotic milk on infections in children attending day care centers: double-blind, randomized trial. BMJ. 2001;322(7298):1327.

Hayashi K, Hayashi T, Kojima I. A natural sulfated polysaccharide, calcium spirulan, isolated from Spirulina platensis: in vitro and ex vivo evaluation of anti-herpes simplex virus and anti-human immunodeficiency virus activities. AIDS Res Hum Retroviruses. 1996;12:1463–1471.

Hewson-Bower B, Drummond PD. Psychological treatment for recurrent symptoms of colds and flu in children. J Psychosom Res. 2001;51(1):369-377.

Hirt M, Nobel Sion, Barron E. Zinc nasal gel for the treatment of common cold symptoms: A double-blind, placebo-controlled trial. ENT J. 2000;79(10):778-780, 782

Jaber R. Respiratory and allergic diseases: from upper respiratory tract infections to asthma. Prim Care. 2002;29(2):231-261.

Jackson JL, Lesho E, Peterson C. Zinc and the common cold: a meta-analysis revisited. J Nutr. 2000;130(5S Suppl):1512S-1515S.

Jonas WB, Jacobs J. Healing with Homeopathy: The Doctors' Guide. New York, NY: Warner Books; 1996: 213.

Kligler B. Echinacea. Am Fam Physician. 2003;67(1):77-80.

Kohut ML, Cooper MM, Nickolaus MS, Russell DR, Cunnick JE. Exercise and psychosocial factors modulate immunity to influenza vaccine in elderly individuals. J Gerontol A Biol Sci Med Sci. 2002;57(9):M557-M562.

Kruzel T. The Homeopathic Emergency Guide. Berkeley, Calif: North Atlantic Books; 1992:190-196.

Lindenmuth GF, Lindenmuth EB. The efficacy of echinacea compound herbal tea preparation on the severity and duration of upper respiratory and flu symptoms: a randomized, double-blind placebo-controlled study. J Altern Complement Med. 2000;6(4):327-334.

Mahady GB. Echinacea: recommendations for its use in prophylaxis and treatment of upper respiratory tract infections. Nutr Clin Care. 2001;4(4):199-208.

McElroy BH, Miller SP. Effectiveness of zinc gluconate glycine lozenges against the common cold in school-aged subjects: a retrospective chart review. Am J Ther. 2002;9(6):472-475.

Melchart D, Linde K, Fischer P, Kaesmayr J. Echinacea for preventing and treating the common cold. [Review]. Cochrane Database Syst Rev. 2000;(2):CD000530.

Melchart D, Walther E, Linde K, Brandmeier R, Lersch, C. Echinacea root extracts for the prevention of upper respiratory tract infections: a double-blind, placebo-controlled randomized trial. Arch Fam Med. 1998;7:541-545.

Prasad AS, Fitzgerald JT, Bao B, Beck FW, Chandrasekar PH. Duration of symptoms and plasma cytokine levels in patients with the common cold treated with zinc acetate. A randomized, double-blind, placebo-controlled trial. Ann Intern Med. 2000;133(4):245-252.

Reid MR, Mackinnon LT, Drummond PD. The effects of stress management on symptoms of upper respiratory tract infection, secretory immunoglobulin A, and mood in young adults. J Psycosom Res. 2001;51(6):721-728.

Rotblatt M, Ziment I. Evidence-Based Herbal Medicine. Philadelphia, PA: Hanley & Belfus, Inc; 2002:166-169, 221-225, 252-258, 369-371.

Roettger B. Homeopathy as an effective treatment for colds and flus. Nutr Sci News Mag. August 1995.

Roxas M, Jurenka J. Colds and influenza: a review of diagnosis and conventional, botanical, and nutritional considerations. Altern Med Rev. 2007 Mar;12(1):25-48. Review.

Scaglione F, Cattaneo G, Alessandria M, Cogo R. Efficacy and safety of the standardized ginseng extract G115 for potentiating vaccination against common cold and/or influenza syndrome. Drugs Exp Clin Res. 1996;22:65-72.

Schulz V, Hansel R, Tyler V. Rational Phytotherapy: A Physicians' Guide to Herbal Medicine. 3rd ed. Berlin, Germany: Springer; 1998:150.

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 Jul;7(7):473-80. Review. Erratum in: Lancet Infect Dis. 2007 Sep;7(9):580.

Takkouche B, Regueira-Mendez C, Garcia-Closas R, Figueiras A, Gestal-Otero JJ. Intake of vitamin C and zinc and risk of common cold: a cohort study. Epidemiology. 2002;13(1):38-44.

Turner RB. Ineffectiveness of intranasal zinc gluconate for prevention of experimental rhinovirus colds. Clin Infect Dis. 2001;33(11):1865-1870.

Turner RB, Riker DK, Gangemi JD. Ineffectiveness of Echinacea for prevention of experimental rhinovirus colds. Antimicrob Agents Chemother. 2000;44:1708-1709.

Ullman D. Homeopathic Medicine for Children and Infants. New York, NY: Penguin Putnam; 1992: 107.

Ullman D. The Consumer's Guide to Homeopathy. New York, NY: Penguin Putnam; 1995: 229.

Van Straten M, Josling P. Preventing the common cold with a vitamin C supplement: a double-blind, placebo-controlled survey. Adv Ther. 2002;19(3):151-159.

Zakay-Rones Z, Varsano N, Zlotnik M, et al. Inhibition of several strains of influenza virus in vitro and reduction of symptoms by an elderberry extract (Sambucus nigra L.) during an outbreak of influenza B Panama. J Altern Complement Med. 1995;1(4):361-369.

Review Date:
12/19/2007
Reviewed By:
Steven D. Ehrlich, N.M.D., private practice specializing in complementary and alternative medicine, Phoenix, AZ. Review provided by VeriMed Healthcare Network.

A.D.A.M. Copyright

adam.com

Pneumonia

FitSugar — Wed, 08 Oct 2008 17:35:27 -0700

In This Report

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

HEALTH GUIDE REFERENCE FROM A.D.A.M

Highlights

Diagnosis:

Diagnosing pneumonia may be difficult, since lab tests to grow the bacteria from samples can take many days to process, and chest x-rays cannot always distinguish between pneumonia and other conditions. New tests have the potential to make diagnosis easier and quicker. One is a blood test that identifies a marker of severe inflammation in the body. A new 15-minute urine test shows promise in identifying Legionella pneumophila and Streptococcus pneumoniae in patients on ventilators. Physicians may now sample fluid from the trachea or lungs to identify the pneumonia-causing bacteria.

Treatment:

Treating pneumonia has become increasingly complex as bacteria develop resistance to widely used antibiotics. New antibiotics and combinations of older antibiotics are proving effective against many hardy strains of bacteria. Moreover, guidelines for the appropriate treatment of patients at high risk for pneumonia -- those with heart disease, diabetes, asthma, HIV infection, leukemia, and other lung diseases, for example -- are improving the ability to prevent pneumonia and reduce deaths from the disease.

Drug Warning:

In February 2007, the Food and Drug Administration (FDA) announced that the antibiotic telithromycin (Ketek) would no longer be approved for acute bacterial sinusitis and acute bacterial exacerbations of chronic bronchitis, but it would remain on the market for the treatment of mild-to-moderate pneumonia acquired outside of hospitals or long-term care facilities (community-acquired pneumonia, or CAP). In addition to warnings for liver damage, Ketek will now carry warnings of additional drug-related adverse events, including visual disturbances and loss of consciousness.

Introduction

Pneumonia is an inflammation of the lung that is most often caused by infection with bacteria, viruses, or other organisms. Occasionally, inhaled chemicals that irritate the lungs can cause pneumonia. Healthy people can usually fight off pneumonia infections. However, people who are sick, including those who are recovering from the flu (influenza) or an upper respiratory illness, have weakened immune systems that make it easier for bacteria to grow in their lungs.

When air is inhaled through the nose or mouth, it travels down the trachea to the bronchus, where it first enters the lung. From the bronchus, air goes through the bronchi, into the even smaller bronchioles and lastly into the alveoli.

Pneumonia may be defined according to its location in the lung:

Lobar pneumonia occurs in one part, or lobe, of the lung.
Bronchopneumonia tends to be scattered throughout the lung.

Doctors often classify pneumonia based on where the disease is contracted. This helps predict which organisms are most likely responsible for the illness and, therefore, which treatment is most likely to be effective.

Community-Acquired Pneumonia (CAP). People with this type of pneumonia contracted the infection outside a hospital setting. It is one of the most common infectious diseases. It often follows a viral respiratory infection, such as the flu.

One of the most common causes of bacterial CAP is Streptococcus pneumoniae. Other causes include Haemophilus influenzae, mycoplasma, and Chlamydia.

Hospital-Acquired Pneumonia. Hospital-acquired pneumonia is an infection of the lungs contracted during a hospital stay. This type of pneumonia tends to be more serious, because hospital patients already have weakened defense mechanisms, and the infecting organisms are usually more dangerous than those encountered in the community. Hospital patients are particularly vulnerable to Gram-negative bacteria and staphylococci. Hospital-acquired pneumonia is also called nosocomial pneumonia.

A subgroup of hospital-acquired pneumonia is ventilator-associated pneumonia (VAP), a highly lethal form contracted by patients on ventilators in hospitals and long-term nursing facilities.

Click the icon to see an image of hospital-acquired pneumonia.

Pneumonia-causing agents reach the lungs through different routes:

In most cases, a person breathes in the infectious organism, which then travels through the airways to the lungs.
Sometimes, the normally harmless bacteria in the mouth, or on items placed in the mouth, can enter the lungs. This usually happens if the body's "gag reflex," an extreme throat contraction that keeps substances out of the lungs, is not working properly.
Infections can spread through the bloodstream from other organs to the lungs.

However, in normal situations, the airways protect the lungs from substances that can cause infection.

The nose filters out large particles.
If smaller particles pass through, sensors along the airway prompt a cough or sneeze. This forces many particles back out of the body.
Tiny particles that reach the small tubes in the lungs (bronchioles) are trapped in a thick, sticky substance called mucus. The mucus and particles are pushed up and out of the lungs by tiny hair-like cells called cilia, which beat like a drum. This action is called the "mucociliary escalator."

Click the icon to see an image of respiratory cilia.

If bacteria or other infectious organisms manage to avoid the airway's defenses, the body's immune system attacks them. Large white blood cells called macrophages destroy the foreign particles.

Click the icon to see an image of a macrophage.

The above-mentioned defense systems normally keep the lung healthy. If these defenses are weakened or damaged, however, bacteria, viruses, fungi, and parasites can easily infect the lung, producing pneumonia.

The lungs are two spongy organs in the chest surrounded by a thin, moist membrane called the pleura. Each lung is composed of smooth, shiny lobes; the right lung has three lobes and the left has two. Approximately 90% of the lung is filled with air. Only 10% is solid tissue. There are several parts to each lung.

When a person takes a breath (inhales), air travels from the trachea (windpipe) into the lung through the main bronchus, which branches into tiny flexible tubes called bronchi.

The bronchi divide, like the branches of a tree, into smaller airways called bronchioles.

The bronchioles lead to a group of microscopic sacs called alveoli, which look like clusters of grapes. Each healthy adult lung contains millions of tiny alveoli. (Note: The singular of alveoli is alveolus.)

Click the icon to see an image of the lungs.

Each alveolus has a thin membrane that allows oxygen and carbon dioxide to pass in and out of the capillaries, the smallest of the blood vessels. When you take a deep breath, the membrane unfolds and expands. Fresh oxygen moves into the capillaries, and carbon dioxide passes from the capillaries into the bloodstream, where it is carried out of the body through the lungs.

Blood vessels carry the oxygen-rich blood to the heart, where it is pumped throughout the body.

Causes

Bacteria are the most common cause of pneumonia. However, pneumonia can also be caused by viruses, fungi, and other agents. It is often impossible to identify the specific culprit.

Many bacteria are grouped into one of two large categories by the laboratory procedure used to look at them under a microscope. The procedure is known as Gram staining. Bacteria are stained with special dyes, then washed in a special solution. The color of the bacteria after washing determines whether they are Gram-negative or Gram-positive. Knowing which group the bacteria belong to helps determine the severity of the disease, and how to treat it. Different bacteria are treated with different drugs.

Gram-Positive Bacteria. These bacteria appear blue on the stain and are the most common organisms that cause pneumonia. They include:

Streptococcus (S.) pneumoniae (also called pneumococcus), the most common cause of pneumonia. This Gram-positive bacterium causes 20 - 60% of all community-acquired bacterial pneumonia (CAP) in adults. Studies also suggest it causes 13 - 38% of CAP in children.
Staphylococcus (S.) aureus, the other major Gram-positive bacterium responsible for pneumonia, causes about 2% of CAP and 10 - 15% of hospital-acquired pneumonias. It is the organism most often associated with viral influenza, and can develop about five days after the onset of flu symptoms. Pneumonia from S. aureus most often occurs in people with weakened immune systems, very young children, hospitalized patients, and drug abusers who use needles. It is uncommon in healthy adults.
Streptococcus pyogenes or Group A streptococcus.

Gram-Negative Bacteria. These bacteria stain pink. Gram-negative bacteria commonly cause infections in hospitalized or nursing home patients, children with cystic fibrosis, and people with chronic lung conditions.

Haemophilus (H.) influenzae is the second most common organism causing community acquired pneumonia, accounting for 3 - 10% of all cases. It generally occurs in patients with chronic lung disease, older people, and alcoholics.
Klebsiella (K.) pneumoniae may be responsible for pneumonia in alcoholics and other people who are physically debilitated. It is also associated with recent use of potent antibiotics.
Pseudomonas (P.) aeruginosa is a major cause of hospital-acquired pneumonia (nosocomial pneumonia). It is a common cause of pneumonia in patients with chronic or severe lung disease.
Moraxella (M.) catarrhalis is found in everyone's nose and mouth. Experts have identified this bacterium as an uncommon cause of certain pneumonias, particularly in people with lung problems such as asthma or emphysema.
Neisseria (N.) meningitidis is one of the most common causes of meningitis (central nervous system infection), but the organism has been reported in pneumonia, particularly in epidemics of military recruits.
Other Gram-negative bacteria that cause pneumonia include E. coli, proteus (found in damaged lung tissue), enterobacter and acetinobacter.

Atypical pneumonias produce mild symptoms and a dry cough. Organisms that cause atypical pneumonias include:

Mycoplasma (M.) pneumoniae, the most common atypical pneumonia organism. Mycoplasma is a very small bacterium that lacks a cell wall. Pneumonia caused by M. pneumoniae spreads when someone carrying the infection comes in close contact with others for a long period of time. It is most often found in school-aged children and young adults. The condition, commonly called "walking pneumonia," is usually mild.
Chlamydia (C.) pneumoniae is now thought to cause 10% of all CAP cases. This atypical pneumonia is most common in young adults and children, and is usually mild. It is less common, but usually more severe, in the elderly.
Legionella pneumophila causes Legionnaire disease. It is contracted by breathing in drops of contaminated water. Outbreaks are often been reported in hotels, cruise ships, and office buildings, where people are exposed to contaminated droplets from cooling towers and evaporative condensers. They have also been reported in people who have been near whirlpools and saunas. Legionella pneumophila is not passed from person to person. Some experts believe the organism causes 29 - 47% of all pneumonia cases.

Legionnaire disease was first described in 1976 after an outbreak of fatal pneumonia at an American Legion convention. The newly described organism that caused the disease was named Legionella pneumophila, shown in this picture. (Courtesy of the Centers for Disease Control.)

A number of viruses can cause pneumonia either directly or indirectly. They include:

Influenza (Flu). Pneumonia is a major complication of the flu and can be very serious. It can develop about 5 days after flu symptoms start. The flu weakens the body's defense systems, making it easier for bacteria to grow in the lungs.
Respiratory syncytial virus (RSV). Most infants are infected with RSV at some point, but it is most often mild. However, RSV is a major cause of pneumonia in infants as well as adults with damaged immune systems. Studies indicate that RSV pneumonia may be more common in adults, especially the elderly, than previously thought.
Severe acute respiratory syndrome (SARS). SARS is a respiratory infection caused by a newly-described coronavirus, which appears to have jumped from animals to humans. The disease was first reported in China in 2003.
Human parainfluenza virus. This virus is a leading cause of pneumonia and bronchitis in children, the elderly, and patients with damaged immune systems.
Adenoviruses. Adenoviruses are common and usually are not problematic, although they have been linked to about 10% of childhood pneumonia.
Herpesviruses. In adults, herpes simplex virus and varicella zoster (the cause of chickenpox) can cause pneumonia in people with impaired immune systems.
Avian influenza. Type A influenza subtype H5N1 in birds is spreading around the globe. Fortunately, only a few hundred human cases have been identified. Most have resulted from close contact with infected birds. Person-to-person contact is rare. All patients diagnosed with "bird flu" show signs of pneumonia, although symptoms may be mild. Oseltamivir (Tamiflu) is the most effective treatment for this type of influenza, which can be fatal.

The mouth contains a mixture of bacteria that is normally harmless. However, if this mixture reaches the lungs, it can cause a serious condition called aspiration pneumonia. This may happen after head a injury or general anesthesia, or when a patient takes drugs or alcohol. In such cases, the gag reflex doesn't work as well as it should, so bacteria can enter the airways. Unlike other organisms that are inhaled, bacteria that cause aspiration pneumonia do not need oxygen to live. These bacteria are called anaerobic bacteria.

Impaired immunity leaves patients vulnerable to serious, life-threatening pneumonias known as opportunistic pneumonias. They are caused by organisms that are harmless to people with healthy immune systems. Infecting organisms include:

Pneumocystis carinii, renamed Pneumocystis jiroveci in 2002, is an atypical organism. Originally thought to be protozoa, it is now classified as a fungus. P. jiroveci is very common and generally harmless in people with healthy immune systems. It is the most common cause of pneumonia in AIDS patients.

Click the icon to see an image of pneumocystis carinii.

Fungi, such as Mycobacterium avium
Viruses, such as cytomegalovirus (CMV)

Click the icon to see an image of CMV.

In addition to AIDS, other conditions also put patients at risk for opportunistic pneumonia. They include cancers such as lymphoma and leukemia. Long-term use of corticosteroids and drugs known as immunosuppressants also increase the risk for these pneumonias.

Exposure to chemicals can also cause inflammation and pneumonia. Where you work and live can put you at higher risk for exposure to pneumonia-causing organisms.

Workers exposed to cattle, pigs, sheep, and horses are at risk for pneumonia caused by anthrax, brucella, and Coxiella burnetii, which causes Q fever.

Click the icon to see an image of inhalation anthrax.

Agricultural and construction workers in the Southwest are at risk for coccidoidomycosis (Valley fever). The disease is caused by the spores of the fungus Coccidioides immitis.
Those working in Ohio and the Mississippi Valley are at risk for histoplasmosis, a lung disease caused by the fungus Histoplasma capsulatum.

Click the icon to see an image of coccidoidomycosis.

Workers exposed to pigeons, parrots, parakeets, and turkeys are at risk for psittacosis, a lung disease caused by the bacteria Chlamydia psittaci.
Hantavirus, a rare virus carried by rodents, causes a dangerous form of lung disease. It does not spread from person to person. Cases have occurred in New Mexico, Arizona, California, Washington, and Mexico.

Click the icon to see an image of the hantavirus.

Severe acute respiratory syndrome (SARS) is a contagious respiratory infection that was recognized as a worldwide threat in 2003. It was first identified as a new disease by World Health Organization (WHO) physician Dr. Carlo Urbani. Urbani diagnosed SARS in a 48-year-old American businessman, who had traveled from the Guangdong province of China through Hong Kong to Hanoi, Vietnam. The businessman died from the illness. Dr. Urbani died from SARS just a month later, on March 29, 2003 at the age of 46. SARS spread fast. Within 6 weeks of Urbani's discovery, the disease had infected thousands of people around the world on every continent except Antarctica. Schools closed throughout Hong Kong and Singapore, and national economies were affected. The WHO officially identified SARS as a global health threat, and issued an unprecedented travel advisory. It wasn't clear at the time whether SARS would become a global pandemic or settle into a less aggressive pattern. The latter seems to have happened. As of a May 2005, there was no known SARS transmission anywhere in the world, according to the U.S. Centers for Disease Control and Prevention (CDC). The SARS outbreak is a dramatic example of how quickly world travel can spread a disease. According to reports from the CDC and WHO, more than 8,000 people became sick with SARS during the outbreak. Of that group, 774 died. The outbreak is also an example of how quickly a networked health monitoring system can respond to an emerging threat

Causes And Risk Factors. SARS is a serious form of atypical pneumonia that causes acute respiratory distress and sometimes death. It is caused by a new member of the coronavirus family, the family that includes the virus that causes the common cold). The discovery of the SARS-related virus represents one of the fastest identifications of a new organism in history.

SARS is spread by droplet contact. When someone with SARS coughs or sneezes, infected droplets are sprayed into the air. Like other coronaviruses, the SARS virus may live on hands, tissues, and other surfaces for up to 6 hours in these droplets and up to 3 hours after the droplets have dried. While droplet transmission through close contact has been responsible for most cases of SARS, there is evidence that SARS might also spread by infected droplets carried on hands and other objects the droplets had touched. Airborne transmission was a real possibility in some cases. Live virus had even been found in the stool of people with SARS, where it has been shown to survive for up to 4 days. And the virus may be able to live for months or years when the temperature is below freezing.

With other coronaviruses, re-infection (contracting the same disease after recovery or during initial illness) is common. Preliminary reports suggest that this may also be the case with SARS.

The estimated incubation period is 2 - 10 days, although there have been documented cases where the onset of illness was considerably faster or slower. People with active symptoms of illness are clearly contagious. It is not known, however, how early contagion begins before symptoms appear, or how long contagion might linger after the symptoms have disappeared.

Prevention. The best way to prevent SARS is to avoid direct contact with people who have SARS until 10 days after their fever and other symptoms are gone. Reduce travel to locations where there is an uncontrolled SARS outbreak. The CDC has identified hand hygiene as the cornerstone of SARS prevention. Wash your hands often with soap and water, or use an alcohol-based instant hand sanitizer. Cover your mouth and nose when sneezing or coughing. Consider respiratory secretions infectious. Clean commonly touched surfaces with an EPA-approved disinfectant. In some situations, masks, and goggles may be useful for preventing the spread of airborne or droplet infection. Gloves should be used in handling potentially infectious secretions.

Vaccine. In December 2004, the U.S. National Institutes of Health began a small clinical trial to test a preventive SARS vaccine. Interim results showed the vaccine to be safe and well tolerated. Chinese researchers began testing a SARS vaccine in May 2004.

Symptoms. The hallmark symptoms of SARS are fever of 100.4° F (38.0° C) or higher and a dry cough, with difficulty breathing or other respiratory symptoms. The following symptoms, listed in order of how often they appeared, were found in more than half of the first SARS patients:

Fever
Chills and shaking
Muscle aches
Cough
Headache

Less common symptoms (also in order) include:

Dizziness
Cough that produces mucus (sputum)
Sore throat
Runny nose
Nausea and vomiting
Diarrhea

Signs and Tests. Listening to the chest with a stethoscope (auscultation ) may reveal abnormal lung sounds. In most people with SARS, progressive chest x-ray changes or chest CT changes reveal the presence of pneumonia.

Much attention was given early in the outbreak to the development of a quick, sensitive test for SARS. Specific tests for the SARS virus include the PCR for SARS virus, antibody tests to SARS (such as ELISA or IFA), and direct SARS virus isolation. All current tests have some limitations. General tests used in the diagnosis of SARS might include:

Chest x-ray or chest CT is abnormal.
CBC. People with SARS tend to have a low white blood cell count (leukopenia), a low lymphocyte count (lymphopenia), or a low platelet count (thrombocytopenia).
Clotting profiles. SARS patients often have prolonged blood clotting times.
Metabolic blood tests. Lactate dehydrogenase (LDH) and alanine transaminase (ALT) levels are often high. ALT and LDH are most often measured to evaluate the presence of tissue damage.
CPK blood test. Creatine phosphokinase (CPK) is an enzyme found predominantly in the heart, brain, and skeletal muscle. Levels of the CPK enzyme are sometimes elevated in patients with SARS.
Sodium and potassium blood tests are sometimes below normal levels.

Treatment. People suspected of having SARS should be evaluated immediately by a physician. Antibiotics are sometimes given in an attempt to treat bacterial causes of atypical pneumonia. Antiviral medications have also been used. High doses of steroids have been employed to reduce lung inflammation. In some serious cases, serum from people who have already gotten well from SARS (convalescent serum) has been given. Evidence of general benefit of these treatments has been inconclusive.

Other supportive care such as supplemental oxygen, chest physiotherapy, or mechanical ventilation is sometimes needed.

Prognosis. The overall worldwide death rate due to SARS at the end of the outbreaks was 14 - 15%, although it was up to 50% in infected people over age 65. Many more were sick enough to require breathing assistance from a machine (mechanical ventilation). Many others required ICU care.

Today, intensive public health policies are proving to be effective in controlling outbreaks. Many nations have stopped the epidemic within their own countries. All nations must be vigilant, however, to keep this disease under control.

Complications.

Respiratory failure
Liver failure
Heart failure
Myelodysplastic syndromes (bone marrow abnormalities leading to anemia, low platelet counts, and low white blood cell counts)

Call Health Care Provider. Call your health care provider if you suspect you or someone you have had close contact with has SARS.

Symptoms

General Symptoms. The symptoms of bacterial pneumonia develop very quickly and typically include:

A single episode of shaking chills followed by fever
Chest pain on the side of the infected lung. Severe abdominal pain sometimes occurs in people with pneumonia in the lower lobes of the lung.
Shortness of breath
Rapid breathing and heart beat
Cough, which may be initially dry, but eventually produces sputum
Nausea, vomiting, and muscle aches

Emergency Symptoms. Symptoms of pneumonia indicating a medical emergency include the following:

High fever
Rapid heart rate
Bluish-toned (cyanotic) skin
Labored and heavy breathing.
Mental confusion
Coughing up mucus (sputum) containing pus or blood

Symptoms in the Elderly. It is important to note that older people may have fewer or different symptoms than younger people. Symptoms may come on much more slowly. An elderly person who experiences even a minor cough and weakness for more than a day should seek medical help. Some elderly people may exhibit confusion, lethargy, and general deterioration.

Pneumonia caused by anaerobic bacteria such as prevotella (formerly called bacteroides) can produce dangerous abscesses in the lungs. People with such pneumonias may have prolonged fever and a productive cough. There is frequently blood in the mucus that is coughed up. Blood may indicate dead lung tissue. About a third of these patients experience weight loss.

General Symptoms for Atypical Pneumonias. Atypical pneumonia is most commonly caused by mycoplasma and usually appears in children and young adults.

The disease progresses gradually.

General flu-like symptoms often occur first. They may include fatigue, fever, weakness, headache, nasal discharge, sore throat, earache, and stomach and intestinal distress.
Vague pain under and around the breastbone may occur, but the severe chest pain associated with typical bacterial pneumonia is uncommon.
Patients may have a severe hacking cough, but it usually does not produce sputum.

Symptoms of Legionnaire Disease. Symptoms of Legionnaire disease usually occur more rapidly and include high fever, a dry cough, and shortness of breath. These symptoms are often accompanied by headache, muscle pains, fatigue, gastrointestinal problems, and mental confusion.

Prognosis

More than a million people are hospitalized each year for pneumonia, making it the third most frequent cause of hospitalizations (births are first, and heart disease is second). Although the majority of pneumonias respond well to treatment, the infection kills 40,000 - 70,000 people each year.

Hospitalized Patients. For patients who require hospitalization for pneumonia, the death rate is 10 - 25%. If pneumonia develops in patients already hospitalized for other conditions, death rates range from 50 - 70%, and are higher in women than in men.

Older Adults. Community-acquired pneumonia is responsible for 350,000 - 620,000 hospitalizations in the elderly every year. Older adults have lower survival rates than younger people. Even when older individuals recover from CAP, they have higher-than-normal death rates over the next several years. Elderly people who live in nursing homes or who are already sick are at particular risk.

Very Young Children. About 20% of deaths in stillborn and very young infants are due to pneumonia. Small children who develop pneumonia and survive are at risk for developing lung problems in adulthood.

Pregnant Women. Pneumonia poses a special hazard for pregnant women, possibly due to changes in a pregnant woman's immune system. This complication can lead to premature labor and increases the risk of death during pregnancy.

Patients With Impaired Immune Systems. Pneumonia is particularly serious in people with impaired immune systems. This is particularly true for AIDS patients, in whom pneumonia causes about half of all deaths.

Patients With Serious Medical Conditions. Pneumonia is also very dangerous in people with diabetes, cirrhosis, sickle cell disease, cancer, and in those whose spleens have been removed.

Specific organisms vary in their effects. Mild pneumonia is usually associated with the atypical organisms mycoplasma and chlamydia. Severe pneumonia is most often associated with a wide range of organisms. Some are very virulent (potent) but are extremely curable, while others are difficult to treat.

Mycoplasma and chlamydia are the most common causes of mild pneumonias and are most likely to occur in children and young adults. They rarely require hospitalization when they are appropriately treated, although recovery may still be prolonged. Severe and life-threatening cases are more likely to occur in elderly people with other medical conditions.
Streptococcus pneumoniae is the most common cause of pneumonia and, in fact, all bacterial upper respiratory infections. It can produce severe pneumonia, with mortality rates of 10%. Nevertheless, pneumococcal pneumonia is very responsive to many antibiotics.
Staphylococcus aureus is a Gram-positive bacterium that often causes severe pneumonia in hospitalized and high-risk patients and following influenza A and B. People who get this form of pneumonia may develop pockets of infection in their lungs (abscesses) that are difficult to treat and can cause the death of lung tissue (necrosis). Mortality rates are 30 - 40%, in part because the patients who develop this infection are generally very ill or vulnerable.
Pseudomonas aeruginosa and Klebsiella pneumoniae are Gram-negative bacteria that pose a risk for abscesses and severe lung tissue damage.
Legionella pneumophila is very virulent and can cause widespread damage. Treatments have improved dramatically since it was first identified. However, a 2002 study suggested that many patients experience long-term problems, including coughing, shortness of breath, fatigue, and neurological and muscular complications.
Viral pneumonia is usually very mild, but there are exceptions. Respiratory syncytial virus (RSV) pneumonia rarely poses a danger for healthy young adults, but it can be life-threatening in infants and serious in the elderly.

Abscess. An abscess in the lung is a thick-walled, pus-filled cavity that forms when infection has destroyed lung tissue. It typically occurs as a result of aspiration pneumonia, when a mixture of organisms is carried into the lung. Untreated abscesses can cause hemorrhage (bleeding) in the lung, but targeted antibiotic therapy significantly reduces their danger. Abscesses are more common with Staphylococcus aureus, Pseudomonas aeruginosa, or Klebsiella pneumoniae, and uncommon with Streptococcus pneumoniae.

Respiratory Failure. Respiratory failure is one of the top causes of death in patients with pneumococcal pneumonia. Acute respiratory distress syndrome (ARDS) is the specific condition that occurs when the lungs are unable to function and oxygen is so severely reduced that the patient's life is at risk. Failure can occur if pneumonia leads to mechanical changes in the lungs (ventilatory failure) or oxygen loss in the arteries (hypoxemic respiratory failure).

Bacteremia. Bacteremia, bacteria in the blood, is the most common complication of pneumococcus infection, although it rarely spreads to others sites. Bacteremia is a frequent complication of infection from Gram-negative organisms, including Haemophilus influenzae.

Pleural Effusions and Empyema. The pleura are two thin membranes that line the chest and lungs:

The visceral pleura cover the lungs.
The parietal pleura cover the chest wall.

In some cases of pneumonia the pleura become inflamed, which can result in breathlessness and acute chest pain when breathing.

In about 20% of pneumonia cases fluid builds up between the pleural membranes, a condition known as pleural effusion. Ordinarily, the narrow zone between the two membranes contains only a tiny amount of fluid, which lubricates the lungs.

In most cases, particularly in Streptococcus pneumoniae, the fluid remains sterile (no bacteria are present), but occasionally it can become infected and even filled with pus, a condition called empyema. Empyema is more likely to occur with specific organisms such as Staphylococcus aureus or Klebsiella pneumoniae infections. The condition can cause permanent scarring.

Collapsed Lung. In some cases, air may fill up the area between the pleural membranes, causing the lungs to collapse. This is called pneumothorax. It may be a complication of pneumonia (particularly Streptococcus pneumoniae ) or of the invasive procedures used to treat pleural effusion.

Pneumothorax occurs when air leaks from inside of the lung to the space between the lung and the chest wall. The lung then collapses. The dark side of the chest (right side of the picture) fills with air from outside of the lung tissue.

Other Complications of Pneumonia. In rare cases, infection may spread from the lungs to the heart and possibly throughout the body. This can cause abscesses in the brain and other organs. Severe hemoptysis (coughing up blood) is another potentially serious complication of pneumonia, particularly in patients with lung problems such as cystic fibrosis.

Kidney complications and electrolyte imbalances are common in patients admitted to the hospital with pneumonia. If not treated, these problems cause more severe illness and increase the risk of death. Treatment with intravenous saline can usually resolve the problem.

The pneumonias cased by the atypical organisms mycoplasma and chlamydia are usually mild. Some research suggests, however, that chlamydia may have powerful inflammatory effects in the blood vessels. This effect may have certain adverse long-term consequences even in healthy younger individuals.

Heart Disease and Stroke. Research has suggested that chlamydia may trigger the immune system to react, causing inflammation in the coronary arteries. Over time, this can cause hardening of the arteries (atherosclerosis). Atherosclerosis can lead to heart attacks and strokes. Studies on a causal relationship between chlamydia and heart disease have been mixed.

Click the icon to see an image of arterial plaque.

Chylamydia pneumoniae has been associated with a thickening in the carotid arteries that lead to the brain -- a risk factor for stroke. It is not clear whether the organism poses any significant risk for stroke.

Click the icon to see an image of atherosclerosis of the internal carotid artery.

Asthma. Chlamydia pneumoniae, Mycoplasma pneumoniae, and RSV are becoming suspects in many cases of severe adult asthma. One small Australian study found evidence of previous chlamydia infection in 64% of the asthmatic patients tested.

Risk Factors

Risk factors for pneumonia often depend on the specific type of disease.

CAP is the most common type of pneumonia. It develops outside of the hospital. Each year 2 - 4 million people in the US develop CAP, and 600,000 are hospitalized. The elderly, infants, and young children are at greatest risk for the disease.

Pneumonia that is contracted in the hospital is called hospital-acquired or nosocomial pneumonia. It affects an estimated 5 -10 of every 1,000 hospitalized patients every year. More than half these cases may be due to strains of bacteria that have developed resistance to antibiotics. In fact, methicillin-resistant Staphyllococcus aureus and multidrug-resistant Pseudomonas aeruginosa are leading causes of death from hospital-acquired pneumonia. The elderly, the very young, and those with chronic or severe medical conditions, are at highest risk.

In addition, the following conditions within the hospital put patients at higher risk:

Surgery, particularly in people over the age of 80. Among the surgical procedures that pose a particular risk are splenectomy (removal of the spleen), abdominal aortic aneurysm repair, or operations that impair coughing.
Being in the intensive care unit (ICU). This is particularly true for newborns or patients on breathing machines (mechanical ventilators). In one study, 10% of ICU patients on a breathing machine developed pneumonia. Such patients who lie flat on their backs are at particular risk for aspiration pneumonia. Raising the patient up may reduce this risk.
Sedation. Hospital patients who receive sedatives also have a higher risk of developing nosocomial pneumonia.
Previous use of antibiotics, particularly within 6 months.

Hospitalized patients are particularly vulnerable to Gram-negative bacteria and staphylococci, which can be especially dangerous in people who are already ill.

Chronic Lung Disease. Chronic obstructive lung diseases (COPD), which include chronic bronchitis and emphysema, affect 15 million people in the U.S. This condition is a major risk factor for pneumonia. In patients with COPD, vaccination with the pneumococcal vaccine can substantially reduce the risk of developing pneumonia or decrease its severity.

Bronchitis is the inflammation of the bronchi, the main air passages to the lungs. It generally follows a viral respiratory infection. Symptoms include coughing, shortness of breath, wheezing, and fatigue.

Click the icon to see an image of emphysema.

People With Compromised Immune Systems. People with impaired immune systems are extremely susceptible to pneumonia. It is a common problem in people with HIV and AIDS. In one study, the primary bacteria were found to be Legionella pneumophilia and Streptococcus pneumoniae. Smoking and chemotherapy for cancer were more common in those with legionella pneumonia. The patients tended to have a higher CD4 count, undetectable viral load, and more frequent need for antiretroviral therapy. Their pneumonia was more severe than in HIV patients diagnosed with pneumococcal pneumonia. Those with legionell were more likely to have respiratory failure, need ventilation, have pneumonia in both lungs, and were more likely to die. However, AIDS was more common in the patients with pneumococcal pneumonia.

In addition to AIDS, other conditions that compromise the immune system include organ transplantation, chemotherapy, and adult and pediatric cancers, especially leukemia and Hodgkin's lymphoma. Patients who are on corticosteroids or other medications that suppress the immune system are also prone to infection.

Gastroesophageal Reflux Disease. Gastroesophageal reflux disease (GERD) is a condition in which acids from the stomach move up into the esophagus. This is called reflux. Current studies indicate an association between GERD and various problems that occur in the sinuses, ears, nasal passages, and airways of the lung. People with GERD appear to have an above-average risk for chronic bronchitis, chronic sinusitis, emphysema, pulmonary fibrosis (lung scarring), and recurrent pneumonia. If a person inhales fluid (aspirates) from the esophagus into the lungs, serious pneumonia can occur. GERD may contribute to these conditions by triggering inflammation in these upper passages.

However, GERD drugs may increase one's risk. Patients at high risk for pneumonia should take gastric acid-suppressing drugs only when necessary and at the lowest possible dose. A 2004 study found that the use of gastric acid-suppressing drugs raises the risk of developing CAP. The highest risks were associated with proton pump inhibitors (PPIs) such as Prilosec and Nexium, but H2-receptor antagonists such as Tagamet and Pepcid also elevated risk. The researchers theorize that reducing levels of germ-killing stomach acid allow germs to spread in the upper gastrointestinal tract and move into the respiratory tract. The risk posed by these medications is highest in the elderly, children, and patients with asthma, COPD, and compromised immune systems.

Acute stroke. Acute stroke is a risk factor for developing pneumonia. In one German study, the incidence of stroke-associated pneumonia (SAP) was 22% in patients admitted to the intensive care following a stroke. Dysphagia, non-lacunal basal-ganglia infarction, or any infection present on admission, and National Institutes of Health Stroke Scale score greater than or equal to 10 were found to be independent risk factors for the development of SAP. Other risk factors included combined brainstem and cerebellar infarction, infarction affecting more than 66% of the middle cerebral arterial territory, hemispheric infarction exceeding middle cerebral artery territory, impaired vigilance, mechanical ventilation, age of 73 or greater, and cardioembolic stroke. Patients with lacunal strokes were found to be at less risk of SAP.

Click the icon to see an image of gastric reflux.

Dormitory or Barrack Conditions. Recruits on military bases and college students living in dormitories are at higher than average risk for Mycoplasma pneumonia. These groups are at lower risk, however, for more serious types of pneumonia.

Smoke and Environmental Pollutants. The risk for pneumonia in people who smoke more than a pack a day is three times that of nonsmokers. Those who are chronically exposed to secondhand cigarette smoke, which can injure airways and damage the cilia, are also at risk. Quitting smoking reduces the risk of dying from pneumonia to normal, but the full benefit takes 10 years to be realized. Toxic fumes, industrial smoke, and other air pollutants may also damage cilia function, which is a defense against bacteria in the lungs.

Drugs and Alcohol. Alcohol or drug abuse is strongly associated with pneumonia. These substances act as sedatives and can diminish the reflexes that trigger coughing and sneezing. Alcohol also interferes with the actions of macrophages, the white blood cells that destroy bacteria and other microbes. Intravenous drug abusers are at risk for pneumonia from infections that originate at the injection site and spread through the bloodstream to the lungs.

Fatty Diet: A diet high in fatty acids such as palm oils appears to increase the risk of CAP in young and middle-aged women by as much as 54%. Higher intake of monosaturated fats appears to decrease the risk of pneumonia.

Certain children have a higher-than-normal risk for pneumonia and recurrence. Conditions that predispose infants and small children to pneumonia include:

Impaired immune system
Leukemia
Infection with the respiratory syncytial virus (RSV)
Gastroesophageal reflux disorder
Inborn lung or heart defects
Abnormalities in muscle coordination of the mouth and throat
Asthma
Certain genetic disorders such as sickle-cell disease, cystic fibrosis, and Kartagener's syndrome, which result in poorly functioning cilia, the hair-like cells lining the airways

Diagnosis

Diagnostic Difficulties in Community-Acquired Pneumonia (CAP). It is important to determine whether the cause of CAP is a bacterium, atypical bacterium, or virus, since they require different treatments. In children, for example, S. pneumonia is the most common cause of pneumonia, but respiratory syncytial virus may also cause the disease. Although symptoms may differ, they often overlap, which can make it difficult to identify the organism by symptoms alone.

Nevertheless, in many cases of mild-to-moderate CAP, the physician is able to diagnose and treat pneumonia based solely on a history and physical examination.

Diagnostic Difficulties with Hospital-Acquired (Nosocomial) Pneumonia. Diagnosing pneumonia is particularly difficult in hospitalized patients for a number of reasons:

Many hospitalized patients have similar symptoms, including fever or signs of lung infiltration on x-rays.
In hospitalized patients, sputum or blood tests often indicate the presence of bacteria or other organisms, but such agents do not necessarily indicate pneumonia.

Doctors making a diagnosis of pneumonia should rule out other conditions, using a chest x-ray, two sets of blood cultures, a urine analysis for legionella, and a lung fluid sample, among other tests.

The patient's history is an important part of making a pneumonia diagnosis. Patients should be sure to report any of the following:

Recent or chronic respiratory infection
Exposure to people with pneumonia or other respiratory illnesses (such as tuberculosis)
History of smoking
Alcohol or drug abuse
Recent travel
Occupational risks

Use of the Stethoscope. The most important diagnostic tool for pneumonia is the stethoscope. Sounds in the chest that may indicate pneumonia include:

Rales, a bubbling or crackling sound. Rales on one side of the chest or heard while the patient is lying down are strongly suggestive of pneumonia.
Rhonchi, abnormal rumblings indicating the presence of thick fluid.
A dull thud obtained by percussion. The physician will also use a test called percussion, in which the chest is tapped lightly. A dull thud, instead of a hollow drum-like sound, indicates certain conditions suggestive of pneumonia. These conditions include including consolidation (a condition in which the lung becomes firm and inelastic), and pleural effusion (fluid build-up in the space between the lungs and the lining around it).

Although current antibiotics can destroy a wide spectrum of organisms, it is best to use an antibiotic that targets the specific one making a person sick. Unfortunately, people carry many bacteria, and sputum and blood tests are not always effective in distinguishing between harmless and harmful kinds.

In severe cases, a doctor needs to use invasive diagnostic measures to identify cause of the infection. Standard lab tests used to help diagnose pneumonia include:

Sputum Tests. The color of the mucus (sputum) sample coughed up from the lungs can reveal the severity of the disease. Only a sputum sample will reveal the infecting organism.

The patient coughs as deeply as possible to bring up mucus from the lungs, since a shallow cough produces a sample that usually only contains normal mouth bacteria. Some people may need to inhale a saline spray to produce an adequate sample. In some cases, a tube will be inserted through the nose into the lower respiratory tract to induce a deeper cough.

The physician will check the sputum for:

Blood, which means an infection is present
Color and consistency: If it is yellow, green, or brown, an infection is likely.

The sputum sample is sent to the laboratory, where it is analyzed for the presence of bacteria and to determine whether the bacteria are gram-negative or Gram-positive.

Blood Tests. The following blood tests may be performed:

White blood cell count (WBC). High levels indicate infection.
Blood cultures. Cultures are done to determine the specific organism causing the pneumonia, but they usually can not distinguish between harmless and dangerous organisms. They are accurate in only 10 - 30% of cases. Their use is generally limited to severe cases.
Detection of antibodies to S. pneumoniae. Antibodies are immune factors that target specific foreign invaders. One type of immunohistochemical test for S. pneumoniae is showing tremendous promise.
Polymerase Chain Reaction (PCR). In some difficult cases, PCR may be performed. A test makes multiple copies of the genetic material (RNA) of a virus or bacteria to make it detectable.
Procalcitonin test. This marker of systemic inflammatory response to infection is increasingly recognized as a valuable method of determining which patients need antibiotics, and when antibiotic therapy can be safely stopped. Such information is critical to preventing the development of antibiotic-resistant bacteria.

Urine Tests. Urinary antigen tests for Legionella pneumophila and Streptococcus pneumoniae may be performed in patients with severe CAP. The S. pneumoniae test takes only 15 minutes and may identify up to 77% of pneumonia cases and rule out S. pneumoniae infection in 98% of patients. It may not be useful in children.

Invasive Tests. In critically-ill patients with ventilator-associated pneumonia, physicians have tried sampling fluid taken from the lungs or trachea. The techniques enabled the physicians to identify the pneumonia-causing bacteria and start the appropriate antibiotics. However, this made no difference in the length of stay in the ICU or hospital, and there was no significant difference in outcome.

Laboratory Tests for Less Common Organisms

If uncommon organisms -- such as legionella, mycoplasma, and chlamydia -- are strongly suspected, more advanced laboratory tests may be used:

Specialized techniques can detect antibodies to the organisms in blood samples, but these antibodies, such as those responding to mycoplasma or chlamydia, are not present early enough in the course of pneumonia to permit prompt diagnosis and treatment.
PCR is useful for identifying certain atypical strains, including mycoplasma and Chlamydiapneumoniae and, possibly, Haemophilus influenzae type b, but it is expensive.
A urine test can be used to diagnose some cases of Legionnaire disease.
Specialized tests called DNA probes are being developed to detect these organisms in respiratory secretions.

X-Rays. A chest x-ray is nearly always taken to confirm a diagnosis of pneumonia.

X-rays are a form of electromagnetic radiation (like light). They are of higher energy, however, and can penetrate the body to form an image on film. Structures that are dense (such as bone) will appear white, air will be black, and other structures will be shades of gray depending on density. X-rays can provide information about obstructions, tumors, and other diseases, especially when coupled with the use of barium and air contrast within the bowel.

A chest x-ray may reveal the following:

White areas in the lung called infiltrates, which indicate infection
Complications of pneumonia, including pleural effusions and abscesses

Other Imaging Tests. Computed tomography (CT) scans or magnetic resonance imaging (MRI) scans may be useful in some circumstances, especially when:

X-ray results are unclear
Patients do not respond to antibiotics
Complications occur
Patients have other serious health problems

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

CT and MRI can help detect the presence of tissue damage, abscesses, and enlarged lymph nodes. They can also detect some tumors that block bronchial tubes. No imaging technique can determine the actual organism causing the infection. However, features on CT scan of patients with certain forms of pneumonia -- for example, that caused by Legionella pneumophila -- are usually different from features produced by other bacteria in the lungs.

Invasive diagnostic procedures may be required when:

Patients have life-threatening complications
Standard treatments have failed for no known reason
AIDS or other immune problems are present

Invasive procedures include:

Thoracentesis. If a doctor detects pleural effusion during the physical exam or on an imaging study, and suspects that empyema (pus) is present, a thoracentesis is performed.

Fluid in the pleura is withdrawn using a long thin needle inserted between the ribs.
The fluid is then sent to the lab for multiple tests.

Complications of this procedure are rare, but can include collapsed lung, bleeding, and introduction of infection.

Bronchoscopy. A bronchoscopy is done in the following way:

The patient is given a local anesthetic, supplementary oxygen, and sedatives.
The physician inserts a fiber optic tube into the lower respiratory tract through the nose or mouth.
The tube acts like a telescope into the body, allowing the physician to view the windpipe and major airways and look for pus, abnormal mucus, or other problems.
The doctor removes specimens for analysis and can also treat the patient by removing any foreign bodies or infected tissue encountered during the process.

Click the icon to see an image of bronchoscopy.

Bronchoalveolar lavage (BAL) may be done at the same time as bronchoscopy. This involves injecting high amounts of saline through the bronchoscope into the lung and then immediately sucking the fluid out. The fluid is then analyzed in the laboratory. Studies find BAL to be an effective method for detecting specific infection-causing organisms.

The procedure is usually very safe, but complications can occur. They include allergic reactions to the sedatives or anesthetics, asthma attacks in susceptible patients, and bleeding. Fever may follow the procedure.

Lung Biopsy. In very severe cases of pneumonia or when the diagnosis is unclear, particularly in patients with damaged immune systems, a lung biopsy may be required. A lung biopsy involves taking some tissue from the lungs and examining it under a microscope.

Lung Tap. This procedure typically uses a needle inserted between the ribs to draw fluid out of the lung for analysis. It is known by a number of names including lung aspiration, lung puncture, thoracic puncture, transthoracic needle aspiration, percutaneous needle aspiration, and needle aspiration. It is a very old procedure that is not done often any more, since it is invasive and poses a slight risk for collapsed lung. Some experts argue, however, that a lung tap is more accurate than other methods for identifying bacteria, and the risk it poses is slight. Given the increase in resistant bacteria, they believe its use should be reconsidered in young people.

Common Causes of Persistent Coughing. Over 30 million people seek medical help each year for persistent coughing, which is nearly always temporary and harmless when other symptoms, such as fever, are not present. The four most common causes of persistent coughing are asthma, postnasal drip, gastroesophageal reflux disease (GERD), and chronic bronchitis. Other obvious common causes of chronic cough include heavy smoking or the use of heart drugs known as ACE inhibitors.

Acute Bronchitis. Acute bronchitis is an infection in the passages that carry air from the throat to the lung. The infection causes a cough that produces phlegm. Acute bronchitis is almost always caused by a virus and usually clears up on its own within a few days. In some cases, acute bronchitis caused by a cold can last for several weeks.

Chronic Bronchitis. Chronic bronchitis causes shortness of breath and is often accompanied by infection, mucus production, and coughing, but it is a long-term and irreversible condition. The same microbes that cause pneumonia can cause chronic bronchitis, and symptoms of the two disorders are often similar. They include fatigue, coughing, fever, and production of sputum. There are significant differences between chronic bronchitis and pneumonia:

Patients with bronchitis are less likely to have wheezing, shortness of breath, chills, very high fevers, and other signs of severe illness.
Those with pneumonia usually cough up heavy sputum, which is also more likely to contain blood.
X-rays of patients with bronchitis do not show fluid or consolidation in the lung.

Asthma. In asthma, the cough is accompanied by wheezing and occurs mostly at night or during activity. Fever is rarely present (unless the patient also has an infection). Asthmatic symptoms from occupational causes can cause persistent coughing, which is usually worse during the work week. Tests -- the methacholine inhalation challenge and pulmonary function studies -- may be effective in diagnosing asthma.

Anthrax. Because of current terrorist concerns, it is important to differentiate between anthrax and community-acquired pneumonia. According to one study, people with inhalation anthrax are more likely to have rapid heart rate and less likely to have headache, nasal symptoms, and muscle aches than those with pneumonia. Blood tests with anthrax also show high hematocrit and low albumin and sodium levels. Certain chest x-ray findings also raise the likelihood of anthrax.

Other Disorders that Affect the Lung. Many conditions mimic pneumonia, particularly in hospitalized patients. They include:

Tuberculosis
Bronchial asthma
Bronchiectasis, an irreversible widening of the airways usually associated with birth defects, chronic sinus or bronchial infection, or blockage
Atelectasis, a collapse of lung tissue
Heart failure. If it affects the left side of the heart, fluid build-up can occur in the lungs and cause persistent cough, shortness of breath, and wheezing.
Severe allergic reactions, such as reactions to drugs
Acute respiratory distress syndrome (ARDS)
Lung cancer
Interstitial pulmonary fibrosis, a non-infectious inflammation of the lung marked by progressive damage and scarring

Ruling Out Causes in Children. Important causes of coughing in children at different ages include:

Asthma
Physical abnormalities in infants under 18 months
Sinusitis in children 18 months to 6 years
Psychologic causes in older children and adolescents

Acute bronchitis is an infection in the passages that carry air from the throat to the lung. In such cases, the airway tubes become inflamed and collect mucus, causing a cough that produces phlegm. In 95% of cases, acute bronchitis is caused by a virus and is spread from person to person through coughing. In some cases, mycoplasma or chlamydia may be responsible.

Symptoms. The cough in acute bronchitis usually lasts for 7 - 10 days. In about half of patients, coughing can last for up to 3 weeks, and 25% of patients continue to cough for more than one month.

Complications. Acute bronchitis is usually temporary. It can last for weeks to months if the airways are not healing properly. Pneumonia should be suspected if coughing is continuous and hacking, if blood appears in the sputum, and if the patient has a high fever and signs of severe illness. These signs include shortness of breath or extreme weakness and fatigue. [See In-Depth Report #94: Colds and the flu. ]

Of particular interest and some concern are the roles of mycoplasma and chlamydia, two of the infectious organisms that cause acute bronchitis. These agents are being investigated for their roles as possible causes of asthma. Chlamydia is also being investigated as a trigger for coronary artery disease.

Treatments.

Bronchodilators. For some patients with acute bronchitis, inhaled medications called bronchodilators may be effective. These drugs relax and open the airways and may relieve symptoms and reduce the duration of the coughing. The most common bronchodilator used for acute bronchitis is albuterol (Proventil, Ventolin). It is called salbutamol outside the US. The drug is a short-acting beta-2 agonist.
Antibiotics. Acute bronchitis almost never warrants antibiotics. (Coughing caused by pneumonia, however, does require antibiotics.) A 5-year study of more than 800 patients found that those with uncomplicated acute bronchitis all recovered within the same time period, regardless of whether or not they received antibiotics. For most patients, coughing lasted an average of 12 days. For a quarter of the patients, coughing lasted 17 days.

Treatment

Patients with pneumonia are generally treated with:

Antibiotics
Respiratory support with oxygen, if needed

Up to 10% of all adult hospitalizations in the U.S. are due to pneumonia. Studies indicate that many patients are hospitalized unnecessarily for pneumonia, and those patients could be released sooner. A number of strategies are being devised to determine when and which patients can be safely discharged. Studies have shown that low-risk patients with mild-to-moderate pneumonia do just as well when treated as outpatients and return to work and normal activities faster than those treated in the hospital.

One approach for determining whether a patient should be hospitalized categorizes patients into 5 classes depending on risk factors for severity, with class 1 being the least severe (having less than a 0.5% risk for death) and class 5 being the most severe (having at least a 10% risk of death).

Ruling out the Least Severe Cases. The procedure for determining the need for hospitalization starts by selecting patients in the lowest risk groups (classes 1 and 2) who can be discharged with outpatient care only. This can often be done with a simple physical examination, which can rule out a severe condition. Patients in low-risk categories have the following characteristics:

Under age 50 and not a patient in a nursing home
No other major illnesses
No serious symptoms such as altered mental state, breathing problems, bluish skin, very low blood pressure, or very high fever

Even these criteria, however, are flexible. Physicians must use their own judgment and take all factors into consideration. As examples, the following young people with signs of pneumonia should be hospitalized, even if they otherwise fit low-risk (class 1) categories:

Any infant under the age of one month
Young adults with alcoholism or severe psychiatric condition
Young adults or children with abnormal heart rhythm
Young adults or children who are vomiting heavily
Children who are dehydrated

Determining The Next Levels of Severity. If a patient is not in a class 1 category or does not appear to need hospitalization, the next step is to determine which of the other 4 higher classes the patient fits into. This step involves assigning points to other findings, including:

Laboratory test results
X-ray findings
Demographics (Is the patient male or female? Does the patient live in a nursing home?)

The points are added and the patients are scored:

Patients who score the lowest are assigned class 2 and 3. They can usually be treated at home or need only to be hospitalized for 24 hours for observation.
Patients with higher scores are placed in classes 4 and 5, and are hospitalized.

Home care may be possible even in severe cases when there is good support and available home nursing services. Often, caregivers can even be trained to administer intravenous antibiotics and chest therapy to patients at home.

Joint guidelines issued in 2007 by the Infectious Disease Society of America and the American Thoracic Society (ITSA/ATS) recommend that mild CAP in otherwise healthy patients be treated with oral macrolide antibiotics (azithromycin, clarithromycin, or erythromycin).

Many patients with heart disease, kidney disease, diabetes, or other comorbid conditions may still be treated as outpatients. However, they should be given a fluoroquinolone (moxifloxacin, gemifloxacin, or levofloxacin) or a beta-lactam (preferably high-dose amoxicillin or amoxicillin-clavulanate), plus a macrolide, unless they live in an area with high S. pneumoniae resistance to macrolides.

The following tips are also suggested:

Drink plenty of liquids.
Do not suppress a cough. Coughing is an important reflex for clearing the lungs. Some doctors advise taking expectorants, such as guaifenesin (Breonesin, Glycotuss, Glytuss, Hytuss, Naldecon Senior EX, Robitussin) to loosen mucus. However, there is no proof that any of these products make much difference in outcome.
Mild pain can be treated with aspirin (in adults only), acetaminophen (Tylenol), or ibuprofen (Advil, Motrin).
For severe pain, codeine or other stronger pain reliever may be prescribed. It should be noted, however, that codeine and other narcotics suppress coughing, so they should be used with care in pneumonia. Such pain relievers often require monitoring.
A laboratory study reported that aromatic oils containing oregano, thyme, and rosewood destroyed S. pneumoniae. It is not known whether they have any effect on pneumonia in people.
Patients should practice chest therapy.

Treatment. If the pneumonia is severe enough for hospitalization, the standard treatment is intravenous administration of antibiotics for 5 - 8 days. In cases of uncomplicated pneumonia, many patients may require only 2 or 3 days of intravenous antibiotics followed by oral therapy. Antibiotics taken by mouth are prescribed when the patient has improved substantially or leaves the hospital.

ITSA/ATS guidelines recommend patients admitted to the hospital (but not the ICU) be treated with fluoroquinolones or a beta-lactam plus a macrolide (preferably cefotaxime or ceftriaxone and ampicillin).

Duration of Stay. Patients should remain in hospital until all their vital signs are stable. Most patients become stabilized in 3 days. Many experts use 7 variables to measure stability and to determine whether the patient can go home:

Temperature. (Some experts believe that patients can go home when their temperature drops to 101° F. Stricter criteria require that it be at or close to 98.6° F.)
Respiration rate. (Goal is a normal breathing rate, although expert opinion differs on the degree of normality required to be discharged.)
Heart rate. (Goal is 100 beats per minute or less.)
Blood pressure. (Goal is systolic blood pressure of 90 mmHg or greater.)
Oxygenation. (Goal is determined by the physician.)
The ability to eat. (Goal is regular appetite.)
Mental function. (Goal is normal.)

Patients or their families should discuss these criteria with their doctor. In a 2002 study, 42% of patients who had 2 or more signs of instability when they left the hospital were either readmitted or died within 30 days, compared with 10.5% of completely stabilized patients.

Chest therapy using incentive spirometry, rhythmic inhalation and coughing, and chest tapping are all important techniques to loosen the mucus and move it out of the lungs. It should be used both in the hospital and during recovery at home.

Incentive Spirometry. The patient uses an incentive spirometer at regular intervals to improve breathing and loosen sputum. The spirometer is a hand-held clear plastic device that includes a breathing tube and a container with a movable gauge. The patient exhales and then inhales forcefully through the tube, using the pressure of the inhalation to raise the gauge to the highest level possible.

Rhythmic Breathing and Coughing. During recovery, the patient performs rhythmic breathing and coughing every 4 hours:

Before starting the breathing exercise, the patient should tap lightly on the chest to loosen mucus within the lung. If available, a caregiver should also tap on the patient's back.
The patient inhales rhythmically and deeply 3 or 4 times.
The patient then coughs as deeply as possible with the goal of producing sputum.

Medications

Dozens of antibiotics are available for treating pneumonia, but selecting the best drug is sometimes difficult. Patients with pneumonia need an antibiotic that is effective against the organism causing the disease. When the organism is unknown, "empiric therapy" is given, meaning the doctor guesses which antibiotic is likely to work based on factors such as the patients' age, health, and severity of the illness.

In determining the appropriate antibiotic, the physician must first answer a number of questions:

How severe is the pneumonia? Mild-to-moderate cases can be treated at home with oral antibiotics, while severe pneumonia usually requires intravenous antibiotics administered in the hospital.
If the organism causing the pneumonia is not known, was the disorder community- or hospital-acquired? Different organisms are usually involved in each setting, and the physician can use this information to guess the most likely organism causing the pneumonia.
If the organism is known, is it typical or atypical? Community-acquired pneumonias, for example, are usually caused by the typical bacteria Streptococcus pneumoniae, Haemophilus influenzae, or Moraxella catarrhalis, which have traditionally been treated with penicillin or other standard antibiotics. These antibiotics do not affect atypical organisms, such as legionella, mycoplasma, or chlamydia. These organisms are generally treated with a macrolide or possibly a newer quinolone.
Does the patient have an impaired immune system? Antibiotics used to treat such patients may differ from those used in patients with healthy immune systems.

Once an antibiotic has been chosen, there are still difficulties:

Individuals respond differently to the same antibiotic, depending on age, health, size, and other factors.
Patients can be allergic to certain antibiotics, thus requiring alternatives.
Patients may harbor strains of bacteria that are resistant to certain antibiotics.

For a more detailed discussion of the different types of antibiotics, see the "Antibiotic Classes" section below.

Many cases of community-acquired pneumonia are caused by S. pneumoniae, Gram-positive bacteria that usually respond to antibiotics known as beta-lactams (which include penicillin,) and to macrolides. However, resistant strains of S. pneumoniae are increasingly common. Most resistant strains respond to fluoroquinolines such as levofloxacin (Levaquin), gemifloxacin (Factive) or moxifloxacin (Avelox), or to ketolides (telithromycin).

In addition, other important causes of CAP, particularly in younger people, are atypical bacteria, which respond to macrolides (erythromycin, clarithromycin, or azithromycin), to ketolides, or to newer fluoroquinolones.

Antibiotic treatment for CAP is determined by a number of factors, including the patient's history of antibiotic therapy, co-existing diseases (such as COPD, diabetes, and heart failure), and whether the patient is well enough to be treated at home or requires hospitalization or nursing home care. Treatment options can include a single drug, such as levofloxacin or doxycycline, or combination treatment, such as a macrolide administered with a beta-lactam.

Antibiotics taken by mouth are generally sufficient for patients whose CAP is mild enough to be treated at home. Intravenous antibiotics are required for hospitalized patients with CAP. Antibiotic therapy should be given for a minimum of 5 days -- longer if the patient still has a fever and more than one sign of clinical instability.

Gram-Positive Pneumonia. S. aureus is a common cause of hospital-acquired pneumonia and is a potentially life-threatening infection. Resistance to penicillin is the rule in these cases, but certain specialized penicillins such as nafcillin may be effective. The alternatives to penicillins are first- or second generation cephalosporins. Unfortunately, resistance to these agents is increasing as well. Vancomycin is used for highly resistant bacteria.

Gram-Negative Pneumonia. Patients with hospital-acquired pneumonia are at high risk for infection from Gram-negative organisms such as Pseudomonas aeruginosa and Klebsiella pneumonia, which require aggressive therapy. Powerful antibiotics used against these organisms include the fourth-generation cephalosporins, carbapenems, or ciprofloxacin alone or in combination with an aminoglycoside (entamicin or tobramycin). A pilot study of inhaled (aerosol) tobramycin showed the novel form of this aminoglycoside to be as effective against P. aeruginosa as its intravenous formulation. Multidrug therapy may be necessary, particularly for patients on mechanical ventilators, who are at very high risk for multiple dangerous organisms. A 2006 study of high-dose ampicillin-sulbactam for multidrug-resistant (MDR) Acinetobacter baumannii pneumonia showed the combination to be 66.7 - 77.8% successful in curing critically ill, ventilator-dependent patients of the bacterial infection.

Trimethoprim-sulfamethoxazole is the first choice for both preventing and treating P. Jiroveci (formerly called P. carinii) pneumonia in HIV-positive patients. Clindamycin-primaquine may be used in patients who do not respond to standard therapies.

A study of children with leukemia found atovaquone to be an excellent alternative for preventing P. jiroveci pneumonia in children who cannot tolerate trimethoprim-sulfamethoxazole, the current standard preventing therapy.

Most antibiotics have the following side effects (although specific antibiotics may have other side effects or fewer of the standard ones).

The most common side effect for nearly all antibiotics is stomach problems.
Antibiotics raise the risk of vaginal infections. Taking acidophilus supplements or eating yogurt with active acidophilius cultures may help restore healthy bacteria that offset the risk for such infections.
Overuse of antibiotics can cause infection with Clostridium difficile, a pathogen responsible for causing severe diarrhea, colitis, and abdominal pain. It can be fatal.
Allergic reactions can occur with all antibiotics, but are most common with medications derived from penicillin or sulfa. These reactions can range from mild skin rashes to rare but severe -- even life-threatening -- anaphylactic shock.
Certain drugs, including some over-the-counter (OTC) medications, interact with antibiotics. Patients should inform the physician of all medications and OTC preparations they are taking and of any drug allergies they might have.

Beta-Lactams

Beta-lactam antibiotics share common chemical features. They include penicillins, cephalosporins, and some newer similar agents. They interfere with bacterial cell walls.

Penicillins. Penicillin was the first antibiotic. There are many forms to this still-important agent:

Natural penicillins include penicillin G (for intravenous use) and V (for oral use).
Penicillin derivatives called aminopenicillins, particularly amoxicillin (Amoxil, Polymox, Trimox, Wymox, or any generic formulation), are now the most common penicillins used. Amoxicillin is inexpensive and, at one time, was highly effective against S. pneumoniae. Unfortunately, bacterial resistance to amoxicillin has increased significantly, both among S. pneumoniae and H. influenzae. Ampicillin is similar and is an alternative to amoxicillin, but requires more doses and has more severe gastrointestinal side effects.
Amoxicillin-clavulanate (Augmentin) is an augmented penicillin that works against a wide spectrum of bacteria. An extended release form has been approved for treating adults with community-acquired pneumonia caused by bacterial strains that have become resistant to penicillin.
Antistaphylococcal penicillins were developed to treat Staphylococcus aureus. The standard drug was methicillin, but it is no longer used routinely due to very high rates of resistance in hospital-acquired pneumonias. Resistance in community-acquired Staphylococcus aureus is also increasing. Alternatives include vancomycin and linezolid.
Certain penicillins used against Pseudomonas aeruginosa include ticarcillin and piperacillin. Piperacillin is more effective that ticarcillin.

Many people have a history of an allergic reaction to penicillin, but research suggests that the allergy may not recur in a significant number of adults. Skin tests are available to help determine if those with a history of penicillin allergies could use these important antibiotics.

Cephalosporins. Most of these agents are not very effective against bacteria that have developed resistance to penicillin. They are classed according to their generation:

First generation includes cephalexin (Keflex), cefadroxil (Duricef, Ultracef), and cephradine (Velosef).
Second generation includes cefaclor (Ceclor), cefuroxime (Ceftin), cefprozil (Cefzil), and loracarbef (Lorabid),
Third generation includes cefpodoxime (Vantin), cefdinir (Omnicef) cefditoren (Sprectracef), cefixime (Suprax), and ceftibuten (Cedex). Ceftriaxone (Rocephin) is an injected cephalosporin. These are effective against a wide range of Gram-negative bacteria. Cefditoren has also been shown to be 85% effective against Haemophilus influenzae and 90% effective against penicillin-resistant strains of S. pneumoniae.

Other Beta-Lactam Agents. Carbapenems include meropenem (Merrem), biapenem, faropenem, ertapenem (Invanz) and combinations (imipenem/cilastatin [Primaxin]). These agents cover a wide spectrum of bacteria. They are now used for serious hospital-acquired infection and for bacteria that have become resistant to other beta-lactams. Imipenem has serious side effects when used alone, so it is given in combination with cilastatin to offset these adverse effects. The newer agents are less toxic, although they may not be as potent.

Sanfetrinem, a novel beta-lactam antibiotic known as a trinem is proving to be effective against S. pneumoniae,H. influenzae, and M. catarrhalis.

Ceftobiprole is an investigational beta-lactam in phase III clinical trials for methicillin-resistant Staphylococcus aureus (MRSA), penicillin-resistant streptococci, and other Gram-negative pathogens. Other anti-MRSA beta-lactams in clinical development include CS-023/RO-4908463, a carbapenem, and ceftaroline, a cephalosporin (PPI-0903).

Fluoroquinolones

Fluoroquinolones (quinolones) interfere with the bacteria's genetic material to prevent reproduction.

Ciprofloxacin (Cipro), a second-generation quinolone, remains the most potent quinolone against Pseudomonas aeruginosa. It is not very effective for Gram-positive bacteria such as Streptococcus pneumoniae.
"Respiratory" quinolones are currently the most effective drugs available for a wide range of bacteria. Such drugs include levofloxacin (Levaquin), sparfloxacin (Zagam), and gemifloxacin (Factive). Some of the newer fluoroquinolones only need to be taken once a day.
The fourth generation quinolones Moxifloxacin (Avelox) and clinafloxacin, which is still under development, are proving to be effective against anaerobic bacteria.

S. pneumoniae -- strains resistant to the "respiratory" quinolones are uncommon in the U.S., but resistance is dramatically increasing.

Many quinolones cause side effects, including sensitivity to light and neurologic, psychiatric, and heart problems. Pregnant women should not take these agents. The drugs also enhance the potency of oral anti-clotting agents.

Macrolides, Azalides, and Ketolides

Macrolides and azalides also affect the genetics of bacteria. They include:

Erythromycin
Azithromycin (Zithromax, Zmax)
Clarithromycin (Biaxin)
Roxithromycin (Rulid)

These antibiotics are effective against atypical bacteria such as mycoplasma and chlamydia. They are also used in some cases for S. pneumoniae and M. catarrhalis, but there is increasing bacterial resistance to these agents. All but erythromycin are effective against H. influenzae. Macrolide-resistance rates doubled between 1995 and 1999 as more and more children were being treated with these antibiotics. Some research suggests these agents may reduce the risk of a first heart attack in some patients by reducing inflammation in the blood vessels.

Extended-release (ER) azithromycin (Zmax) is the first anti-pneumonia antibiotic that can be given in a single dose. It is effective against Gram-positive, Gram-negative, and atypical pathogens. Studies have shown the results to be equal (noninferior) to that acheived with 7 days of levofloxacin or clarithromycin ER in patients wtih CAP. A single-dose antibiotic decreases the likelihood that a patient will discontinue taking the antibiotic early, which rapidly contributes to the development of drug-resistant bacteria.

Ketolides. Ketolides are a new class of antibiotic drugs. They are derived from erythromycin and were developed to combat organisms that have become resistant to macrolides. Telithromycin (Ketek), the first antibiotic in the ketolide class, was approved by the FDA in 2004 for treatment of community-acquired pneumonia (CAP).

In February 2007, the FDA withdrew approval of Ketek for treatment of acute bacterial sinusitis. The agency decided that the serious risks of telithromycin outweigh its benefits for sinusitis treatment. The decision followed several 2006 reports of patient deaths due to severe liver damage. Telithromycin is approved for treatment only of CAP. The drug carries a black box warning noting the potentially serious side effects, including liver failure, vision problems, loss of consciousness, and neuromuscular problems.

Tetracyclines

Tetracyclines inhibit bacterial growth. They include doxycycline, tetracycline, and minocycline. They can be effective against S. pneumoniae and M. catarrhalis, but bacteria that are resistant to penicillin are also often resistant to doxycycline. The side effects of tetracyclines include skin reactions to sunlight, burning in the throat, and tooth discoloration.

Aminoglycosides

Aminoglycosides (gentamicin, kanamycin, tobramycin, amikacin) are given by injection for very serious bacterial infections. They can be given only in combination with other antibiotics. Some are available in inhaled forms or by applying a solution directly to mucous membranes, skin, or body cavities. They can have very serious side effects, including hearing damage, balance problems, and kidney damage.

Lincosamide

Lincosamides prevent bacteria from reproducing. The most common lincosamide is clindamycin (Cleocin). This antibiotic is useful against S. pneumoniae and S. aureus, but not against H. influenzae.

Glycopeptides

Glycopeptides (vancomycin, teicoplanin) are used for Staphylococcus aureus infections that have become resistant to standard antibiotics. The drug can be taken by mouth or given intravenously. The latest generation of glycopeptides, a derivative of vancomycin, is called telavancin. Currently in phase III studies of hospital-acquired pneumonia, it looks positive for the treatment of Gram-positive pneumonia.

Trimethoprim-Sulfamethoxazole

Trimethoprim-sulfamethoxazole (Bactrim, Cotrim, Septra) is less expensive than amoxicillin. It is particularly useful for adults with mild bacterial upper respiratory infections who are allergic to penicillin. The drug is no longer effective against certain streptococcal strains. It should not be used in patients whose infections occur after dental work, or in people allergic to sulfa drugs. Allergic reactions can be very serious.

Oxazolidinone

Linezolid (Zyvox) is the first antibacterial drug in a new class of synthetic antibiotics called oxazolidinones. It has been shown to work against certain aerobic Gram-positive bacteria.

Other Agents

Inhaled polymyxin, a drug used in cystic fibrosis patients, is showing efficacy against pneumonia caused by multidrug-resistant Gram-negative bacteria, including pseudomonas and klebsiella.

Prevention of RSV. Two agents have been approved for protecting high-risk infants against RSV pneumonia:

Palivizumab (Synagis) is known as a monoclonal antibody, a genetically engineered antibody that targets the RSV virus. It is given by an injection into the muscle. Early studies of motavizumab, another monoclonal antibody in development, also show potent protection against RSV.
RSV immune globulin (RespiGam) is made up of antibodies to RSV that are obtained from the blood of healthy infants. RespiGam is given as a shot.

Treatment of RSV. Ribavirin is the first treatment approved for RSV pneumonia, although it has only modest benefits. The American Academy of Pediatrics recommends it for children at high risk for serious complications of RSV. In one study, a combination of ribavirin with RSV immune globulin was more effective than either drug used alone.

Drugs called bronchodilators, which open up the airways, are sometimes used to treat RSV infection. However, evidence is conflicting. One study involving albuterol, a common bronchodilator, found that epinephrine may be more effective.

Surgery

Although most patients with pneumonia do not require invasive therapy, it may be necessary in patients with abscesses, empyema, or certain other complications.

Thoracotomy is the standard surgery for pneumonia. It requires general anesthesia and an incision to open the chest and view the lungs. This procedure allows the surgeon to remove dead or damaged lung tissue. In severe cases, the entire lobe of the lung is removed. This is calledalobectomy. Remaining healthy lung tissue re-expands after surgery to make up for tissue that has been removed.

Chest tubes are used to drain infected pleural fluid. Tubes are not typically required for pneumonia or abscesses. The tubes are inserted after the patient is given a local anesthetic. They remain in place for 2 - 4 days, and are removed in one quick movement. This can be very distressing, although some patients experience no discomfort. Complications of chest tubes include infection, accidental injury of the lung, perforation of the diaphragm, and fluid build-up within the lung if the pleural fluid is removed too rapidly. Removing the chest tubes may cause the lung to collapse, requiring the reintroduction of a chest tube to inflate the lung.

Click the icon to see an illustrated series detailing chest tube insertion.

Prevention

The best way to prevent serious respiratory infections such as pneumonia is to avoid those who are sick (if possible), and to practice good hygiene. [See In-Depth Report #94: Colds and influenza.]

Colds and flu are spread primarily from infected persons who cough or sneeze. A very common method for transmitting a cold is by shaking hands. Hands should always be washed before eating and after going outside. Using ordinary soap is sufficient. Alcohol-based gels are also effective for every day use, and may even kill cold viruses. If extreme hygiene is required, 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). Wiping surfaces with a solution that contains one part bleach to 10 parts water is very effective in killing viruses.

Bacteria abound in hospitals and long-term care facilities, and are particularly virulent in areas with the sickest patients, such as intensive care units. Health care facilities are revising many of their practices and educating physicians, nurses, and therapists how to reduce the likelihood of transmitting bacteria.

A Swiss study found that coating endotracheal tubes with a solution of silver chloride and silver salts inhibited the growth of bacteria and reduced the transmission of Pseudomonas aeruginosa.
Another more widely adopted method involves the daily use of oral antibiotics to clean the mouths of patients on ventilators. This practice has been shown to lower the incidence of ventilator-associated pneumonia.

Foods Containing Lactobacilli (Good Bacteria). Friendly bacteria inside the intestines may help keep you healthy. Researchers are studying the possible protective value of certain strains of lactobacilli bacteria found in the intestines. One such strain is acidophilus, which is used to make yogurt. According to a Finnish study, children attending day care who drank milk containing the strain lactobacilli GG reduced their risk of respiratory infections by 10 - 20%. More research is needed. (The strain used in the Finnish study was not the kind found in most commercial yogurt products.)

Vitamins. Studies are mixed when it comes to whether or not 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. Two studies in 2002 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.

A review of more than 134,000 Swiss patients found that use of cholesterol-lowering statin drugs was associated with a significantly lower risk of fatal pneumonia and a somewhat lower risk of less-severe pneumonia.

Breast-feeding. Some evidence suggests that women who breast-feed reduce the risk of respiratory infections in their children.

Low Stress and Active Social Life. Several studies have reported that socially active people with low stress have fewer colds than people who have high stress levels or those who have low stress and few social connections.

Zinc appears to have certain important effects on the immune system, and it may have a direct effect on viruses. Zinc preparations in lozenge or nasal gel form are now available as cold treatments. However, research findings regarding the benefits of zinc have varied. (The differing results may be due to different zinc preparations.)

A nasal gel containomg zinc gluconate has shown some success, possibly because the gel sticks to the nasal passages long enough for the zinc to interact with the virus. In a 2003 study, patients who took the nasal gel within 14 - 48 hours of getting sick had less severe symptoms and felt better faster than those who took a placebo. The finding supports earlier studies reporting that Zicam shortened the duration of a cold by about two days.
Zinc lozenges are showing mixed results. One 2000 study suggested that the use of zinc acetate lozenges (e.g., Fast-Dry, Galzin) may be more effective and have a better taste than other formulations, such as zinc gluconate (Cold-Eeze, Orazinc). On the other hand, a 2002 study reported that zinc gluconate reduced the duration of colds significantly. To further confuse matters, the two zinc lozenge preparations were directly compared in a 2000 study, and neither was effective. The reasons for these conflicting results are not clear.
A small 2001 study on a nasal spray preparation found no benefits. The spray preparation had less zinc than the nasal gel.

In any case, no one with an adequate diet and a healthy immune system should take zinc for prolonged periods for preventing colds.

Side Effects of Zinc. Side effects include:

Dry mouth
Constipation
Nausea
Bad taste (possibly only with zinc gluconate lozenges)
Overdose may cause severe vomiting, dehydration, and restlessness. Call a physician if any of these symptoms occur.
In rare cases, an allergic response may occur.

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.
Used in high doses for long periods of time, zinc can cause copper deficiencies.

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 a number of reported cases of serious and even deadly side effects from herbal products.

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

Echinacea. The herbal remedy echinacea is commonly taken to prevent onset and ease symptoms of cold or flu. Studies have been mixed on its effectiveness. It is difficult to test, however, since it is available in different species (notably, E. purpurea and E. augustifolia ), and preparations vary from using extracts to dried forms of the root, the herb, or the whole plant. If echinacea is helpful at all, it may be more effective taken before symptoms develop than during the cold or flu. However, evidence suggests that it is not helpful at all. In addition, allergic reactions have been reported. People with autoimmune diseases or who have plant allergies should avoid taking it. There have also been some reports of a reaction called erythema nodosum associated with echinacea. This involves a rash, sometimes accompanied by fever, headache, muscle and joint aches, and sore throat.
Grapeseed extract is sometimes touted as a natural antihistamine. A 2002 study, however, reported no benefits from it.
Chinese herbal cold and allergy medications may contain trace amounts of aristolochic acid, a chemical that is toxic to the kidneys and considered a carcinogen. Products containing aristolochic acid have been associated with several reports of kidney failure in Europe. Of specific concern are studies suggesting that up to 30% of herbal patent remedies imported from China having been laced with potent pharmaceuticals such as phenacetin and steroids. Most reported problems occur in herbal remedies imported from Asia, with one study reporting a significant percentage of such remedies containing toxic metals.

Brands and Benefits. Zanamivir (Relenza) and oseltamivir (Tamiflu) are called neuraminidase inhibitors. They are newer agents that have been designed to block a key viral enzyme called neuraminidase, which helps viruses spread (replicate).

Both zanamivir and oseltamivir have the following benefits:

Neuraminidase inhibitors are effective for treating both A and B strains of influenza. M2 inhibitors, which prevent the virus from reproducing, are only effective against type A.
They shorten the duration of the flu by 1 - 3 days.
They may help reduce transmission of the virus, although evidence is needed to confirm these findings.
They may have a lower risk than M2 inhibitors for emerging viral strains that are resistant to their effects. In January 2006, the Centers for Disease Control and Prevention (CDC) released a Heath Alert (the highest level of importance) regarding the use of M2 inhibitors (amantadine and rimantadine) for the prevention or treatment of flu. Due to significant increase in influenza A resistance to this class of antiviral medication, the CDC recommended against its use for the remainder of the 2005 - 2006 flu season.
Oseltamivir has been shown to prevent influenza from progressing to pneumonia in 50% of children who were given the drug within 1 day of being diagnosed with the flu.
They have fewer serious side effects than the M2 inhibitors.
Both have some benefits for preventing influenza. Only oseltamivir has been approved for this purpose, however, and only in people over age 13.

Limitations and Side Effects. Although they have many advantages compared to the M2 inhibitors, they are much more expensive. They also need to be taken within 2 days of symptoms to be effective. There are also some differences between the two agents that could be significant for some individuals:

Zanamivir (Relenza) 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 minor in most patients. Of concern, however, was a 2001 British study, which found that a majority of elderly patients were not able to properly use the zanamivir (Relenza) inhaler device, rendering the medicine virtually ineffective. The study was small, however, and other reports suggest that zanamivir is sill effective in this older group.
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.

To date both M2 inhibitors and oseltamivir have been approved for prevention of influenza.

M2 inhibitors. Amantadine and rimantadine protect against the influenza A infection itself in about half of individuals. Rimantadine is preferred for prevention during outbreaks of influenza A because it has fewer adverse side effects. Unfortunately, a majority of influenza A strains are now resistant to both M2 inhibitors.
Neuraminidase Inhibitors. Both zanamivir (Relenza) and oseltamivir (Tamiflu) help prevent both influenza A and B. Only oseltamivir has been approved for this purpose, however, and only in people over 13. Both appear to be very effective in preventing influenza in people who have been exposed to family members with the flu.

Antiviral drugs are not a substitute for vaccines, but they are extremely important add-on therapy for people in certain high-risk groups. They may also be used:

In combination with the flu vaccine during seasons where there is a poor match between the virus and vaccine.
In high-risk individuals who are vaccinated after the flu season has started. In such cases, it takes about 2 weeks (or longer in children) for the vaccine to take effect. The anti-viral drugs offer protection during that period.
As supplementary protection for vaccinated people in high-risk groups, such as the elderly or people with compromised immune systems.
In people who cannot have vaccinations for whatever reason.
For people who provide care for high-risk individuals.
For high-risk individuals who cannot or will not be vaccinated.

Viral Influenza Vaccines (Flu Shot)

Description of Vaccines. Vaccines against the flu (or a "flu shot") 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 and targets for attack.

Antigens are large molecules (usually proteins) on the surface of cells, viruses, fungi, bacteria, and some non-living substances such as toxins, chemicals, drugs, and foreign particles. The immune system recognizes antigens and produces antibodies that destroy them.

Unfortunately, the antigens in these influenza viruses undergo genetic alterations (called antigenic drift) over time, so they are likely to become resistant to a vaccine that worked in the previous year. Vaccines must be 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 chickens, 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 who have not developed immunity to the virus will experience severe flu if they are exposed to type B.

A live but weakened intranasal vaccine (FluMist) for healthy people aged 5 - 49 years is approved by the FDA. It is known as a live, attenuated, trivalent, 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 a nasal spray. In one study it protected up to 93% of children against the flu.

Timing and Effectiveness of the Vaccine. Ideally, people should get a flu shot 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. Immunity peaks within 4 - 6 weeks, then gradually wears off. That is why most people should get a flu shot every year.

In healthy adults, the flu shot reduces the chance of illness by 70 - 90%. The current flu vaccines may be slightly less effective in the elderly and those with certain chronic diseases. Even in people with weak immune systems, however, the vaccine usually protects 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 American Academy of Pediatrics (AAP) and the CDC recommend flu shots for all healthy children 6 - 23 months of age. The flu shot is not approved for children less than 6 months of age.

In addition, any child over the age of 2 years who has a condition that requires regular medical care or who has been hospitalized for a serious illness (particularly lung or kidney disease, diabetes, sickle cell anemia, or immune deficiencies) should also receive a flu shot. 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.

Children with Asthma. Recent and major studies have found that the flu shot is safe for children with asthma. It is very important for these patients to reduce their risk for respiratory diseases. Unfortunately, 90% of asthma patients remain unvaccinated.

All adults age 65 and older. Older adults who receive a flu shot have lower hospitalization rates than those who don't. Evidence now suggests that vaccination may help protect against adverse heart events (including after heart surgeries), stroke, and death from all causes in the elderly. Still, studies suggest that only two-thirds of 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. While 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.
Adults ages 50 - 64 with chronic medical conditions. The US Advisory Committee on Immunization Practices (ACIP) suggests that all adults over age 50 be vaccinated, although this is not recommendation of the CDC.

Other adults who should consider influenza vaccinations include:

People at risk for flu complications 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 flu complications who will be in their second or third trimester during flu season. (Vaccinations should usually be given after the first trimester.)
Health care providers with direct patient contact, child care providers, and residents of long-term care facilities should also be vaccinated.

Side Effects. Possible side effects 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, and sore throat. Such symptoms tend to occur 2 - 24 hours after the vaccination and generally last up to 2 days. These symptoms are not the flu itself, but are 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. Isolated cases of Guillain-Barre syndrome occurred in about one of every 100,000 people vaccinated with the swine-flu vaccine in 1976, but it has not been a problem with subsequent vaccines. Guillain-Barre disease can cause paralysis.

The pneumococcal vaccine protects against S. pneumoniae bacteria, the most common cause of respiratory infections. There are two effective vaccines available: One called a 23-valent polysaccharide vaccine (Pneumovax, Pnu-Immune) for adults, and another called 7-valent conjugate vaccine (Prevnar or PCV7) for infants and young children. Experts are now recommending that more people, including healthy elderly people, be given the pneumococcal vaccine, particularly in light of the increase in antibiotic-resistant bacteria.

Click the icon to see an image of pneumococcal pneumonia.

Pneumococcal Vaccine in Young Children. The pneumococcal vaccine (Prevnar or PCV7) is very effective in children. Evidence suggests that this vaccination, plus the vaccination against Haemophilus influenzae (an important cause of meningitis), has led to 25,000 fewer cases of serious bacterial infections each year.

The pneumococcal vaccine is now recommended by many experts for the following groups:

All children up to age 2. The pneumococcal vaccine (Prevnar or PCV7) has now been added to the Recommended Childhood Immunization Schedule. The pneumococcal vaccine (Prevnar or PCV7) is very effective in children. Studies are suggesting that it prevents common ear infections as well as serious infections such as pneumonia. In one study, a similar vaccine under investigation protected not only children in day care from serious respiratory infections, but their younger unvaccinated siblings had fewer infections as well.
Children up to age 5 who are at risk for pneumonia or complications of influenza, such as those with sickle-cell disease, immune deficiencies, or chronic medical conditions.
Other children aged 2 - 5 who are higher risk for serious pneumococcal infections should be considered for vaccinations. They include African-Americans, Native Americans, children in group child care, socially or economically disadvantaged children, or those who have had frequent or complicated acute middle ear infections within the past year. (In one study, the vaccine reduced the number of ear infections episodes by 6%.)

The recommended schedule of immunization for Prevnar (PCV7) is four doses, given at 2, 4, 6, and 12 - 15 months of age. Infants starting immunization between 7 and 11 months should have three doses. Children starting their vaccinations between 12 and 23 months only need 2 doses. Those who are over 2 years old need only 1 dose.

Pneumococcal Vaccine in Older Children and Adults. The vaccine is proving to help reduce the rate of pneumonia in young adults, although not to the degree that it protects young children. Its benefits for the elderly, other than protection against bloodstream infection, are unclear. Still, pneumonia is declining among adults, which may be due to fewer infections transmitted from vaccinated young children. Many experts now recommend the vaccine for the following older children or adults:

All people over age 65. (Anyone vaccinated more than 5 years previously should be revaccinated.) The vaccination is protective against pneumococcal bacteremia (blood infection) in this group, but it does not appear to protect against community-acquired pneumonia itself.
Adults with any chronic condition that increases the risk for pneumonia. This includes patients with heart disease, chronic lung disease (COPD or emphysema, but not asthma), or diabetes.
Individuals with immune deficiencies, such as HIV, or those undergoing treatments to suppress the immune system.
Patients with autoimmune diseases, such as rheumatoid arthritis and lupus. Unfortunately, studies suggest the vaccine may not be as effective in these patients as it is in those with healthy immune systems. Nevertheless they are at high risk for serious respiratory infections and should be vaccinated.
Patients with kidney disease or kidney transplants. Older people who have had transplant operations or those with kidney disease may require a revaccination after 6 years.
Patients with problems in the spleen.
Alcoholics (especially those with cirrhosis).
People living in long-term care facilities.
Alaska Natives or Native Americans who may be at increased risk for pneumonia.

Because the vaccine is inactive, it is safe for pregnant women and people with immune deficiencies. In fact, when the vaccine is administered to pregnant women, it may actually protect their infants against certain respiratory infections.

Protection lasts for more than 6 years in most people, although it may wear off faster in elderly people than in younger adults. Anyone at risk for serious pneumonia should be revaccinated 6 years after the first dose, including those who were vaccinated before age 65. Subsequent booster doses, however, are not recommended.

Side Effects. Pain and redness at the injection site, fever, and joint aches are possible with the pneumococcal vaccine. Children are more likely to have fever side effects within 48 hours if they receive other vaccines at the same time. They are also likely to have fewer side effects after the second dose. In rare cases, such local reactions can be severe. Even if a person is mistakenly re-vaccinated before the effects of the first vaccination have worn off, the risk for severe side effects is very low. Allergic reactions are very rare.

Resources

www.lungusa.org -- American Lung Association
www3.niaid.nih.gov -- National Institute of Allergy and Infectious Diseases
www.cdc.gov -- Centers for Disease Control and Prevention

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Review Date:
4/3/2007
Reviewed By:
Harvey Simon, MD, Associate Professor of Medicine, Harvard Medical School; Physician, Massachusetts General Hospital. Review provided by VeriMed Health Network.

A.D.A.M. Copyright

adam.com

Vitamins

FitSugar — Wed, 08 Oct 2008 17:35:00 -0700

In This Report

Highlights
Introduction
Carotenoids
Phytochemicals
Healthy Foods
Dietary Health Benefits
Resources
References

HEALTH GUIDE REFERENCE FROM A.D.A.M

Highlights

Cancer

Growing evidence suggests that vitamins and micronutrients, especially from foods, may play important roles in the prevention or treatment of certain cancers:

One study found that the risk of prostate cancer risk dropped as consumption of vegetables high in vitamin C, such as broccoli and bell peppers, rose.
A diet high in cruciferous vegetables has been found to reduce the risk of kidney cancer; low consumption of cruciferous vegetables increases the risk.

On the other hand, high amounts of folic acid (a B vitamin) may be associated with colorectal cancer, and beta-carotene supplements are associated with increased lung cancer risk in smokers and people exposed to asbestos.

Macular Degeneration

In 2007, the National Eye Institute recommended that people with intermediate or advanced macular degeneration in one eye take a vitamin formula shown to reduce the risk of macular degeneration in the other eye by 25%. The formula contains vitamin C, vitamin E, beta-carotene, and zinc.

Osteoporosis

Vitamin K is widely used in Japan to treat osteoporosis, and studies suggest it also may be effective in treating rheumatoid arthritis.

Heart Disease

Although people with high levels of homocysteine are prone to developing blood clots in their arteries and veins, a 2007 study found that lowering homocysteine with B vitamins and folic acid does not reduce the incidence of deep vein thrombosis (DVT). A 2007 trial in adults with stable coronary artery disease found that lowering homocysteine levels 33% with folic acid and other B vitamins had no effect on arterial inflammation, meaning that lower levels were unlikely to offer protection against heart attack or stroke.

Introduction

Vitamins do not share a common chemistry, but they do share certain characteristics. They are all organic nutrients that are necessary in small amounts for normal metabolism and good health. Your diet or supplements provide most vitamins. The body can manufacture only three vitamins (D, K, and the B vitamin biotin) from nondietary sources. Unlike carbohydrates, fats, and proteins, vitamins are not sources of energy. Instead, vitamins are chemical partners for the enzymes involved in the body's metabolism, cell production, tissue repair, and other vital processes.

Vitamins are either fat soluble or water soluble. The fat-soluble vitamins, which include A, D, E, and K, are absorbed by the body using processes that closely parallel the absorption of fat. They are stored in the liver and used up by the body very slowly. The water-soluble vitamins include C and the B complex vitamins. The body uses these vitamins very quickly. Excess amounts are eliminated in urine.

The Recommended Daily Allowance (RDA) for vitamins, set by the Food and Nutrition Board of the National Academy of Sciences-National Research Council, has been used for years as a guide for determining the amount of vitamins needed for a healthy diet. The RDA refers to an estimate of the average daily requirement. It is not completely adequate, however, for informing people about the amounts of vitamins they may need.

The RDA is gradually being enhanced using a new standard called the Dietary Reference Intake (DRI). The DRI is based on the following ratings, which will eventually appear on labels:

The recommended daily allowance (RDA). This is the current rating on most vitamins.
The estimated average requirement (EAR). This is the amount adequate for 50% of all people, which will be put on labels when it can be calculated.
Adequate intake (AI). This is an amount that will be used if there is insufficient data to calculate the EAR.
Tolerable upper intake level (UL). This is the maximum dose likely to be safe in nearly all individuals. It will be included on labels if this amount is known.

Food and supplement labels now typically list the Daily Value (DV). This is the percentage of the amount of a nutrient that experts believe a person needs in their daily diet. On food labels it is usually based on one serving size for a person who takes in 2,000 calories a day.

Regulation of dietary supplements by the U.S. Food and Drug Administration (FDA) is a complex issue.

Labels on vitamins and other dietary supplements now include nutrient information and list all ingredients, including identifying parts of plants from which ingredients may be taken. Unlike the labels for drugs, however, labels for vitamins and supplements may not claim to prevent or treat any specific disease. Labels for vitamins and supplements include one of the following:

Health claim -- description of how the substance may reduce the risk of a health-related condition
Nutrient claim -- description of the amount of the nutrient in the product or
Structure or function claim -- description of how the product may affect organs or systems of the body, without claiming to prevent or treat specific disease

The quality of dietary supplements depends on the manufacturer and is not ensured by FDA. The U.S. government does not require that supplements be standardized, meaning that the amounts or quality of nutrients may vary depending on the batch. So, more expensive supplements are not necessarily better than the less expensive ones. Government regulations are in the process of catching up to the boom in the supplement industry. In the meantime, some companies voluntarily adhere to rigorous quality controls, while others do not.

The U.S. Pharmacopeia (USP), an independent organization that sets quality standards for drugs, has also implemented standards for vitamins. Consumers may look for the USP label on products of companies that adhere to these standards. USP verification means the following:

What is in the bottle matches what is listed on the label.
There are no harmful levels of contaminants.
The supplement will be absorbed properly into the body.
It has been produced according to good manufacturing standards.

Before selling any supplement introduced after 1994, manufacturers must submit information as to why the product is considered safe for people. The FDA may refuse to allow it on the market if it finds the evidence insufficient. The FDA does not require manufacturers to provide any scientific evidence that dietary supplements are safe and effective before a product is sold (unlike drugs, which must be proven both safe and effective through clinical trials). If a supplement causes side effects in people once it is for sale, the government may place restrictions on the supplement or withdraw it from the market. The FDA may also withdraw products from the market if their labels are misleading or false.

About 30% of Americans take at least one vitamin or mineral supplement daily. In a large study that examined the death rates of 11,000 people, however, there was no difference in mortality rate between those who took vitamin supplements and those who didn't. Most people who have a healthy diet do not need vitamins, but there are some exceptions.

Pregnant and Breast-Feeding Women. Women who are pregnant or who are breast-feeding generally need additional vitamins. Vitamins B6, B12, and folic acid are particularly important. Women who are vegetarians must be sure to avoid deficiencies, which can harm their offspring. Folic acid reduces the risk for neural tube defects and possibly facial abnormalities, such as cleft palate. Studies also show that low folate levels during pregnancy are associated with low birth weight, a risk factor for the development of cardiovascular disease in adulthood. Multivitamins that contain folic acid also appear to be somewhat protective. A woman's best approach is to take extra folic acid plus multivitamin supplements (which have additional benefits), starting them before becomming pregnant.

The human body stores several years' worth of vitamin B12, so nutritional deficiency of this vitamin is extremely rare. Although, people who follow a strict vegetarian diet and do not consume eggs or dairy products may require vitamin B12 supplements.

Pregnant women with healthy diets may have low folate levels and need to take supplements. Requirements are as follows:

The recommended daily allowance (RDA) for folic acid prior to conception and during pregnancy is 400 mcg.
During breast-feeding 260 - 280 mcg is recommended.

The following vitamins may have some value for pregnant women:

Choline, another vitamin B, is also essential for pregnant (450 mg) and nursing women (550 mg). Choline plays a key role in brain development. Not getting enough during pregnancy can lead to memory and cognitive defects in the baby. Choline supplements can also lessen the cognitive defects of prenatal alcohol exposure.
Vitamin B6 may help improve morning sickness.
Vitamin C may reduce the risk of urinary tract infections during pregnancy.
Vitamin D may help prevent preeclampsia.
One study also suggested that if pregnant women took vitamin K supplements, their infants might not need the required injection of this vitamin after birth, but supplements of vitamin K during pregnancy are not currently recommended.

Some women have low vitamin A reserves in their liver. It is important to note, however, that too much vitamin A significantly increases the risk for birth defects. Daily amounts of 10,000 IU (international units) of vitamin A in supplements and food (an amount not far above the RDA level) can pose a danger. Experts recommend that pregnant women take in no more than 8,000 IU per day and avoid eating liver.

Infants and Children. Infants who are breast-fed by healthy mothers receive enough vitamins except, in some cases, vitamins K and D. Human milk has low levels of K, and the newborn's immature intestinal tract may not produce enough of the baby's own supply. Most babies are given an injection of this vitamin at birth. Infants being breast-fed by malnourished women or those who lack sufficient exposure to sunlight may be deficient in vitamin D. In these cases, supplements of 200 - 300 IU are recommended. Formulas are required to contain sufficient vitamins and minerals. One study suggests that vitamin supplements for infants under 1 year of age may help protect them from developing type 1 diabetes later on. Beyond infancy, most American children receive all the vitamins they need from their diet unless they are living in severely deprived circumstances.

Smokers. Smoking interferes with absorption of several vitamins, importantly vitamins C and D. In one study nearly 25% of female smokers and 31% of male smokers were deficient in vitamin C. Smoking can interfere with the metabolims of vitamin D, resulting in poor muscle function. Taking high doses of antioxidant vitamins, however, may actually be harmful in smokers, especially beta carotene. Instead of taking supplements, most smokers should be sure their diets are rich in fresh fruits and vegetables and whole grains. Of course, smoking cessation is the most important intervention of all.

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

Alcoholics. Alcoholics often suffer from multiple vitamin deficiencies. The most dangerous deficiencies are from vitamins B1 (thiamin), folic acid, B6 (pyridoxine), B2 (riboflavin), and vitamin C. Low levels of B6 are associated with increased risk of colorectal cancer in men who drink large amounts of alcohol.

Overweight Adults. Overweight and obesity causes many problems that often result in metabolic syndrome or type 2 diabetes. Evidence suggests that isoflavones can help regulate cholesterol levels and reduce body weight and fat mass. Because some medications used to control blood sugar levels reduce folic acid and vitamin B12, some people may need vitamin supplements.

People Who Have Had Gastric Bypass Surgery. Vitamin deficiency is a recognized complication of gastric bypass surgery. Women, African-Americans of both sexes, and adults who have had laparoscopic Roux-en-Y bypass surgery are at highest risk. The deficiency is treated with water-soluble vitamin supplements.

Strict Vegetarians. Strict vegetarians need supplements of vitamin B12, unless they get enough of it from fortified cereals and other grain products.

Dieters and Vegetarians. People on weight-reduction diets with less than 1,000 calories a day should probably take a multivitamin and should also check regularly with a physician.

Vegetarians may need riboflavin, vitamin B12, and vitamin D supplements. Vegans, who do not eat dairy or eggs as well as meat, may be at further risk for vitamin A deficiencies if they do not also have plenty of dark colored fruits and vegetables. Those who eat eggs and dairy products need only watch their iron levels.

Deficiencies in vegetarian children may be particularly harmful. (One study, for example, reported that adolescents who had been on macrobiotic diets before age 6 and were deficient in vitamin B12 scored lower on psychological tests.) Pregnant and breast-feeding women who are vegetarians must be sure to have sufficient vitamins. Of special note, maternal deficiencies in vitamin B12 may cause delayed growth and neurologic problems in their newborns.

Click the icon to see an image of sources for vitamin D.

Older Adults. Deficiencies of vitamins and important minerals have been observed in almost a third of elderly people. Often their dietary habits slip and they fail to eat balanced meals regularly. Multiple drug regimens may prevent absorption of some vitamins. Elderly people, particularly if they are not exposed to sunlight, may be deficient in vitamin D. They also may have low levels of important B vitamins. (Older adults showing signs of dementia should be checked for B12 deficiencies as well as other disorders causing mental disturbances.) One study reported that the immune systems of elderly people may benefit from higher levels of vitamin E than the daily recommended dosage. It should be noted, however, that metabolism slows down as a person ages, and in elderly people it takes the liver longer to eliminate drugs and vitamins from the body. The effect of some vitamin supplements, therefore, may be intensified. Dosage levels of vitamin A, for instance, which might be harmless in a younger adult, could be toxic in an elderly patient. Nevertheless, experts are increasingly recommending extra vitamin and mineral supplements for older people.

People Who Need to Avoid Sunlight. People who need to avoid sunlight or are housebound, and whose diet is low in foods that contain vitamin D should take supplements. People with darker skin are at higher risk for deficiencies than those with whiter skin. (Note: vitamin D is toxic in high doses, and no one should exceed the recommended daily intake of vitamin D except under the direction of a physician.)


Benefits	Essential for growth, bone development, night vision, reproduction, and healthy skin.
Recommended daily allowance (RDA) or dietary reference intake (DRI) (mcg = micrograms, mg = milligrams, IU = international units)	Vitamin A RDA and Upper Limit (when toxicity is risk) are the following: For children: 1,000 IU ages one to three (upper limit is 2,000 IU); 1,333 IU ages 4 - 8 (upper limit is 3,000 IU); and 2,000 IU for 9 - 13 (upper limit is 5,665 IU). For nonpregnant women: 2,330 IU ages 14 through adulthood. (Upper limit is 9,335 IU for ages 14 - 18 and 10,000 IU for women over 19.) For pregnant women: 2,500 IU for pregnant women under 18; 2,565 IU for pregnant women over 19. (Upper limit is 9,335 IU for ages 14 - 18 and 10,000 IU for women over 19. It should be noted that some experts recommend 8,000 IU as the upper limit during pregnancy.) Warning: Use of the topical acne medication tretinoin, a vitamin A derivative, during pregnancy can cause birth defects. For nursing women: 4,000 IU for nursing mothers under 18; 4,335 IU for nursing mothers over 19. (Upper limit is 9,335 IU for ages 14 - 18 and 10,000 IU for women over 19.) For men: 3,000 IU ages 14 - 18; 3,000 IU for ages 19 and above. (Upper limit is 10,000 IU.) Note: In determining the daily vitamin A allowance, experts also take note of provitamins, such beta carotene, that convert to vitamin A. Some experts recommend 3 - 6 mg of beta-carotene. Vitamin A is also now being measured with a new unit called the Retinol Activity Equivalent (RAE or RE). One RE is equal to 1 mcg. Retinol is the most active form of vitamin A and it is also converted in the liver from carotenoids. One RE is equal to 12 mcg of beta-carotene or 24 mcg of alpha-carotene or beta-cryptoxanthin).
Foods containing the vitamin	Animal products, such as liver, dairy products, eggs, and fish liver oil. Provitamin A carotenoids are also found in dark red, green, and yellow vegetables and fruits. Requires some dietary fat to be absorbed.
Effects of deficiencies	Skin disorders, severe diarrhea, and eye damage. In less developed countries severe deficiencies cause blindness in 250,000 children each year. Diets low in vitamin A may also increase the risk of developing cancer. Low dietary intake of vitamin A has been associated with impaired lung function in children.
People at risk for deficiencies	Preschool children and any child with inadequate intake of protein, calories, and zinc. Iron deficiency may also impair metabolism of vitamin A. People with asthma. People with serious disorders in the intestine, liver or pancreas, such as cystic fibrosis, steatorrhea, biliary obstruction, inflammatory bowel disease, cirrhosis, and others. People who have undergone Roux-en-Y gastric bypass surgery. Vegans (vegetarians who do not eat eggs and dairy). Such individuals should be sure to have plenty of deep-colored fruits and vegetables. People who abuse alcohol. It should be noted, however, that people with alcoholism may be at risk for vitamin A deficiency, but a combination of high-dose vitamin A and alcohol may cause toxic effects in the liver. Healthy adults usually have a year's store of vitamin A in the liver, so temporary nutritional deficiencies or problems with fat absorption are unlikely to cause serious vitamin A deficiency problems.
Toxicities	Very toxic when taken in high-dose supplements for long periods of time. Symptoms of overdose include dizziness, nausea, vomiting, headache, skin damage, mental disturbances, and, in women, infrequent periods. Can affect almost every part of the body, including eyes, bones, blood, skin, central nervous system, liver, and genital and urinary tracts. Severe toxicity can cause blindness and may even be life threatening. In children, chronic overdose can cause fluid on the brain and as well as adult complications. High consumption of vitamin A may also increase the risk of gastric cancer and the risk of osteoporosis and fractures in both men and women. Pregnant women who take amounts not much higher than RDA levels increase the risk for birth defects in their children. Liver damage can occur in children who take RDA-approved adult levels over prolonged periods of time or in adults who take as little as five times the RDA-approved amount for 7 - 10 years.


	B Vitamins: General Information	Vitamin B1 (thiamin)
Benefits	The B vitamins have a wide and varied range of functions in the human body. Most B vitamins are involved in the process of converting blood sugar into energy.	Essential for converting blood sugar into energy and is involved in metabolic activities in nerves, heart, and muscles and in the production of red blood cells.
Recommended daily allowance (RDA) or dietary reference intake (DRI) (mcg = micrograms, mg = milligrams, IU = international units)		RDA is 1.2 mg per day for men and 1.1 mg for women.
Foods containing the vitamin		Best source is pork and good sources are dried fortified cereals, oatmeal, corn, nuts, cauliflower, and sunflower seeds. Supplements for people with normal diets and health are unnecessary.
Effects of deficiencies	Deficiencies are uncommon in the U.S., but when they occur, they usually involve several B vitamins, since many of them come from the same food groups.	Severe vitamin B1 deficiency is known as beriberi. It can cause visual disturbances, paralysis, staggering, loss of sensation in the legs and feet, psychosis, and congestive heart failure.
People at risk for deficiencies	Alcohol interferes with these vitamins, and some of the physical and mental problems that alcoholics experience may be attributed to a deficiency of B vitamins. Elderly people are also at risk for deficiencies because of inadequate diets and potential interference with B-vitamin absorption by medications. Deficiencies can occur in severely malnourished people or in those receiving long-term dialysis or intravenous feeding. Vegetarians may be at risk.	See general vitamin B description.
Toxicities	Because the B vitamins are water-soluble and eliminated in the urine, toxic reactions from oral administration of most of them are extremely rare. (Exceptions are niacin and B6.) It should be noted that substances known as B15 (pangamic acid) and B17 (laetrile) are neither vitamins nor nutrients; both chemicals are highly dangerous and have no proven nutritional or health value.	No toxic effects have been reported from thiamin.


	Vitamin B2 (riboflavin)	Vitamin B3 (niacin) also known as nicotinic acid	Vitamin B5 (Pantothenic Acid)
Benefits	Important in the production of energy.	Helps break down blood sugar for energy. Acts as a vasodilator, widening blood vessels and increasing blood flow. May be prescribed for improving cholesterol levels.	Important for metabolism of fats, carbohydrates, and proteins, as well as production of steroid hormones and other important chemicals.
Recommended daily allowance (RDA) or dietary reference intake (DRI) (mcg = micrograms, mg = milligrams, IU = international units)	DRI is 1.7 mg.	DRI is 20 mg.	Adequate intake (AI) is 4 - 7 mg.
Foods containing the vitamin	Liver, dried fortified cereals, dairy products, fish. Some dark green vegetables. Supplements for people with normal diets and health are unnecessary.	Mackerel, swordfish, chicken, veal, dried fortified cereals, pork, salmon, and beef liver. Supplements are unnecessary in people with normal health and diets.	Whole grains, beans, milk, eggs, and liver. Supplements are unnecessary in people with normal health and diets.
Effects of deficiencies	Deficiencies affect the skin and mucous membranes and can cause cracks on the lips or corners of the mouth, eczema of the face and genitals, a burning sensation on the tongue, eye irritation. May contribute to anemia when iron levels are low and contribute to elevated levels of homocysteine, a heart risk factor.	Deficiency causes pellagra; symptoms can include eczema, intestinal and stomach distress, depression, headache, thinning of the hair, and excess saliva production.	Deficiency is unlikely except in company with other B vitamin deficiencies. Symptoms include abdominal distress, burning sensation in the heels, and sleep problems.
People at risk for deficiencies	See general vitamin B description.	Alcoholics and any malnourished persons.	Alcoholics and any malnourished persons.
Toxicities	Until recently, no toxic effects had been reported even from large doses of riboflavin. However, one study indicated that high consumption of vitamin B2 might increase the risk of stomach cancer. More research is needed. (In the same study, vitamins B1, B3, and B6 were protective.)	Even mildly high doses of niacin can cause hot flushing of the face and shoulders, headache, itchiness, and stomach problems. Some report heart disturbances and temporarily lowered blood pressure. Large doses may produce ulcers, gout, diabetes, and liver damage, which are usually reversed when high doses are discontinued.	Although no toxicity has been reported in humans, high dosages have caused liver damage in rats.


	Vitamin B6 (pyridoxine)	Vitamin B12 (cobalamin)
Benefits	Has an effect on over 60 proteins in the body, importantly, those that play a role in the nervous system, in red and white blood cell production, and in heart disease.	Essential for the production of blood cells, manufacturing genetic material, and for healthy functioning of the nervous system. New evidence suggests that high levels of B12 may protect against colon and rectal cancer.
Recommended daily allowance (RDA) or dietary reference intake (DRI) (mcg = micrograms, mg = milligrams, IU = international units)	RDA is 1.3 mg in adults under 50 and 1.7 mg for older men and 1.5 for older women. (Some experts recommend 3 to 6 mg for people who need heart protection.) Upper limit is 100 mg for adults.	RDA is 2.4 mcg in men and nonpregnant women, 2.6 mcg in pregnant women, and 2.8 mcg in nursing mothers.
Foods containing the vitamin	Meats, oily fish, poultry, whole grains, dried fortified cereals, soybeans, avocados, baked potatoes with skins, watermelon, plantains, bananas, peanuts, and brewer's yeast.	The only natural dietary sources are animal products, including meats, dairy products, eggs, and fish (clams and oily fish are very high in B12). Like other B vitamins, however, B12 is added to commercial dried cereals.
Effects of deficiencies	Increased levels of homocysteine, associated with heart disease and possibly Alzheimer's disease. Skin problems and nervous system disorders, including impaired memory and concentration. Increased risk for kidney stones. One study found a correlation between vitamin B6 deficiency and inability to conceive or carry a child to term. In unborn children, some evidence shows that lack of vitamin B6, in addition to vitamin B12 and folic acid, may be responsible for defects such as cleft lip and palate and spina bifida. Supplementation with these vitamins is advised during pregnancy. Note: People who have been taking more than 50 mg for some time and stop suddenly are at risk for a so-called rebound deficiency. When people stop, they should taper off slowly.	Deficiencies elevate homocysteine, a possible risk factor for heart disease and Alzheimer's disease. Increased risk of bone fractures. Abnormal gaits in the elderly. May cause severe depression, memory loss, instability, disorientation, and decreased reflexes, and possibly hearing loss. Children who are deficient may experience growth failure. Deficiencies in pregnant and breast-feeding women may cause neurologic harm in their offspring. A genetic defect that causes vitamin B12 deficiencies is responsible for pernicious anemia, a serious disorder that causes rapid heart rate, shortness of breath, dizziness, weakness, and fatigue. It must be treated with injections of vitamin B12 or else neurologic damage may occur.
People at risk for deficiencies	Alcoholics and any malnourished person. In rare cases, infants are born unable to metabolize pyridoxine; in such cases, seizures or convulsions can occur and vitamin B6 must be administered.	Alcoholics and any malnourished persons. Evidence suggests deficiencies may be caused by Helicobacter pylori (H. pylori) bacteria (a cause of ulcers). Nearly 30% of patients with inflammatory bowel disease have vitamin B6 deficiency, as well as low levels of iron and vitamin D. People who take the antibiotic isoniazid, high blood pressure medication hydralazine, and the drug penicillimine are at risk for vitamin B6 deficiency. The elderly and people with Crohn’s disease and those who have undergone ileal and ileocolonic resection may have trouble absorbing natural vitamin B12 and require supplements. Some evidence shows that patients with Parkinson’s disease treated with levodopa plus dopa decarboxylase inhibitor (DDC-i) and catechol-O-methyltransferase inhibitor (COMT-i) have low levels of both vitamin B12 and folate. As a result, they need to take supplements of these vitamins. Other studies have found that patients with diabetes treated with metformin, but not roziglitazone, are at risk for low levels of vitamin B12. Vitamin B12 deficiency is also common in patients with polyneuropathy. In up to one-third of patients, vitamin B12 deficiency is the sole or major contributing cause of their neuropathy. Treatment with vitamin B12 has a high success rate in improving the symptoms. Vegetarians are at higher risk for deficiencies.
Toxicities	Very high doses can cause nerve damage with symptoms of instability and numbness in the feet and hands, which may be permanent in some cases. Of specific concern are possible adverse effects on nerve development in the offspring of pregnant women who take large doses, such as for morning sickness.	There is no evidence of toxicity with this vitamin.


	Biotin (a B vitamin)	Choline (a B vitamin)	Folate, or Folic Acid, its synthetic form (a B vitamin)
Benefits	Involved in the production of amino acid proteins and fatty acids.	Essential for fetal brain development and for learning and memory.	Important for many metabolic processes in the body. It is used in the manufacturing of neurotransmitters (chemical messengers in the brain), in protecting the heart, and for synthesizing genetic materials (DNA) in the cells. It may improve blood flow.
Recommended daily allowance (RDA) or dietary reference intake (DRI) (mcg = micrograms, mg = milligrams, IU = international units)	There is no DRI for biotin; some experts suggest 30-100 mcg.	RDA 425 mg for nonpregnant women, 450 mg for pregnant women, and 550 mg for nursing women.	Supplements may be folate (natural) or folic acid (synthetic). Folic acid is nearly twice as potent as folate. DRI is 400 mcg (.4 mg) of folate for the general population, 600 mcg during pregnancy and 500 mcg while nursing. Women who are planning to be pregnant should certainly take 400 mcg of folic acid before conception, during pregnancy, and while nursing.
Foods containing the vitamin	Dietary sources are eggs, milk, liver, mushrooms, bananas, tomatoes, whole grains, nuts, and brewer's yeast. Also produced by bacteria in the intestines.	Peanuts, eggs, cauliflower, and meats, especially liver.	Avocado, bananas, orange juice, cold cereal, asparagus, green leafy vegetables, dried beans and peas, and yeast. Folic acid supplements are now added to commercial breads and cereals.
Effects of deficiencies	Deficiencies are almost unheard of.	Low levels during pregnancy increase risk of birth defects in newborns.	As with vitamins B6 and B12, deficiencies of folate elevate levels of homocysteine, an amino acid in the body that may increase the risk for heart disease, and possibly Alzheimer's disease. Folic acid supplements lower homocysteine levels, but with little or no impact on risk of atherosclerotic disease in the heart or in the peripheral arteries and veins. This suggests that homocysteine may be a marker of cardiovascular disease, rather than a cause. This being said, one 2007 study found that folic acid supplementation in patients with low folic acids levels substantially reduced the risk of a first stroke. Low levels during pregnancy increase risk of birth defects in newborns, and folic acid supplementation plays a key role in preventing birth defects. Folic acid deficiencies Deficiencies can also cause depression and megaloblastic anemia and impair concentration, memory, and hearing.
People at risk for deficiencies			Alcoholics, malnourished persons, people with conditions that disturb the small intestine, people taking certain drugs, particularly methotrexate. Other risk factors for deficiency: high-dose aspirin, smoking, treatment for seizures, taking oral contraceptives.
Toxicities		Excessive doses can cause intestinal problems, and there is also some concern that high doses can be carcinogenic.	Possible connection between high consumption of folate/folic acid and colorectal cancer now under exploration. Some link between high doses and central nervous system disorders, zinc deficiency, and seizures in epileptics. This risk appears to be low, but results indicate that megadoses should be avoided. High amounts in the elderly may mask symptoms of vitamin B12 deficiencies.


Benefits	Vitamin C is a water-soluble vitamin. Acts as an antioxidant (reduces harm from damaging chemical processes in the body). Essential for the production of collagen, the basic protein in bones, cartilage, tendons, and ligaments. A 2007 study found that vitamin C supplements can help prevent the development of complex regional pain syndrome following wrist fracture. Another study found that prostate cancer risk dropped as consumption of vegetables high in vitamin C, such as broccoli and bell peppers, rose. It may also protect against brochoconstriction during exercise in people with asthma. May help boost the immune system.
Recommended daily allowance (RDA) or dietary reference intake (DRI) (mcg = micrograms, mg = milligrams, IU = international units)	DRI is 75 mg (women) and 90 mg (men). (Smokers need an additional 35 mg.)
Foods containing the vitamin	Citrus fruits and juices, papayas, hot chili peppers, bell peppers, broccoli, potatoes, dark leafy greens, kale, red cabbage, cauliflower, cantaloupe, sweet potatoes, and Brussels sprouts. Orange juice is the most important source of vitamin C in the U.S., with frozen juice being the best source of the vitamin.
Effects of deficiencies	Scurvy is the primary deficiency disease. Affects most body tissues, particularly bones, teeth, and blood vessels. Early symptoms include tiredness, weakness, irritability, weight loss, and vague muscle aches. Later symptoms are bleeding gums, wounds that won't heal, rough skin, and wasting away of the muscles. Deficiencies may contribute to periodontal disease and gallstones. Low dietary intake of vitamin C has been associated with impaired lung function in children. Low intake may also increase lead levels in the blood.
People at risk for deficiencies	Deficiency has been uncommon in the U.S., usually occurring in the elderly, alcoholics, cancer patients, and some people on severely limited diets low in fresh fruits and vegetables. Surprisingly, however, studies now suggest that as many as 16% of middle-aged Americans, with the highest risk in smokers and middle aged men, are deficient in vitamin C. High doses of aspirin taken over a long period of time can interfere with vitamin C.
Toxicities	Tolerable upper limit is 2000 mg/day. High doses may cause headaches and diarrhea. Long-term high doses may increase risk for kidney stones. Ascorbic acid increases iron absorption so people with blood disorders, such as hemochromatosis, thalassemia, or sideroblastic anemia, should avoid high doses. Large doses may also thin blood and interfere with anticoagulant medications, blood tests used in diabetes, and stool tests. Rebound scurvy can occur after abrupt withdrawal from long-term large doses. This may affect infants or pregnant women who withdraw suddenly from high doses.


Benefits	Vitamin D is actually a single term for several hormones that are stored mainly in the liver and also in fat and muscle tissue. It is essential for the absorption of calcium into the bone and for normal bone growth.
Recommended daily allowance (RDA) or dietary reference intake (DRI) (mcg = micrograms, mg = milligrams, IU = international units)	RDA is 200 IU (5 mcg) per day for children and most adults to age 50, 400 IU (10 mcg) for people between ages 50 and 60, and 600 IU over age 70. and 1000 IU (15 mcg) for those over 70. People who are housebound, do not have sufficient exposure to sunlight, or are dark-skinned individuals, as well as breast-fed infants, should take need vitamin D supplements. The maximum tolerated dose after the age of 12 months is 2,000 IU/day
How the body gets the vitamin	There are two forms of vitamin D. Vitamin D3 is made in the body from a chemical reaction to the ultraviolet radiation in sunlight. Vitamin D2 is found in a few food sources, including vitamin D fortified milk, fatty fish, egg yolk, and liver.
Effects of deficiencies	Softening of the bones caused by low levels of calcium and phosphorous (called rickets in children and osteomalacia in adults). Also increases the risk for bone-related knee problems, and hip fractures in postmenopausal women. Associated with a higher risk for prostate cancer and breast cancer risk. Evidence suggests that vitamin D deficiency may be responsible for poor muscle strength after bone fracture. The deficiency is associated with high blood pressure and diabetes, but it is unknown whether supplementation with vitamin D impacts these diseases. Studies now suggest vitamin D plays a role in age-related macular degeneration (AMD), and that drinking milk with added vitamin D can help protect against AMD.
People at risk for deficiencies	Older people, particularly if they live in the North, who are underexposed to sunlight. Obesity may also increase risk. There is some concern, in fact, that vitamin D deficiency may be a growing problem in the US among younger adults as sunscreen use becomes widespread. Individuals at highest risk for vitamin D deficiency are those who assiduously avoid the midday sun, wear protective clothing, regularly use sunscreen, and have dark skin. Exposure to sunlight for about 15 - 20 minutes at mid-morning or mid-afternoon three times a week is recommended for most people who live in temperate climates.
Toxicities	Vitamin D is very toxic in high doses. In infants, daily amounts higher than 1,000 IU can cause mental and growth retardation, kidney failure, and death. In children and adults, daily amounts over 50,000 IU can cause weakness, anorexia, vomiting, diarrhea, and mental changes. Prolonged use of megadoses can cause calcification of soft tissue and life-threatening kidney failure. Low-calcium diets and withdrawal from the vitamin can usually reverse the side effects except for kidney failure.


	Vitamin E (Tocopherol or Tocotrienol)	Vitamin K
Benefits	A fat-soluble antioxidant vitamin that helps prevent cell membrane damage and may inhibit oxidation of LDL cholesterol (a process that increases its harmful effects on arteries). Researchers once thought that vitamin E might protect against cardiovascular disease. This theory has been debunked. However, a 2007 study found that vitamin E supplementation reduced the risk of deep vein thrombosis (DVT) in women at risk for, or with a history of, DVT. Vitamin E supplements have also been shown to produce a statistically significant decrease in menopausal hot flashes. There is also early evidence that vitamin E may protect against ovarian cancer.	The most important function of vitamin K is its role in blood clotting and prevention of bleeding. As a result, the vitamin may be able to help treat hepatoma, leukemia, and hepatocellular carcinoma, a form of liver cancer. The vitamin also contributes to maintaining healthy bones and healing fractures. Vitamin K is widely used in Japan to treat osteoporosis, and studies suggest it may be effective in treating rheumatoid arthritis.
Recommended daily allowance (RDA) or dietary reference intake (DRI) (mcg = micrograms, mg = milligrams, IU = international units)	RDA is 15 mg (22 IU) for all adults, including pregnancy women. Nursing mothers need 19 mg (28 IU). (Supplements should be taken along with some oil or fat to be absorbed.) Vitamin E is composed of 8 compounds (four tocopherols and four tocotrienols). Vitamin E is most often available as supplements of dl alpha tocopherol (a synthetic form). Other vitamin E compounds may prove to be more active than the standard synthetic supplement. They include natural vitamin E, called d-alpha- or RRR-alpha-tocopherol succinate (VES). Other vitamin E compounds of interest are tocotrienol and beta and gamma tocopherol. Supplements that contain a combination of some of these forms may be most beneficial.	RDA is 60 - 65 micrograms (women) and 70 - 80 micrograms (men).
Foods containing the vitamin	Vegetable oils (particularly wheat germ oil), sweet potatoes, turnip greens, mangos, avocados, nuts, sunflower seeds, and soybeans. Tocotrienol (a possibly beneficial form) is found in natural tropical oils. Palm oil sold in the US is refined and does not contain tocotrienol.	Best dietary sources are canola oil, cruciferous vegetables, and soybean oil. Good sources are beef liver, bran, and olive oil. Also produced by bacteria in the intestines.
Effects of deficiencies	Deficiencies have not been established.	Easy bruising, bleeding. May increase the risk of hip fractures in women.
People at risk for deficiencies	Low-birth weight infants. People who eat a low-fat diet. People with medical problems that impair fat absorption, such as Crohn's disease, cystic fibrosis, steatorrhea, liver diseases (such as cirrhosis). People with abetalipoproteinemia, a rare genetic disorder that impairs fat metabolism.	Deficiency may occur in patients who have problems absorbing fats, such as those with cirrhosis, people who are on long-term antibiotic therapy, or who are taking other medications, including cholestyramine, Dilantin, and phenobarbital. Some evidence suggests that more young people may be deficient than previously believed.
Toxicities	Upper level recommended is 1,500 IU of alpha tocopherol. Large doses may cause bleeding problems, particularly in people taking anti-clotting medications. Some research now indicates that vitamin E, like other antioxidants, may have pro-oxidant and damaging effects. Although vitamin E is one of the best studied vitamins, research has yielded conflicting results, and definitive conclusions about the benefits and toxicity of vitamin E have not yet been determined. In a major 2005 study, there was no significant difference in cancer rates between people who took 400 IU of vitamin E daily and those who did not, although those who took the supplement had a higher risk of heart failure. Additional studies also link high levels of vitamin E with a slightly increased risk of heart failure and death. On the other hand, studies show that vitamin E may reduce heart problems in high-risk patients such as certain people with diabetes.	Allergic-type responses, including rash and itching, to high doses have been reported. Those who are taking Coumadin, an anticoagulant, should not take vitamin K without consulting a physician. Vitamin K deficiency can cause anorexia, lethargy, growth retardation, bone loss, soft tissue calcification, and death.

Carotenoids

Carotenoids are a group of more than 700 fat soluble nutrients that produce the colors in foods such as carrots, pumpkins, sweet potatoes, tomatoes, and other deep green, yellow, orange, and red fruits and vegetables. Many are proving to be very important for health. Beta carotene is the most widely studied carotenoid, but others are proving to be of great interest. As with some, but not all, carotenoids, beta carotene is known as a provitamin A because it converts to the vitamin in the body.

They are categorized as either xanthophylls or carotenes according to their chemical composition.

Carotenes are hydrocarbons and most are found in yellow, orange, and red vegetables. They include beta and alpha carotene and lycopene.

Beta Carotene and other Provitamin A Carotenoids. Beta carotene, alpha-carotene, and beta-cryptoxanthin are carotenes that are converted into vitamin A or retinol (the active form of vitamin A) in the body. They are found in many yellow fruits and vegetables. Beta carotene is the most widely studied carotenoid. Evidence now strongly suggests that when taken as a separate supplement it can have harmful effects.
Lycopene. Lycopene is responsible for the red color in fruits and vegetables, including tomatoes, red grapes, watermelon, and pink grapefruit. It is also found in papayas and apricots. It does not convert to vitamin A but may have important cancer fighting properties and other health benefits.
The beneficial actions of most carotenes such as those tomatoes, corn, and carrots, appear to be enhanced by cooking them, especially in oil (preferably olive, canola, or another monounsaturated oil). (Note: Cooking can also destroy certain nutrients, such as vitamin C, in these vegetables.)

Xanthophylls contain oxygen and most are found in green vegetables, such as broccoli, cabbage, and kale. They are also in yellow fruits and vegetables. Xanthophylls include lutein and zeaxanthin, which are both stored in the retina of the eye. Neither converts to vitamin A. Both are powerful antioxidants and may be very important for healthy eyes. Unlike carotenes, cooking may reduce the antioxidant activity of some xanthophylls in foods, although probably not to any significant degree.

Phytochemicals

The word phytochemicals means plant chemicals. Hundreds of phytochemicals are being studied. Many are believed to have a major positive impact on human health. Some contribute to the bright and vivid colors found in fruits and vegetables. The results of studies on specific phytochemicals are not necessarily applicable to the vegetables or fruits that harbor small concentrations of these chemicals.

Nevertheless, it is obvious that vegetables and fruits are healthful, which is probably due to some balance of phytochemicals, carotenoids, vitamins, fibers, and minerals rather than any single substance.

The benefits of individual phytochemical supplements are largely unproven. Furthermore, they are not regulated and high concentrations of some may behave like drugs and can be toxic and possibly even contribute to cancer cell growth.

Polyphenols are important phytochemicals, and flavonoids (or catechins) are members of the polyphenol family that may have significant health benefits. Laboratory studies have shown that specific flavonoids suppress tumor growth, interfere with sexual hormones, prevent blood clots, and have anti-inflammatory properties. In general, flavonoids are found in celery, cranberries, onions, kale, dark chocolate, broccoli, apples, cherries, berries, tea, red wine or purple grape juice, parsley, soybeans, tomatoes, eggplant, and thyme. Most common berries contain flavonoids and are particularly rich in potent antioxidants.

Among the important flavonoids are resveratrol, quercetin, and catechin. Evidence suggests that resveratrol (found in red wine, grapes, olive oil) may be extremely potent. In laboratory studies, it increases cell survival and has been shown to increase the life span of worms and fruit flies. Catechins are the primary flavonoids in tea and may be responsible for its possible beneficial effects. Flavonoids in dark chocolate may also be health protective.

Isoflavones, commonly known as phytoestrogens, have actions that are similar to the female hormone estrogen. A high consumption of soy, which is primarily composed of isoflavones, may reduce symptoms resulting from estrogen depletion during menopause. In a recent study, supplementation with isoflavones decreased hot flashes by 57% and night sweats by 43%, but other research is less favorable.

Lignan is another phytoestrogen and is found in the fiber layers of whole-grains, berries, some seeds, some vegetables, and a few fruits.

Isothiocyanates and related substances, indoles, are also known as mustard oils and are responsible for the sharp taste in cruciferous (also called brassica) vegetables. Such vegetables include broccoli, cabbage, Brussels sprouts, cauliflower, collards, kale, kohlrabi, mustard greens, rutabaga, turnips, and bok choy. Isothiocyanates also stimulate enzymes that convert estrogen to a more benign form and may block steroid hormones that promote breast and prostate cancers. (Cruciferous vegetables are also high in fiber, vitamin C, and selenium.)

Monoterpenes have two important phytochemicals, perillyl alcohol and limonene. They block proteins that stimulate cell growth and reproduction and are being tested for actions against cancer. Limonene is found in the peels of citrus fruits.

Organosulfurs are part of the allium family of phytochemicals. Compounds, such as allicin, may have benefits on the immune system, assist the liver in rendering carcinogens harmless, and reduce production of cholesterol in the liver. These compounds are found in garlic, leeks, onions, chives, scallions, and shallots.

Capsaicin seems to reduce levels of substance P, a compound that contributes to inflammation and the delivery of pain impulses from the central nervous system. Research suggests that it may inhibit cancer-generating substances. It is found in hot red peppers.

Sterols, which include sitosterol, stigmasterol, campesterol, and squalene, are found in vegetable oils. Sitosterol is the most studied and appears to have cholesterol-lowering effects.

Beta-sitosterols may help improve urine flow and urinary symptoms in men with enlarged prostate glands (benign prostatic hyperplasia, or BPH). A recent review study of five randomized trials (519 men) found that urinary flow and other urinary symptoms improved in men who took the herbal remedy from 4 - 26 weeks. The study’s authors cautioned that while beta-sitosterols show effectiveness in the short term, their long-term effectiveness, ability to prevent complications from BPH, and safety are not known. More research is necessary. Beta-sitosterols come from South African star grass, Hypoxis rooperi, or species of Pinus and Picea.

Healthy Foods

Evidence increasingly suggests that a varied diet, not individual food chemicals, is essential for basic health and a longer life. Such diets are rich in fresh fruits and vegetables and whole grains, and low in saturated fats.


Foods	Phytochemicals and Carotenoids	Vitamins and other valuable food components	Benefits
Apples	Flavonoids		May have activity against certain cancers (lung). Also may help maintain healthy cholesterol. May protect against asthma.
Beans	Flavonoids	Folate, iron, potassium, and zinc	Some experts believe beans are the perfect food.
Berries, all kinds of dark colored	Ellegic Acid	Vitamin C, minerals	The anthocyanins in berries such as bilberries, blueberries, cranberries, elderberries, and others, have numerous healthful properties including anti-cancer and antioxidant effects. Bilberry (Vaccinium myrtillis) is widely used to prevent macular degeneration. Blueberries may protect the aging brain. (In one study blueberries were most effective.)
Broccoli (also kale, Brussels sprouts, cauliflower)	Flavonoids, isothiocyanates, lutein, beta and alpha carotene. Note: Young sprouts of broccoli and cauliflower contain much higher levels of isothiocyanates than their mature forms.	Vitamin C, folate, fiber, and selenium	Anticancer properties. Protective against heart disease and stroke.
Carrots and other bright yellow vegetables	Lutein, beta carotene and other provitamin A carotenoids	Vitamin A (converted from carotenoids), vitamin C	Protects eyes, lungs. (Cooking carrots may increase the potency of food nutrients.)
Chocolate, dark. Note: Milk chocolate does not have benefits.	Flavonoids		Heart protective (may improve lipids and help prevent blood clotting. May have protective properties against lung cancer (not other cancers).
Eggs	Lutein	Many B vitamins, vitamin A, vitamin D	Although egg yolks are high in cholesterol, very little of it has a negative effect on people with normal levels. And the health benefits of eggs are now known to be very high. (People with diabetes or those with high cholesterol should restrict eggs, however.)
Fish, oily (mackerel, salmon, sardines)		Vitamin B3, B12. Essential fatty acids, selenium	Heart and brain protective.
Garlic	Allium (organosulfurs)		Possibly protective against certain cancers, heart diseases, and infection. Heating garlic can reduce benefits. Allowing crushed fresh garlic to stand 10 minutes before heating, however, may preserve beneficial chemicals while cooking.
Ginger	Zingiberaceae		Cancer fighting properties.
Grains (whole)	Lignans (phytoestrogens)	Vitamin B, Selenium (important antioxidant mineral), fiber, folate	May help reduce the ability of cancer cells to invade health tissue.
Grapes, including purple grape juice, and red wine	Flavonoids, (resveratrol, quercetin and catechin)		Fight heart disease and cancer. May help lower the risk for asthma.
Nuts		Vitamin E, vitamin B1, essential fatty acids, folate	Protects the heart and may help prevent stroke.
Onions	Flavonoids, allium (organosulfurs)		May have activity against certain cancers (lung).
Oranges	Monoterpenes	Vitamin C, folate, potassium.	Many health benefits. Increases HDL levels.
Potatoes (Sweet)		Vitamin C, vitamin E, vitamin A	Many health benefits.
Soy. The best products are tofu, soy milk, or whole soy protein.	Isoflavones (phytoestrogens), flavonoids, phytosterol, phytate, saponins.		May have effects similar to estrogen, including maintaining bone and benefiting the heart in women. May also be protective against prostate cancer and possibly other cancers. More studies are needed. Effects on breast cancer are uncertain. (Note: Soy may have different effects in men than in women. Of some concern is one study reporting more mental decline in men who consume greater amounts of tofu.)
Spinach and other dark green leafy vegetables	Zeaxanthin, Beta carotene	Vitamin C, folate, vitamin A (converted from carotenoids)	Protects lungs and brain.
Tea (Both black and green tea are beneficial. Best results associated with green tea.)	Flavonoids (primarily catechins)		Cancer fighting properties, particularly in green tea, which may be especially beneficial for smokers. Both black and green tea may protect against heart disease and stroke, although studies are mixed. Tea drinking also may help with weight control and help prevent osteoporosis.
Tomatoes	Lycopene, Flavonoids	Vitamin C, biotin, minerals	Studies link to reductions in prostate and other cancers. Infection fighters.
Note on Organic versus Inorganic Products. There is some evidence that organic produce has higher levels of antioxidants and that some agricultural chemicals may destroy flavonoids. Nevertheless, organic produce is expensive, and fruits and vegetables, no matter how they are grown, are still filled with healthful nutrients.

Dietary Health Benefits

The benefits of any dietary factors are very difficult to prove, and, to date, there is little evidence that most dietary supplements protect against major diseases in otherwise healthy people with normal eating habits. An exception is lutein, which is known to reduce the risk of macular degeneration. However, a diet naturally high in vitamins and minerals can be the best defense against many diseases. Fresh fruits and vegetables and whole grains are the primary sources of vitamins, carotenoids, and vitamins, as well as of fiber and important minerals.

Description of Oxygen-Free Radicals (Oxidants). Currently, the most important benefit claimed for vitamins A, C, E, and many of the carotenoids and phytochemicals is their role as antioxidants, which are scavengers of particles known as oxygen-free radicals (also sometimes called oxidants). These chemically active particles are by-products of many of the body's normal chemical processes. Their numbers are increased by environmental assaults, such as smoking, chemicals, toxins, and stress. In higher levels, oxidants can be very harmful in the following way:

They can damage cell membranes and interact with genetic material, possibly contributing to the development of a number of disorders including cancer, heart disease, cataracts, and even the aging process itself.
Oxygen-free radicals can also enhance the dangerous properties of low-density lipoprotein (LDL) cholesterol, a major player in the development of atherosclerosis.

Description of Antioxidants and Warnings on High-Dose Supplements. Antioxidant vitamins (A, C, and E), carotenoids, and many phytochemicals can neutralize free radicals. Unfortunately, although it is clear that vitamins are required to prevent deficiency diseases, high doses of vitamin C, vitamin E, and beta carotene supplements may also have pro-oxidant effects, which can be harmful in patients with cancer. In these people, high doses of antioxidant vitamins may actually protect cancer cells just as they do healthy cells.

The strongest evidence on negative effects to date comes from studies reporting an increase in lung cancer and overall mortality rates among smokers who took beta carotene supplements. In determining reasons for this disturbing effect, one animal study suggested that beta carotene increased enzymes in the lungs that actually promote cancerous changes. One study also reported a higher risk for cancer in male smokers who took multivitamins plus A, C, or E.

Some evidence also indicates that high doses of vitamin C may speed up atherosclerosis, or hardening of the arteries. In one study, women with heart disease who took antioxidant vitamins had a higher risk for heart attack or death than those who didn't take one.

Another study also reported a higher incidence and greater severity of respiratory infections in older adults who took 200 mg of vitamin E daily. Some researchers speculate that certain immune factors generate oxidants to fight bacteria. This antioxidant vitamin, then, may block that action. Research published in 2005 suggests that those who take large amounts of vitamin E (1,500 IU/day) may slightly increase their risk for heart failure and death, but this evidence is not considered conclusive. Further study is necessary.

Vitamins and Heart Protection.

Antioxidant Vitamins A, C, and E. Deficiencies in vitamins A, C, E, and beta carotene have been linked to heart disease. All of these nutrients have antioxidant effects and other properties that should benefit the heart. A study in patients with heart failure has shown that vitamin C can work with dobutamine, a powerful intravenous medication, to strengthen the heart’s ability to contract following a heart attack. In fact, a 2005 study has found that taking high doses of vitamin E is associated with an increased risk of heart failure. In 2007, the Women’s Antioxidant Cardiovascular Study failed to find that vitamins C, E, and beta carotene could reduce the risk of heart attack, stroke, need for revascularization, or cardiovascular death in women. According to the U.S. Preventive Service Task Force, evidence is insufficient to confirm or refute the benefits of supplements of any of these vitamins in protecting against heart disease.
Folate and B12 Vitamins. Deficiencies in the B vitamins folate (known also as folic acid) and B12 have been associated with elevated blood levels of homocysteine, an amino acid that has been associated with a higher risk for heart disease, stroke, and heart failure. One study, reported lower failure rates after heart surgery in patients who took folic acid and vitamins B12 and B6. And a major 2002 study suggested that lowering homocysteine levels with folic acid would reduce the risk for heart disease by 16% and stroke by 24%. However, a 2007 trial in adults with stable coronary artery disease found that lowering homocysteine levels 33% with B vitamins and folic acid had no effect on arterial inflammation, meaning that lower levels were unlikely to offer protection against heart attack or stroke. More evidence is needed to determine whether homocysteine plays a causal role in cardiovascular disease and whether the B vitamins are protective. Folate improves blood flow through the arteries, which may be important for the heart, regardless of its effect on homocysteine. Although people with high levels of homocysteine are prone to damaging blood clots in their arteries and veins, a 2007 study found that lowering homocysteine with folic acid and other B vitamins does not reduce the incidence of blood clots in the peripheral veins (deep venous thrombosis).
Niacin. Niacin (vitamin B3) is used for lowering unhealthy cholesterol levels. Although vitamin B3 is available over the counter, it can have significant side effects. A physician should prescribe niacin in order to ensure its safety and effectiveness. [See In-Depth Report #23, Cholesterol.]

Carotenoids and Heart Protection. Studies have reported that a diet high in fruits and vegetables containing beta carotene, lycopene, and other carotenoids may reduce the risk of heart attack. A small Finish study found that a diet high in tomatoes reduced total cholesterol and LDL ("bad") cholesterol. Diets low in lycopene (particularly from tomatoes) were associated with a significantly higher risk of heart disease and stroke.

Atherosclerosis is a disease of the arteries in which fatty material is deposited in the vessel wall, resulting in narrowing and eventual impairment of blood flow. Severely restricted blood flow in the arteries to the heart muscle leads to symptoms such as chest pain. Atherosclerosis shows no symptoms until a complication occurs.

Phytochemicals and Heart Protection. Several phytochemicals are associated with heart protection.

Flavonoids. Certain flavonoids, found in both black and green tea, dark chocolate, onions, red wine or red grape juice, and apples, appear to be strongly heart protective. In one study, people who consumed the most flavonoids in foods had a 20% lower risk for heart disease than those with low consumption. Flavonoids may protect against damage done by cholesterol and help prevent blood clots. A number of studies have now reported heart protection from the flavonoid catechin, which is found in both black and green tea. The flavonoid resveratrol, which is found in grape skin, appears to be responsible for the well-known heart protective effects in red wine and purple grape juice.
Organosulfurs. Organosulfurs found in onions and garlic have been under investigation for possible beneficial effects on cholesterol levels. One study reported an association between taking garlic capsules and significantly lower cholesterol-build up in the arteries of older women but not in older men. In the study, daily garlic supplements dramatically reduced the build-up of newly formed plaque in the arteries, while having much less effect on older, harder plaque deposits. Garlic supplements for cardiovascular disease may be most beneficial when used during earlier years among men and later years among women.
Isoflavones. Soy protein is the most studied source of isoflavones (known as phytoestrogens, or plant estrogens). Not all studies are consistent, but the majority has shown an improvement in at least one of the cholesterol components in people who consumed at least 25 grams of soy protein. A 2007 meta-analysis of all soy protein studies performed from 1990 - 2006 found that soy protein significantly decreased total cholesterol and LDL cholesterol, but had no effect on HDL or triglycerides. The effect was particularly evident in people with hypercholesterolemia. A 2007 study found that 12 weeks of soy supplement lowered total cholesterol and LDL levels in both Caucasian and African-American postmenopausal women. Soy may also reduce other heart risk factors, at least in certain populations. For example, in one 2002 study, soy was beneficial for controlling blood sugar and lowering LDL in postmenopausal women with type 2 diabetes. In a 2007 study of overweight men and postmenopausal women, soy protein reduced blood pressure and arterial stiffness. In another study, soy protein was associated with lower systolic blood pressure in men. The best sources are soy products (tofu, soy milk) or whole soy protein. Powdered soy protein that contains at least 60 mg of isoflavones may provide similar benefits.
Sterols. The plant sterols, including sitosterol, are also proving to be potent cholesterol fighters by blocking the absorption of cholesterol in the intestine. Sitostanol, a derivative of sitosterol, is being used in new margarine products to lower cholesterol levels. Sterols and stanols are now found in breads, cereals, yogurt, and fruit juices.

A healthy diet rich in fruits and vegetables and low in salt and saturated fats may significantly lower the risk for a first stroke, perhaps by helping to protect against high blood pressure -- a major risk factor for stroke.

Vitamins and Stroke Protection. The effects of antioxidant vitamins and carotenoids on stroke, dementia, or both are being studied. Studies are conflicting, however. A 2007 study of 8,171 women with cardiovascular disease reported that vitamins C, E, and beta carotene offered no protection against heart attack and stroke.

The B vitamin folate (usually in the form of folic acid) may protect against stroke. However, exactly which people benefit from this therapy has yet to be determined. Studies have suggested that people who have higher blood levels of folate have a lower than average risk for stroke. Its primary benefit in this case appears to be to reduce levels of homocysteine, an amino acid that has been strongly linked to an increased risk of coronary artery disease, stroke, and Alzheimer's disease. A 2007 meta-analysis of 8 trials found that folate supplements decreased homocysteine 20% and lowered stroke risk 18%. Interestingly, lowering homocysteine with folic acid and B vitamins had no effect on heart attack, strokes, amputations, need for dialysis, or death in patients with chronic or end-stage kidney disease.

Carotenoids and Stroke Protection. Some, but not all, studies have reported a lower risk of stroke from carotenoids, including beta carotene and lycopene.

Many fresh fruits and vegetables contain chemicals that may fight many cancers, including lung, breast, colon, and prostate cancers. Examples of important cancer fighting foods include the following:

Cruciferous vegetables (such as cabbage, Brussels sprouts, and broccoli)
Tomatoes (which contain lycopene)
Carrots (which contain alpha carotene)

Some evidence suggests that antioxidants may enhance the anticancer effects of chemotherapy. In multiple studies, patients who maintained their antioxidant levels were better able to withstand the high stress caused by chemotherapy or radiation therapy compared to those with low antioxidant levels. Antioxidant nutrients that may help reduce the side effects of chemotherapy include vitamins E and C, beta carotene, genistein and daidzein (isoflavones found in soy), and quercetin (found in red wine an purple grape juice).

Any protective effects of vitamins or specific phytochemical against cancer, however, appear to depend on the cooperative effort among them. Individual supplements of any vitamin or food chemical have not as yet shown any benefits.

Additionally, certain supplements may actually encourage tumor growth, particularly when taken in large amounts. Two 2007 studies found a connection between folate supplements and colorectal cancer. In one study, which was designed to evaluate the benefits of folic acid in patients who had previous colorectal adenomas (precancerous polyps), the researchers instead found that folic acid was associated with a higher risk of having 3 or more adenomas and noncolorectal cancers. In another study, it was noted that the downward trend in colorectal cancer diagnoses abruptly started to rise in 1996 when mandatory folate enrichment of grains within the U.S. and Canada began. Rates continue to exceed pre-1996 levels. Additionally, a large 2007 National Cancer Institute/AARP study found an increased risk of advanced and fatal prostate cancer in men who took more than 7 multivitamins a week, but no association between multivitamin use and localized prostate cancer.

High consumption of cruciferous vegetables (at least once per week) was associated with lower risk of kidney cancer, and low consumption (less than once per month) of cruciferous vegetables was associated with higher risk of kidney cancer in a multinational 2007 European study. Cruciferous vegetables also appear to offer protection against head and neck cancer resulting from chemical toxins found in cigarettes and alcohol, for example.

Vitamins and Cancer Protection. Because many cancers are thought to be initiated by the effects of oxygen-free radicals on DNA, the antioxidants A, C, and E and beta carotene have been intensively studied. A major study found that men who took selenium for 6 or 7 years reduced their risk of prostate cancer by 52%. Nevertheless, most individual supplements have not been proven to protect against cancer, and high doses may be dangerous.

A 2007 review of the diets of men exposed to asbestos found a decreased risk of prostate cancer associated with increasing intakes of vitamin C-rich vegetables, but not fruits and vegetables high in vitamin A. The chemopreventive role of silymarin (Silybum marianum), found in milk thistle extract, has been extensively studied and has shown anticancer efficacy against various cancers, especially prostate and skin, by inhibiting UVB radiation.

A review of 13 cancer registries found 416,134 cases of skin cancer and 3,776,501 cases of non-skin cancer as a first cancer. Rates from cancer registries in sunny countries (such as Australia and Spain) and less sunny countries (such as Canada and Iceland) were compared. The researchers concluded that vitamin D production in the skin decreases the risk of several solid cancers, especially stomach, colorectal, liver and gallbladder, pancreas, lung, female breast, prostate, bladder, and kidney cancers. The apparently protective effect of sun exposure against second primary cancer is more pronounced after non-melanoma skin cancers than melanoma.

Consumption of aflatoxins, a common fungus-related toxin infecting cereal grains, oil seeds, spices, tree nuts, and the milk of animals fed contaminated feed, is known to cause hepatocellular carcinoma, a deadly form of liver cancer. Rodent studies have shown that phenolic antioxidants, dithiolethiones, isothiocyanates, and triterpenoids may act as chemopreventive agents, dispersing aflatoxins and protecting against hepatocellular carcinoma. Human trials are planned. A similar study found that several isothiocyanates, diallyl sulfide, and polyphenolic compounds can prevent esophageal dysplasia from progressing to squamous cell carcinoma.

A review of all articles on vitamins and cancer published through February 2007 found that multivitamin/mineral supplement use may prevent cancer in individuals with poor or suboptimal nutritional status. One trial on poorly nourished Chinese showed supplementation with combined Beta-carotene, vitamin E and selenium reduced gastric cancer incidence and mortality, and overall cancer mortality. In a French trial, combined vitamin C, vitamin E, beta-carotene, selenium, and zinc reduced cancer risk in men but not in women. With few exceptions, neither beta-carotene nor vitamin E had benefits for preventing cancer. Beta-carotene supplementation increased lung cancer risk in smokers and persons exposed to asbestos.

A 2007 study of nearly 82,000 men and women in Sweden found that high intake of methionine was associated with reduced risk of pancreatic cancer. The same relationship was not seen with vitamin B6 or folate.

Vitamin A, C, and E. Although some studies have reported an association between low blood levels of these antioxidant vitamins and a higher risk for cancer, supplements of vitamins A, C, and E appear to have few advantages in most cases. And there are some studies finding higher cancer risks with high intakes of antioxidants. For example, a 2003 study reported a higher risk in melanoma in people with vitamin-C rich diets. Another study also reported a higher risk for cancer in male smokers who took multivitamins plus A, C, or E. (Vitamin E may be protective against bladder cancer and ovarian cancer.)
Vitamin D. Some studies have suggested that certain vitamin D compounds may inhibit certain cancer cells, specifically prostate cancer, from proliferating. More research is needed. In 2007, the National Cancer Institute confirmed that ultraviolet (UV) radiation exposure may reduce the risk of developing non-Hodgkin lymphoma (NHL), but only in patients with certain variations in the D vitamin receptor gene. A second 2007 study found that variations in this gene increase the risk of diffuse large B-cell lymphoma. A 2007 prospective analysis of 31,500 women in the Women’s Health Study evaluated calcium and vitamin D intake. The researchers found a moderately lower risk of premenopausal, but not postmenopausal, breast cancer with higher intakes of total calcium and vitamin D. A 2007 review of breast cancer cases reported in Ontario, Canada, found reduced breast cancer risks were associated with increasing sun exposure in women ages 10 - 19, less evidence for associations in women ages 20 - 29, and no evidence for ages 45 - 54. Researchers concluded that sun exposure earlier in life, particularly during breast development, may be key in the connection between vitamin D exposure and breast cancer risk.
Folic acid and B12. These B vitamins convert the amino acid homocysteine to methionine, a substance that helps prevent cells from becoming malignant. Folic acid may provide some protection against cervical and colon cancer. One small study showed a reduction of lung cancer cells in smokers taking folic acid and vitamin B12, but the study was very small, of short duration, and other factors might have biased the results. Still another study reported that folic acid may reduce the risk for breast cancer among women who regularly drink alcohol. (In the study, folic acid had no other effect on breast cancer.)

In 2006, a study for the National Institutes of Health reviewed randomized trials evaluating the effectiveness and safety of multivitamin and mineral supplements in preventing cancer and chronic disease. The studies had mixed results, and some supplements reduced cancer rates in certain populations. However, the reviewers concluded that current evidence is not sufficient to determine whether multivitamin and mineral supplements may prevent cancer and chronic disease.

Carotenoids and Cancer Protection. A number of studies have reported that fruits and vegetables rich in carotenoids are associated with protection against many cancers. Lycopene, found in tomatoes, may have particular value in protection against prostate, colon, lung, and bladder cancer. A 2005 study found that in one out of four men with genetic variations that cause them to be more sensitive to oxidative stress, supplementation with selenium, vitamin E, and lycopene significantly reduces the risk of prostate cancer. Individual supplements, however, do not offer any advantage. In fact, evidence now strongly suggests that beta carotene supplements increase the risk for lung cancer in smokers and people exposed to asbestos

Phytochemicals and Cancer Protection. The following phytochemicals appear to have cancer-protecting properties.

Isothiocyanates. Isothiocyanates and sulforaphane, found in cruciferous vegetables, may block the effects of carcinogens and suppress tumor growth. In one study, for example, women with the highest consumption of cruciferous vegetables had a 24% lower risk of breast cancer than women with the lowest consumption.
Isoflavones. Isoflavones, found in soy beans and flax seed, behave like estrogen in some ways and not in others. Researchers are very interested, then, in their effects on hormone-related cancers, including breast and prostate cancers. Much research has focused on soy. In general, a number of Asian studies have reported an association between a higher intake of soy and a lower incidence of reproductive and breast cancers. The effects of phytoestrogens, however, in all women are far from settled. Some evidence suggests the genistein in soy may have properties that are protective against lung cancer. Nonfermented soy products (tofu, soy milk) also may protect against stomach cancer, while fermented soy products (miso, soy paste) appears to increase the risk.
Organosulfurs. The organosulfur compounds found in the onion and garlic family may have very potent properties in suppressing or blocking carcinogenic substances. A 2007 study found that synthetic organosulfur compounds act as selective inhibitors of growth in breast cancer cells. Studies indicate that people who regularly consume fresh or cooked garlic have about half the risk of developing stomach cancer and two thirds the risk of colorectal cancer as people who eat little or no garlic. One possible explanation for garlic's anti-cancer effect in the stomach is its antibacterial action against H. pylori, which can promote stomach cancer. Taking garlic supplements, however, did not offer these benefits.

It should be noted that studies on the health benefits of vitamins and minerals have some important limitations. Some are held to rigorous standards, while others are not. In most cases, the results of existing research are complex, as they can easily be complicated by factors such as diet, exercise, the presence of healthy or unhealthy lifestyle behaviors, environmental factors, and more.


Disease or Condition	Vitamins	Carotenoids, Phytochemicals, and Healthy Foods
Alzheimer's Disease	Vitamin E. Some reports, including a large 2002 population study, have suggested that vitamin E intake, from food or supplements, may protect against mental decline. (One study suggested that the vitamin protected only those who carried the apoE4 gene. No strong evidence to date has found any protection from antioxidant supplements.) Some studies performed since 2002 challenge this finding, while others agree with it. B Vitamins. Some studies suggest that deficiencies of the B vitamins B6, B12, and folate may be a risk factor for Alzheimer' diseases, possibly because deficiencies elevate homocysteine levels, which some research now associated with a higher risk for Alzheimer's disease. Of these, folates may offer the best protection. In 2007, researchers at Tufts-New England Medical Center reviewed all human studies on folate, vitamin B-6, vitamin B-12, and cognitive function in the elderly conducted between 1966 and November 2006. Six of 10 folate studies reported a significant association between low baseline blood folate concentrations and poor cognitive test performance; 4 of 9 folate studies found associations between low blood folate concentrations and increased prevalence of Alzheimer's disease. No association between vitamin B-6 and vitamin B-12 blood concentrations and cognitive-test performance or Alzheimer's disease was seen, and B-vitamin dietary intake was not associated with cognitive function. Although the majority of studies indicated that low blood folate concentrations predicted poorer cognitive function, data are not solid, due to variations in the way the studies were conducted and lack of agreement on what constitutes a low B-vitamin status.	According to several studies, eating plenty of darkly colored fruits and vegetables may slow brain aging. The estrogen-like properties in isoflavones are of interest in the study of Alzheimer's disease. Animal studies suggest that soy might be protective against AD, particularly in postmenopausal women. Of some concern, however, were one population and a few animal studies suggesting that soy intake may pose a risk for greater mental decline among older men. More research is needed to confirm the effects of soy on the aging brain and to determine if there are gender differences.
Infectious Disease	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 in 2002 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. A review of all studies on vitamin C and pneumonia prevention found only 1 placebo-controlled, randomized trial conducted in an English boarding school during World War II. The trial found a statistically significant (80% or greater) reduction in pneumonia incidence among boys consuming vitamin C. Two less-well-constructed trials arrived at the same conclusion. Therapeutic trials were even scarcer. Only one randomized, double-blind, placebo-controlled study of vitamin C for treatment of pneumonia was found. In this trial, elderly patients given vitamin C had lower mortality and respiratory symptom scores. However, the benefits were restricted to the sickest patients. One other trial of adults in the former Soviet Union found a dose-dependent reduction in the time to recover with two vitamin C doses. One 2007 study on vitamin D found that a single dose by mouth of this vitamin might prevent healthy individuals from activating the bacterium that causes tuberculosis in patients who harbor the infection. Studies on vitamin E specifically have been mixed. A 2002 study, in fact, reported a higher incidence and greater severity of respiratory infections in older adults who took 200 mg of vitamin E daily. However, a 2004 clinical trial conducted among elderly nursing home residents found that daily supplementation with 200 IU of vitamin E did provide protection from upper respiratory infections, especially the common cold. At present, there is not enough evidence to recommend vitamin E for infection prevention. Diarrhea is a worldwide problem, particularly in developing countries and those with poor sanitation. Taking supplements with B-complex vitamins, vitamin C, vitamin E, and selenium may reduce the risk of diarrhea, depending upon the organism that causes the disease. Meanwhile, iron supplements appear to increase the risk of infection from organisms that cause diarrhea. Vitamin A has not been shown to prevent diarrhea. Urinary tract infections (UTIs) may affect as many as 25% of pregnant women. A 2007 study found that women who took vitamin C (100 mg) for 3 months had significantly fewer UTIs than women who did not take vitamin C supplements. Rotavirus is a common cause of acute gastric pain in children under age 5. A 2007 study showed that the high amount of isoflavones found in soy-based infant formula can help prevent rotavirus infection.	Lycopene, found in tomatoes, appears to have properties that protect infection-fighting white blood cells. Saponins extracted from ginseng and allicin (found in garlic) have properties that boost the immune system. Both ginseng and garlic have long been traditionally used for their health benefits.
Asthma	Vitamin C from diet has been associated with lower risk for asthma. In one study, some people with exercise-induced asthma benefited from taking vitamin C one hour before strenuous physical activity. In a 2007 study, taking 1,500 mg supplements of vitamin C for 2 weeks helped prevent exercise-induced airway narrowing in patients with asthma.	Flavonoids found in apples and red wine may help lower the risk for asthma. Some evidence indicates that a low dietary intake of antioxidant nutrients could increase the risk for lung damage. Such nutrients should be obtained from fresh, deep green and yellow-orange fruits and vegetables. A 2007 study found low blood lycopene levels in people with asthma. Increasing lycopene- and vitamin A-rich foods may help raise lycopene levels.
Eye Disorder	Cataracts and Macular Degeneration. Oxygen-free radicals play a role in cataract formation and age related macular degeneration, the most common cause of irreversible blindness in the elderly. Bilberry (Vaccinium myrtillis), which contains powerful anthocyanins, is widely used to prevent macular degeneration. Low levels of vitamin C in the lens of the eye have been particularly strong predictors of cataracts. People with cataracts are frequently deficient in vitamin A, the carotenes, lutein, and zeaxanthin. Studies on protection against cataracts using antioxidant supplements have been mixed, including two identically conducted studies that reported opposite results. Vitamin C currently has the strongest evidence for protection, but even with this antioxidant studies are not consistent. A combination of zinc and antioxidants, including vitamin C and E, may slow the progression of macular degeneration. (Vitamin E alone does not appear to be protective.) Glaucoma. Although no evidence exists that antioxidants will prevent glaucoma, some studies reported an association between vitamin E and improved visual fields in patients with glaucoma.	Several studies report that the consumption of antioxidant-rich foods is associated with a decreased risk for cataracts. Carotenoids, especially lutein, lycopene, and zeaxanthin, are especially eye-protective and may help prevent cataracts and macular degeneration. The National Eye Institute in 2007 suggested that people with intermediate- or advanced macular degeneration in one eye may want to take a vitamin formula shown to reduce the risk of macular degeneration in the other eye by 25%. The formula contains vitamin C, vitamin E, beta-carotene, and zinc. They also suggest that a diet high in lutein and zeaxanthin may help reduce the risk of advanced age-related macular degeneration. Several studies report that the consumption of antioxidant-rich foods is associated with a decreased risk for cataracts. Carotenoids, especially lutein lycopene, and zeaxanthin are especially eye-protective and may help prevent cataracts and macular degeneration.
Skin Disorders and Wrinkles	Topical vitamin A (retinol) has been shown to improve fine wrinkles due to aging, by increasing glycosaminoglycan, which retains water, and increasing collagen production. One small study found that taking a combination of vitamins oral C and E supplements may help reduce sunburn reactions, although the protection is much less than from sunscreens. Taking the vitamins singly did not have any effect. In fact, a 2002 study reported that oral vitamin C had no effect on sunburn reaction. Of concern, in the same study some natural antioxidants in the body were reduced in people who took the vitamin. Also of concern are studies reporting no benefits and possibly harm from topical vitamin C in the form of ascorbyl palmitate, which is soluble in fat. One study reported that older adults had fewer wrinkles if they ate whole grains, fresh fruits and vegetables, and the use of healthy oils (such as olive oil). Diet played a role in improving skin regardless of whether the people in the study smoked or lived in sunny countries.	The following foods and phytochemicals may be especially skin protective: Both green tea and ginger appear to have properties that may provide some protection against skin cancer. Green tea skin care products are now available. The substance silymarin, found in the milk thistle family (which includes artichokes), may inhibit UVB-promoted cancers in animals. In one interesting study, eating garlic protected animals very effectively against UVB damage by interfering with urocanic acid in the skin. Whether these results may apply to humans (and what quantities of garlic might be beneficial) is still unknown.
Osteoporosis	Vitamin D. Vitamin D is the essential companion to calcium in maintaining strong bones. Supplements may be needed for people who have poor exposure to sunlight. It should be noted that diet supplies most people's need and high amounts of vitamin D can be toxic. Of interest: Taking vitamin D supplements does not prevent bone loss in post-menopausal African American women, according to research published in 2005. Further study will be needed to determine whether vitamin D prevents bone loss in women from other ethnic groups. Vitamin K. Studies suggest that vitamin K has properties that protect bone and prevent fracture. Vitamin K2 (menatetrenone), a form of vitamin K, is proving to prevent fractures in people with osteoporosis. Vitamin K affects blood clotting, and supplements are not recommended without specific physician instruction. Vitamin B12. One study reported that in people with osteoporosis and pernicious anemia, taking vitamin B12 (which is used to treat the anemia) also increased bone density. Vitamin C and E. There has been some indication of a positive association between vitamin C and E intake and bone density, although evidence proving actual benefits is weak. Note on Vitamin A. High amounts of dietary vitamin A reduces bone density and may even increase the risk for fracture in both postmenopausal women and men. (A form of vitamin A, retinoic acid, has been found to stimulate bone break down.) Beta carotene does not appear to increase risk. Studies suggest that diets rich in fresh fruits and vegetables (which include those high in potassium and magnesium) reduce elimination of calcium from the body and help preserve bones.	Studies suggest that diets rich in fresh fruits and vegetables (which include those high in potassium and magnesium) reduce elimination of calcium from the body and help preserve bones. Studies are suggesting that isoflavones-rich soy products may actually improve bone density in postmenopausal women. A 2007 study of postmenopausal women in Italy found that 24 months of treatment with genistein plus calcium and vitamin D increased bone density, while women who took calcium and D alone lost bone density. Flavonoids and other compounds in tea may protect the bones.
Menstrual Disorders	Vitamin B6. Limited clinical evidence suggests that vitamin B6 may be beneficial in reducing premenstrual symptoms, including depression. Typically, women take 100 mg per day, although one study suggested that a lower dose (50 mg) may have the same effect. Other preliminary research indicates that women who receive the equivalent of 1,200 mg of calcium and 400 IU of vitamin D per day (through food or supplements) have a significantly lower incidence of premenstrual symptoms than women who did not. Vitamin B1. One study reported relief from menstrual pain using vitamin B1 (thiamin). Vitamin E. Several randomized controlled trials have shown that vitamin E significantly improves both physical and emotional premenstrual symptoms. One study reported that high doses of vitamin E helped reduce menstrual cramps. The doses were much higher than those recommended and could possibly increase the risk for bleeding. Although anecdotal evidence reports that vitamin E helps reduce the frequency of hot flashes for menopausal women, there is no clinical evidence to support this claim.

Resources

http://fnic.nal.usda.gov -- The Food and Nutrition Information Center
http://dietary-supplements.info.nih.gov -- Office of Dietary Supplements, National Institutes of Health
www.ars.usda.gov/ba/bhnrc/ndl -- Nutrient Data Laboratory
www.fda.gov -- Food and Drug Administration
www.eatright.org -- The American Dietetic Association
www.acsh.org -- American Council on Science and Health
www.aicr.org -- American Institute for Cancer Research
www.nutritiondata.com -- Information on vitamins and nutrients in foods
www.consumerlab.com -- Independent testing of nutritional supplements' contents and quality
www.usp.org -- US Pharmacopeia
www.herbs.org -- Herb Research Foundation

References

Age-Related Eye Disease Study Research Group, SanGiovanni JP, Chew EY, Clemons TE, Ferris FL 3rd, Gensler G, Lindblad AS, Milton RC, Seddon JM, Sperduto RD. The relationship of dietary carotenoid and vitamin A, E, and C intake with age-related macular degeneration in a case-control study: AREDS Report No. 22. Arch Ophthalmol. 2007;125(9):1225-1232.

Ambrosini GL, de Klerk NH, Fritschi L, Mackerras D, Musk B. Fruit, vegetable, vitamin A intakes, and prostate cancer risk. Prostate Cancer Prostatic Dis. 2007 May 22; [Epub ahead of print]

Aubertin-Leheudre M, Lord C, Khalil A, Dionne IJ. Six months of isoflavone supplement increases fat-free mass in obese-sarcopenic postmenopausal women: a randomized double-blind controlled trial. Eur J Clin Nutr. 2007 Feb 21; [Epub ahead of print]

Bermudez Y, Ahmadi S, Lowell NE, Kruk PA. Vitamin E suppresses telomerase activity in ovarian cancer cells. Cancer Detect Prev. 2007;31(2):119-28. Epub 2007 Feb 28.

Bodnar LM, Catov JM, Simhan HN, Holick MF, Powers RW, Roberts JM. Maternal vitamin d deficiency increases the risk of preeclampsia. J Clin Endocrinol Metab. 2007 ;92(9):3517-22. Epub 2007 May 29.

Clements RH, Katasani VG, Palepu R, Leeth RR, Leath TD, Roy BP, Vickers SM. Incidence of vitamin deficiency after laparoscopic Roux-en-Y gastric bypass in a university hospital setting. Am Surg. 2006;72(12):1196-202.

Coull DB, Tait RC, Anderson JH, McKee RF, Finlay IG. Vitamin B12 deficiency following restorative proctocolectomy. Colorectal Dis. 2007;9(6):562-566.

Dietary Guidelines for Americans 2005. Dept of Health and Human Services, US Dept of Agriculture. Accessed 10/3/2007.

Fischer Walker CL, Black RE. Micronutrients and diarrheal disease. Clin Infect Dis. 2007;45 Suppl 1:S73-S77.

Glynn RJ, Ridker PM, Goldhaber SZ, Zee RY, Buring JE. Effects of random allocation to vitamin E supplementation on the occurrence of venous thromboembolism: report from the Women's Health Study. Circulation. 2007;116(13):1497-503.

Headstrom PD, Rulyak SJ, Lee SD. Prevalence of and risk factors for vitamin B(12) deficiency in patients with Crohn's disease. Inflamm Bowel Dis. 2007 Sep 20; [Epub ahead of print]

Inderjeeth CA, Glennon D, Petta A, Soderstrom J, Boyatzis I, Tapper J.Vitamin D and muscle strength in patients with previous fractures. N Z Med J. 2007;120(1262):U2730.

Ishihara J, Otani T, Inoue M, Iwasaki M, Sasazuki S, Tsugane S; Japan Public Health Center-based Prospective Study Group. Low intake of vitamin B-6 is associated with increased risk of colorectal cancer in Japanese men. J Nutr. 2007;137(7):1808-1814.

J.G. Ray, C. Kearon, Q. Yi, P. Sheridan, and E. Lonn, for the Heart Outcomes Prevention Evaluation 2 (HOPE-2) Investigators. Randomized Trial of Homocysteine-Lowering Therapy and Risk for Venous Thromboembolism. Ann Intern Med. 2007;146(11):761-767.

Kitchin B, Morgan SL. Not just calcium and vitamin D: other nutritional considerations in osteoporosis. Curr Rheumatol Rep. 2007;9(1):85-92.

Kune G, Watson L. Colorectal cancer protective effects and the dietary micronutrients folate, methionine, vitamins B6, B12, C, E, selenium, and lycopene. Nutr Cancer. 2006;56(1):11-21.

Lim MR, Huang RC, Wu A, Girardi FP, Cammisa FP Jr. Evaluation of the elderly patient with an abnormal gait. J Am Acad Orthop Surg. 2007;15(2):107-117.

Martin H, Lindblad B, Norman M. Endothelial function in newborn infants is related to folate levels and birth weight. Pediatrics. 2007;119(6):1152-1158.

Mason JB, Dickstein A, Jacques PF, Haggarty P, Selhub J, Dallal G, Rosenberg IH. A temporal association between folic acid fortification and an increase in colorectal cancer rates may be illuminating important biological principles: a hypothesis. Cancer Epidemiol Biomarkers Prev. 2007;16(7):1325-1329.

Nardin RA, Amick AN, Raynor EM. Vitamin B(12) and methylmalonic acid levels in patients presenting with polyneuropathy. Muscle Nerve. 2007;36(4):532-535.

Ochoa-Brust GJ, Fernández AR, Villanueva-Ruiz GJ, Velasco R, Trujillo-Hernández B, Vásquez. Daily intake of 100 mg ascorbic acid as urinary tract infection prophylactic agent during pregnancy. Acta Obstet Gynecol Scand. 2007;86(7):783-787.

Parekh N, Chappell RJ, Millen AE, Albert DM, Mares JA. Association between vitamin D and age-related macular degeneration in the Third National Health and Nutrition Examination Survey, 1988 through 1994. Arch Ophthalmol. 2007;125(5):661-669.

Pham DQ, Plakogiannis R. Vitamin E supplementation in Alzheimer’s disease, Parkinson’s disease, tardive dyskinsia, and cataract: Part 2. Ann Pharmacother. 2005;39(12): 2065-2072.

Riccioni G, Bucciarelli T, Mancini B, Di Ilio C, Della Vecchia R, D'Orazio N. Plasma lycopene and antioxidant vitamins in asthma: the PLAVA study. J Asthma. 2007;44(6):429-432.

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Sahin M, Tutuncu NB, Ertugrul D, Tanaci N, Guvener ND. Effects of metformin or rosiglitazone on serum concentrations of homocysteine, folate, and vitamin B12 in patients with type 2 diabetes mellitus. J Diabetes Complications. 2007;21(2):118-123.

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Triantafyllou NI, Kararizou E, Angelopoulos E, Tsounis S, Boufidou F, Evangelopoulos ME, Nikolaou C, Vassilopoulos D. The influence of levodopa and the COMT inhibitor on serum vitamin B12 and folate levels in Parkinson's disease patients. Eur Neurol. 2007;58(2):96-99.

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Review Date:
10/29/2007
Reviewed By:
Harvey Simon, MD, Associate Professor of Medicine, Harvard Medical School; Physician, Massachusetts General Hospital.

A.D.A.M. Copyright

adam.com

Benign prostatic hyperplasia

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

In This Report

Highlights
Introduction
Symptoms
Causes of Benign Prostatic ...
Causes of Lower Urinary Tra...
Risk Factors
Complications
Diagnostic Tests
Treatment
Lifestyle Changes
Medications
Other Treatments
Resources
References

HEALTH GUIDE REFERENCE FROM A.D.A.M

Highlights

Self-Management for Benign Prostatic Hyperplasia (BPH)

Men who receive training in lifestyle and behavioral approaches may be able to successfully manage BPH without drugs or surgery, suggests a 2007 study in the British Medical Journal. Men in the study were trained to self-manage their lower urinary tract symptoms (LUTS), a condition that often accompanies BPH. Self-management approaches included limiting daily fluid intake, avoiding caffeine and alcohol, and urinating at least once every 3 hours.

Diet and BPH

Eating lots of fruits and vegetables, especially those high in beta-carotene and vitamin C, may help protect against BPH, suggests a 2007 study in the American Journal of Clinical Nutrition. Another study, published in Urology, indicated that high consumption of cereal, bread, eggs, and poultry may increase the risk of BPH.

High Intake of Zinc Increases BPH Risk

High doses of zinc supplements may increase the risk for urinary problems, especially for men, indicates a 2007 study in the Journal of Urology. Patients in the study who took 80 mg/day of zinc were more likely to be hospitalized for urinary complications than those who did not take zinc. In general, the upper limit for zinc supplements should not exceed 40 mg/day.

Tamsulosin and Tolterodine Combination Treatment

For men with moderate-to-severe LUTS, including overactive bladder, a combination of tamsulosin (Flomax) and tolterodine (Detrol) works better than either drug alone, according to a study published in 2006 in the Journal of the American Medical Association.

Botox for BPH?

Botulinum toxin A (Botox) is being investigated as a treatment for BPH. In research presented at the 2007 meeting of the American Urological Association, men who had Botox injected into their prostate glands experienced symptom relief and improved quality of life for up to a year after treatment.

Introduction

Hyperplasia is a general medical term referring to excess cell replication. Benign prostatic hyperplasia (BPH), also called benign prostate hyperplasia, is a noncancerous growth of the prostate gland. It is the most common noncancerous form of cell growth in men and usually begins with microscopic nodules in younger men. BPH, however, is not a precancerous condition. Prostate cancer usually occurs in the outer area of the prostate, called the peripheral zone.

The prostate gland is an organ that surrounds the urinary urethra in men. It secretes fluid that mixes with sperm to make semen. The urethra carries urine from the bladder and sperm from the testes to the penis.

As BPH progresses, overgrowth occurs in the central area of the prostate, called the transition zone, which wraps around the urethra (the tube that carries urine through the penis). This pressure on the urethra can cause lower urinary symptoms that have been the basis for diagnosing BPH. In 2000, an expert committee suggested that the impact of such symptoms on quality of life, including sexual activity, is also important in assessment of the disease.

Click the icon to see an image of BPH.

Description of the Prostate Gland. The prostate gland is located between the bladder and the rectum and wraps around the urethra (the tube that carries urine through the penis). It is basically composed of three different cell types:

Glandular cells, which produce a milky fluid that liquefies semen.
Smooth muscle cells, which contract during sex and squeeze the fluid from the glandular cells into the urethra, where it mixes with sperm and other fluids to make semen. Molecules called alpha adrenergic receptors stimulate the muscle cells.
Stromal cells (which form the structure of the prostate).

Click the icon to see an image of the male reproductive anatomy.

The central area of the prostate that wraps around the urethra is called the transition zone. The entire prostate gland is surrounded by a dense, fibrous capsule.

Functions of the Prostate Gland. The prostate gland provides the following functions:

The glandular cells produce a milky fluid, and during sex the smooth muscles contract and squeeze this fluid into the urethra. Here, it mixes with sperm and other fluids to make semen.
The prostate also secretes another substance that may have antibacterial properties.
The prostate gland also contains an enzyme called 5 alpha-reductase that converts testosterone to dihydrotestosterone, another male hormone with a major impact on the prostate.

Changes During the Lifespan. The prostate gland undergoes many changes during the course of a man's life. At birth, the prostate is about the size of a pea. It grows only slightly until puberty, when it begins to enlarge rapidly. It reaches normal adult size and shape, about that of a walnut, when a man is in his early 20s. The gland generally remains stable until about the mid-40s, when, in most men, the prostate begins to grow again through a process of cell multiplication.

Hormonal changes also occur in the prostate gland. Testosterone levels fall while dihydrotestosterone remain at normal levels.

Symptoms

The symptoms commonly associated with BPH are collectively called lower urinary tract symptoms (LUTS). BPH is not always the cause of these symptoms. An enlarged prostate may be accompanied by few symptoms, while severe LUTS may be present with normal or even small prostates and are most likely due to other conditions. Many experts are now categorizing LUTS as either voiding or storage symptoms to help define the source of the problem.

Voiding symptoms, also referred to as obstructive symptoms, can be caused by an obstruction in the urinary tract. They are often due to BPH. Obstruction is the most serious complication of BPH and requires medical attention. Voiding symptoms include:

Weak or intermittent urinary stream
Straining when urinating
A hesitation before urine flow starts
A sense that the bladder has not emptied completely
Dribbling at the end of urination or leakage afterward
Painful urination
Hematuria (blood in the urine)

Storage symptoms, also referred to as irritative symptoms, include:

An increased frequency of urination, particularly at night
An urgent need to urinate
Bladder pain or irritation when urinating

Urine flows from the kidney through the ureters into the urinary bladder where it is temporarily stored. As the bladder becomes distended with urine, nerve impulses from the bladder signal the brain that it is full, giving the individual the urge to void. By voluntarily relaxing the sphincter muscle around the urethra, the bladder can be emptied of urine. Urine then flows out through the urethra.

The process of urination is more complicated than it appears:

It begins when waste fluids flow out of the kidneys into two long tubes called ureters.
The ureters empty into the bladder, which rests on top of the pelvic floor, a muscular structure similar to a sling running between the pubic bone and the base of the spine.
The brain regulates muscles in the urinary tract through a pathway of nerves. As the bladder fills to its capacity of 8 - 16 oz of fluid, the nerves send signals from the bladder to the brain that indicate how full the bladder is.
As the bladder swells, the muscles contract to prevent urination.
At the time of urination, the spinal cord initiates the voiding reflex. The detrusor muscles (which surround the bladder) contract, while the internal sphincter (a strong muscle encircling the neck of the bladder) relaxes.
When the internal sphincter is open, urine flows out of the bladder into the urethra (the tube that carries urine from the bladder out through the penis).

Causes of Benign Prostatic Hyperplasia

The causes of benign prostatic hyperplasia are not fully known. Several theories have been proposed to explain benign cell growth in older men.

Male Hormones. Androgens (male hormones) most likely play a role in prostate growth. The most important androgen is testosterone, which is produced throughout a man's lifetime. The prostate converts testosterone to a more powerful androgen, dihydrotestosterone (DHT). DHT stimulates cell growth in the tissue that lines the prostate gland (the glandular epithelium) and is the major cause of the rapid prostate enlargement that occurs between puberty and young adulthood. DHT is a prime suspect in prostate enlargement in later adulthood.

Estrogen. Some authorities believe that the female hormone estrogen may also play a role in BPH. (Some estrogen is always present in men.) As men age, testosterone levels drop, and the proportion of estrogen increases, possibly triggering prostate growth.

Another theory focuses on cells in a certain section of the gland that may become active late in life, signaling other prostate cells to replicate or causing them to be sensitive to growth-stimulating hormones.

This theory suggests that a process known as apoptosis, in which cells naturally self-destruct, goes awry and results in cell proliferation.

Some experts theorize that the blood vessels in the prostate gland may deteriorate as men age, causing abnormal blood flow and oxygen loss, which would stimulate cell growth. Such a theory is supported by the presence of heart and circulatory problems in many men with BPH.

Causes of Lower Urinary Tract Symptoms

Several structural or medical conditions, either independently or in conjunction with BPH, can cause lower urinary tract symptoms. In addition, prostate growth does not always explain symptoms normally attributed to BPH. Men with large prostates do not always have symptoms, and men with small or normal-sized prostates sometimes have symptoms that are more severe than in those with enlarged glands.

Abnormalities in the urinary tract can cause BPH-like symptoms in men with or without enlarged prostate glands. Such conditions can produce obstruction, impair or weaken the detrusor muscles surrounding the bladder, or cause other damage that impacts the urinary tract. They include:

Muscle contractions in the area where the bladder and urethra meet
A narrowing of the urethra
A weakened bladder
Overactivity in prostate muscles

The male and female urinary tracts are relatively the same except for the length of the urethra.

The process of aging weakens the detrusor muscles that surround the bladder, which causes the bladder to become unstable and lose capacity. Unstable detrusor muscles may also impair bladder storage capacity, which then produce irritative or storage symptoms. Studies also indicate that as men get older they may produce more urine at night, although the total daily output of urine is similar to that in middle-aged men. It is not fully known why this occurs.

Prostatitis is an inflammation of the prostate gland. It can be caused by bacterial infection, which is the easiest cause to diagnose. However, the most common form of prostatitis is nonbacterial.

Bacterial Prostatitis. A prostatitis infection can occur abruptly (acute) or be long-term (chronic). Chronic bacterial prostatitis (CBP) is often subtle and may persist for weeks or months with low-grade symptoms, including an urgent need to urinate, frequent urination, and the need to urinate at night. Pain may occur in the lower back or rectum, or it may develop after ejaculation. Because the prostate isn't swollen, doctors may mistake chronic prostatitis for BPH. A urine culture should always be taken, which, in the case of both acute and chronic bacterial prostatitis, will reveal bacteria and confirm a diagnosis. Antibiotics are required to treat CBP. Fluoroquinolones and trimethoprim-sulfamethoxazole (Bactrim, Septra) are particularly effective, but prolonged treatment may be necessary.

Nonbacterial Prostatitis. In nonbacterial prostatitis, inflammation occurs, but no bacteria are present. It is 8 times more common than bacterial prostatitis. The causes of nonbacterial prostatitis have not been determined. In one study, alfuzosin, an alpha-blocker drug that is used for BPH, provided some modest relief in patients with prostatitis and chronic pain. The routine use of drug therapy does not seem to help this condition. More research is needed.

Prostatodynia. Although it is considered a form of prostatitis, prostatodynia is a noninflammatory disorder characterized by prostate pain, but neither inflammation nor bacteria are present. The causes of prostatodynia are unknown.

Congestion of the prostate, sometimes called prostatosis, is a benign condition in which the prostate seems to be swollen by excess fluid. It can cause frequent, slow, or uncomfortable urination, but it responds well to a program of frequent ejaculation and sitz baths.

On occasion, prostate cancer can mimic BPH, since both conditions may cause obstruction of the urethra. Bladder cancer can sometimes cause urinary bleeding, frequency of urination, or a sense of urgency, also symptoms of BPH.

Click the icon to see an image of prostate cancer.

Several other conditions can impair the lower urinary tract, including tumors, reactions to medications, and spinal cord injuries. Diseases that affect the nervous system, such as diabetes, multiple sclerosis, and shingles, can desensitize the nerves so that they fail to sense fullness and do not trigger the contraction of the bladder.

Risk Factors

About 5.5 million American men have benign prostatic hyperplasia (BPH) that could warrant medical attention. Age is the major risk factor. BPH occurs in about 60% of men over 60 years of age and over 80% of men over age 80.

A family history of BPH appears to increase a man's chance of developing the condition. One study reported that men with BPH who had three or more family members with the condition had much larger prostate glands than men with BPH without such a family history.

Some evidence suggests a higher incidence of benign prostatic hyperplasia -- particularly fast-growing BPH -- in men with obesity, heart and circulatory diseases, and type 2 diabetes. Diabetes and hypertension, in any case, worsen urinary tract symptoms in men with BPH. In one study, diabetes adversely affected flow rates, although residual urine volumes were not significantly greater.

Complications

The progression of symptoms in benign prostatic hyperplasia (BPH) is typically very slow, and additional symptoms, when they occur, often come and go. Individual response to these symptoms also varies widely. Some men can tolerate very uncomfortable sensations of abnormal urination, while other men seek relief from mild symptoms. BPH does not appear to impair sexual function. Problems with urination, however, can be very distressing and severely affect quality of life in some cases.

Click the icon to see an animation about BPH.

Men are more apt to tolerate voiding symptoms (intermittent flow, hesitancy before urinating) and seek help for storage symptoms (urgency, frequency, urination at night). Voiding symptoms, however, may indicate an obstruction blocking the bladder, which if extensive can severely reduce urine flow and cause other complications, some serious.

Acute Urinary Retention. Sometimes a man is unaware of an obstruction until he suddenly cannot urinate at all. This condition is called acute urinary retention. It is a dangerous complication that can damage the kidneys and may require emergency surgery. In general, BPH progresses very slowly, and long-term urinary retention is very uncommon. Men with BPH at highest risk for this problem tend to be elderly and to have moderate-to-severe lower voiding symptoms. Taking anti-hypertensive drugs (except for diuretics) or antiarrhythmic drugs may also increase the risk.

Other Complications. Bladder obstruction can also cause bladder stones, blood in the urine, urinary tract infection, and incontinence. It may also increase the risk for chronic kidney disease. Unfortunately, no current tests can accurately predict which men are at higher risk for complications, although men with a weak urine stream and larger prostates are at higher risk for urinary retention.

Click the icon to see an image of prostate cancer.

Debate is ongoing over whether BPH and prostate cancer have any association. Both occur in men in the same age groups, and BPH causes prostate enlargement. Most evidence finds no significantly higher risk for prostate cancer in men with BPH. For one reason, the two conditions develop in different parts of the prostate:

BPH occurs in the inner transition zone, while
Cancer tends to develop in the peripheral outer zone

A 10-year study found no higher risk for prostate cancer in men with BPH. Unsuspected prostate cancer is detected during surgery in about 15% of BPH patients, but the risk of this slow-growing cancer is high in all older men. Some estimates suggest that up to a third of men over age 50 have at least microscopic prostate cancer.

Still, there is some evidence that men with fast-growing BPH may be at higher than average risk for prostate cancer. This prostate condition is also associated with obesity, heart disease, and diabetes. Some experts suspect that insulin resistance may be the common factor in all of these conditions, including prostate cancer.

Diagnostic Tests

An indexing tool called the International Prostate Symptoms Score (IPSS) can help evaluate the key lower urinary tract symptoms. As opposed to laboratory tests or other objective tests, this scoring system measures the patient's own experience. The higher the score, the more severe the conditions. It is useful for many reasons:

The patient's score on this test gives a highly accurate assessment of the effect of lower urinary tract symptoms on the quality of a man's life.
It is a reasonable basis from which the patient and doctor can discuss treatment options.
The index is also often used to gauge treatment outcomes and may be a better indicator of success than objective tests, such as the measurement of the prostate gland or the rate of urine flow.

Limitations. The IPSS is useful only as a measure of symptom severity, and has the following limitations:

Other conditions can produce similar scores, so the test is not used as a diagnostic tool for BPH.
The index does not include other urinary symptoms, such as dribbling and incontinence or sexual health, that are important for quality of life. At the very least, the patient should have a frank discussion with his doctor if such symptoms are present and affect his life.
It also does not reflect regional or ethnic differences that can vary the responses to these symptoms.


Symptoms over past month	Never	Less than 1 time in 5	Less than half the time	About half the time	More than half	Almost always
Sensation that the bladder is not empty after urinating	0 = None	1 = One time	2 = Twice	3 = three times	4 = four times	5 = five times or more
Need to urinate within two hours of a previous urination	0 = None	1 = One time	2 = Twice	3 = three times	4 = four times	5 = five times or more
Need to stop and start again several times while urinating	0 = None	1 = One time	2 = Twice	3 = three times	4 = four times	5 = five times or more
Have a weak urinary stream	0 = None	1 = One time	2 = Twice	3 = three times	4 = four times	5 = five times or more
Need to strain to urinate	0 = None	1 = One time	2 = Twice	3 = three times	4 = four times	5 = five times or more
Number of times during the night awakened by the need to urinate	0 = None	1 = One time	2 = Twice	3 = three times	4 = four times	5 = five times or more
Circle appropriate number. Totals of 7 or less = mild symptoms; 8-19 = moderate; 20-35 = severe.

Other indexing systems, such as Symptom Problem Index (SPI) and the BPH Impact Index (BII), which gauge different quality-of-life and disease issues, are being used in addition to the IPSS to help assess the patient.

Digital Rectal Exam. The digital rectal exam is used to detect an enlarged prostate. The doctor inserts a gloved and lubricated finger into the patient's rectum and feels the prostate to estimate its size and to detect nodules or tenderness. The exam is quick and painless, but embarrassing for some, and far from infallible. The test helps rule out prostate cancer or problems with the muscles in the rectum that might be causing symptoms, but it generally underestimates the prostate's size. It is never the sole diagnostic tool for either BPH or prostate cancer.

Other Physical Examinations. The doctor will usually press on and manipulate (palpate) the abdomen and sides to detect signs of kidney or bladder abnormalities. The doctor will also check for signs of anemia or swelling in the legs and arms. Certain procedures that test reflexes, sensations, and motor response may be performed in the lower extremities to rule out possible neurologic causes of bladder dysfunction.

To determine whether the bladder is obstructed, an electronic test called uroflowmetry measures the speed of urine flow. The test cannot determine the cause of obstruction, which can be due not only to BPH but possibly also to problems in the urethra, weak bladder muscles, or other causes.

The patient is instructed not to urinate for several hours before the test and to drink plenty of fluids so he has a full bladder and a strong urge to urinate.
To perform this test, a patient urinates into a special toilet equipped with a uroflowmeter.
It is important that the patient remains still while urinating to help ensure accuracy, and that he urinates normally and does not exert strain to empty his bladder or attempt to retard his urine flow.
Many factors can affect urine flow (such as straining or holding back because of self-consciousness) so experts recommend then that the test be repeated at least twice.

Q[max]. The rate of urine flow is calculated as milliliters of urine passed per second (mL/s). At its peak, the flow rate measurement is recorded and referred to as the Q[max]. The higher the Q[max], the better the patient's flow rate. Men with a Q[max] of less than 12 mL/s have four times the risk for urinary retention than men with a stronger urinary flow.

The Q[max] measurement is sometimes used as the basis for determining the severity of obstruction and for judging the success of treatments. It is not very accurate, however, for several reasons:

Urine flow varies widely among individuals as well as from test to test.
The patient's age must be considered. Flow rate normally decreases as men age, so the Q[max] typically ranges from more than 25 mL/s in young men to less than 10 mL/s in elderly men.
The Q[max] level does not necessarily coincide with a patient's perceptions of the severity of his own symptoms.

A urinalysis can detect signs of bleeding or infection. A urinalysis involves a physical and chemical examination of urine. In addition, the urine is spun in a centrifuge to allow sediments containing blood cells, bacteria, and other particles to collect. This sediment is then examined under a microscope. Although urinary infection is uncommon in younger men, it occurs more frequently in older men, particularly those with BPH. A urinalysis also helps rule out bladder cancer.

To rule out prostatitis (infection or inflammation of the prostate gland), a simple test called the Pre and Post Massage Test (PPMT) is about 90% accurate. This test requires two cultures and microscopic examinations of urine samples, taken before and after massage of the prostate gland. To massage the prostate the doctor simply inserts a gloved finger into the rectum and presses several times on the prostate. The following results are indicated by findings on cultures after massage:

Category II prostatitis (Chronic bacterial). Bacteria are found on post-massage.
Category IIIA prostatitis (Inflammatory chronic pelvic pain syndrome). Leukocytes or other cells are found that indicate inflammation.
Category IIIB prostatitis (Noninflammatory chronic pelvic pain syndrome). No signs of inflammation or bacteria.

In men with symptoms, blood tests can measure a substance called serum creatinine, which is a marker for kidney trouble. Kidney problems exist in an average of 13.6% of BPH patients. Studies have reported rates as high as 30% and as low as 0.3%.

A PSA test measures the level of prostate-specific antigen (PSA) in the patient's blood. It is the standard screening test for prostate cancer. A PSA is recommended annually for all men over 50 years old and for men over age 40 who are at high risk for prostate cancer.

BPH itself can also raise PSA levels, but the test has generally been optional for men with suspected BPH. One 2000 study indicated that PSA levels may be good predictors of future prostate growth in men with BPH. In the study, men with the lowest PSA level groups (0.2 - 1.3 ng/mL) had prostate growth rates of only 0.7 mL per year while those in the high PSA groups (3.3 - 9.9) had growth rates of 3.3. mL per year. Other research has detected a specific molecular form of PSA, called BPSA because it may be a specific marker for BPH. Such findings could eventually lead to a shift from focusing on symptoms and flow rates for diagnosis to a more specific and possibly preventive approach.

Certain treatments for BPH, including the drug finasteride (Proscar) and the surgical procedure transurethral resection of the prostate (TURP), can reduce PSA levels and possibly mask the existence of prostate cancer.

A more recent test identifies so-called free PSA, which is found in lower levels when prostate cancer is present and in higher levels with benign prostate hyperplasia. This may be more accurate than total PSA, regardless of whether a man is taking finasteride or not.

One of the important tests for urinary incontinence is the postvoid residual urine volume (PVR), the amount of urine left after urination. Normally, about 50 mL or less of urine is left; more than 200 mL is a definite sign of abnormalities. Measurements in between require further tests. The most common method for measuring PVR is with a catheter, a soft tube that is inserted into the urethra within a few minutes of urination. PVR can also be measured using transabdominal ultrasonography.

Ultrasound of the prostate does not require a catheter and gives an accurate picture of the size and shape of the prostate gland. Ultrasound is very beneficial when planning surgery and determining treatment options and gauging their effectiveness. Ultrasound may also be used for detecting kidney damage, tumors, and bladder stones. Ultrasound tests of the prostate generally use one of two methods:

Transrectal ultrasonography (TRUS) uses a rectal probe for assessing the prostate. TRUS is significantly more accurate for determining prostate volume. It can sometimes detect cancer.
Transabdominal ultrasonography uses a device placed over the abdomen. It can give an accurate measure of postvoid residual urine and is less invasive and expensive than TRUS.

Filling cystometry, also called cystometrography, is usually used for patients who cannot urinate and in whom nerve damage or injury of the bladder is suspected. The test is used to determine the absence or presence of a condition called uninhibited detrusor contractions (UDC), which often occurs in men with storage urinary tract symptoms. The detrusor is the group of muscle fibers that cover the outside of the bladder. The test does not add much information to results from less invasive tests and is not used routinely.

A urethrocystoscopy, also called cystourethroscopy, may be performed in men diagnosed with BPH, particularly if they are surgical candidates or if other urinary tract problems are suspected. Such problems include blood in the urine, infection, interstitial cystitis, bladder cancer, or prior surgery or injury. The doctor can determine the presence of a number of structural problems, including enlargement of the prostate, obstruction of the urethra or neck of the bladder, anatomical abnormalities, or the presence of stones.

Procedure. In this procedure, a flexible or rigid fiberoptic tube (an endoscope) is inserted into the urethra to allow doctors to view the lower urinary tract.

Complication. The procedure is not without risks. Complications are uncommon but can include allergic response to the anesthetic, urinary tract infection, bleeding, and urine retention.

An x-ray called an intravenous excretory urography (IVU) is an invasive test that is used only when complications in the upper urinary tract, particularly in the kidney, are suspected. Alternatively, an abdominal ultrasound plus a normal x-ray may be as useful as IVU for most patients with suspected upper urinary tract problems.

Complications and Side Effects. If there is any danger of kidney failure, the test should not be performed, since it can exacerbate the condition. Severe side effects of the test occur in 0.1% of patients.

Some doctors believe that a number of men may be incorrectly diagnosed with BPH when they have interstitial cystitis (an inflammation of the bladder that may be associated with allergic or autoimmune response). The potassium sensitivity test is sometimes used to diagnose IC. Some experts believe this test missed too many IC patients, although a 2001 study concluded that a combination of potassium sensitivity and urodynamic tests is useful in distinguishing between BPH and interstitial cystitis.

Treatment

Because BPH rarely causes serious complications, men usually have a choice between treating it or opting for watchful waiting:

Watchful Waiting. Watchful waiting (also known as active surveillance) involves lifestyle changes and an annual examination. Even when choosing watchful waiting, an initial examination is critical to rule out other disorders.
Treatment Options. The primary goals of treatment for BPH are to improve urinary flow and to reduce symptoms. Many options are available. They include drug therapies, minimally invasive procedures, and major surgery.

The choice between watchful waiting and treatment usually depends on a number of factors, such as urine flow rates, prostate size, and PSA levels. Men with BPH who develop symptoms at around age 50 are more likely to need treatment within their lifetimes than older men. Unfortunately, there is no current way to determine who specifically might be at risk for serious problems and need early treatment.

The development of the International Prostate Symptoms Score (IPSS) has made the evaluation of symptoms somewhat easier. This scoring service serves as a benchmark for determining severity. The decision to treat or not to treat is typically based on the guidelines described below, but the ultimate choice is often guided primarily by a man's perception of his own symptoms.

Mild, or No, Symptoms. Men with mild, or no, symptoms (IPSS scores of 7 or below) usually choose watchful waiting even if their prostates are enlarged. BPH eventually progresses to the point of needing treatment in about 15% of men with mild symptoms who wait.

Moderate Symptoms. The choice is most difficult for men with moderate symptoms (scores between 8 - 19) and may simply depend on a man's ability to tolerate them. Some studies have reported that up to 40% of men with moderate symptoms eventually seek treatment, and a quarter require surgery. In a small percentage of patients, symptoms improve.

Severe Symptoms. Men with severe symptoms (scores over 20) nearly always choose treatment, although if their prostate glands are small or normal-sized, symptoms may improve.

If a man opts for treatment, there are several choices. Most experts recommend a staged approach as follows:

Mild Symptoms. Medications are the best choice for men with mild symptoms who decide to have their condition treated. There are two standard choices: alpha-blockers and anti-androgens, nearly always finasteride (Proscar). Specific conditions determine the choice, although most men take an alpha-blocker. Men with mild symptoms who choose surgery only experience minor improvement afterward but face the same risks as patients with more severe symptoms.
Moderate-Severe-Symptoms. Men with moderate-to-severe symptoms often respond to the same medications as men with mild symptoms. (Combinations of alpha-blockers and finasteride are under investigation.) Recent developments in drug therapy have reduced the number of surgical procedures needed and delayed their use. However, a quarter of men with moderate symptoms, and even more men with severe symptoms eventually need surgery. If a man chooses surgery, there are many choices. Transurethral resection of the prostate (TURP) is the standard procedure, but less invasive procedures, particularly those using heat or lasers to destroy prostate tissue, are gaining prominence.

Click the icon to see an illustrated series detailing transurethral resection of the prostate surgery.

The most common reason for choosing surgery is obstruction of the bladder outlet, which causes urinary retention. Surgery is also typically a reasonable option when BPH is clearly related to one or more of the following conditions:

Recurrent urinary tract infection.
Hematuria (blood in the urine). Studies have suggested that when hematuria is left untreated, two-thirds of patients continue to bleed and one third require surgery. The drug finasteride may help some men with this condition and should probably be tried before surgery.
Bladder stones.
Kidney problems.
Some experts believe that surgery might benefit patients for whom an early diagnosis of prostate cancer is important. Unsuspected prostate cancer is detected during surgery in about 15% of cases.

The greatest improvements resulting from surgery are usually increased urinary flow and reduced urine retention. In one study, men who chose surgery reported more worry and depression before the procedure, but afterward they had less depression and anxiety than those who had chosen medication. Often, however, the benefits of surgery are not permanent.

Lifestyle Changes

Certain lifestyle changes can help relieve symptoms and are particularly important for men who choose to avoid surgery or drug therapy. A 2007 study found that men who were educated on behavioral and lifestyle management of BPH were less likely to require surgery or drug therapy. Men should limit daily fluid intake to less than 2,000 mL (about 2 quarts) and, in particular, avoid alcohol and caffeine intake. Men should try to urinate at least once every 3 hours. “Double-voiding” may also be helpful -- after urinating, wait and try to urinate again. Cold weather and immobility may increase the risk for urine retention. Keeping warm and exercising may be useful. Stress reduction techniques may also help.

Studies have suggested the following:

Avoid fluids after your evening meal.
Coffee has been associated with a higher risk for BPH. Some evidence suggests that drinking green tea, however, may benefit the prostate.
Moderate alcohol consumption may be protective. (Heavy alcohol consumption, however, may increase the risk for lower urinary tract symptoms, and, in any case, is harmful.)
Genistein, a chemical found in soy, reduced the growth of BPH tissue in the laboratory. Although Asians have a low incidence of BPH and prostate cancer and also have diets rich in soy, it is not yet known if eating soy products will reduce the risk of BPH or improve any symptoms.
Fruits and vegetables rich in beta-carotene and vitamin C may help protect against BPH. Conversely, high consumption of cereals, bread, eggs, and poultry may increase the risk for BPH.
High doses of zinc supplements may increase the risk of BPH.

Decongestants and Antihistamines. Men with BPH should avoid, if possible, the many medications for colds and allergies that contain decongestants, such as pseudoephedrine (Sudafed). Such drugs, known as adrenergics, can exacerbate urinary symptoms by preventing muscles in the prostate and bladder neck from relaxing to allow urine to flow freely. Antihistamines, such as diphenhydramine (Benadryl), can also slow urine flow in some men with BPH.

Diuretics. Men who are taking diuretics, which increase urination, may want to talk to their doctor about reducing the dosage or switching to another drug. These are important drugs for many people with high blood pressure, with a proven track record for saving lives. No one should go off these medications without medical supervision.

Other Drugs. Other drugs that may worsen symptoms are certain antidepressants and drugs used to treat spasticity.

Some, but not all, research suggests that moderate exercise can reduce urinary tract problems associated with BPH.

Kegel (pelvic floor muscle) exercises, first developed to help women with childbirth, can also help men prevent urine leakage. They strengthen the pelvic floor muscles that both support the bladder and close the sphincter.

Performing the Exercises. Since the muscle is internal and sometimes hard to isolate, doctors often recommend practicing while urinating:

The patient is asked to contract the muscle until the flow of urine is slowed or stopped. He attempts to hold each contraction for 20 seconds.
He then releases the contraction.
In general, patients should perform 5 - 15 contractions, three to five times daily.

Medications

The two primary drug classes used for BPH are:

Alpha-blockers. These drugs relax smooth muscles, especially in the urinary tract and prostate. They include terazosin (Hytrin), doxazosin (Cardura), tamsulosin (Flomax), and alfuzosin (Uroxatral). Alpha-blockers help relieve BPH symptoms, but they do not reduce the size of the prostate. The can help improve urine flow and reduce risk of bladder obstruction. They are often the first choice, especially for men with smaller prostates.
5-alpha-reductase inhibitors. Finasteride (Proscar) and dutasteride (Avodart) block the conversion of testosterone to dihydrotestosterone, the male hormone that stimulates the prostate. These drugs are better for men with significantly enlarged prostates. In addition to relieving symptoms, they increase urinary flow and may even help shrink the prostate. However, patients may have to take these drugs for up to 6 - 12 months to achieve full benefits.

Because these two types of drugs work in different ways, researchers are investigating combinations of the two for selected patients. Results from the Medical Therapy of Prostatic Symptoms (MTOPS) trial, published in 2003, reported that a combination of doxazosin and finasteride delayed progression of BHP more effectively than either drug alone. The combination treatment may work best for high-risk patients with larger prostate glands and higher PSA readings. Many men, however, can control their condition with a single drug.

General Guidelines for Alpha-Blockers.Alpha-adrenergic antagonists, commonly called alpha-blockers, were originally used to treat high blood pressure. They are prescribed for BPH to relax smooth muscles in the prostate. The muscle cells in the prostate are stimulated by molecules called alpha adrenergic receptors. This can cause lower urinary tract symptoms.

Drugs that block these receptors relax the muscles in and around the prostate, increase urinary flow and improve symptoms, sometimes significantly. Improvement occurs within days to weeks. Because these drugs are short-acting, symptoms return very quickly once a man stops taking the medication. They neither affect PSA levels nor shrink the size of the prostate. Research also indicates that they may even promote a natural process called apoptosis, in which cells in the prostate gland self-destruct. Investigators are studying whether these drugs may help prevent the development of prostate cancer.

Alpha-blockers are prescribed for most men with BPH symptoms whose prostates are not significantly enlarged. Even men with moderately enlarged prostates might try alpha-blockers before more intense treatments because these drugs work fairly quickly, have no effect on sexual drive, and are the least expensive treatment for BPH. Some experts now recommend alpha-blockers as first-line treatment for patients with moderate-to-severe symptoms.

These drugs are generally referred to as either nonselective or selective alpha-blockers. Drugs in both categories are similar in effectiveness for reducing symptoms and improving urinary flow. There are some differences, however. Patients should discuss the appropriate alpha-blocker for their individual condition with their doctors.

Nonselective Alpha-Blockers. Nonselective alpha-blockers (also referred to as alpha-specific antagonists) include terazosin (Hytrin), doxazosin (Cardura), and alfuzosin (Uroxatral). Alfuzosin is the newest drug and can be taken once a day. They relax all smooth muscles, not only in the prostate but also those that surround any blood vessel in the body. These drugs work within a few weeks, are inexpensive, and produce long-lasting benefits. Alfuzosin begins to improve urine flow within hours.

Side Effects. Nonselective alpha-blockers can reduce blood pressure, which may cause dizziness, headache, rapid heartbeat, and fatigue. Orthostatic hypotension, a sudden drop in blood pressure when standing, can occur and increases the risk of falling. Taking the medication close to bedtime can help reduce these side effects. (Alfuzosin's extended-release formulation appears to pose a much lower risk than the other drugs.) Alpha-blockers can also cause headache, sore throat, and weakness. Nasal congestion occurs in about 2% of cases. Men may also experience a decreased ejaculate. (Impotence is not a common side effect of alpha-blockers, as it is with finasteride.)
Long-Term Effects. These drugs slow the progression of BPH but do not help prevent urinary retention.
Best Candidates. Nonselective alpha-blockers may be a good choice for many men with severe urinary problems and especially those with hypertension, high cholesterol levels, or both. However, alpha-blockers can exacerbate heart failure symptoms in men with this condition.

Selective Alpha-Blockers. Tamsulosin (Flomax) is the only selective alpha-blocker (sometimes called alpha1A-urospecific antagonists) approved for treatment of BPH. Naftopidil is a similar drug under investigation. These drugs target receptors that affect only the smooth muscles of the prostate. Tamsulosin seems to work as well as nonselective alpha-blockers. It is not clear if it reduces long-term complications of BPH.

Selective alpha-blockers appear to be very safe, even for years. Side effects are minimal. Most common ones include nasal congestion. The risk for low blood pressure and dizziness is lower than with the nonselective alpha-blockers. They may pose a higher risk for problems in ejaculation than nonselective alpha-blockers, but do not appear to cause impotence or reduce sexual drive as finasteride does. These drugs can interact with certain medications, including calcium channel blockers (particularly verapamil).

Researchers are studying the combination of tamsulosin and tolteridine (Detrol). Tolteridine is an anticholinerogic medication used to treat urinary incontinence. Tamsulosin targets the prostate while tamsulosin helps inhibit involuntary contractions of the bladder. A 2006 study in the Journal of the American Medical Association found that a combination of tolterodine and tamsulosin worked better than either drug alone for men with lower urinary tract symptoms (LUTS), including overactive bladder.

Specific Benefits. The prostate gland contains an enzyme called 5 alpha-reductase that converts testosterone to another androgen called dihydrotestosterone. Finasteride (Proscar) and dutasteride (Avodart), known as a 5-alpha-reductase inhibitors, block this enzyme and thus reduce dihydrotestosterone in the prostate.

Finasteride is not as effective as alpha-blockers in improving BPH and urinary tract symptoms, but it can be helpful. Follow-up studies have reported that the drug is safe and effective over the long-term. The 5 alpha-reductase inhibitors are perhaps most effective in reducing symptoms in men with large prostates. (Men with larger prostates and high PSA values may also benefit from combination therapy of finasteride and the alpha-blocker doxazosin.) In such cases, studies on finasteride also suggest it reduces the risk of acute urinary retention and the need for surgery. It also helps control bleeding in the urine that is related to BPH. A side benefit of finasteride is reduction of hair loss related to male hormones and in some cases hair growth in men with mild-to-moderate male pattern baldness.

Dutasteride (Avodart) is a newer drug that inhibits two types of the 5-alpha-reductase enzymes and achieves a more rapid suppression of dihydrotestosterone than finasteride. A 4-year study reported sustained improvements in urinary symptoms and prostate volume reduction. Comparison studies are needed to determine if the dual actions of dutasteride offer significant benefits over those of finasteride. Researchers are also investigating whether dutasteride can help prevent the development of prostate cancer.

Candidates. Some experts recommend 5-alpha-reductase inhibitors for men of any age who have all three of the following conditions:

Very large prostates (40 mL or larger)
Low urinary flow rates
Prostate enlargement related primarily to hormone-stimulated overgrowth of glandular tissue

Finasteride is also proving to be helpful for patients who have hematuria (blood in the urine) related to BPH.

Dosing. Finasteride and dutasteride are taken once a day. It may take as long as 6 - 12 months for a man to notice a change in symptoms.

Effects on PSA. Finasteride and dutasteride decrease prostate-specific antigen (PSA) levels, which are measured for screening prostate cancer. Lower PSA levels may mask the presence of the cancer. Doctors calculate PSA levels in men taking these drugs by doubling the PSA values. Studies confirm that this doubling equation helps provide an accurate measurement.

Side Effects. Finasteride has been associated with:

Sexual dysfunction, including low sexual drive and impotence, in about 6 - 19% of patients. Such problems appear to occur only during the first year of use and diminish over time in most men who take finasteride.
Reductions in energy.
Breast tenderness.
Possible weight loss in some men.

Other anti-androgens, including drugs known as gonadotropin-releasing hormone agonists, are effective against BPH, but they can reduce sexual drive and are much more likely to cause impotence. Flutamide is an anti-androgen that may be an alternative to surgery in certain patients with BPH who have physical or mental disorders.

Popular herbal treatments for BPH include:

Saw Palmetto. Saw palmetto is one of the most popular herbal remedies for BPH. It comes from the berry of the plant Serenoa repens. A major 2006 study in the New England Journal of Medicine found that saw palmetto had no benefit for treating BPH. The study enrolled 225 men with moderate-to-severe BPH. The men received either placebo or 160 mg of saw palmetto twice daily. After 1 year, there were no differences in symptom improvement between the placebo and saw palmetto groups.

Beta-Sitosterol. Beta-sitosterol preparations come from South African star grass, Hypoxis rooperi, and other plant species. Some studies have shown beta-sitosterol to improve urinary symptoms and flow. They may increase the risk for impotence, however.

Pygeum Africanum. The herbal Pygeum africanum is an extract from the bark of an African plum tree. In an analysis of 18 trials, the herb provided a moderate improvement in urinary symptoms compared to placebo. Side effects were mild. The studies were short in length, however.

Cernilton. Cernilton is prepared from rye grass pollen. Studies have been limited, but some suggest it may help improve symptoms, including nighttime urinary problems. Other studies have found no benefit.

Other popular herbs include nettle root extract (Urtica dioica) and pumpkin seed oil (Cucurbita peponis). There is no scientific evidence that any of these remedies help treat BPH.

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. Patients should check with their doctor before using any herbal remedies or dietary supplements.

Botulinum. Botulinum toxin A (Botox) injections, a common wrinkle treatment, cause small muscles to relax. This approach is now being investigated for treating many disorders that involve overexcited muscle activity, including BPH. Preliminary studies are showing promising results in improving urine flow and reducing urinary retention. Research, presented at the 2007 annual meeting of the American Urological Association, reported that men with BPH who had Botox injected directly into their prostate gland had symptom relief and improved quality of life for up to a year after treatment.

PDE5 Inhibitors. Phosphodiesterase-5 (PDE5) inhibitors can treat erectile dysfunction (ED). They include sildenafil (Viagra), vardenafil (Levitra), and tadalafil (Cialis). Because lower urinary tract symptoms (LUTS) and ED often occur together in older men, researchers are investigating whether PDE5 inhibitors may help improve BPH symptoms. Research presented at the 2006 American Urological Association meeting suggested that sildenafil improves urinary symptoms in men who have both ED and LUTS. Another study indicated that a combination of sildenafil and the alpha-blocker alfusozin (Uroxatral) worked better for treating LUTS and ED than either drug alone.

Other Areas of Investigation. Researchers are looking at several different drugs for future BPH therapies. Most drugs being researched for BPH, such as arylpiperazines, target molecules in the prostate that may help suppress cell growth. Some efforts are focusing on drugs that affect the central nervous system or nerve fibers in the bladder and urethra to reduce urinary tract symptoms.

Other Treatments

Several surgical approaches are now available for treating BPH.

Invasive Procedures. The most effective surgical procedures, transurethral resection of the prostate (TURP) and open prostatectomy, are also the most invasive. They carry the highest risks for significant complications, including impotence and incontinence. Greater surgeon experience with TURP, however, has reduced complications and hospital stays. Because it is more effective than less invasive procedures, TURP remains the procedure of choice for many doctors. When considering invasive surgery, the patient should be sure his surgeon performs at least 50 of these procedures each year. The complication rates of the surgeon should be no higher than 1% for incontinence and 4% for impotence. Transurethral incision of the prostate (TUIP) is an alternative to TURP for men with smaller prostate glands.

Less Invasive Procedures. Minimally invasive procedures use some form of heat to destroy excess prostate tissue. The heat may be delivered by:

Radio frequency: transurethral needle ablation (TUNA)
Microwave: transurethral microwave thermotherapy (TUMT)
Electrical current: transurethral electrovaporization (TUVP)
Ultrasound: high-intensity focus ultrasound (HIFU)
Hot water: water-induced thermotherapy (WIT)
Laser: interstitial laser coagulation (ILC) and holmium laser enucleation of the prostate (HoLEP)

One laser procedure, photoselective vaporization (PVP), is typically done as an outpatient procedure. The patient goes home on the same day. However, there is no long-term data for this procedure.

None of the other minimally invasive procedures have proven superior to TURP to date, but they vary by complications. Some may be appropriate for certain patients, such as the following:

Younger men. (Many of the less invasive procedures carry a lower risk for impotence and incontinence than TURP, although the risk for TURP is not high.)
Debilitated elderly patients
Patients with severe medical conditions, including uncontrolled diabetes, cirrhosis, active alcoholism, psychosis, and serious lung, kidney, or heart disease
Men who are on blood-thinning drugs

Transurethral resection of the prostate (TURP) involves surgical removal of the inner portion of the prostate where BPH develops. It is the most common surgical procedure for BPH, although the number of procedures has dropped significantly over the past decades because of the availability of effective medications.

Click the icon to see an illustrated series detailing transurethral resection of the prostate surgery.

Procedure. TURP usually requires a 1 - 3 day hospital stay. The surgeon inserts a fiberoptic endoscope, which is a thin tube, into the urethra. No incision is needed. The surgeon uses the endoscope to cut away excess prostatic tissue, and water solutions are used to flush away the excised matter.

Risk of Water Intoxication. If the fluids used during TURP build up, water intoxication can develop, which can be serious. This condition is referred to as the transurethral resection (TUR) syndrome and includes abdominal cramps, nausea, vomiting, lethargy, and dizziness. Patients who undergo TURP for longer than 1 hour and those with larger prostate glands seem to be at greater risk for this complication. An irrigation system that uses a mechanical valve may reduce the risk.

Postoperative Catheterization. A Foley catheter generally remains in place for 3 - 5 days after surgery to allow urination. This device is a tube inserted through the opening of the penis to drain the urine into a bag. The catheter can cause bladder spasms that can be painful, but they eventually cease.

Some studies have suggested that in selected patients the catheter can safely be removed within 24 - 48 hours, allowing patients to go home earlier. Early catheter removal is not appropriate for patients with intense urine retention, signs of infection, bleeding, or other complications.

Recuperation. Urine flow is stronger almost immediately after most TURP procedures. After the catheter is removed, patients often experience some pain or sense of urgency as the urine passes over the surgical wound. These sensations gradually subside. Complete healing takes about 2 months. The following are some tips for hastening recovery and avoiding complications:

During recuperation at home, the patient should avoid driving, operating heavy equipment, lifting, sudden movements, and straining the muscles in the lower tracts, such as during a bowel movement.
Drinking 8 glasses of water a day after surgery is important to flush the bladder and help healing.
Foods that help prevent constipation, such as fruits and vegetables, are important. A laxative may be needed if constipation occurs.
Kegel exercises can help reduce incontinence. Performing three to four sets of 30 contractions daily is recommended. In one study, improvement due to Kegel exercises was significant within a month after surgery.

Postoperative Complications. Complications after TURP can be high, depending on the skill of the surgeon and other factors, but their incidence has decreased considerably over the past decades because of advances in surgical technique and more widespread expertise.

Bleeding. Some blood and small clots appear in the urine after surgery, and if the bladder is flushed with water, the urine may turn red. Such bleeding is normal. Occasionally, the scab on the surgical wound loosens, causing a sudden appearance of blood in the urine that can be alarming. Usually this stops after a rest, but the patient should notify the doctor at once if he is concerned about abnormal bleeding or clotting or has unusual feelings of discomfort. Rarely, hemorrhage may occur, requiring a transfusion.
Infection. Urinary tract infections occur in 5 - 10% of TURP patients. The risk is particularly high if a catheter is required. Antibiotics may be given to prevent infections, although often a doctor will choose to monitor a patient and administer antibiotics only if an infection is evident.
Incontinence. Temporary stress incontinence (urine leakage after activities such as sneezing, coughing, or lifting) occurs in most surgical patients. Urge incontinence is the involuntary loss of urine following an uncontrollable urge to urinate. About 2.1% of TURP patients experience stress incontinence, and nearly 2% have urge incontinence. In general, however, there is no significant risk for incontinence. [See In-Depth Report #50: Urinary incontinence.]
Sexual Dysfunction. Some men report certain sexual differences after the procedure, particularly low volume of fluid at ejaculation. Studies, however, do not report any significant risk for impotence. For most men who report this complication, sexual function returns in short order. (In some men it may take up to a year for complete recovery.) If potency was diminished before the operation, the procedure will not restore it. [See In-Depth Report #15: Erectile dysfunction.]
Retrograde Ejaculation and Low Semen. Many TURP patients report a lower volume of semen after the procedure. Between 66 - 75% of these patients experience retrograde ejaculation, in which semen is forced backward into the bladder instead of forward out of the urethra during orgasm. During most invasive procedures, the muscle that blocks off the bladder may be cut in order to widen the outlet. In such cases, the semen flows back through the wider opening rather than out of the penis. This condition can impair fertility and is of particular concern in younger men. Neither retrograde ejaculation nor the operation itself typically affects orgasm, although it takes many men some time to emotionally adjust to these conditions.
Low PSA Levels. PSA levels may be lowered after TURP, which might cause a doctor to miss a diagnosis of prostate cancer during routine screening.

Repeat Operations. Symptomatic relief is usually maintained for at least 15 years after surgery, but BPH may return or patients may need a second operation for other reasons. Up to 10% of TURP patients require a repeat operation within 10 years. In some cases, scarring in the bladder severe enough to cause obstruction occurs within a year of the procedure and may require transurethral incision (TUIP). More often, the urethra is scarred and narrows, but usually this condition can be corrected by a simple stretching procedure performed in the doctor's office.

In transurethral incision of the prostate (TUIP), the surgeon makes only one or two incisions in the prostate, causing the bladder neck and the prostate to spring open and reduce pressure on the urethra.

Candidates. TUIP is generally used only for men with minimally enlarged prostates (30 grams or less) who have obstruction of the neck of the bladder. Some experts believe TUIP is not performed enough and could benefit many patients, particularly those with severe medical conditions who are not good candidates for more invasive surgeries and men who want to lessen their risk for sterility.

Postoperative Complications. TUIP is less invasive than TURP, has a lower rate of the same complications, particularly retrograde ejaculation, and usually does not require a hospital stay. More studies are still needed, however, to determine whether they are comparative in long-term effectiveness.

In open prostatectomy, the enlarged prostate is removed through an open incision in the abdomen using standard surgical techniques. This is major surgery and requires a hospital stay of several days. Open prostatectomy is used only for severe cases, about 2 - 3% of BPH patients, when the prostate is severely enlarged, the bladder is damaged, or other serious problems exist. Up to 14% of patients require a second operation because of scarring. In making a decision about prostatectomy, it is essential that the doctor explains the consequences of a diminished sexual capacity that occurs after this procedure. When the situation of the patient does not constitute an emergency, prostatectomy should be considered a last resort if the patient still has an active sex life. Other complications are similar to those of TURP.

Click the icon to see an illustrated series detailing prostatectomy surgery.

Procedures. Laser technology is used for removal of prostate tissue. Laser procedures can usually be done as an outpatient procedure, and there is little risk for bleeding. Different procedures are used to provide different degrees of thermal cell destruction that range from coagulation to complete vaporization:

Interstitial laser coagulation (ILC) involves insertion of a scope through the prostate. A fiberoptic tip is threaded through the scope to direct a diode laser emission to targeted areas of the prostate. The coagulated tissue is naturally absorbed back into the body. Approved in 1998, this procedure is being performed less frequently as urologists turn to newer laser technologies (HoLEP, PVP).
Holmium laser enucleation of the prostate (HoLEP) is a newer technique that can actually cut and vaporize the tissue. Vaporization is effective immediately and also may pose lower risks for prolonged urinary retention and reoperation rates than coagulation. The Holmium laser is showing very good results with low complication rates in small studies, and trials have reported benefits lasting more than four years. (HoLEP is actually proving to be better than TURP or even open prostatectomy for removing very large prostate glands.)
Photoselective vaporization of the prostate (PVP) uses a potassium-titanyl-phosphate (KTP) laser ("green-light" laser) to vaporize prostate tissue. The procedure is virtually bloodless and may be a better option for men taking anticoagulant medication. Results from several recent clinical trials report sustained improvement up to 1 year after the procedure. More studies are needed to confirm long-term efficacy.

Complications. The laser procedure carries a lower risk for incontinence than TURP or TUVP, another minimally invasive procedure. Studies have been mixed on whether laser surgery poses any risk for sexual dysfunction. In one study, TURP had a lower risk for sexual dysfunction, although the risk from either procedure was very low and it wasn't clear that lasers had even been responsible for this complication. After laser procedures, and especially after coagulation, the prostate often temporarily enlarged and caused obstruction and irritation. Sometimes these symptoms were severe. Most men require a temporary catheter to drain urine after laser procedures. Newer laser procedures may significantly reduce these adverse effects.

Transurethral Microwave Thermotherapy (TUMT). Transurethral microwave thermotherapy (TUMT) delivers heat using microwave pulses to destroy prostate tissue. Studies have found that between 60 - 80% of men respond favorably to the treatment and the benefits seem to last. A 2001 study reported that it remained effective for at least 18 months and was superior over the long-term to the alpha-blocker drug terazosin. Improvement is not as complete as with TURP, but TUMT has fewer complications.

Candidates. TUMT may be beneficial for men with larger prostates and moderate to severe bladder obstruction, including those who require indwelling catheters. A 2000 study, for example, concluded that is was a safe and effective therapy for treatment of urinary retention. In general, the procedure should not be performed on men who have pacemakers, defibrillators, or any metal implants. One possible exception, the Targis System, was approved for use for patients with hip or penile implants that are located at least 1.5 inches from the urethra. Men who have had previous radiation therapy to the pelvic area are at higher risk for injuries from this procedure.
Procedure. A microwave antenna is inserted through the urethra with ultrasound used to position it accurately. The antenna is enclosed in a cooling tube to protect the lining of the urethra. Computer-generated microwaves pulse through the antenna to heat and destroy prostate tissue. When the temperature becomes too high, the computer shuts down the heat and resumes treatment when a safe level has been reached. The procedure takes 30 minutes to 2 hours, and the patient can go home immediately afterward. About 30% of patients experience some pain during the procedure. The patient should report any pain that appears to be unusually severe, however, since this could indicate improper application.
Complications. Swelling in the urinary tract often occurs later, which prevents urination and requires the use of a temporary catheter for about 3 days until the swelling subsides. There have also been reports of serious injuries to the penis and urethra from overheating due to improper application. It is important to note that TUMT does not significantly affect sexuality or cause incontinence or retrograde ejaculation, which are risks with some other prostate procedures.

Transurethral Needle Ablation. Transurethral needle ablation (TUNA) is a simple, safe, and relatively inexpensive procedure using needles to deliver high-frequency radio waves that heat and destroy prostate tissue. The procedure usually requires only a local anesthetic. One study reported that improvement was maintained in most patients after 2 years, although older men (over 70) had slightly worse symptoms and quality-of-life scores. Although small clinical studies have reported that TUNA is as effective as TURP, some experts believe that in actual medical practice TURP is still more effective.

Some studies have reported urinary retention, blood in the urine, retrograde ejaculation, and painful urination after the procedure, although in general TUNA has few or none of TURP's severe side effects. TUNA poses a very low to no risk for incontinence and impotence, and may be a good option for younger men.

Transurethral Electrovaporization. Transurethral electrovaporization (TUVP) uses high voltage electrical current delivered through a resectoscope to combine vaporization of prostate tissue and coagulation that seals the blood and lymph vessels around the area. Deprived of blood, the excess tissue dies and is sloughed off over time. Patients who have TUVP may be able to have their catheter removed within hours after the procedure compared to normal removal time of 3 - 5 days after TURP. A 5-year study reported that it was as effective as TURP over the long-term and had a similar complication rate.

Ultrasound. High-intensity focus ultrasound (HIFU) is a heat procedure under investigation that uses ultrasound to destroy specific prostate tissue. The principles are similar to transurethral microwave thermotherapy, but ultrasound techniques may destroy excess tissue without damaging other parts of the urethra.

Water-Induced Thermotherapy. A device called Thermoflex, which circulates heated water through a catheter to destroy prostatic tissue, has been approved for treating BPH. Another technique uses a balloon filled with hot water to destroy tissue around the urethra. Water-induced thermotherapy (WIT) does not require anesthesia and can be completed during a single outpatient visit.

Prostatic stents used for BPH are flexible mesh tubes that are inserted into the urethra. They are made of special alloys that do not cause reactions in the body. Typically, the insertion procedure takes only 15 minutes and requires only regional anesthetic and mild sedation. It usually requires minimal recuperation and no overnight hospital stay. Unfortunately, long-term studies are reporting high rates of dissatisfaction. Between 8 - 37% of the stents need to be removed later because of poor placement or complications, including irritation when urinating, urinary tract infections, and treatment failure. At this point stents seem to be best suited for high-risk surgical patients and those with a limited life expectancy. Stents composed of new materials and properties may increase their role.

Resources

www.niddk.nih.gov -- National Institute of Diabetes and Digestive and Kidney Diseases
www.urologyhealth.org -- American Urological Association

References

Bravi F, Bosetti C, Dal Maso L, Talamini R, Montella M, Negri E, et al. Food groups and risk of benign prostatic hyperplasia. Urology. 2006 Jan;67(1):73-9.

Johnson AR, Munoz A, Gottlieb JL, Jarrard DF. High dose zinc increases hospital admissions due to genitourinary complications. J Urol. 2007 Feb;177(2):639-43.

Kaplan SA, Roehrborn CG, Rovner ES, Carlsson M, Bavendam T, Guan Z. Tolterodine and tamsulosin for treatment of men with lower urinary tract symptoms and overactive bladder: a randomized controlled trial. JAMA. 2006 Nov 15;296(19):2319-28.

Rohrmann S, Giovannucci E, Willett WC, Platz EA. Fruit and vegetable consumption, intake of micronutrients, and benign prostatic hyperplasia in US men. Am. J. Clin. Nutr. 2007 Feb;85(2):523-9.

van der Meulen J, Brown CT, Yap T, Cromwell DA, Rixon L, Steed L, et al. Self management for men with lower urinary tract symptoms: randomised controlled trial. BMJ. 2007 Jan 6;334(7583):25. Epub 2006 Nov 21.

Review Date:
6/16/2007
Reviewed By:
Harvey Simon, MD, Associate Professor of Medicine, Harvard Medical School; Physician, Massachusetts General Hospital.

A.D.A.M. Copyright

adam.com

Crohn's disease

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

In This Report

Highlights
Introduction
Causes
Symptoms
Complications
Risk Factors
Diagnosis
Dietary Factors
Symptom Management
Medications
Surgery
Resources
References

HEALTH GUIDE REFERENCE FROM A.D.A.M

Highlights

Biologic Drugs

In February 2007, the FDA approved adalimumab (Humira) for treatment of adult patients with moderate-to-severe Crohn’s disease. Adalimumab and infliximab (Remicade) are now the two biologic drugs approved for Crohn’s disease. Infliximab is approved for treating both adults and children.
As of August 2007, the FDA was considering approving natalizumab (Tysabri) for moderate-to-severe Crohn’s disease in patients who have not responded to, or cannot tolerate, other therapies. However, natalizumab has serious risks -- in 2007, the European medicine agency rejected natalizumab for Crohn’s disease treatment.
Certolizumab (Cimzia) is another biologic drug that is showing promise for Crohn’s disease, according to several 2007 studies in the New England Journal of Medicine.
The risks of biologic drugs need to be weighed against their potential benefits, according to a 2007 consensus statement from the American Gastroenterological Association. These drugs may be appropriate as initial treatments for select patients who have fistulas or for patients who have not been helped by corticosteroid drugs.

Genetic Research

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

The interleukin-23 receptor (IL23R) gene is associated with variations that can either increase or decrease the risk for Crohn’s disease and ulcerative colitis.
The ATG16L1 gene regulates a process called autophagy, which involves how a cell digests itself. Scientists think that waste build-up from improperly regulated autophagy may play a role in the inflammatory response associated with Crohn’s disease.
Other recently identified genes that may be linked with Crohn’s disease include PHOX2B and NCF4.

Pregnancy Complications

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

Introduction

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

Ulcerative colitis (UC)
Crohn's disease (CD)

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

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

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

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

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

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

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

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

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

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

First it enters the duodenum
Then the jejunum, and
Finally the ileum

Most of the digestive process occurs in the small intestine.

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

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

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

The first section, the ascending colon, extends upward from the cecum on the right side of the abdomen.
The second section, the transverse colon, crosses the upper abdomen to the left side.
The third section extends downward on the left side of the abdomen toward the pelvis and is called the descending colon.
The final section is the sigmoid colon.

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

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

Click the icon to see an image of the stomach.

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

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

Causes

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

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

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

B cells produce antibodies, which are separate substances that can either ride along with a B cell or travel on their own to attack the antigen.
T cells have special receptors attached to their surface that recognize the specific antigen.

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

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

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

TH cells stimulate other white blood cells called B cells to produce antibodies. In this case, however, they appear to direct the B cells to produce autoantibodies, which are directed against the body's own cells.
TH cells also secrete or stimulate the production of powerful immune factors called cytokines. In small amounts, cytokines are indispensable for healing. If overproduced, however, they can cause serious damage, including inflammation and cellular injury. Cytokines, particularly specific ones known as tumor necrosis factor, interferon-gamma, and interleukins, cause intestinal inflammation and damage, which, in a vicious cycle, attract even more helper T cells.

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

Ulcerative colitis patients favor a TH2 response, which activates the interleukins IL-5, IL-6, and IL-10. These mostly affect mucosal areas in the intestine.
Research indicates that patients with Crohn's disease have increased activity in TH1 cells, activating interleukin-2 (IL-2) and interferon-gamma, which affect intestinal cells. Tumor necrosis factor (TNF) may be a particularly potent immune factor in Crohn's disease. It is important in properties that regulate inflammation and cell proliferation. If genetic or other factors increase production of this immune compound, it can lead to great harm.

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

Symptoms

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

Symptoms usually appear in young adults.
Symptoms can develop gradually or have a sudden onset.
Both are chronic. In either disease, symptoms may flare up (relapse) after symptom-free periods (remission) or symptoms may be continuous without treatment.
Symptoms can be mild or very severe and disabling.
The severity of symptoms and relapse rates of both IBDs vary with seasons, with the highest risk in the winter and autumn and lowest in summer.

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


Symptoms	Ulcerative Colitis	Crohn's Disease
Diarrhea	Recurrent diarrhea is very common, but onset may be very gradual and mild or it may not be present. Feces may also contain mucus.	Recurrent diarrhea is fairly common.
Rectal Bleeding	Blood is almost always present in stools. It may be readily visible or visible only using a microscope (called occult blood).	Bleeding not as common as in UC, but can occur.
Constipation	Constipation can be a symptom of UC, but not as common as diarrhea. Can occur during flare-ups. May occur when the inflamed rectum triggers a reflex response in the colon that causes it to retain the stool.	Constipation in Crohn's disease is usually a symptom of obstruction in the small intestine.
Abdominal Symptoms	Pain is not prominent symptom, but can vary. May cause vague discomfort in the lower abdomen, an ache around the top of the hipbone, or cramps in the middle of the abdomen. Severe pain can occur during flare-ups. Vomiting and nausea.	Main symptom is recurrent episodes of pain in the lower right part of the abdomen or above the pubic bone. Often preceded by and relieved by defecation. Bloating, nausea, and vomiting may also occur. Intestinal pain may also be an indication of a serious condition, such as an abscess, or a perforation of the intestinal wall.
Fever	May occur with severe attacks.	Usually low-grade. Spiking fever and chills indicates complications.
Loss of appetite, weight loss, and impaired growth in children	Often not evident in mild or even moderately severe UC. Occasionally impairs growth in children and teenagers.	Common. Typical weight loss is 10 - 20% of normal. Commonly impairs growth in children and teenagers.
Abnormal defecation: Increased frequency, a feeling of incomplete evacuation, and tenesmus (a painful urge for a bowel movement even if the rectum is empty). Fecal incontinence.	Symptoms may be mild or severe.	Can occur in active stages.
Anal ulcers and fistulas: (channels that can burrow between organs, loops of the intestine, or between the intestines and skin).	Almost never a symptom.	Fistulas and ulcers around the anus may be early symptoms.
Neurologic or psychiatric symptoms	No.	May be early signs of Crohn's disease when accompanied by gastrointestinal problems.

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

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

Complications

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

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

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

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

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

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

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

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

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

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

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

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

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

Click the icon to see an image of nail clubbing.

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

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

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

Click the icon to see an image of gallstones.

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

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

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

Click the icon to see an image of a thrombus.

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

Click the icon to see an image of kidney stones.

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

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

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

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

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

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

Risk Factors

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

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

Women may be slightly more at risk for Crohn's disease than men. Both genders are equally at risk for ulcerative colitis.
IBDs in general are diagnosed most often in young people age 10 - 19, but they can occur at any age. Another lesser peak onset occurs in people ages 50 - 80. About 2% of IBD cases appear in children below age 10. Between 10 - 15% of patients with Crohn's are children, and the childhood prevalence appears to be increasing.
IBD occurs four times more often in Americans of Northern European descent than in African-Americans. Scandinavia has the highest rate of Crohn's disease in the world. Studies in Britain suggest, however, that Asians may have a higher rate of IBD than people of European descent. Ashkenazi Jewish people have an even higher risk, five times that of the general population.
IBD seems to be more common among city than country dwellers and occurs more frequently in developed than in less developed nations, indicating that both genetic factors and environmental conditions, such as diet, may be involved in its development.
People who are left-handed have a significantly higher risk for both IBDs as well as certain other diseases associated with problems in the immune system.

Diagnosis

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

Several laboratory tests may be performed:

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

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

Sigmoidoscopy, which is used to examine only the rectum and left (sigmoid) colon, lasts about 10 minutes and is done without sedation. It may be mildly uncomfortable, but it is not painful.
Colonoscopy allows a view of the entire colon and requires a sedative, but it is still performed on an outpatient basis. It is important in differentiating between Crohn's disease and ulcerative colitis and in screening for colon cancer.

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

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

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

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

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

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

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

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


Endoscopy	Ulcerative colitis almost always involves the lower left colon and rectum and can be diagnosed using sigmoidoscopy. Crohn's disease may require colonoscopy as well. Endoscopy often reveals ulcers, diseased regions that have a cobblestone-like appearance in Crohn's disease, but not in ulcerative colitis.
X-Rays (Barium Enema) or Computed Tomography Scans	In ulcerative colitis, inflammation is usually evenly distributed on the surface lining of the intestine, and the bowel wall bleeds easily when touched with a swab. The pattern observed in Crohn's disease is usually one of scattered patches of ulcers that are deep, thick, and large. Crohn's disease produces pockets (fissures) or channels (fistulas). They do not occur with UC. In ulcerative colitis the ileum (the lower part of the small intestine) is often dilated while it is narrowed in Crohn's disease.
Laboratory Tests	Tissue samples obtained from a patient with Crohn's disease may reveal granulomas, small collections of inflammatory cells. Granulomas may also be present in other conditions, however. Tissue samples should also be examined for the presence of cancerous cells. About 70% of antibody tests for patients with UC will show immune factors called perinuclear-staining antineutrophil cytoplasmic antibodies, and over 50% of Crohn's patients have anti-Saccharomyces cerevisiae antibodies. Each antibody group shows up only occasionally in the other disorder. Researchers are also investigating other antibodies, such as antilaminaribioside and antichitobioside, which may serve as new markers for Crohn’s disease.

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

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

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

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

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

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

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

Click the icon to see an image of the appendix.

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

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

Dietary Factors

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

As important add-on treatment to medical therapies for maintaining nutrition and correcting any nutritional deficiencies
As primary treatment for reducing disease activity
As maintenance therapy on a long-term basis in the case of severe intestinal failure or short-bowel syndrome
For reversing growth-failure in children

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

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

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

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

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

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

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

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

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

Fats. Fats appear to worsen intestinal inflammation in Crohn's disease. Patients should limit fats, particularly saturated fats, found in meat and dairy products. However, certain fatty acids, such as those found in fish oil, may be helpful. The optimal balance between a low-fat diet with addition of these fatty acids is under investigation.
Milk products. Some people with IBD are lactose intolerant (unable to digest the sugar lactose, found in milk products). However, milk, along with the calcium it contains, has been associated with a lower risk for colon cancer. Taking lactase tablets or specially prepared dairy products may help. (Many lactose-intolerant patients are still able to eat yogurt with active cultures, which could be helpful for IBD.)
Foods associated with inflammation (alcohol, simple sugars, and caffeine).
Fruits may be protective, but patients should avoid dried fruits or high-sugar fruits, such as grapes, watermelon, or pineapple.
Products containing corn or gluten (those made from wheat, oats, barley, or triticale).
Common allergenic foods, such as soy, eggs, peanuts, tomatoes.
Foods that may irritate the intestine, particularly so-called Brassica vegetables (cabbage, Brussels sprouts, broccoli, cauliflower, kale).

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

The most important dietary recommendation is to increase fluid and restrict sodium intake.
Limiting protein is recommended for reducing kidney stones. However, people with IBD who have frequent diarrhea are protein deficient. Having enough protein in the diet, particularly in children with IBD, is very important. Patients should weigh the importance of protien against any risk for kidney stones.
Patients should eat more potassium-rich foods (bananas, watermelon, cantaloupe, oranges, tomatoes, beans).
Patients should try to correct any dietary habits that cause acidic or alkaline imbalances in the urine that promote stone formation.
Many kidney stones are formed from calcium-oxalate stones. Patients should avoid or limit intake of oxalate-rich foods, such as beets, beet tops, black tea, chenopodium, chocolate, cocoa, dried figs, ground pepper, lamb quarters, lime peel, nuts, parsley, poppy seeds, purslane, rhubarb, sorrel, spinach, and Swiss chard. A high calcium diet does not appear to increase the risk for kidney stones as long as it also contains plenty of fluids, dietary potassium, and phosphate. Importantly, calcium is associated with protection against colon cancer and osteoporosis -- two conditions that are associated with IBD.
Patients who have stones associated with short-bowel syndrome should eat less fat and foods that contain oxalates. In these people, calcium may bind to unabsorbed fat instead of to oxalates, which increase oxalate levels.

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

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

Probiotics are bacterial strains that by themselves may provide a barrier against harmful bacteria, possibly through various mechanisms such as excreting certain acids (lactate, acetate) that inhibit harmful bacteria or compete with them for nutrients. It has been suggested that probiotics may help maintain remission in patients with inflammatory bowel disease (IBD). The specific bacterial strains that might be beneficial, however, are not fully known. The most well-known probiotics are the lactobacilli strains, such as acidophilus, which are found in yogurt and other fermented milk products. Others, however, may prove to be more important, such as bifidobacteria and GG lactobacilli. Other probiotics that may be beneficial for patients with IBD include lactobacilli rhamnosus, casel, plantarium, bulgaricus, and salivarius, and also Enterococcus faecium and Streptococcus thermophilus.
Prebiotics are specific non-digestible molecules called fructo-oligosaccharides, which stimulate the growth of probiotics. These molecules are found in many foods, including Jerusalem artichokes, onions, salsify, bananas, honey, garlic, and leeks. (However, some of these foods can irritate the intestine in patients with IBD.)

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

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

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

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

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

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

Calcium and magnesium are critical for health and strong bones. Many patients with IBD suffer from calcium and vitamin D deficiencies, which cause low bone density. Studies indicate that calcium and vitamin D supplements may be adequate to increase bone density without drugs.
Selenium is a potent antioxidant.
Zinc is important for wound healing, and deficiencies may promote fistulas in Crohn's disease.
Iron supplements may be required for anemia. However, iron overdose is very dangerous. As few as three adult iron tablets can poison children, even fatally. No one, even adults, should take a double dose of iron if one is missed. A doctor should advise patients on correct dosage.

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

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

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

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

Symptom Management

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

Mild-to-moderate diarrhea may be reduced by taking 1 teaspoon of psyllium hydrophilic colloid (Metamucil) twice a day in a glass of water.
Antidiarrheal drugs include loperamide (Imodium) and a combination of atropine and diphenoxylate (Lomotil). In very ill patients, large doses of some antidiarrheal drugs, such as Lomotil, can trigger the onset of toxic megacolon. Toxic megacolon is a life-threatening complication of other intestinal conditions. It is characterized by a very inflated colon, abdominal distention, and sometimes fever, abdominal pain, or shock.
Opiates or drugs used to relax muscle spasms may help relieve mild-to-moderate diarrhea and abdominal cramps, but they should be used for very short periods and not for severe cases.
Cholestyramine (Questran) has been found to be useful for reducing diarrhea in patients who have had ileal resections.
Bulk-type laxatives can help constipation.

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

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

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

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

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

Medications

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

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

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

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

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

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

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

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

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

Abdominal pain and cramps (mesalamine, balsalazide)
Diarrhea (mesalamine, olsalazine)· Gas (mesalamine)
Nausea (mesalamine)
Hair loss (mesalamine)
Headache (mesalamine, balsalazide)
Dizziness (mesalamine)

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

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

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

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

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

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

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

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

Susceptibility to infection
Weight gain (particularly increased fatty tissue on the face and upper trunk and back)
Acne
Excess hair growth
High blood pressure (hypertension)
Weakened bones (osteoporosis)
Cataracts and glaucoma
Diabetes
Muscle wasting
Menstrual irregularities
Upper gastrointestinal ulcers
Personality change, including irritability, insomnia, psychosis, and depression; such emotional changes are sometimes severe enough to produce suicidal thoughts

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

Surgery

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

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

The entire colon (proctocolectomy) or a section of it (subtotal colectomy) may need to be removed in cases of extensive disease in the large intestine.
Resection or strictureplasty, which removes limited sections of the colon, may be appropriate for many patients.

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

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

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

A balloon attached to a catheter (a thin tube) is passed along the intestine.
If it becomes blocked, then a stricture (an obstruction) is indicated.
The surgeon widens the intestine at the point, but does not remove sections of it.
The procedure is by no means foolproof. Nearly half of patients require re-operation, but strictureplasty in the jejunum and ileum of the small intestine is safe and generally effective over the long term. It may not be useful for Crohn's disease in duodenum (the first section of the small intestine).

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

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

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

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

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

An incision is made in the abdomen.
The diseased portion of the colon is identified and removed. (Strictureplasty is sometimes used alone with resection.)
Once a diseased segment of the colon is removed, the two ends are reconnected, and this connection is called an anastomosis.

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

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

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

Short-bowel syndrome. If large segments of the small intestine are removed, the patient is at higher risk for short-bowel syndrome, a complication in which there is a problem absorbing nutrients. The risk is far lower with strictureplasty. The condition used to be fatal, but patients now can live normal and productive lives using total parenteral nutrition (the intravenous administration of nutrients), which can be self-administered at home in many cases.
Leakage or obstruction in the areas where the colon has been reconnected (the anastomosis).
Infections. In a 2003 study, the use of drugs that modify the immune system (azathioprine, 6-MP, methotrexate, and infliximab) was effective in reducing the risk for serious infection in the abdomen.

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

To perform proctocolectomy, the surgeon removes the entire colon, including the lower part of the rectum and the sphincter muscles that control bowel movements.
To perform ileostomy, the surgeon makes a small opening in the lower right corner of the abdomen called a stoma. The surgeon then connects cut ends of the small intestine to this opening. A bag is placed over the opening and accumulates waste matter. It requires emptying several times a day.

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

Patients at highest risk for recurrence include:

Smokers
Those whose disease occurred in the ileum (the lowest part of the small intestine) and colon
Those with abscesses or fistulas
Those have had previous surgeries

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

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

Stop severe intestinal bleeding
Clear small bowel obstruction
Drain and heal abscesses or fistulas
Repair perforation

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

Resources

www.ccfa.org -- Crohn's & Colitis Foundation of America
www.gastro.org -- American Gastroenterological Association
www.acg.gi.org -- American College of Gastroenterology
www2.niddk.nih.gov -- National Digestive Diseases Information Clearinghouse

References

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

A.D.A.M. Copyright

adam.com

Cirrhosis

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

In This Report

Highlights
Introduction
Causes
Risk Factors
Symptoms
Complications
Diagnosis
Treatment
Lifestyle Changes
Abdominal Infections
Encephalopathy
Ascites
Bleeding Episodes
Resources
References

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

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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.

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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.

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Review Date:
8/31/2007
Reviewed By:
Harvey Simon, MD, Associate Professor of Medicine, Harvard Medical School; Physician, Massachusetts General Hospital.

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