FitSugar

Great New Site: Diets in Review

FitSugar — Fri, 22 Jun 2007 03:00:00 -0700

There are so many diets out there that it's hard to keep track of them all. Wouldn't it be nice if there were one place where you could go online to get reviews of all the latest diets?

DietsinReview.com is a cool new site where you can find reviews of nearly 100 diets and weight loss plans, including weight loss supplements like the ever-so-controversial OTC pill alli. The site is easy to use so you can quickly find diets in four categories and compare and contrast them with informative reviews of each plan. I really like that there is a section to leave your own comments and/or reviews on the specific diet.

E-Patients Explore Online Communities

FitSugar — Tue, 17 Nov 2009 03:00:32 -0800

Researching your health problems online can be a great way to educate yourself - or scare yourself silly. A whopping 97 percent of Fit readers 'fess up to doing some Internet sleuthing before heading to the doc. There's even a word for us: e-patients.

According to a new study by the Pew Internet and American Life Project, about 20 percent of e-patients use social-networking and similar sites to chat with medical experts and other patients.

Of course, we're big fans of community around here as a place to share information and links and get a conversation going. To find out more about the online health community revolution, read more.

Says Pew's Susannah Fox:

"They are posting their first-person accounts of treatments and side effects from medications. They are recording and posting those podcasts. They're tagging content. They are part of the conversation. And that, I think, is an indicator of where we could be going in terms of the future of participatory medicine."

In addition to connecting with fellow patients suffering from the same ailments, users are posting their health records online so they can track their test results, blood pressure, and other vital stats. All they're doing all this despite the fact that doctors are behind the times, with only about 17 percent reporting the use of online medical records.

When you're suffering from an ailment, it can be very reassuring to hear from other patients who've gone through the same thing; often, it calms me down and makes me realize I'm not alone. But do you see any danger in patients posting about their medical problems in online communities?

Meanwhile, don't forget to check out our FitSugar Community and join the conversation!

Tired of Your Old Fitness DVDs? Swap Them

FitSugar — Fri, 30 Oct 2009 09:00:05 -0700

I've accumulated a bunch of fitness DVDs over the years. Some will forever be favorites, like Core Fusion Body Sculpt, and some I've only tried once, like Valerie Bertinelli's Losing It and Keeping Fit.

What's a girl to do with the stacks of fitness DVDs she never uses? Trade them for something she will use. SwapaDvd.com is a website that allows you to post DVDs you no longer want. Once you post 10 to your "DVD Tower," you get one "gift" credit from the site. Then you can start swapping with other users. When someone wants your DVD, you mail it to them (yes, you pay the postage, which is typically $1.85), and you earn one credit toward a video you want. When you request a DVD, the owner will mail it to you. It's a great way to get rid of workout videos you're bored with, and to try something new. Once you're done with exercise DVDs you've received, you can always re-post them for others to request. Great idea, huh?

Tweet What You Eat: Food Journals in the Digital Age

FitSugar — Tue, 27 Oct 2009 07:00:09 -0700

If the whole world knew what you ate all day, would it motivate you to make better food choices? That's what the folks behind Tweet What You Eat (TWYE) are hoping.

TWYE is a Twitter-based online food diary that is updated in real time via the web or a text message. And unless a member has opted to keep their diary private, the 15,000 (and growing) members of TWYE get to see what you eat, all day, every day. Most users do go public and the founders admit that this has been key to finding success on TWYE. Users might think twice before gorging on cake, cookies, or donuts if their diary is open to all.

To learn how to use TWYE, read more.

Basically you text or tweet what you eat throughout the day to TWYE, including calories. You can also submit calorie-burning activities to get a more accurate reflection of everything that's going in and out. If you don't know how many calories a particular food item has, that's OK, because the site has a database of popular foods and their caloric breakdown. At the end of each day you are given a grand total of the calories you took in.

The service is fairly new, so all you can really do is track calories - there's no breakdown of fats, carbs, or nutrients - but it's a great tool if that's all you're interested in doing. It seems incredibly helpful for those times when you're on the go, since you only need your cell phone to make an entry.

Would you use TWYE?

Immunizations

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

In This Report

Highlights
Introduction
Diphtheria, Tetanus, and Pe...
Measles, Mumps, and Rubella...
Varicella-Zoster Virus (Chi...
Varicella-Zoster Virus (Shi...
Hepatitis A
Hepatitis B
Pneumococcal Pneumonia
Poliomyelitis
Viral Influenza
Haemophilus Influenzae Type...
Human Papillomavirus (HPV)...
Rotavirus
Smallpox
Other Vaccinations
Resources
References

HEALTH GUIDE REFERENCE FROM A.D.A.M

Highlights

Vaccines

The Centers for Disease Control and Prevention now recommends that children receive 2 doses of the varicella-zoster (Chickenpox) vaccine: the initial vaccine between ages 12 - 15 months, and a booster between 4 - 6 years. Children aged 12 and older and adults who have not had the vaccine should receive 2 doses. Immunization guidelines were changed following research that indicated the effectiveness of the vaccine declines over time. A 2007 study indicated that children who were vaccinated 5 or more years earlier were 2.6 times more likely to have a moderate-to-severe breakthrough case of chickenpox than those who had been vaccinated more recently.
A study finds that the conjugate pneumococcal vaccine, which was introduced for children in 2000, has reduced hospital admissions for pneumonia in children under age 2 by about 39%. The vaccine has also caused hospital admissions to drop 26% among adults aged 18 - 39. Another study found that recurrent ear infections have fallen by 28% since the introduction of the vaccine.
In April 2007, the U.S. Food and Drug Administration approved the first vaccine against the avian flu virus. The avian flu vaccine is designed for people ages 18 - 64 who are at risk for exposure to the virus. The vaccine is given in 2 shots, spaced about 1 month apart. The U.S. government is stockpiling the vaccination in case of an avian influenza outbreak, but the vaccine is not available to the general public.
Research finds that the human papillomavirus (HPV) vaccine (Gardisil) is 100% effective against cervical, vaginal, and vulvar diseases caused by 4 types of HPV (6, 11, 16, and 18).

Introduction

Immunizations against childhood diseases have saved millions of lives. American vaccination rates are now at an all-time high. Disease and death from diphtheria, pertussis, tetanus, measles, mumps, rubella, and Haemophilus influenzae (H. influenzae) type b are at or near record lows. In adults, immunizations against influenza (the flu), pneumococcal pneumonia, hepatitis, and other ailments have likewise saved many lives and prevented many more cases of serious illness. A new vaccine has been shown to be highly effective for preventing the virus that leads to cervical cancer.

More than 70 bacteria, viruses, parasites, and other infectious microbes cause major human disease. Fortunately, vaccines are either available or being developed against many of them. With the advent of new or newly feared biological threats, emerging infections, and bacterial resistance to common antibiotics, immunizations are assuming an increasingly important role in maintaining the health of billions of people worldwide.

Immunizations (vaccinations) are given to initiate or augment resistance to an infectious disease. Immunizations provide a specialized form of immunity that provides long-lasting protection against specific antigens, which cause disease.

Routine Childhood Vaccines. Experts recommend that all children be routinely vaccinated against the following diseases:

Measles
Mumps
Rubella (German measles)
Diphtheria
Tetanus
Pertussis (whooping cough)
Poliomyelitis (polio)
Varicella (chickenpox)
Hepatitis B
Hepatitis A
H. influenzae type B (a cause of meningitis)
Influenza (children aged 6 - 59 months)
Pneumococcal disease
Meningococcal disease (for selected populations)
Rotavirus (children aged 6 - 32 weeks)

Many vaccinations are first given during infancy. Even premature infants can, in most cases, be given vaccinations on a normal schedule. There is even some evidence that doing so may offer some slight protection against sudden infant death syndrome. Note: These facts pertain to children in the United States. Children from other countries have not been well studied. Parents who adopt internationally may want to have their children's immunity assessed by a physician. Some evidence suggests that their medical records may not correctly reflect immunization status and that many adopted children, such as those from China, have not had many important vaccinations.

Click the icon to see an animation about vaccines.

Common Adult Vaccines. Vaccinations against the following disorders are also recommended routinely for certain adults:

Influenza (flu). Every year in high-risk adults under 49 and everyone over 50. When supplies are limited, as with the 2004 - 2005 flu season, the vaccine should be administered preferentially to adults only over age 65 and to individuals with heart disease, lung disease, and other significant chronic illnesses. Health care providers with direct patient contact, child care providers, and residents of long-term care facilities should also be vaccinated.
Pneumococcal pneumonia. One dose in high-risk adults under 64 and a first dose or a revaccination in everyone over 65.
Hepatitis A and B and Meningococcal vaccine. Given to high-risk individuals.
Tetanus. Adults need a booster shot every 10 years.
Measles, mumps, rubella. Typically given to adults under 56 who are unsure of their vaccination history. High-risk individuals may receive two doses.
Diphtheria and pertussis are now recommended with tetanus (Tdap vaccine) booster every 10 years until age 65.
Herpes zoster (shingles) vaccine. One dose for adults 60 and older.
Human papillomavirus (HPV). Three doses in young women aged 11 - 26.

Vaccines are currently taken by mouth (orally) or given by a shot (injection). Vaccines are usually made of one of two agents that cause the body to produce antibodies that attack a specific disease. A vaccine may contain:

A live but weakened virus. Live-virus vaccines provide longer immunity than inactivated ones, but they can cause serious infection in people with weakened immune systems and have also been associated with severe medical disorders in rare instances.
Inactivated bacteria, viruses, or toxoids. Inactivated vaccines are safe even in people with impaired immune systems.

Click the icon to see an image of antibodies.

The weakened or inactivated agent in the vaccine teaches the immune system to recognize the real, harmful substance and attack it when the person becomes exposed to the infection. The antibodies remain in the body, preventing future illness from the disease. This is called immunity.

Combination Vaccines. The American Academy of Pediatrics and American Academy of Family Physicians recommend that health care providers use, whenever possible, combination vaccines instead of individual components. Combination shots containing vaccines for diphtheria, tetanus, and pertussis (DTaP), and for measles, mumps, and rubella (MMR), have been available for years. New combinations that cover up to 5 vaccinations are being developed and are proving to be safe and well tolerated in infants as young as 2 months. For example, one that combines DTaP, hepatitis B, and the polio vaccine (Pediarix) has been approved and should simplify the immunization process.

There is some concern that increasing use of combinations may reduce the potency of some of the vaccines. Some parents are also worried about increased side effects. Studies to date, however, are reporting that combinations are effective and safe.

Passive Immunity. Another form of protection against disease is called passive immunity. This approach uses immune globulin, which are blood products containing antibodies. Immune globulin is generally used for people who cannot be vaccinated, when immediate protection is required, or to prevent severe complications of the disease. In some circumstances, passive immunity can interfere with active vaccinations, particularly live-virus vaccines, so, if possible, they should not be administered within weeks or even months of each other.

General Information on Side Effects. Vaccines can have side effects, such as swelling at the injection site or fever, which are nearly always mild. There have been a number of reports in the popular press about alarming side effects in many vaccines. Anti-vaccine groups vocally oppose immunizations in children. Although it is true that no vaccine is 100% safe, childhood infections have not been wiped out. Without immunization, children risk diseases that have in the past killed millions of young children.

Thimerosal is a preservative used in many vaccines. It has been in use since the 1930s. The preservative contains small amounts of mercury. Some people are concerned about possible neurologic consequences from cumulative doses of mercury contained in vaccines given to infants. A 2003 study did report an association between thimerosal in DTaP vaccines and a higher risk for problems in neurologic development, including autism and speech problems.

In 2004, the Institute of Medicine (IOM) Safety Review Committee reported the results of studies in the U.S. and several European countries evaluating a possible association between thimerosal and autism. They concluded that scientific studies did not find that thimerosal caused autism.

In any case, manufacturers have been removing this preservative from vaccines. At the time of this report, all vaccines recommended for children age 6 or younger contain either no thimerosal or only trace amounts, with the exception of the inactivated influenza vaccine (although a limited supply of a version of the vaccine containing only trace amounts of thimerosal is available for use in infants, children, and pregnant women). A trace amount means that a given dose of vaccine contains less than 1 part per million.

Inactivated-virus and toxoid vaccines are usually safe in pregnant women, although any vaccination should be delayed, if possible, until the second or third trimester. Because of a possible risk to the fetus, live-virus vaccines should not be given to pregnant women or those likely to become pregnant within 28 days unless such women need immediate protection against life-threatening diseases, such as yellow fever, that are only prevented using live-virus vaccines. The live-virus MMR combination, which vaccinates against measles, mumps, and rubella, is not given to pregnant women because of the theoretical risk of the live-rubella vaccine on the fetus.

Click the icon to see an image of rubella syndrome.

Live-virus vaccines are not usually given to people whose immune system has been compromised by illness or the use of medication such as long-term corticosteroids. They include:

Click the icon to see an image of HIV.

Persons who have immune deficiency diseases (such as HIV or AIDS).
Patients with active leukemia or lymphoma.
Patients who are taking treatments that suppress the immune system, such as corticosteroids, alkylating drugs, antimetabolites, or radiation. (There are important exceptions, however, which are noted in the discussion of individual vaccinations below.) Short-term corticosteroids (given for less than 2 weeks) do not suppress the immune system and so should not affect any live-virus vaccination. It should be noted that some topical corticosteroids are suppressive. Patients who need vaccinations and who take long-term or high-dose topical steroids should check with their physicians.

In general, vaccines are not completely effective for patients whose immune systems are compromised by disease or medications. Often, such patients are given immune globulin if they are exposed to infection. It may take 3 months to 1 year before a person who has stopped taking immunosuppressant drugs regains the full ability to be successfully immunized against disease.

People who are traveling to developing countries should check with the US Centers for Disease Control (www.cdc.gov/travel) for up-to-date information on immunization requirements for their destination.

Below are some general guidelines for vaccinations, immunizations, and other preventive steps for travel:

Everyone should be up-to-date on any recommended vaccinations for childhood diseases, regardless of their age. Booster shots may be required for travelers to developing countries even if they have completed the initial series. Vaccinations may include polio, H. influenzae, the series for diphtheria, pertussis, and tetanus (DTaP), hepatitis B, rotavirus, measles, and varicella-zoster (chickenpox). If children have not completed their DTaP series, parents should consider having it completed while overseas.
Pregnant women should have vaccinations that are appropriate to their trimester. Not all vaccinations are safe during pregnancy.
Older adults may not respond to a vaccination as quickly as younger people or they may have a higher risk for side effects. They should check with their physicians.
Upper respiratory infections are very common after foreign travel. The flu vaccine may be recommended when traveling to any country during flu season, particularly for the elderly and people at risk for serious illness. This group may also need the pneumococcal vaccine.
Travelers to areas where there are tuberculosis (TB) outbreaks should have skin tests before traveling; those with negative tests should have a repeat test 2 - 4 months after they return.
Vaccination against hepatitis A is recommended for all travelers to developing countries. Some expert groups believe that such travelers should have hepatitis B vaccinations as well, but the CDC does not generally recommend them at this time except under certain circumstances.
Travelers to countries with malaria should take preventive agents.
Some countries may require vaccinations against yellow fever, meningitis, typhoid, cholera, Japanese encephalitis, and rabies under certain circumstances. Some of these vaccinations are covered in this report.
Studies indicate that multiple vaccines may be given at the same time to most adults without significantly increasing adverse effects.

[For more information, see In-Depth Report #1: Travel to developing countries.]

Childhood Immunization Schedule**
Age	Chickenpox (Varicella Zoster)	Diphtheria, Tetanus, Pertussis (DTaP)*	Haemophilus influenzae type (Hib)	Hepatitis A	Rotavirus
Birth
2 months		DTaP*	Hib		Rotavirus
4 months		DTaP*	Hib		Rotavirus
6 months		DTaP*	Hib (Depending on brand. For example, no third dose is required for PedvaxHIB or ComVax.)		Rotavirus
12 to 15 months	Varicella	DTaP* (Typically between 15 and 18 months. May be given as early as 12 months in high-risk children as long as 6 months have passed since the third dose.)	Hib (Sometime between 12 and 15 months.)	HepA (In 2 does, between 12 and 23 months)
2 years old				In children who have not been fully vaccinated.
4 to 6 years	Varicella	DTaP
11 to 12 years	Varies. (If previously missed, two doses should be given at least four weeks apart.)			In adolescents through age 18 in selected areas.

Age	Hepatitis B (Hep-B)*	Measles, Mumps, Rubella (MMR)	Pneumococcal Vaccine (PCV7)	Polio (Inactive virus) (IPV)*	Human Papillomavirus (HPV)
Birth	Hep-B immediately after birth. (This is very important when mothers are infected.) No later than 2 months in children of noninfected mothers. *
2 months	Hep-B some time between 1 and 4 months depending on risk. *		PCV7	IPV*
4 months			PCV7	IPV*
6 months	Hep-B some time between 6 and 18 months. *		PCV7	IPV* (Advised at some point between 6 and 18 months.) *
12 to 15 months	Varies.	MMR (Some time between 12 and 15 months.)
2 years old			PCV7 -- 1 dose for children not previously vaccinated.
4 to 6 years		MMR	PCV7 -- 1 dose in high-risk children.	IPV*
11 to 12 years	Hep-B (If vaccinations were previously missed). Two or 3 doses a few months apart.	MMR (If vaccinations were previously missed).			HPV (Females)
* A one-shot combination vaccine (Pediarix) has been approved that covers polio, hepatitis B, diphtheria, pertussis, and tetanus (DTaP) and should simplify the immunization process. It would be given as a single injection at 2, 4, and 6 months with booster shots given at 12 to 15 months and 4 to 6 years. **All children aged 6 - 59 months should receive an annual flu shot. Children older than 5 years of age who have chronic medical conditions should also receive the influenza vaccination. The flu shot is not approved for children younger than 6 months of age.

Of great concern are anti-immunization organizations and websites, which were formed mostly because of unsubstantiated reports linking small numbers of serious problems to some vaccines. The following watchdog systems are now in effect to monitor side effects from vaccination:

VAERS (Vaccine Adverse Event Reporting System) is a government service that registers all adverse events reported after vaccination, including those not related to the vaccine. It is useful for surveillance but has limitations. For example, the service may record the same case more than once. In addition, more serious events that occur after a vaccination are more likely to be reported than later and milder events, and such events are not necessarily linked to the vaccine.
VSD (Vaccine Safety Datalink) is a linked database that analyzes the records of more than 5 million patients each year. It is more accurate than VAERS, although the information it contains is not as timely.
The CDC has established the national network of Clinical Immunization Safety Assessment (CISA) Centers. It will provide services to physicians to help them evaluate and manage patients who may have had a side effect.

Studies using these systems are ongoing and none to date have confirmed reports of any significant association between most vaccines and severe side effects that would outweigh the benefits of these important and lifesaving agents.

No vaccine is 100% safe. Allergic and serious reactions are possible. In 2 cases, the early polio vaccine and the rotavirus vaccine, problems did occur, and some were serious. It is important to note, however, that even in these cases, the vaccines were withdrawn and the severe events still were far fewer than the number of lives saved.

The focus on vaccination side effects is ironic due to the fact that reports of such adverse effects outnumber the number of actual infections. Because vaccinations have been in existence for so long, today's parents have no direct knowledge of the consequences of these dreaded infections, which killed or severely sickened millions of children in the past.

It should be noted that studies are reporting that the risk for infection increases significantly in children who are not vaccinated. There is also a rise in infections among immunized children, suggesting resistance to the vaccines.

Infants often accept the first injection easily, since they are not expecting it. It gets more difficult, however, with each additional shot. Simply providing love and warmth can help children of all ages tolerate immunizations.

Additional tips:

Do not lie and tell an older child that a shot will be painless. Some health care providers suggest telling them that it stings a little and to count to 5 while it is being administered.
Ask the doctor if it is OK to give the child a dose of acetaminophen (Tylenol) before or after a shot. Ibuprofen (Motrin, Advil) or other non-aspirin pain relievers may be acceptable alternatives. (Children should NEVER take aspirin after vaccinations.)
Ask the doctor about EMLA cream, a topical anesthetic containing lidocaine and prilocaine. This product can be applied about an hour before the injection. (Note: EMLA may interact with acetaminophen and certain vaccinations, so be sure to check with the doctor first.)
A cooling spray may work as well as EMLA and have fewer side effects.
Longer needles, rather than shorter ones, may help reduce pain. One study reported that using longer needles decreased redness at the injection site by about two-thirds. Parents may want to ask their doctor about this study.
Have your child take a deep breath right before the shot and blow out very hard while it is being given. One study reported very good results with this breathing technique.
Give a sweet fluid before the shot and a little reward, such as a lollipop, immediately after the shot. Sugar actually has mild pain relieving properties for infants.

Diphtheria, Tetanus, and Pertussis

Diphtheria. Diphtheria is caused by the bacterium Corynebacterium diphtheriae, which can occur as either a toxic or nontoxic strain. When only the skin is involved, it is known as cutaneous diphtheria, and is likely to be a nontoxic strain. If the toxic strain affects the mucus linings in the body, such as the throat, diphtheria becomes life threatening. Between 1900 and 1925, diphtheria infected 200,000 people every year and killed between 5 - 10% of them, mostly the very young and very old. Because of immunizations, only one case was reported in 2000.

Tetanus. Tetanus is a disease that causes severe muscular contractions and convulsions. It is caused by a powerful toxin secreted by the bacterium Clostridium tetani. The bacterium is anaerobic, which means it lives without oxygen. People become infected by this dangerous bacterium through wounds in the skin. It is fatal in 15 - 40% of cases. Only 35 cases were reported in the U.S. in 2000, mostly in adults. One case, however, occurred in a 12-year-old boy whose parents refused to vaccinate him.

Pertussis. Pertussis (whooping cough) was a very common childhood illness throughout the first half of the 1900s. The disease is very easily spread from one person to another, and it is most severe in babies. Because of immunizations, which began in the 1940s, cases of whooping cough reached an all-time low of 1,010 in 1976 in the U.S. The incidence has risen recently, with almost 25,837 cases reported in 2004. 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. One study suggested that as many as 25% of adults who see a doctor for persistent cough may actually have pertussis, but it may go undiagnosed 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 even with vaccination, protection is incomplete.

The Initial Vaccination. Diphtheria, tetanus, and pertussis (DTaP) are very different disorders, but a combination injection has been routinely given to children since the 1940s. Since the early 1990s, the standard vaccine is DTaP, which uses a form of the pertussis component known as acellular pertussis that consists of a single weakened toxoid. (The older vaccine, DTP, includes a pertussis vaccine that contains multiple toxins against different variants of the disease. DTaP is just as effective but has fewer side effects than DTP.)

Pertussis is increasing among adults; the Centers for Disease Control data indicate that there were more than 25,000 cases of pertussis in 2004.

The Booster. Protection against diphtheria and tetanus from the vaccine lasts about 10 years. At that point a booster may be given against tetanus and diphtheria (Td). The Td vaccine contains the standard dose against tetanus and a less potent one against diphtheria and does not contain the pertussis component. In April 2005, the FDA approved the first pertussis booster shot ("Boostrix") for kids aged 10 - 18. Boostrix is a lower dose of infant pertussis vaccine. The infant pertussis vaccine can start to wear off after about 5 years, and some previously immunized teens and adults can get a mild form of the disease. The booster shot may help reduce the number of pertussis cases in adolescents and adults. The FDA also approved in 2005 another novel booster vaccine called Adacel for protection against tetanus, diphtheria and pertussis from adolescence through adulthood.

DTaP Schedule in Childhood. All children younger than 7 years old should receive the DTaP vaccine. In general, the vaccinations are given as follows:

Infants receive a series of three vaccinations at 2, 4, and 6 months of age (doctors may delay a vaccination in infants with suspected neurologic problems until their neurologic situation is clarified, but no later than their first birthday). Children with neurologic problems that have been corrected can be vaccinated.
A fourth dose is given between 15 and 18 months. (Infants at higher risk, such as those exposed to an outbreak of pertussis, may be given this vaccination earlier.) Of note, children who receive their third shot late in the schedule are at higher risk for skipping the fourth dose than children who were on schedule. Parents should be sure to adhere to a schedule that includes the fourth shot, even if they were late on the third.
A fifth dose is given at 4 - 6 years. This fifth shot now usually includes a vaccine against H. influenzae as well.
Children between the ages of 11 and 15 years old should receive a tetanus and diphtheria (Td) booster shot.
Boostrix is a single-dose booster that can be given to children age 10 - 18 years.
Adacel is a single-dose booster Tdap for people age 11 - 64 years.

If a child has a moderate or severe current or recent fever-related illness, vaccinations should be postponed until after recovery. Colds or other mild respiratory infections are no cause for delay. Parents should not be unduly concerned if the interval between shots is longer than that recommended. The immunity from any previous vaccinations persists, and the doctor does not have to start a new series from scratch.

Recommendations for Adults. All vaccinated adults should have a Td booster at least every 10 years throughout their lifetimes. One study reported that fewer than half of adult Americans ages 20 and older were protected against both tetanus and diphtheria, and immunity rates were even lower in those over 70. The results indicate that many people are not getting routine boosters.

Other recommendations for adults are as follows:

Adults who did not receive the primary childhood vaccinations should have the tetanus, diphtheria, and pertussis (Tdap) vaccine, approved in 2005, every 10 years.
Unvaccinated pregnant women should receive two doses of Td, properly spaced, and previously vaccinated women should have a booster.

Preventing Tetanus in Individuals with Wounds. Wounds that put patients at highest risk for tetanus are puncture wounds or wounds contaminated with dirt, feces, or saliva. However, any patient who requires medical care for any wound is a candidate for tetanus immunity.

Some considerations for tetanus vaccinations in wounded people are as follows:

A booster is needed if the last shot was 5 or more years before the injury.
Children under 7 are usually given DTP if they are not fully vaccinated.
Most individuals are given the Td vaccination if they have been vaccinated.
Older patients who had experienced an allergic response to a previous tetanus booster may be given the tetanus immune globulin (TIG).

Allergic Reactions. In rare cases, people may be allergic to the older diphtheria, tetanus, and pertussis vaccine, DTP. Parents should tell their doctor if their children have any allergies. The newer vaccine, DTaP, may pose a slightly higher risk for an allergic reaction than the older vaccine, DTP. Children who have severe responses should not be given further vaccinations. A rash that occurs after a dose of DTP is of little consequence. In fact, it does not usually indicate an allergic response but only a temporary immune reaction and does not usually recur with subsequent shots. It should be noted that no deaths have been reported from allergic reactions, even severe (anaphylactic) ones, to the DTP vaccine.

Pain and Swelling at the Injection Site. Children may feel pain at the injection site. In some cases, a small lump may remain at the site for several weeks. Placing a clean, cool washcloth over any swollen, hot, or red area can help. Children should not be covered or wrapped tightly in clothes or blankets.

The risk for swelling, including of the whole arm or leg, increases with subsequent injections, particularly the fourth and fifth doses. If possible, parents should request that their children receive the same vaccine brand each time to help reduce the risk of side effects.

Feverand Other Symptoms. A child may develop a mild fever, irritability, drowsiness, and loss of appetite after a shot.

The following remedies may be helpful:

Acetaminophen (for example, Children's Tylenol) and a sponge bath in lukewarm -- NOT cold -- water may help relieve fever and pain.
The doctor may suggest that children who have had previous high fevers or other reactions to the shot be given acetaminophen at the time of the vaccination and every 4 hours afterward for 24 hours. (The doctor will determine the dosage according to the weight of the child.)
Children should NEVER be given aspirin.

Fevers that should cause concern include the following:

The older DTP vaccine posed some risk for fever-related seizures on the day of vaccination. The newer DTaP has significantly reduced this side effect. Any very high fever in children (over 105° F) that causes convulsions should be reported immediately to the doctor. Although frightening, such fever-related seizures are uncommon and rarely have any long-term effect, and a recurrence after a subsequent vaccination is very unlikely.
A new fever that develops 24 hours after the vaccination, a fever that persists for longer than 24 hours, or seizures without fever are most likely due to other causes.

Hypotonic-Hyporesponsive Episode (HHE). HHE is an uncommon response to the pertussis component and occurs within 48 hours of the injection in children under 2. The child usually starts out feverish and irritable and then becomes pale, limp, and unresponsive. Breathing is shallow, and the child's skin may turn bluish. The reaction lasts an average of 6 hours and, although it is frightening, virtually all children return to normal. This side effect is less common since the introduction of the DTaP vaccine, but it can still occur.

Neurologic Effects in Pertussis Component. Of concern have been a few reports of permanent neurologic abnormalities that have occurred after children have been vaccinated. Such reports include attention deficit disorder, learning disorders, autism, brain damage (encephalopathy), and even death.

It is well known that the diphtheria and tetanus components cause no adverse neurologic effects, so some people suspect the pertussis component. However, many major studies, including an important statistically sound analysis in 2002, found no causal relationship between neurologic problems and the pertussis vaccination. In fact, one study indicated that children who received pertussis vaccine had fewer problems in school than those who were not vaccinated, regardless of family income levels. Studies on the newer DTaP have reported no safety concerns to date.

There may be some exceptions. Studies now suggest that in cases where neurologic problems have been strongly linked to the vaccination, high fevers -- not immunization -- are responsible. Children with known neurologic abnormalities may also be at risk for an outbreak of symptoms 2 or 3 days after the vaccination. Such a temporary worsening of their disease rarely poses a danger to the child. (Some experts suggest that children who have new neurologic events following their shot may already have a preexisting impairment, such as epilepsy, which is revealed -- but not caused -- by the vaccine.) To date, there is no proof that the pertussis vaccine causes these neurologic events, which, in any case, are so infrequent as to be nearly statistically unmeasurable.

Important Note: Unwarranted fears of side effects from vaccinations can be dangerous. In England such fears have caused a significant decline in immunization rates since the 1970s. Outbreaks of whooping cough have occurred as a result, causing a number of deaths and brain damage in many children. Small babies are particularly endangered if they become infected from older unvaccinated children (who usually have a mild disease).

Call the doctor immediately if a child has any of the following symptoms.

Extremely High Fever. A rectal temperature of 105° F or higher. (Temperatures taken under the arm or by mouth often register lower than actual temperatures.)
Inconsolable Crying. The child has been crying for over 3 hours without stopping or has a cry that isn't normal, such as being high-pitched.
Convulsions. The child's body starts shaking, twitching, or jerking. This is usually in response to a high fever. Place the child face down with the head to one side, protecting the head from hitting anything hard. Be sure the child can breathe freely. Seizures caused by fevers usually last less than 15 minutes.
Shock. The child collapses, turns pale, and becomes unresponsive.
Severe Allergic (Anaphylactic) Reaction. Swelling in the mouth and throat, wheezing and breathing difficulties, dizziness. The child collapses or is pale and limp.

Call the doctor if the following symptoms persist for more than 24 hours:

The injection site is still red and tender.
Fever does not go down.
The child is still fussy.

Measles, Mumps, and Rubella

Measles. Measles, one of the most contagious of all human infections, used to be a very common childhood disease. Most cases go away without serious complications. In severe cases, however, measles can cause pneumonia, and in about 1 out of 1,000 cases it can lead to encephalitis (inflammation in the brain) or death. The risk for these severe complications is highest in the very young and very old. In pregnant women, measles increases the rates for miscarriage, low birth weight, and birth defects.

Measles outbreaks still occur in the United States, usually among groups of people who do not believe in immunizations or in areas where immunization levels have fallen below the critical level. It is a fairly serious childhood infection that is recognized by the rash (as seen here), Koplik spots (small white spots on red background), red eyes, photophobia (sensitivity to light), and coughing.

Aggressive vaccination programs have reduced the incidence of measles in the U.S., to a low of 86 cases in 2000, most imported from other countries. Full-blown measles cases among unvaccinated children still remain a serious international problem, with 42 million cases and over 1 million deaths in small children each year.

Mumps. Mumps is at record lows in the US, with only 338 cases reported in 2000. In about 15% of cases, mumps affects the lining of the brain and spinal cord, although this is usually not ultimately harmful. Swelling of the testicles occurs in between 20 - 30% of males who have reached puberty, although sterility is rare. Deafness in one ear occurs in one patient out of 20,000 with mumps.

Click the icon to see an image of the meninges of the brain.

Rubella (German Measles). When rubella, commonly known as German measles, infects children or adults, it causes a mild illness that includes a rash, enlarged lymph nodes, and sometimes a fever. If a pregnant woman is infected during her first trimester, however, her baby has a 80% chance for developing birth defects, including heart abnormalities, cataracts, mental retardation, and deafness.

Click the icon to see an image of a cataract.

Before the vaccine became available, about 56,000 cases of rubella occurred annually in the U.S. Vaccination programs have dramatically reduced the number of cases to a low of 176 in 2000, but between 6 - 11% of adults are still susceptible, particularly unvaccinated Hispanic Americans who were born outside of the U.S.

Click the icon to see an image of rubella.

Safe and effective live-virus vaccines for measles, mumps, and rubella have been developed over recent decades. They are usually combined in children as the measles, mumps, and rubella (MMR) vaccine. Individual live-virus vaccines or the combined MMR may be given to adults, depending on their risk factors.

Measles-Mumps-Rubella (MMR) Vaccine in Early Childhood. The combined MMR vaccine should be given in two doses:

Between ages 12 and 15 months for the first dose. (Some doctors believe that the vaccine may be effective and safe in children younger than 9 months who are in areas of measles outbreaks. It should be noted that there were only 86 reported cases of measles in the U.S. in 1999.)
Between ages 4 and 6 years for the second dose. (Children who receive only one dose at 15 months or older have five times the risk of measles compared to those who had two doses.)

Measles-Mumps-Rubella (MMR) Vaccine in Adolescents and Adults. The general recommendations for adult MMR vaccinations are as follows:

Most people born before 1957 have experienced these once-common childhood diseases and do not require vaccination.
All unvaccinated people born after 1956 who did not already have measles and mumps should be given two doses of the live MMR vaccine administered at least 1 month apart.
Many people received an inactivated measles-virus vaccine in the early 1960s or an inactivated mumps-virus vaccine between 1950 and 1978; such people need revaccination with two doses of the live MMR vaccine. (This will cause no harm even if someone had a previous live-virus-mumps vaccination.)
The American Academy of Pediatrics now recommends the live-virus MMR vaccine for HIV-infected children, teenagers, and young adults, except for those who are severely immunocompromised. At this time, however, the vaccine appears to be safe in HIV-infected children, and it should be stressed that measles is very dangerous in this population.

Rubella Vaccinations During Pregnancy. It is particularly important for any unvaccinated nonpregnant woman who wants children to be vaccinated against rubella. It is recommended that women wait at least 28 days after vaccination to start trying to conceive. Except under very special circumstances, no live-virus vaccine, especially MMR, is given to an already pregnant woman, since there is a theoretical risk for birth defects from the rubella vaccine. Fortunately, the risk is low. In fact, studies have reported no increase in birth defects in women who were inadvertently vaccinated for rubella early in their pregnancy.

Common side effects from the MMR vaccination include fever, rash, and joint pain. Children are more likely to experience such side effects from the second dose (at 10 - 12 years) than from the first (at 4 - 6 years).

Fever. About 5 - 15% of people who are vaccinated with any live measles virus vaccine develop a fever of 103° F or greater, usually between 5 and 15 days after the vaccination. It usually lasts 1 or 2 days but can persist up to 5 days. In very young children, seizures can occur from high fever 8 - 14 days after vaccination, but they are rare and almost never have any long-term effects.

Swollen Glands. The live-mumps vaccine can cause mild swelling in the glands that are situated near the ears.

Joint Pain. Up to 25% of women have joint pain 1 - 3 weeks after a vaccination with a live-rubella virus; it lasts for 1 day to 3 weeks. Such pain does not usually interrupt daily activities. Rarely, it recurs or becomes persistent.

Allergic Reaction. People who have known anaphylactic allergies (very severe reactions) to eggs or neomycin are at high risk for a severe allergic response to the MMR vaccine. People with allergies that do not cause anaphylactic shock to these substances are not at higher risk for a serious allergic reaction to the vaccine. Mild allergic reactions may occur in some people, including rash and itching. A rash occurs in about 5% of people who are vaccinated with a live-measles vaccine. A live-mumps vaccination has caused rash and itching, but these symptoms are usually mild.

Interaction with Tuberculosis Test. The live-measles vaccine may interfere with a tuberculosis test, so the two should be administered at least 4 - 6 weeks apart. No evidence exists that the vaccine has an adverse effect on tuberculosis itself.

Mild Infection. One study suggests that a mild form of measles that has no symptoms may develop in previously immunized people who are exposed to the virus, although this mild infection may not be significant.

Idiopathic Thrombocytopenic Purpura (ITP). In about 1 in 22,300 doses, MMR can cause a rare bleeding disorder called idiopathic thrombocytopenic purpura (ITP). This can cause a purple, bruise-like discoloration that can spread across the body, nose bleeds, or tiny red spots. It is nearly always mild and temporary. (Of note, the risk for ITP is much higher with the actual infections, particularly rubella.)

Note: Unsubstantiated Reports of Neurologic Side Effects and Decline in Immunization. Much controversy has arisen over unsubstantiated reports of neurologic side effects attributable to MMR. This is of great concern since such reports have resulted in a decline in immunizations in certain areas, notably affluent areas in England where the vaccination rate has dropped from 92% in 1996 to 84% currently. Here, measles outbreaks are now climbing, and doctors fear that unless immunization rates increase rapidly, case numbers will significantly increase. In these and other regions, some parents mistakenly believe that the dangers of immunization outweigh a dangerous childhood illness that only older people remember. It should be strongly noted that measles still cause about 745,000 deaths in unvaccinated children who live in underdeveloped countries, primarily in Africa.

Most publicity has centered on a possible link between the MMR vaccine, which was introduced in 1988, and a variant of autism that includes inflammatory bowel disease (IBD) and impaired behavioral development. Such findings have been rigorously reviewed and refuted in a number of well-conducted studies. Of special note, a 2002 analysis of vaccination records of children born between 1979 and 1998 found no higher incidence in autism, with or without behavioral problems and gastrointestinal disorders. In the study, there was a link between impaired behavioral development and bowel problems, but they were not related to the vaccine.

Despite considerable publicity, there is no evidence linking MMR vaccination with the development of autism. The Centers for Disease Control & Prevention website provides extensive information on this matter. The popular media has incorrectly reported the possible link between autism and MMR as causing a split in the scientific community, but virtually all experts refute any association. In fact, reports of symptoms related to autism increased only after widespread publicity of this supposed side effect.

The potential benefits from receiving the MMR vaccine far outweigh the potential adverse effects. Measles, mumps, and rubella are all very serious illnesses and each may have complications resulting in lifetime disabilities or even death. The incidence of such complications, related to having the actual diseases, is far greater than the potential of developing serious, or even moderate, adverse effects due to the MMR vaccine.

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

Varicella-Zoster Virus (Chickenpox)

Chickenpox (caused by the varicella-zoster virus) is one of the most contagious childhood diseases. Nearly every unvaccinated child becomes infected with it. The affected child or adult may develop hundreds of itchy, fluid-filled blisters that burst and form crusts.

The infection rarely causes complications in healthy children, but it is not always harmless. Five out of every 1,000 children are hospitalized and, in rare cases, it can be fatal. Before the vaccination became widespread, chickenpox resulted in about 11,000 hospitalizations and 100 deaths a year.

This is a close-up picture of chickenpox. Early chickenpox lesions consist of small red papules that quickly fill with a yellowish or straw colored fluid to form small blisters (vesicles), as seen in this photograph. Later, these vesicles will rupture, forming shallow erosions that crust over and then ultimately heal.

Click the icon to see an x-ray of pneumonia following exposure to chickenpox.

Chickenpox can be especially severe in adults and very serious in anyone with a compromised immune system. In addition, the varicella virus (which persists after the childhood disease) erupts as a painful and distressing condition called herpes zoster (shingles) in about 20% of adults with a history of chickenpox. Chickenpox itself usually occurs only once, although a few cases of mild second infections, marked by the telltale rash, have been reported in older children years after their first infection.

Click the icon to see an image of the shingles.

A live-virus vaccine (Varivax) produces persistent immunity against chickenpox. Data show that the vaccine can prevent chickenpox or reduce the severity of the illness even if it is used within 3 days, and possibly up to 5 days, after exposure to the infection.

Recommendations for the Vaccine in Children. The vaccine against chickenpox is now recommended in the U.S. for all children between the ages of 18 months and adolescence who have not yet had chickenpox. Children are given one dose of the vaccine. Two doses 1 - 2 months apart are given to people over 13 years of age. To date, more than 75% of children have been vaccinated.

Doctors recommend that the chickenpox vaccine be given at the same time as the measles-mumps-rubella (MMR) vaccine or that there is a delay of at least 1 month between the two vaccinations. (If the chickenpox vaccination is given within that 30-day period -- but not at the same time -- there is a higher risk for a breakthrough infection later on.)

A chickenpox vaccine is part of the routine immunization schedule. It is about 100% effective against moderate or severe illness, and 85 - 90% effective against mild chickenpox. Parents often express concern that the immunity from the vaccine might not last. The chickenpox vaccine, though, is the only routine vaccine that does not require a booster.

Recommendations for the Vaccine in Adults.

Some doctors suggest that every healthy adult without a known history of chickenpox be vaccinated. In general, however, the following adults should consider vaccinations:

Older people without a history of chickenpox and who are at high risk of exposure or transmission (such as hospital or day care workers and parents of young children)
People who live or work in environments in which viral transmission is likely
Nonpregnant women of childbearing age
Adolescents and adults living in households with children
International travelers

As with other live-virus vaccines, the chickenpox vaccine is not recommended for the following:

Pregnant women (including the 3 months prior to pregnancy). Of note, an encouraging study suggested that pregnant women who were inadvertently vaccinated did not face a higher risk for birth defects in their offspring.
People whose immune systems are compromised by disease or drugs (such as after organ transplantation). The vaccine is being studied, however, for its safety in some of these patients, particularly children with cancer or other high-risk conditions. Experts report that it is safe in children with acute lymphoblastic leukemia (ALL), who should receive two doses. Certain children who are HIV positive may be candidates for the vaccine. An inactivated varicella vaccine may be safe and effective in patients undergoing bone marrow transplants, when given before and after the operation.
Most patients who cannot be vaccinated but are exposed to chickenpox are given immune globulin antibodies against varicella virus. This helps prevent complications of the disease if they become infected.

Discomfort at the Injection Site. About 20% of vaccine recipients have pain, swelling, or redness at the injection site.

Mild Rash and Risk of Transmission. The vaccine may produce a mild rash within about a month of the vaccination, which has been known to transmit chickenpox to others. Individuals who have recently been vaccinated should avoid close contact with anyone who might be susceptible to severe complications from chickenpox until the risk for a rash has passed.

Severe Side Effects. Between 1995 and 2001, 759 serious adverse effects were reported. Such events included seizures, pneumonia, anaphylactic reaction, encephalitis, Stevens-Johnson syndrome, neuropathy, herpes zoster, and blood abnormalities. Anecdotal reports have found a higher association of side effects when varicella vaccine is given at the same time as the measles, mumps, and rubella (MMR) vaccination. Because combined vaccinations are being developed, such effects should be closely studied.

There is intense debate over the long-term protection of the vaccine. The incidence of breakthrough infections after vaccination stimulates the controversy. It should be noted, however, that evidence is showing improvements in quality of life and better survival rates since the introduction of the vaccine. Any negative studies to date on long-term effectiveness simply raise the question of the need for booster or higher doses -- not the elimination of the vaccine altogether.

Long-Term Protection in Vaccinated Children. Most studies suggest that the vaccine is not wholly effective in up to 30% of vaccinated children. However, they also report if chickenpox occurs, more than 95% of the cases are mild. It is also usually less contagious. In such people, the infection appears to be caused by a wild virus, not a reactivation of the vaccine. (Of concern was a 2002 study of a day care center reporting a much higher rate -- 56% -- of break-through infection, with only 86% of cases being mild. The implications of this study are unclear.) The longer the interval since vaccination occurs, the higher the risk for a breakthrough infection.

This does not necessarily mean, however, that children who are vaccinated eventually lose total immunity. A breakthrough infection is often due to issues with the primary vaccine (improper storage, low potency, the duration between the chickenpox and measles, mumps, and rubella vaccines being less than a month) or the child's history (having asthma, being less than 14 months at the time of vaccination). Nevertheless, there is also some evidence that either having the vaccination or even having chickenpox itself is not as protective against a later infection as experts have thought.

Long-Term Protection in Vaccinated Adults. The protective effects for adults are even less clear. An encouraging 2002 study of adults vaccinated between 1979 and 1999 reported that 9% developed chickenpox months to years after their last vaccination. The length of time since the vaccination did not seem to affect whether the adults would catch chickenpox or not. (Nearly half of those had been exposed to the disease in their homes.) In all cases, infection was mild, with none of the serious complications of adult chickenpox.

Vaccine's Effect on Shingles. A primary concern is whether the vaccine protects against shingles later on, particularly in people who have breakthrough infections -- however mild. As more and more children get vaccinated, the actual protection of the vaccine and the implication of the breakthrough infection will become clearer.

[For more information, see In-Depth Report #82: Shingles and chickenpox (Varicella-zoster virus).]

In September, 2005, the Food and Drug Administration approved a combination vaccine to protect against measles, mumps, rubella, and chickenpox. Proquad, produced by Merck & Co., protects against all four infections with one shot, thus sparing young children from multiple painful injections. Proquad is approved for use in children from 12 months to 12 years of age. Proquad was studied in four randomized trials involving 5,446 healthy children aged 12 - 23 months received Proquad. Proquad’s immune response rates were 97.4% for measles, 95.8 - 98.8% for mumps, 98.5% for rubella, and 91.2% for chickenpox, similar to the rates induced by the concomitant administration of single doses of M-M-R II and Varviax at separate injection sites in 2,038 children.

Varicella-Zoster Virus (Shingles)

Shingles is a painful infection caused by the varicella zoster virus, the same virus responsible for chickenpox. Once a person has chickenpox, the virus lies dormant in the body. It can emerge years later as shingles.

Shingles causes a painful, red, and sometimes blistery rash to form on the body or face. The disease can cause intense pain, called post herpetic neuralgia. Other symptoms include fever, headache, and chills. In rare cases, complications, such as pneumonia, blindness, and brain inflammation (encephalitis), can occur. Shingles is most common in adults over age 50.

In May 2006, the U.S. Food and Drug Administration licensed the herpes zoster vaccine (Zostavax) for the prevention of shingles. The vaccine can reportedly cut the incidence of shingles in half for adults over age 60.

Recommendations for the Vaccine in Adults. All adults age 60 or older should get a single dose of the herpes zoster vaccine, regardless of whether they have previously had shingles.

The following people should not receive the herpes zoster vaccine:

Anyone who has a weakened immune system due to HIV/AIDS or cancer of the lymph, bone, or blood, or due to treatments such as radiation or corticosteroid drugs
Women who are pregnant, or anyone who is in close contact with a pregnant woman who has not had chickenpox
Children -- they should receive only the chickenpox vaccine

Redness, pain, and swelling. About 1 out of every 3 people who get the vaccine have mild redness, soreness, swelling, or itching at the injection site.

Headache. About 1 in 70 people experience headache after taking the vaccine.

There have been no serious side effects reported with the shingles vaccine.

Research has found that the herpes zoster vaccine reduces the incidence of shingles by about 50%. The benefit is as high as 64% in people ages 60 - 69. In people who are vaccinated but still develop shingles, the vaccine reduces the duration of the pain involved with the disease.

One 2007 study found that doing tai chi might boost the immune response to the vaccine. According to the study, people aged 59 - 86 who took part in a 16-week tai chi program had immunity similar to that of 30- and 40-year-old adults who had been vaccinated. Combining tai chi with the vaccine increased the effects of the vaccine by about 40%.

Hepatitis A

The hepatitis A virus infected an estimated 56,000 people in 2004. Hepatitis A, formerly called infectious hepatitis, is always acute and never becomes chronic. The virus is excreted in feces and transmitted by contaminated food and water. Eating shellfish taken from sewage-contaminated water is a common means of contracting hepatitis A. It can also be acquired by close contact with individuals infected with the virus. It is estimated that 11 - 16% of reported cases occur among children or employees in daycare centers or among their contacts. The hepatitis A virus does not directly kill liver cells, and experts do not yet know how the virus actually injures the liver.

A fly may act as a mechanical vector of diseases such as hepatitis A. The fly may carry the infective organism on its feet or mouth parts and contaminate food or water, which a person then consumes. A biological vector actually develops an infective organism in its body and passes it along to its host, usually through its saliva. A fly can be a biological vector, as in the transmission of leishmaniasis by the sandfly.

All children should get 2 doses of the hepatitis A vaccine starting at 1 year, according to CDC recommendations. The doses should be given at least 6 months apart. Others who should be vaccinated against hepatitis A include travelers to developing countries, people living in communities where outbreaks occur, people with blood-clotting disorders, sexually active homosexual men, and health care workers exposed to the virus. People with chronic liver disease, including those with hepatitis C, should also be vaccinated, particularly if they have not been exposed to hepatitis A, since the infection can cause liver failure in these patients.

The hepatitis A vaccine can be given along with immune globulin and other vaccines. Individuals should also receive immune globulin if they are exposed within 4 weeks of the vaccination. A combined vaccine against both hepatitis A and B is now available as well for those at high risk for both these infections. People should get 3 doses of this vaccine, and the last dose should be given 6 months after the first dose.

Side Effects. The vaccine is very safe and effective, although allergies can occur. The most common side effects reported are soreness at the injection site, headache, and general malaise.

Click the icon to see an image about hepatitis A immunization.

Hepatitis B

About 2 billion people have been infected with the hepatitis B virus (HBV) worldwide, and each year 1 million people die, mostly due to cirrhosis and liver cancers that develop in the chronic form of this disease. In the U.S., about 1.25 million people have chronic hepatitis B.

Hepatitis B is also known as serum hepatitis. It spreads through blood and sexual contact. The infection is seen with increased frequency among intravenous drug users who share needles and among the homosexual population. This photograph is an electronmicroscopic image of hepatitis B virus particles. (Courtesy of the CDC.)

Pregnant women with hepatitis B can transmit the virus to their babies. Even if they are not infected at birth, unvaccinated children of infected mothers run a 60% risk of developing hepatitis B before age 5. Although hepatitis B infections have dropped 95% since routine immunization began in the early 1990s, there are still children who aren't immunized, and the disease persists. Universal vaccination against this disease during childhood is very important.

Several inactivated virus vaccines, including Recombivax HB, GenHevac B, Hepagene, and Engerix-B, can prevent hepatitis B. Twinrix is a vaccine against both hepatitis A and B. They are safe, even for infants and children. Vaccination programs are proving to reduce the risk for liver cancer.

Click the icon to see an image of hepatitis B.

Hepatitis B Vaccine for Early Childhood. Experts now recommend that all infants and children not previously vaccinated be immunized by the time they reach seventh grade. Typical schedules for hepatitis B vaccinations in childhood are as follows:

All infants should receive the hepatitis B vaccine soon after birth and before hospital discharge. (The first dose may be delayed if the mother has no evidence of infection, but only with the doctor's permission.) The second dose should be given at 1 - 2 months; and the third between 6 and 18 months (at least 16 weeks after first dose and 8 weeks after second dose). (A fourth dose may also be given if any of the previous doses was a combination vaccine.) This is a safe vaccine, even in newborns, and parents should be sure their infants are immunized.
Infants of mothers infected with hepatitis B should be treated with immune globulin plus the hepatitis vaccine within 12 hours of birth. The second dose should be given at 1 - 2 months and the third at 6 months. Infants should be tested for antibody status at 9 - 18 months to see if they are chronic virus carriers or need to be revaccinated. Immunization rates are still too low in this group.
When it is not known if a mother is infected, the infant should receive the vaccine within 12 hours of birth. The mother's blood should then be tested right away. If she is infected, the infant should receive immune globulin within 1 week of birth.
Children who are 11 - 12 and who have not been immunized should receive 2 or 3 doses of the vaccine (depending on the brand) given over a few months.

Hepatitis B vaccine protection may wane over time. According to a 2007 study, 40% of adolescents who had received a first dose of the vaccine as newborns had declining immunity to the disease by age 14. As of now, routine booster shots are not recommended because more research is needed on the subject. Booster shots may be recommended for those at risk, such as from sexual exposure.

Hepatitis B Vaccine for Adults. The following adults are at very high risk and should be vaccinated:

Health care and public safety workers who may be exposed to blood products. Such individuals have a risk for hepatitis B that ranges from 15 - 30%.
People in the same household ashepatitis B-infected individuals. (Unvaccinated people who have had intimate exposure to people with hepatitis B may be protected with immune globulin, which is sometimes administered with the vaccine.)
Travelers to countries with a high incidence of hepatitis B infection.
Patients who require transfusions and have not been infected with hepatitis B. (Those with blood clotting disorders should have the vaccination administered under the skin, not injected in the muscle.)
Sexually active individuals with multiple partners.
People with any sexually transmitted diseases.

Other people at risk who would benefit from vaccinations include:

Patients and workers in mental institutions
Morticians
Patients undergoing hemodialysis. (These people may need larger doses or boosters; they also may need to be revaccinated if blood tests indicate they are losing immunity.)
People who use injected drugs
Pregnant women at risk for the virus. (There is no evidence that the vaccine is dangerous to the fetus.)
People receiving treatments or who have conditions that suppress the immune system may need the vaccination, although its benefits for this group are unclear except for those at high risk, such as people with HIV or spleen abnormalities.

Click the icon to see an image of the immune system structures.

The regimen in adults is typically 3 doses given over 6 months. One study reported that older adults would benefit from a fourth dose without incurring serious side effects. People who abuse alcohol may need higher doses.

A small percentage of people do not develop immunity, even after a vaccine has been given repeatedly. A more potent vaccine is proving to be effective for these people; it loses its effect after 5 years in about one-third of those who receive it.

Soreness. Soreness at the injection site is the most common side effect.

Nerve Inflammation. There have been some reports of nerve inflammation after vaccinations for hepatitis B, and some questions about multiple sclerosis. A review article published in 2006 found no evidence that hepatitis B vaccine is associated with multiple sclerosis, sudden infant death syndrome, or chronic fatigue syndrome. Earlier studies also found no evidence linking the vaccine to multiple sclerosis. A 2007 study found that the vaccine doesn't increase the risk for rheumatoid arthritis.

Because of even a small theoretical risk of nerve damage in infants, some groups oppose the vaccination in children who are not in high-risk groups. Worldwide, 65 million people with chronic hepatitis are expected to die from liver disease and vaccinations are saving lives. For example, in Taiwan, where infection rates are high and infants are at risk for hepatitis B from infected mothers, vaccination programs have significantly reduced the risk for liver cancer. [For more information see In-Depth Report #59: Hepatitis.]

Pneumococcal Pneumonia

The pneumococcal bacterium (also called Streptococcus pneumoniae or S. pneumoniae ) is responsible for many respiratory infections in the upper and lower airways. This bacterium is dangerous for people with serious underlying chronic medical conditions and illnesses and is the leading cause of ear infections and sinusitis in children. The most serious complication is pneumonia.

More than 200,000 people in the U.S. are hospitalized each year for pneumonia-related complications. Although the majority of pneumonias respond well to treatment, the infection can still be a very serious problem. It kills approximately 36,000 people each year. Together with influenza, pneumonia is the eighth leading cause of death in the U.S.

Of particular concern is the increasing prevalence of pneumococcal bacteria that are resistant to many standard antibiotics. This has created a great sense of urgency in the medical community to find effective measures for preventing infection.

This picture shows the organism pneumococci. These bacteria are usually paired (diplococci) or appear in chains. Pneumococci are typically associated with pneumonia, but may cause infection in other organs, such as the brain (pneumococcal meningitis) and bloodstream (pneumococcal septicemia). (Courtesy of the CDC.)

The pneumococcal vaccine protects against S. pneumoniae (also called pneumococcal) bacteria, the most common cause of respiratory infections. There are 2 effective vaccines available: The 23-valent polysaccharide vaccine (Pneumovax, Pnu-Immune) for adults and the 7-valent conjugate vaccine Prevnar (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.

The 7-valent conjugate vaccine Prevnar (PCV7) is very effective in children. Research finds that the vaccine, which was introduced in 2000, has reduced hospital admissions for pneumonia in children under age 2 by about 39%. The vaccine has even lowered hospital admissions 26% among adults aged 18 - 39 the study found, likely because they are parents of young children who might otherwise have developed the disease. Another study found that the vaccine also has benefited children who regularly get ear infections. Recurrent ear infections have fallen by 28% since the introduction of the vaccine.

Click the icon to see an image of pneumococcal pneumonia.

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

Children up to age 2. The vaccine is very effective in children. In one study, a similar vaccine under investigation not only protected 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 children with sickle cell disease, those with immune deficiencies, a damaged spleen or no spleen, or children with chronic medical conditions. One study has found that the rate of pneumococcal disease among children with sickle cell disease has dropped 90% since the vaccine was introduced.
Other children ages 2 - 5 who are at higher risk for serious pneumococcal infections should be considered for vaccinations. They include African- or 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.

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

All people over 65 years old. Some experts believe that all adults 50 - 64 should also be vaccinated. Unfortunately, although the vaccination is protective against pneumococcal bacteremia (invasive infection) in people over 65, evidence suggests that it does not appear to protect against community-acquired pneumonia.
Adults with any chronic condition that increases the risk for pneumonia. This includes patients with heart disease (such as congestive heart failure), chronic lung disease (COPD or emphysema, but not asthma), or diabetes.
Individuals with immune deficiencies (such as HIV) or those undergoing treatments that suppress the immune system.
Patients with autoimmune diseases, such as rheumatoid arthritis and lupus. Unfortunately, studies show the vaccine may not be as effective in these patients as 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 American Indians, who may be at increased risk for pneumonia.

The safety of the pneumococcal vaccine hasn't been proven during the first trimester of pregnancy; however, there have been no adverse effects reported. 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 the protective value may be lost at a faster rate 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.

The recommended schedule of immunization for Prevnar (PCV7) is 4 doses, given at 2, 4, 6, and 12 - 15 months of age. Infants starting immunization between 7 and 11 months should have 3 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.

Side effects include pain and redness at the injection site, fever, and joint aches. Children are more likely to have fever within 48 hours if they receive other vaccines at the same time, and also after the second dose. Fortunately, severe reactions are very rare, even if a person is mistakenly revaccinated before the effects of the first vaccination have worn off. Allergic reactions are also very rare.

Poliomyelitis

Poliomyelitis, more commonly known as polio, is a disorder caused by a virus and marked by potentially paralyzing nerve-related damage, which can be fatal. Fifty years ago it was a major killer of children, and it remains a threat in parts of Asia and Africa today. Vaccination programs eliminated the disease in the Americas in 1994, with the last case of wild poliovirus in the U.S. reported in 1979. As of 2004, polio has been eradicated in the Americas, the Western Pacific, and Europe.

Poliomyelitis is a communicable disease caused by viral infection and occurs through direct contact with infected secretions. Polio is found worldwide, but immunization has reduced the incidence. Clinical polio affects the central nervous system (brain and spinal cord). Disability is more common than death.

Two poliovirus vaccines have been available in the U.S.: oral poliovirus vaccine (OPV), a live-virus vaccine, and inactivated poliovirus vaccine (IPV), a killed vaccine that is administered by a shot. Both produce immunity in more than 95% of people. The live-virus used in the vaccine, however, has, in some cases, reverted to a form that can cause polio in unvaccinated people. This is a particular danger in developing countries where vaccination rates are low. The Centers for Disease Control and Prevention now recommends only the inactivated IPV vaccine for children. The schedule is 4 doses of IPV at ages 2 months, 4 months, 6 - 18 months, and 4 - 6 years.

Poliovirus Vaccine in Older Children and Adults. The poliovirus vaccine is not usually recommended for people over 18. Exceptions are unvaccinated health care workers, laboratory technicians, or others exposed to polioviruses. Travelers to developing countries where outbreaks of poliovirus have been reported should be vaccinated. Adults should also be given the inactivated poliovirus vaccine (IPV).

Allergic Reactions. The inactivated poliovirus vaccine (IPV) contains small amounts of streptomycin and neomycin, so people allergic to these antibiotics can also have an allergic response to this vaccine. Patients should report any allergies to their physician.

Paralysis. Rare cases of paralysis have occurred in people taking the oral live poliovirus vaccine or in those exposed to recipients of this vaccine. It should be stressed the risk is very small, with only 1 case occurring out of 2.4 million doses. Since the introduction of the current recommended series that uses only IPV, no cases have been reported.

Contamination by Simian Virus 40. The public was alarmed by reports of contamination of polio vaccines given between 1955 and 1963 by a virus known as SV40. The virus has been detected in certain rare cancers, including mesothelioma (a lung cancer normally associated with asbestos exposure), osteosarcoma, some brain tumors, and non-Hodgkin's lymphoma.

Click the icon to see an image of a brain tumor.

Still, about 98 million people may have been exposed, and most of these cancers are very rare (although some, including non-Hodgkin's lymphoma, are increasing). At least 40 years of observation have raised no red flags that indicate any serious problem. However, polio, once a major killer of children, has nearly been wiped out worldwide.

Viral Influenza

Influenza, commonly called the flu, is always caused by a virus.

Influenza, also known as the flu, is caused by a virus.

There are different strains of influenza:

Influenza A is the most widespread and most severe strain. It can affect both animals and humans. Influenza A is the cause of the worldwide epidemics (pandemics) of the flu that have occurred. More than 200,000 hospitalizations per year are due to this strain of the flu. Influenza A is usually further categorized by 2 subtypes based on 2 substances that occur on the surface of the viruses: hemagglutinin (H) and neuraminidase (N).
Avian Influenza A (called “bird flu”) was first detected in humans in 1997 in China and the region of Hong Kong. Bird flu is spread easily from bird to bird. Humans usually contract the flu from contact with infected domesticated birds, such as chickens, turkeys, and ducks. The World Health Organization confirms that there were, as of the publishing of this report, 331 cases of bird flu in humans and 203 deaths. The greatest number of cases have occurred in Indonesia, followed by Vietnam, Egypt, Thailand, and China. In April 2007, the U.S. Food and Drug Administration approved the first vaccine against the avian flu virus.
Influenza B infects only humans. It is less common than type A, but is often associated with specific outbreaks, such as in nursing homes. Flu caused by this strain tends to be milder than that caused by Influenza A.

Based on a final analysis of the 2005 - 2006 flu season, nearly 80% were type A and about 20% were type B. Influenza A usually causes more severe disease than type B. However, because influenza B has been less common in the past few years, there is concern that some people -- particularly small children -- may have fewer antibodies to it and so may be at higher risk for severe infection. (See Flu Vaccines in this report.)

Complications of the Flu. In general, the flu is usually self-limited and not serious. It is responsible, however, for 15 - 30% of the excess number of hospitalizations that occur in winter. More than 200,000 people who contract the flu end up in the hospital, and an estimated 36,000 people currently die each year of flu-related complications. The highest risks for serious complications occur in people age 65 and older and in those who are already sick with another disease. There have also been reports of flu-related deaths in very young children.

Pneumonia is the major serious complication of the flu and can be very serious. It can develop about 5 days after viral influenza. It is an uncommon event, however. It nearly always occurs in high-risk individuals, such as the very young or very old, and hospitalized or immunocompromised patients.

Note on Pandemics. Every year, flu strikes millions of people worldwide. Influenza epidemics are most serious when they involve a new strain against which most people are not immune. Such so-called pandemics can infect more than one fourth of the world's population within a 3-month period. For example, the Spanish flu in 1918 and 1919 killed 20 million people in the U.S. and Europe, and 17 million people in India. Although pandemics are still of great concern, there have been major improvements in private and public health since then, including the discovery of antibiotics to treat bacterial complications, new antiviral agents and vaccines, and intensive worldwide surveillance of outbreaks.

Description of Vaccines. Vaccines against the flu use inactivated (not live) viruses. The influenza vaccine is commonly called a "flu shot." It is 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 so targets for attack.)

Click the icon to see an image of antigens.

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 are 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 will not have developed any immunity to the virus and will experience severe flu if they are exposed to type B.

Until recently the vaccine has been administered only by injection. A vaccine (FluMist) that can be delivered in a nasal spray has now been approved for people aged 5 - 49. The vaccine contains live viruses that have been engineered to replicate in the cool temperatures of the nasal passages, but not in the warmer lungs and lower airways. Its presence in the nasal passages boosts the specific immune factors in the mucous membranes that fight off the epidemic viruses. Studies in 2003 reported protection against the flu that ranged from 66 - 92%, depending on whether the flu was type A or type B. (The lower rates were those observed for influenza B, particularly a new variant.) A 2007 study found that children aged 6 months - 5 years who had the nasal spray had 55% fewer cases of the flu than those given the injection. However, the vaccine is not approved for children in this age group. A preservative-free intramuscular injectable vaccine (Fluzone) is also now available.

The avian flu vaccine is designed for people aged 18 - 64 who are at risk for exposure to the avian H5N1 virus. The vaccine is given as 2 shots, spaced about 1 month apart. In studies, the vaccine appeared to be effective and well tolerated. Currently, the government is stockpiling the vaccination in case of an avian influenza outbreak. The vaccine is not available to the general public.

Ideally, appropriate candidates 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 flu virus usually develop within 2 weeks of vaccination, and immunity peaks within 4 - 6 weeks, then gradually wanes.

Because children under age 9 do not develop strong immune responses to 1 dose, the CDC recommends 2 vaccinations given 1 month apart.
Early research also suggests that it may be equally effective to administer children’s vaccinations in the spring and fall, rather than 1 month apart; further study is ongoing.
It should be noted that if an individual develops flu 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, according to a 2004 Canadian analysis of multiple studies.

In healthy adults, immunization typically reduces the chance of getting the flu 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. Some evidence suggests, however, that even in people with a weaker response, the vaccine is usually protective against serious flu complications, particularly pneumonia. The major outstanding question is whether the vaccination prevents complications of serious illness. One 2003 study, for instance, reported no reduction in severity of chronic lung diseases among vaccinated patients with asthma, emphysema, or chronic bronchitis. Some evidence suggests, on the other hand, that among the elderly, a flu shot 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 the flu:

The American Academy of Pediatrics (AAP) and the CDC recommend flu shots for all healthy children ages 6 - 23 months. In addition, any child over age 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 disease, or immune deficiencies).
Children who are receiving long-term aspirin therapy should also receive a flu shot. Children who get the flu are at higher risk for Reye syndrome, a life-threatening disease.
Some doctors now advocate flu shots for all school-age children. Research indicates that children are responsible for transmitting the vast majority of cases of the flu, and that routine vaccination of school-age children would considerably reduce transmission rates throughout communities.

There has been some question concerning flu shots 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. Yet many children with asthma are not vaccinated. One study by the CDC found that fewer than one-third of children with asthma were vaccinated during the 2004-2005 flu season.

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 2 groups have the highest need for flu shots and are given top priority:

All adults 65 years and older. Older adults who get a flu shot have lower hospitalization rates than those who do not. 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 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 the flu. 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 the flu outweighs any potential adverse effects from the vaccines.)
Adults aged 50 - 64 who have chronic medical conditions. The U.S. Advisory Committee on Immunization Practices (ACIP) suggests that all adults over age 50 should be vaccinated, although this is not a recommendation of the CDC.
All health care workers should be vaccinated, according to the ACIP’s 2005 recommendations.
Household members in contact with individuals who are at high risk for complications from the flu should be vaccinated.

Other adults who should consider flu shots include:

People at risk for complications of the flu 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 the flu and who will be in their second or third trimester during flu season. Women who are pregnant should receive only the inactivated flu vaccine. (Vaccinations should usually be given after the first trimester. Exceptions may be women who are in their first trimester during flu season, because their risk from complications of the flu is higher than any theoretical risk to the baby from the vaccine.)
People such as firemen or policemen who are critical for public safety.

Possible side effects of the flu vaccine 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 or 2 days afterward.
Flu-like Symptoms. Some people actually experience flu-like symptoms, called oculo-respiratory syndrome, which include conjunctivitis, cough, wheeze, tightness in the chest, sore throat, or a combination. Such symptoms tend to occur 2 - 24 hours after the vaccination and generally last for up to 2 days. It should be noted that these symptoms are not the flu 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. Isolated cases of a paralytic illness known as Guillain-Barre syndrome have occurred, but if there is any higher risk, it is very small (one additional case per 1 million people), and does not outweigh the benefits of the vaccine.

Haemophilus Influenzae Type B

Haemophilus influenzae (H. influenzae) type B is a bacterium, which, despite its name, is entirely different from the viruses that cause influenza (the flu). Before vaccination, H. influenzae type B (Hib) was the most common cause of childhood bacterial meningitis, killing 600 American children every year and leaving others deaf, mentally retarded, or epileptic. It is rarely troublesome for adults, although it can be dangerous for anyone with chronic lung disease and those susceptible to infections.

This is a Gram stain of spinal fluid from a person with meningitis. The rod-like organisms seen in the fluid are Haemophilus influenza, one of the most common causes of childhood meningitis (prior to the widespread use of the H. influenza vaccine). The large red-colored objects are cells in the spinal fluid. A vaccine to prevent infection by Haemophilus influenza type B is available as one of the routine childhood immunizations (Hib), typically given at 2, 4, and 12 months.

Three equally effective inactivated bacterial vaccines (commonly called Hib vaccines) are available for H. influenzaetype B. All children under 5 should be vaccinated against H. influenzae type B. The vaccine is administered as an injection at 2 and 4 months. Depending on the vaccination preparation, a third shot in the series is administered at 6 months. A booster is required at some time between 12 and 15 months of age.

Click the icon to see an image of Hib immunization.

In children older than 12 months, the Hib and DTaP vaccines are being combined in a single injection. This combined injection can be given as a booster, but not as the initial Hib immunization.

Evidence suggests that in infants, this combined vaccine using acellular pertussis (the current DTaP standard) is less effective in protecting against Hib than one that uses the older form with whole-cell pertussis. The booster at 1 year should help maintain protection, however.

The Hib vaccine may benefit older people who have had their spleen removed or illnesses that put them at risk for pneumonia, including sickle cell disease, leukemia, and HIV infection.

Click the icon to see an image of sickle cells.

Side effects of the Hib vaccine include redness and pain at the injection site, moderate fever, and, in rare cases, weakness, nausea, and dizziness.

Human Papillomavirus (HPV)

In 2006, the U.S. Advisory Committee on Immunization Practices( ACIP) voted to recommend the use of the first vaccine (Gardasil) to protect against human papillomavirus (HPV). This group of 100 viruses includes some 40 sexually transmitted viruses. Some HPV viruses can significantly increase the risks of cervical cancer, as well as cancers of the vulva, vagina, anus, and penis.

HPV is a very common virus; an estimated 20 million people in the U.S. have it. At least half of all sexually active men and women will eventually develop the virus.

A 2007 study indicated that the Gardasil vaccine is 100% effective against cervical, vaginal, and vulvar diseases caused by 4 types of HPV (6, 11, 16, and 18); however, it does not protect against the other types of the virus. It is less effective in women who were exposed to the virus before they were vaccinated. A 2007 study indicated that the vaccine is effective for 5 years after women receive the initial dose. The manufacturer has applied to the FDA for approval of the vaccine to also help prevent cancers of the vagina and vulva.

A new experimental vaccine, called Cervarix, has been shown in research to be effective for 5 1/2 years against the 2 most prevalent strains of HPV. Research is also indicating that the vaccine might be effective against more types of infections than the Gardasil vaccine. Researchers are studying the vaccine further, and they're looking at whether Cervarix is effective in women over age 25.

Girls ages 11 - 12 should get the vaccine, but they can get it as early as age 9. Adolescents and women ages 13 - 26 also should get the vaccine if they haven't already received it. Young women should ideally get the vaccine before they are sexually active, but it is still effective in sexually active women who haven't yet been infected with HPV. Currently there is no research to confirm the vaccine's effectiveness in women over 26, so there is no recommendation yet for this age group. Gardasil is not recommended for pregnant women.

Young women should get 3 doses of the vaccine. They should get the second dose 2 months after the first dose, and the third dose 6 months after the first dose.

Studies have shown no significant side effects from the HPV vaccine. The most common side effect was soreness at the injection site.

Rotavirus

Rotavirus is the most common cause of diarrhea, cramps, and vomiting in infants, and affects about 3.5 million children in the U.S. each year. As many as 80% of small children become infected with the virus. Although most cases in this country are mild, more than 50,000 American children are hospitalized and as many as 125 die from severe diarrhea every year. Worldwide the virus can be devastating, causing more than 600,000 infant deaths annually. There is also some strong evidence that the virus can lead to childhood diabetes.

An oral vaccine (Rotashield) has been withdrawn after reports of a severe and even life-threatening condition called intussusception following use of the vaccine. Intussusception occurs when the bowel slips inside itself like a telescope and obstructs the intestine. The risk was very small and occurred within a week or two of the vaccination. Any child who previously had the vaccination no longer incurs any increased risk. Preliminary reports suggest that newer rotavirus vaccines may be highly effective in preventing infection among infants, although more research is needed to confirm these findings and to determine their safety record in a large number of children. The association between diabetes and the virus itself raises some alarm that the vaccine might also increase the risk in children who are genetically susceptible to type 1 diabetes.

The U.S. Food and Drug Administration (FDA) approved a new oral rotavirus vaccine (Rotavirus, Live, Oral, Pentavalent vaccine -- trade name RotaTeq) early in 2006, and the Advisory Committee on Immunization Practices (ACIP) recommended that all infants should be immunized (3 liquid doses by mouth at 2, 4, and 6 months of age). In February 2007, the FDA announced there had been 28 reports of intussusception in infants who received the vaccine. After carefully monitoring cases of intussusception and other adverse effects associated with RotaTeq the FDA announced in March 2007 that the vaccine does not pose an increased risk of intussusception.

Because this is a deadly virus for many children worldwide, international groups believe that the few cases of intussusception do not warrant withdrawing its use, at least for countries where the infection is so common and deadly.

Click the icon to see an x-ray of intussusception.

Smallpox

Vaccination against smallpox used to be routine in the U.S. until 1972, and most older Americans bear the telltale small round smallpox vaccination scar on their upper arms. Immunity may last 10 years or longer. The last case of smallpox, a highly contagious and deadly disease caused by the variola virus, occurred in a laboratory worker in the U.K. in 1978.

However, the growing threat of bioterrorism has raised fears that smallpox could be used as a biological weapon, and in 2002 the US government issued plans for vaccinating every citizen against the disease in the event of an outbreak. The vaccination, however, carries some risks. Currently, then, vaccination continues to be recommended only for laboratory workers and scientists who work with the virus.

If an outbreak occurs, guidelines from the CDC call for a so-called "ring vaccination" approach. This involves identifying anyone who comes into contact with an infected person and vaccinating them and their contacts with a single dose of vaccine. This includes people of all ages and even those at risk for vaccine complications. The vaccine may work even if given within the first few days of infection.

Those at increased risk of vaccine complications but who should still be immunized if they are actually exposed to an outbreak include the following:

Children younger than a year. About 42 infants out of a million will develop brain swelling that may result in retardation or death. A severe, body-wide rash may also occur, especially if children touch the vaccination site.
Pregnant women. There is a small risk of miscarriage or premature delivery, although smallpox itself in pregnant mothers has more serious implications.
People with skin conditions, particularly eczema. They may develop a widespread blistering rash called eczema vaccinatum, which is fatal in 1 - 6% of cases, and they should not be vaccinated unless they've been exposed to the disease. They should also avoid others who have been vaccinated until those persons' vaccination scabs heal and fall off. People with non-chronic skin conditions, such as allergic rashes, severe burns, or chickenpox, may be vaccinated once their skin condition clears up.
People with suppressed immunity due to HIV, organ transplants, high-dose steroids, cancer chemotherapy, or other conditions.
Should a severe rash or other complication develop, patients should notify their doctors immediately. Two investigational medications, vaccine immune globulin (derived from the blood of people who have been vaccinated against smallpox) and an antiviral drug called cidofovir (Vistide), may be administered intravenously in the hospital should serious complications arise.
In the event of an outbreak, current plans specify that vaccination against smallpox will remain voluntary, although unvaccinated people who are exposed to the disease may be quarantined for 18 days to help contain the spread of disease.

Other Vaccinations

Many other types of vaccinations are available.

Rabies is a frequently fatal, acute viral infection that is transmitted to humans by infected animals (often dogs or bats) via a bite or exposing broken skin to an infected animal's saliva. In the past, human cases in the U.S. usually resulted from a dog bite, but more cases of human rabies have been linked to bats. Meanwhile, there have not been any rabies cases caused by dog bites for a number of years. Few cases occur in the U.S. because of extensive animal vaccination programs.

Anyone who is exposed to bats or to secretions of an animal suspected of having rabies should receive the rabies vaccine. Exposed individuals should also receive immune globulin unless they were previously vaccinated. Veterinarians and animal handlers should be vaccinated. This does not eliminate the need for treatment if they are exposed to rabies, but it reduces the intensity of the treatment.

Side effects include pain, redness, swelling at the injection site, headache, nausea, stomach pain, muscle aches, and dizziness. Allergic response can occur after the first shot and as many as 21 days after a booster shot. Rare cases of neurologic disorders that cause pain and paralysis in the legs and arms have also been reported. These neurologic disorders usually clear up in about 12 weeks.

Click the icon to see an image of rabies.

Plague is a severe, and potentially deadly, infection. It is caused by the organism Yersinia pestis. Wild rodents, like rats, spread the disease to humans. Plague is spread among rodents by a flea bite. Humans may get the plague when they touch or eat the infected animal, or when they come in contact with its feces. Certain forms of the plague can be spread from human to human. Plague is rare in the United States, but has been known to occur in parts of California, Utah, Arizona, Nevada, and New Mexico.

Veterinarians and assistants in the western U.S. or anyone who works with potentially plague-infected animals and travelers to developing countries where outbreaks have occurred should be vaccinated. The plague vaccine is not 100%y protective; it may only lessen severity of the disease. Preventive antibiotics are needed for anyone exposed. Side effects include headache, malaise, fever, swollen lymph nodes, and, occasionally, non-infected abscesses. Allergic reactions may occur, particularly in those sensitive to beef, soy, milk, and phenol.

Anthrax is an infectious disease caused by the spore-forming bacteria called Bacillus anthracis. Infection in humans most often involves the skin, the gastrointestinal tract, or the lungs.

Anthrax commonly affects hoofed animals such as sheep and goats, but humans who come in contact with the infected animals can get sick from anthrax, too. Historically, the populations most at risk for anthrax included farm workers, veterinarians, and tannery and wool workers. Anthrax is a potential agent for use as a biological weapon or for bioterrorism. In 2001, bioterrorist activities involving the U.S. Postal Service infected 22 people with anthrax; 7 survivors had confirmed cutaneous anthrax disease.

Military personnel and vaccine researchers, as well as people who work with imported animal hides, furs, bone meal, wool, animal hair (especially goat hair), and bristles, should receive an anthrax vaccine. The anthrax vaccine appears to be safe and effective, even after exposure, but requires 6 shots over 18 months. Up to half of recipients develop temporary soreness; some develop fever. Pregnant women should not get the anthrax vaccine.

Click the icon to see an image of cutaneous anthrax.

Click the icon to see an image of tuberculosis.


Disease	Who Should Get It?	Additional Information
Adenovirus	Military personnel.	Vaccine given orally for the prevention of respiratory illness.
Yellow Fever	Travelers to developing countries where outbreaks have occurred, currently parts of Africa and Central and South America. Residents of these areas, particularly children.	Vaccinations safe and effective for the prevention of jaundice and kidney and liver failure. Anaphylactic reactions in those allergic to eggs. Very rarely, may cause a potentially fatal illness resembling yellow fever, with fever and diarrhea, particularly in seniors. Lower immunity when given with cholera vaccine; the vaccines should be given three weeks apart.
Cholera	Travelers to developing countries where outbreaks have occurred.	Recently developed vaccines (Dukoral, Mutacol) are more effective than previous ones, which provided little protection. Not recommended or available, however, in the US.
Typhoid	Travelers to developing countries where outbreaks have occurred.	Oral vaccines include: (Ty21a, Vivotif). The oral vaccines are not effective against parathyroid fever. One-shot vaccine (Typhim Vi). Can be taken as early as two weeks before travel. Vi-rEPA is a newer injected vaccine that is safe in children and may be more effective-than other vaccines to date. No vaccine is 100% effective. The response to the typhoid vaccine tends to be lower in older people.
Tuberculosis	Individuals exposed to infected people.	Bacille Calmette-Guerin vaccine has been the standard vaccine, but its effectiveness has been questioned. No longer recommended in US except for certain high-risk children. A new recombinant BCG vaccine, shown in early trials to be more effective, is now licensed for use and is undergoing continued study.
Meningitis caused by meningococcal bacteria	U.S. Advisory Committee on Immunization Practices (ACIP) recommendations now call for routine vaccination of all young adolescents (aged 11 - 12) as well as those previously defined as at increased risk: People exposed to single cases or outbreaks; freshmen college students living in dorms; military recruits; travelers to developing countries where outbreaks have occurred; patients with problems in the spleen.	Vaccines are available against four subtypes of meningococcal bacteria but not for serogroup B, which causes up to 40% of meningococcal disease in the U.S. Among young people, fatalities have been higher in 15- to 24-year-olds than those younger than 15.

Resources

www.immunize.org -- Immunization Action Coalition
www.cdc.gov/vaccines/ -- The National Immunization Program
www.fda.gov/cber/vaers/vaers.htm -- Vaccine Adverse Event Reporting System
www.909shot.com/Issues/Injury_Compensation.htm -- National Vaccine Injury Compensation Program
www.immunizationinfo.org -- The National Network for Immunization Information
www.vaccine.chop.edu -- Vaccine Education Center, Children's Hospital of Philadelphia
www.vaccinesafety.edu -- Institute for Vaccine Safety, Johns Hopkins School of Public Health
www.whathealth.com -- National Partnership for Immunization
www.immunofacts.com -- Information on vaccinations
www.vaccines.org -- The Vaccine Page

References

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

Centers for Disease Control and Prevention. Prevention of varicella: recommendations of the Advisory Committee on Immunization Practices (ACIP). Mor Mortal Wkly Rep. June 2007;56:1-40.

Centers for Disease Control and Prevention. Recommended Immunization Schedule for Ages 0-6 Years, United States, 2007.

Chaves SS, Gargiullo P, Zhang JX, Civen R, Guris D, Mascola L. Loss of vaccine-induced immunity to varicella over time. NEJM. March 15, 2007;356:1121-1129.

Garland SM, Hernandez-Avila M, Wheeler CM, Perez G, Harper DM, Leodolter S, et al. Quadrivalent vaccine against human papillomavirus to prevent anogenital diseases. NEJM. May 10, 2007;356:1928-1943.

Grijalva CG, Nuorti JP, Arbogast PG, Martin SW, Edwards KM, Griffin MR. Decline in pneumonia admissions after routine childhood immunisation with pneumococcal conjugate vaccine in the USA: a time-series analysis. Lancet. April 7, 2007;369:1179-1186.

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.

Poehling KA, Szilagyi PG, Crijalva CG, Martin SW, LaFleur B, Mitchel E, et al. Reduction of frequent otitis media and pressure-equalizing tube insertions in children after introduction of pneumococcal conjugate vaccine. Pediatrics. April 4, 2007;119:707-715.

Prevention of influenza in the general population: Recommendation statement from the Canadian Task Force on Preventive Health Care. CMAJ. 2004;171:10.

American Academy of Pediatrics Committee on Infectious Diseases. Prevention and control of meningococcal disease: recommendations for use of meningococcal vaccines in pediatric patients. Pediatrics. 2005 Aug;116(2):496-505.

Pneumococcal vaccine cuts severe bacterial disease in US. Mor Mortal Wkly Rep CDC Surveill Summ 2005;54:893-896.

Wise R, Iskander J, Pratt D, et al. Postlicensure Safety Surveillance for 7-Valent Pneumococcal Conjugate. JAMA. 2004; 292:1702-1710.

Krym VF, MacDonald RD. Global efforts to eradicate polio. CMAJ. 2004 Jan 20;170(2):189-90.

Zuckerman JN. Protective efficacy, immunotherapeutic potential, and safety of hepatitis B vaccines. J Med Virol. 2006 Feb;78(2):169-77.

Review Date:
10/1/2007
Reviewed By:
Harvey Simon, MD, Associate Professor of Medicine, Harvard Medical School; Physician, Massachusetts General Hospital.

A.D.A.M., Inc. is accredited by URAC, also known as the American Accreditation HealthCare Commission (www.urac.org). URAC's accreditation program is an independent audit to verify that A.D.A.M. follows rigorous standards of quality and accountability. A.D.A.M. is among the first to achieve this important distinction for online health information and services. Learn more about A.D.A.M.'s editorial policy, editorial process and privacy policy. A.D.A.M. is also a founding member of Hi-Ethics and subscribes to the principles of the Health on the Net Foundation (www.hon.ch).

A.D.A.M. Copyright

The information provided herein should not be used during any medical emergency or for the diagnosis or treatment of any medical condition. A licensed medical professional should be consulted for diagnosis and treatment of any and all medical conditions. Call 911 for all medical emergencies. Links to other sites are provided for information only -- they do not constitute endorsements of those other sites. © 1997-2009 A.D.A.M., Inc. Any duplication or distribution of the information contained herein is strictly prohibited.

adam.com

Breast cancer

FitSugar — Wed, 08 Oct 2008 17:34:59 -0700

HEALTH GUIDE REFERENCE FROM A.D.A.M

Highlights

Drug Approvals

In September 2007, Evista (raloxifene) was approved for prevention of breast cancer in postmenopausal women with osteoporosis, and postmenopausal women at high risk for invasive breast cancer. Raloxifene and tamoxifen are the only two drugs approved for breast cancer prevention in high-risk women.
In March 2007, lapatinib (Tykerb) was approved in combination with capecitabine (Xeloda) for treatment of advanced HER2-positive breast cancer.
In November 2006, trastuzumab (Herceptin) was approved for treatment of early-stage HER2-positive breast cancer. Trastuzumab is also approved for advanced HER2-positive breast cancer.

Screening

The American College of Physicians’ 2007 guidelines recommend that women with a low risk for breast cancer talk to their doctor before starting to have mammogram screening at age 40. Other associations, including the American Cancer Society, continue to recommend annual mammograms for women age 40 and older.
Women at high risk for breast cancer should have an MRI scan along with their annual mammogram, according to 2007 guidelines from the American Cancer Society.
For women who have been diagnosed with cancer in one breast, an MRI can help detect tumors in the other breast, indicates a 2007 study in the New England Journal of Medicine.

Post-Treatment Guidelines

The American Society of Clinical Oncology (ASCO)’s 2006 post-treatment guidelines recommend regular physical exams, breast self-exam, mammograms, and genetic counseling. Know how to recognize the signs of breast cancer recurrence. ASCO does not recommend blood and imaging tests for routine recurrence screening.

Hormone Replacement Therapy (HRT) and Breast Cancer Risk

Fewer women are using HRT, which may explain why new cases of breast cancer among postmenopausal women have declined, suggests a recent New England Journal of Medicine study.

Aromatase Inhibitors

Drug treatment with aromatase inhibitors is improving survival in women with hormone-sensitive advanced breast cancer, suggest recent studies. Switching from tamoxifen to an aromatase inhibitor may help improve the odds for survival.

Introduction

Breast cancers are potentially life-threatening malignancies that develop in one or both breasts. The structure of the female breast is important in understanding this cancer:

The interior of the female breast consists mostly of fatty and fibrous connective tissues.
It is divided into about 20 sections called lobes.
Each lobe is further subdivided into a collection of lobules, structures that contain small milk-producing glands.
These glands secrete milk into a complex system of tiny ducts. The ducts carry the milk through the breast and converge in a collecting chamber located just below the nipple.
Breast cancer is either noninvasive (referred to as in situ, confined to the site of origin) or invasive (spreading).

The female breast is either of two mammary glands (organs of milk secretion) on the chest.

Noninvasive breast cancers include:

Ductal carcinoma in situ (also called intraductal carcinoma or DCIS). DCIS consist of cancer cells in the lining of the duct. DCIS is a non-invasive, early cancer, but if left untreated, it may sometimes progress to an invasive, infiltrating ductal breast cancer.
Lobular carcinoma in situ, or LCIS. Although noninvasive, lobular carcinoma in situ is a marker for an increased risk of invasive cancer in both breasts. (Some experts prefer to call this condition lobular neoplasia rather than refer to it as a cancer.) According to a 2001 report, for patients with LCIS the risk for developing invasive cancer in the same breast is about 18% -- and 14% in the other breast -- after 20 years. These invasive cancers can be either lobular or ductal.

At the time of diagnosis of these early cancers (DCIS and LCIS), there is no evidence of invasion.

Invasive cancer occurs when cancer cells spread beyond the basement membrane, which covers the underlying connective tissue in the breast. This tissue is rich in blood vessels and lymphatic channels that are capable of carrying cancer cells beyond the breast. Invasive breast cancers include the following:

Infiltrating ductal carcinoma. This is invasive breast cancer that penetrates the wall of a duct. It comprises between 70 - 80% of all breast cancer cases.
Infiltrating lobular carcinoma. This invasive cancer has spread through the wall of a lobule. It accounts for 10 - 15% of all breast cancers. It may sometimes appear in both breasts, sometimes in several separate locations.

Click the icon to see an image of the breast.

There are other less common breast cancers that are not discussed in this report.

Risk Factors

About 12 - 13% of women develop breast cancer in their lifetime. Experts estimate that about 178,480 women will be newly diagnosed with invasive breast cancer in the United States in 2007. Another 2,030 men will be diagnosed with breast cancer during the year. Although breast cancer in men is rare, the incidence has been increasing, and men are diagnosed at a later stage than women. An estimated 40,460 women and 450 men will die from breast cancer in 2007. The earlier breast cancer is diagnosed, the earlier the opportunity for treatment. According to the American Cancer Society, over 2 million women who have been treated for breast cancer are alive today.

Age is a major identifiable risk factor. More than 80% of breast cancer cases occur in women over age 50, and especially in women over age 65. The odds by age are as follows:

From ages 30 - 39, a woman’s chance for being diagnosed with breast cancer is 1 in 233
Ages 40 - 49, the odds are 1 in 69
Ages 50 - 59, the odds are 1 in 38
Ages 60 - 69, the odds are 1 in 27
Ages 70 - 79, the odds are 1 in 11
After age 80, the odds are 1 in 8

Breast cancer is more prevalent among Jewish women of Eastern European (Ashkenazi) descent. Meanwhile, African-American women tend to get breast cancer at an earlier age than Caucasians. Although African-American women have lower overall rates of breast cancer, they represent the highest proportion of women who are diagnosed with the disease before age 45. Comparative studies of breast cancer rates among sub-Saharan Africans suggest a genetic component, as African women are diagnosed most frequently between ages 35 - 45.

The mortality rate in African-Americans is twice that of Caucasians, although it is declining. Social and economic factors make it less likely that African-American women will be screened, so they are more likely to be diagnosed at a later stage. They are also less likely to have access to effective treatments. However, there also appears to be a biological basis for African-American women’s poorer prognosis. According to research presented at the 2007 Breast Cancer Symposium, African-American women are more likely to have estrogen receptor-negative tumors, a type of breast cancer that is more difficult to treat.

An estimated 10% of all women with breast cancer have a very strong family history of the disease. Inherited forms of breast cancer often appear in young women under the age of 50. In such families, some members may also be at higher risk for ovarian cancer. These mutations can be inherited from either a mother or father.

Prior to menopause, a mass on the ovary that is smaller than 2 centimeters is probably a follicle cyst that will go away on its own. However, if the growth is larger and doesn't go away over the course of a few menstrual cycles, then it may need to be removed.

BRCA Genes. Inherited mutations in genes known as BRCA1 or BRCA2 are responsible for 30 - 50% of hereditary breast cancers, ovarian cancers, or both in families with a history of these cancers. According to some studies, the risk each gene carries is:

Between 25 - 35% of BRCA1 carriers develop breast cancer by age 70.
Between 35 - 50% of BRCA2 carriers develop the disease. BRCA2 genes also increase the lifetime risk of breast cancer in men.

These mutations are present in only about 0.5% of the overall population. However, certain ethnic groups -- such as Jewish women of Eastern European (Ashkenazi) descent -- have a higher prevalence (2.5%) of BRCA gene mutations. BRCA gene mutations are also seen in some African-American and Hispanic women.

Screening Guidelines for BRCA Genes. In 2005, the U.S. Preventive Services Task Force (USPSTF) released updated guidelines for BRCA testing. While women at high risk should be tested, the USPSTF does not recommend routine genetic counseling or testing for BRCA genes in low-risk women (no family history of BRCA 1 or 2 genetic mutations).

ESR Genes. Genetic variations in estrogen receptor genes (ESRs) may increase the risk for some women but offer protection to others. Mutations in the ESR1 and ESR2 genes may be associated with breast cancer susceptibility for Ashkenazi women over age 50 years.

Other Genetic Factors. Mutations in the tumor suppressor gene p53 are more common in the breast cancer tumors of African-American women than in Caucasian women. Researchers have also identified other defective genes that contribute to breast cancer, such as NOEY2 (which is inherited from the father), CHEK2, and ATM, a mutant gene for the rare disorder ataxia-telangiectasia. (The disease itself is rare, but 1% of the population carries a single copy -- enough to increase the risk for breast cancer.) Cowden's syndrome is an inherited disorder caused by a defective PTEN gene that is associated with a higher risk of breast cancer.

Not all genetic mutations are inherited. In 2007, scientists announced they had located a genetic mutation found in as many as 30 - 40% of breast cancers. The IKBKE mutation appears to occur during the course of a women’s lifetime. It causes overproduction of a kinase protein (IKK-epsilon) that fuels cell growth and tumor development. By identifying this genetic mutation, scientists hope they can develop drugs that will target and block IKK-epsilon production.

Because growth of breast tissue is highly sensitive to estrogens, the more estrogen a woman is exposed to over her lifetime, the higher her risk for breast cancer.

Duration of Estrogen Exposure. Early age at menarche (first menstrual period) or later age at menopause may slightly increase a women’s risk for breast cancer.

Pregnancy. Women who have never had children or who had their first child after age 30 may have a slightly increased breast cancer risk. Having children at an early age, and having multiple pregnancies, reduces breast cancer risk.

Although a few studies have suggested a slightly increased risk for breast cancer in women who have had abortions, the weight of evidence does not support an association between abortion and breast cancer. A large-scale 2007 study found that neither induced abortions nor spontaneous abortions (miscarriages) increases breast cancer risk. However, interrupting a pregnancy does reduce the protective features of a full-term pregnancy.

Studies have been mixed on whether breast-feeding decreases breast cancer risk. Breast-feeding reduces a woman’s total number of menstrual cycles, and thereby estrogen exposure, which may account for its possible protective effects. Some studies suggest that the longer a woman breast-feeds, the lower her risk.

Oral Contraception. Studies have been conflicting about whether estrogen in oral contraception increases the chances for breast cancer. Some studies have found no evidence that oral contraceptive use increases the risk for breast cancer, even in women who have taken birth control pills for 15 years or more or had taken them at young ages. In contrast, other studies have reported a slightly higher risk in women who are current or recent users and in women who take them for more than 4 years before a first full-term pregnancy.

Hormone Replacement Therapy. Many studies have reported a higher risk for breast cancer in postmenopausal women who take hormone replacement therapy (HRT) that contains both estrogen and progestin. A combination of estrogen and testosterone also increases breast cancer risk. A 2005 study suggested that HRT with no or low progestin is safer than standard estrogen-progestin combination therapy.

Several 2006 studies of women who had a hysterectomy indicated that estrogen alone does not increase overall breast cancer risk when the drug is used for 7 years or less. However, women who take estrogen for 10 - 15 years or more do have an increased risk, especially women who are already at higher risk for breast cancer. In addition, HRT increases breast cancer density, making mammograms more difficult to read. This can cause cancer to be diagnosed at a later stage. Women who take estrogen HRT should be aware that they need frequent mammogram screenings.

As further evidence of the association between HRT and breast cancer, a 2007 New England Journal of Medicine study noted that breast cancer rates have fallen as HRT use has declined. The decline in rates occurred among women over the age of 50 and was particularly associated with cancers that were estrogen receptor-positive. This type of cancer requires estrogen for growth. Experts think that postmenopausal women’s discontinuation of estrogen-containing HRT may explain the decrease in rates of new cases of estrogen receptor-positive cancer.

A 2007 position statement from the North American Menopause Society recommends that women who are at risk for breast cancer should avoid hormone therapy and try other options to manage menopausal symptoms such as hot flashes. At this time, most experts recommend that women use HRT only for short-term relief of menopausal symptoms. [See In-Depth Report #40: Menopause.]

Infertility and Infertility Treatments. There has been concern that infertility treatments using the drug clomiphene may increase the risk for breast cancer. A reassuring 2006 study indicated that ovulation induction with clomiphene does not increase breast cancer risk, and may actually decrease it. (Clomphine is related to tamoxifen, a drug that is used for breast cancer prevention in high-risk women.) The study also suggested that women who are infertile because of ovulatory dysfunction have a 25% lower risk for breast cancer than fertile women.

Abnormalities or Breast Conditions Suggesting a Higher Risk. Certain factors and breast conditions may increase the risk for breast cancer:

Dense breast tissue is associated with a higher risk for breast cancer. Studies suggest that women with highly dense tissue have 2 - 6 times the risk of women with the least dense tissue. Genetic factors play a large role in breast density. Hormone replacement therapy also increases breast density. In addition, dense breasts make mammograms more difficult to read, which increases the likelihood of missing early signs of cancer.
Benign proliferative breast disease, or unusual cell growth known as atypical hyperplasia, is a significant risk factor for breast cancer.

Some common benign breast abnormalities that pose few or no risks include the following:

Cysts. These mostly occur in women in their middle-to-late reproductive years and can be eliminated simply by aspirating fluid from them.

Click the icon to see an image of cysts in the breast.

Fibroadenoma. These are solid benign lumps that occur in women ages 15 - 30.
Breast abscesses during breast-feeding.

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

Nipple discharge. Discharge from the nipple is worrisome to patients, but is unlikely to be a sign of cancer. Unexplained discharge still warrants evaluation, however.

Click the icon to see an image of nipple discharge.

Mastalgia. This is breast pain that occurs in association with, or independently from, the menstrual cycle. About 8 - 10% of women experience moderate-to-severe breast pain associated with their menstrual cycle. In general, breast pain does not need assessment unless it is severe and prolonged.

The following physical characteristics have been associated with increased risk:

Obesity increases the risk for all types of estrogen receptor-positive breast cancers. Women who gain weight after menopause are most at risk. (On a positive note, losing weight after menopause decreases breast cancer risk.) In postmenopausal women, estrogen is produced in fat tissue. High amounts of fatty tissue increase levels of estrogen in the body, leading to faster growth of estrogen-sensitive cancers.
Estrogen is involved in building bone mass. Therefore, women with heavy, dense bones are likely to have higher estrogen levels and to be at greater risk for breast cancer.
Some studies have found a greater risk for breast cancer in taller women, possibly due to the higher estrogen levels associated with greater bone growth. In one study, regardless of their actual height, women who reached their full height at age 13 or younger had a higher risk than those who attained maximum height at age 18, reflecting higher estrogen levels at an earlier age.

Exposure to Estrogen-like Industrial Chemicals. Chemicals with estrogen-like effects, called xenoestrogens, have been under suspicion for years. There has been particular concern with pesticides containing organochlorines (DDT and its metabolites, such as dieldrin) and pyrethroids (permethrin), but at this time evidence of any causal association is very weak.

Exposure to Diethylstilbestrol. Women who took diethylstilbestrol (DES) to prevent miscarriage have a slightly increased risk for breast cancer. Recent studies also suggest a slightly increased risk for their daughters (commonly called "DES daughters"), who were exposed to the drug when their mothers took it during pregnancy.

Radiation Exposure. Heavy exposure to radiation is a significant risk factor for breast cancer. Girls who received high-dose radiation therapy face an increased risk for breast cancer in adulthood. Low-dose radiation exposure before age 20 may increase the risk for women with BRCA genetic mutations.

Researchers theorize that viruses may be involved in some types of breast cancers. A study of breast cancer samples taken from Tunisian women in North Africa found similarities with a virus known to cause breast cancer in mice. The samples were compared with those taken from women living in other global regions. The researchers suggested that a human breast cancer virus may be more prevalent in specific parts of the world.

Prevention and Lifestyle Factors

Evidence indicates that regular exercise, particularly vigorous exercise, may offer some modest protection against breast cancer. Exercise can help reduce body fat, which in turn lowers levels of cancer-promoting hormones such as estrogen. In fact, a 2006 study suggested that physical activity may help women reduce the risk for developing estrogen receptor-positive tumors.

Exercise can also help women who have been diagnosed with breast cancer. Studies indicate that both aerobic and weight training exercises benefit the body and the mind, and improve quality of life for breast cancer survivors. Even moderate exercise can help improve survival. A 2005 study in the Journal of the American Medical Association reported survival benefits for women diagnosed with breast cancer who walked 3 – 5 hours per week at an average pace. The American Cancer Society recommends engaging in 45 - 60 minutes of physical activity at least 5 days a week. A recent study indicated that diet and exercise can reduce the risk of breast cancer recurrence.

Physical activity contributes to health by reducing the heart rate, decreasing the risk for cardiovascular disease, and reducing the amount of bone loss that is associated with age and osteoporosis. Physical activity also helps the body use calories more efficiently, thereby helping in weight loss and maintenance. It can increase basal metabolic rate, reduces appetite, and helps in the reduction of body fat.

Despite much research on the association between diet and breast cancer, there is still little consensus. The best advice is to eat a well-balanced diet and avoid focusing on one "cancer-fighting" food. The American Cancer Society’s dietary guidelines for cancer prevention recommend that people:

Choose foods and amounts that promote a healthy weight.
Eat 5 or more servings of fruits and vegetables each day.
Choose whole grains instead of refined grain products.
Limit consumption of processed and red meat.
Women should limit alcohol consumption to 1 drink per day (women at high risk for breast cancer should consider not drinking alcohol at all).

For breast cancer survivors, the American Cancer Society recommends diets that include lots of fruits and vegetables, low amounts of saturated fat (from meat and high-fat dairy products), moderation in soy foods, and moderate or no alcohol consumption.

Here are results from recent studies evaluating diet and breast cancer, for preventing both the development of cancer and its recurrence:

Fats. Research is still mixed on the role that fats, and which specific types of fats, play in breast cancer risk and prevention. Several studies have indicated that red meat, which is high in saturated fat, may increase breast cancer risk when eaten in large quantities on a daily basis. (Red meat is also high in iron, which in itself may increase breast cancer risk.) According to results from the 2006 Women’s Health Initiative study of dietary fat and breast cancer, experts cannot yet definitely say that a low-fat diet will help prevent breast cancer. However, the study suggested that women who normally eat a very high-fat diet may benefit by reducing their fat intake. In the study, the low-fat diet reduced blood estrogen levels by 15%. The low-fat diet also appeared to reduce the risk for developing progesterone receptor-negative tumors.

Fruits and Vegetables. Fruits and vegetables are important sources of antioxidants, which may help protect against the tissue damage linked to increased cancer risk. Antioxidants include vitamin C, vitamin E, and carotenoids such as beta-carotene and lycopene. Richly colored fruits and vegetables -- not supplements -- are the best sources for these nutrients. These fiber-rich foods are an essential part of a healthy diet. However, it is not clear whether fruits and vegetables can specifically prevent breast cancer development or recurrence. According to a 2007 study of women with early-stage breast cancer, a low-fat diet very high in vegetables, fruit, and fiber does not work any better in preventing breast cancer recurrence than the standard 5 servings a day of fruits and vegetables. (However, a combination of diet and exercise may help.)

Calcium and Vitamin D. Eating lots of foods rich in calcium and vitamin D (such as yogurt and milk) may modestly reduce the risk of breast cancer for premenopausal -- but not postmenopausal -- women, according to a 2007 study. Low-fat or non-fat dairy products are a healthier choice than high-fat ones.

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

Soy. Soy is an excellent low-fat protein alternative to meat. Soy contains phytoestrogens, which are estrogen-like plant chemicals. In particular, soy contains a type of phytoestrogen called isoflavones. Because many soy foods (such as tofu) are eaten in Asian countries where women tend to have a lower incidence of breast cancer, research has focused on whether soy may have a protective effect. To date, the evidence does not indicate that soy foods or supplements can reduce breast cancer risk. In addition, some studies suggest that high intakes of soy may actually increase the risk of estrogen-responsive cancers such as breast cancer. Some animal studies have suggested that the isoflavone compound genistein may reduce the protective properties of tamoxifen, a drug used to prevent breast cancer in high-risk women. The American Cancer Society recommends that women with breast cancer eat only moderate amounts of soy foods and avoid taking dietary supplements that contain high amounts of isoflavones.

Click the icon to see an image of phytochemicals.

Lifestyle Factors. Premenopausal women at higher risk, usually because of family history, should take as many preventive measures as possible, starting at an early age. The following lifestyle choices may be beneficial:

Exercising and eating healthily is the first essential rule.
High-risk premenopausal women may choose alternatives to oral contraceptives and, if feasible, consider having children early in their life.
High-risk postmenopausal women may want to forego hormone replacement therapy.
Any woman at high risk for breast cancer should consider avoiding alcohol or drinking it very sparingly.

In spite of some rumors published in the popular press, antiperspirants or use of deodorants after shaving have not been linked with any higher risk for breast cancer.

Tamoxifen and Raloxifene. Drugs known as selective estrogen-receptor modulators (SERMs) act like estrogen in some tissues but behave like estrogen blockers (anti-estrogens) in others. Two SERMs -- tamoxifen (Nolvadex) and raloxifene (Evista) -- are approved for breast cancer prevention for high-risk women. Tamoxifen and raloxifene are not recommended as prevention for women at low risk for breast cancer or its recurrence. Women at high risk for breast cancer should discuss with their doctors the risks and benefits of SERMs.

Tamoxifen (Nolvadex) is the most studied of these drugs. It is currently used to treat breast cancer and was the first drug approved for prevention. Evidence strongly suggests that it halves the risk for estrogen receptor-positive cancers in high-risk women, including those with BRCA2 mutations (although possibly not BRCA1). It also helps prevent recurrence in women who have been treated for breast cancers. However, it has no protective effects against estrogen receptor-negative (hormone-insensitive) cancers.

Tamoxifen can increase the risk for uterine (endometrial) cancers. It can also increase the risk for blood clots, strokes, and endometriosis. Less serious side effects include hot flashes and vaginal discharge.

Raloxifene (Evista) was approved in 2007 for prevention of breast cancer in postmenopausal women with osteoporosis and postmenopausal women at high risk for invasive breast cancer. Raloxifene was previously approved for prevention and treatment of osteoporosis in postmenopausal women. One of raloxifene’s main benefits is that it has a lower risk than tamoxifen of causing uterine cancer. However, raloxifene also has some serious risks.

According to the prescribing information from the Food and Drug Administration (FDA), raloxifene can increase the risk of blood clots. Women with a history of blood clots in the legs, lungs, or eyes should not take this medicine. Although studies indicate raloxifene does not increase the risk of stroke, it can increase the risk of dying from a stroke. Women with a history of stroke or current risk factors for stroke should discuss with their doctors whether raloxifene is an appropriate choice. Less serious side effects of raloxifene include hot flashes, leg cramps, swelling of the legs and feet, flu-like symptoms, joint pain, and sweating. Raloxifene can cause birth defects and is approved only for postmenopausal women. It should not be taken with the cholesterol-lowering drug cholestyramine (Questran) or with estrogens.

The FDA based its approval of raloxifene on results from several major studies. The comparison trial Study of Tamoxifen and Raloxifene (STAR), published in 2006 in the Journal of the American Medical Association, indicated that raloxifene works as well as tamoxifen in reducing the risk of invasive breast cancer, and has a lower risk of causing blood clots. However, the Raloxifene Use for the Heart (RUTH) trial, published in 2006 in the New England Journal of Medicine, suggested that raloxifene carries its own risks for blood clots and fatal strokes and may not be a safe choice for women at high risk of heart disease.

Investigational Drugs for Breast Cancer Prevention.

Aromatase inhibitors. Aromatase inhibitors such as anastrazole (Armidex), letrozole (Femara), and exemestane (Aromasin) are effective treatments for hormone-receptor positive breast cancer. Like tamoxifen, they are also being investigated for protection in high-risk women. However, these drugs may decrease bone mineral density and cognitive function, and increase the risk for falls.
Retinoids. Analogues of vitamin A called retinoids are being studied for protection against breast cancer. One retinoid, fenretinide, appears to offer some protection against a second breast cancer in previously diagnosed, premenopausal women (but not in postmenopausal women). It can cause birth defects and should not be used during pregnancy.

Symptoms

Breast cancers in their early stages are usually painless. Often the first symptom is the discovery of a hard lump. Fifty percent of such masses are found in the upper outer quarter of the breast. The lump may make the affected breast appear elevated or asymmetric. The nipple may be retracted or scaly. Sometimes the skin of the breast is dimpled like the skin of an orange. In some cases there is a bloody or clear discharge from the nipple. Many cancers, however, produce no symptoms and cannot be felt on examination. They can be detected only with a mammogram.

Monthly breast self-exams should always include: visual inspection (with and without a mirror) to note any changes in contour or texture, and manual inspection in standing and reclining positions to note any unusual lumps or thicknesses.

Diagnosis

Breast Examination by a Health Professional. Early detection of breast cancer significantly reduces the risk of death. Women ages 20 - 49 should have a physical examination by a health professional every 1 - 2 years. Those over age 50 should be examined annually. A breast exam by a health professional can find 10 - 25% of breast cancers that are missed by mammograms. Between 6 - 46% of the lumps detected by examination are malignant. (The yield is lowest in younger women and highest in older women.)

Self-Examinations. Woman have been encouraged to perform a self-examination each month, but well-conducted studies in 2002 reported no difference in mortality rates between women who were intensively instructed in self-examination and those who were not. This does not mean women should stop attempting self-examinations, but they should not replace the annual examination done by a health professional, which evidence suggests is beneficial.

1. Pick a time of the month that is easy to remember and perform self-examination at that time each month. The breast has normal patterns of thickness and lumpiness that change within a monthly period, and a consistently scheduled examination will help differentiate between what is normal from abnormal.

2. Stand in front of a mirror. Breasts should be basically the same size (one may be slightly larger than the other). Check for changes or redness in the nipple area. Look for changes in the appearance of the skin. With hands on the hips, push the pelvis forward and pull the shoulders back and observe the breasts for irregularities. Repeat the observation with hands behind the head. Move each arm and shoulder forward.

3. Lie down on the back with a rolled towel under one shoulder. Apply lotion or bath oil over the breast area.

The finger action should be as follows: Using the 2nd, 3rd, and 4th finger pads (not tips) held together, make dime-sized circles. Press lightly first to feel the breast area, then press harder using a circular motion.

Using this motion, start from the collarbone and move downward to underneath the breast. Shift the fingers slightly over, slightly overlapping the previously checked region, and work upward back to the collarbone. Repeat this up-and-down examination until the entire breast area has been examined. Be sure to cover the entire area from the collarbone to the bottom of the breast area and from the middle of the chest to the armpits. Move the towel under the other shoulder and repeat the procedure.

Examine the nipple area, by gently lifting and squeezing it and checking for discharge.

4. Repeat step 3 in an upright position. (The shower is the best place for this, using plenty of soap.)

Note: A lump can be any size or shape and can move around or remain fixed. Of special concern are specific or unusual lumps that appear to be different from the normal varying thicknesses in the breast.

Click the icon to see an image of a breast self-exam.

Current Recommendations for Screening. Mammograms are very effective low-radiation screening methods for breast cancer. At this time, the U.S. Preventive Services Task Force recommends screening mammograms, with or without breast examination, every 1 - 2 years for all women over age 40.

Guidelines from the American College of Physicians (ACP), however, debate whether women with a low risk for breast cancer should begin mammogram screening at age 40. The 2007 guidelines, instead, recommend that women in their 40s ask their doctor when they should begin having the test. In contrast, the American Cancer Society and the U.S. National Cancer Institute continue to endorse annual screening for women age 40 and older.

The ACP's guidelines have created controversy within the medical community. Supporters of the guidelines believe that these new recommendations reflect some of the risks involved in screening younger women. These risks include radiation exposure and unnecessary biopsies. Mammographies in younger women produce a relatively high rate of false-positive results (when the test falsely indicates breast cancer). Scientists are working on new technologies to improve mammography's accuracy, but more work is needed. For example, a 2007 New England Journal of Medicine study reported that computer-aided detection software, which is used to help radiologists interpret mammograms, may instead make readings less accurate.

Opponents of the ACP guidelines argue that mammograms help catch tumors while they are in their earliest and most treatable stages, and that the most deadly types of breast cancer tend to occur in women in their 40s.

In addition, according to a review in the American Cancer Society's journal, mammography rates have declined since 2000. In fact, while many experts believe that the recent decline in new cases of breast cancer is partially due to reduced use of hormone replacement therapy, other experts are concerned that fewer cases of breast cancer are being detected because fewer mammographies are being performed.

After age 50, all guidelines recommend annual screenings. The older a women gets, the greater her risk for developing breast cancer. (Women over age 65 account for most new cases of breast cancer.) Women with risk factors for breast cancer, including a close family member with the disease, should consider having annual mammograms starting 10 years earlier than the age at which the relative was diagnosed.

Click the icon to see an image of a mammogram.

Magnetic Resonance Imaging and Ultrasound. Magnetic resonance imaging (MRI) and ultrasound techniques can detect very small tumors (less than half an inch). However, they are expensive and time-consuming procedures. Nevertheless, some doctors believe they are important in identifying small tumors missed on mammography in women who are receiving lumpectomy or breast-conserving surgeries. Such findings would allow the surgeons to remove the optimal amount of abnormal tissue. Ultrasound may also be particularly important for women with dense breast tissue who show signs of breast cancer.

In a report published in 2007, the American Cancer Society recommended that high-risk women have an MRI of their breast with their annual mammogram, including those who have:

A BRCA1 or BRCA2 mutation
A first-degree relative (parent, sibling, child) with a BRCA1 or BRCA2 mutation, even if they have yet to be tested themselves
A lifetime risk of breast cancer that has been scored at 20 - 25% or greater
Had radiation to the chest between ages 10 - 30
Li-Fraumeni syndrome, Cowden syndrome, or Bannayan-Riley-Ruvalcaba syndrome, or may have one of these genetic syndromes based on a history in a first-degree relative

For women who have had cancer diagnosed in one breast, MRIs can also be very helpful for detecting hidden tumors in the other breast. A landmark 2007 study in the New England Journal of Medicine reported that MRI scans of women who were diagnosed with cancer in one breast detected over 90% of cancers in the other breast that had been previously missed by mammography or clinical breast exam. Currently, few women who are diagnosed with cancer in one breast are offered an MRI of the other breast. Some experts advocate MRIs for all women newly diagnosed with breast cancer; others oppose this view. MRI scans may be most useful for younger women with breast cancer who have dense breast tissue that may obscure tumors from mammography readings. MRIs are less likely to be helpful for older women with early tumors in one breast and clear mammography readings in the other.

It is very important that women have MRIs at qualified centers that perform many of these procedures each year. MRI is a complicated procedure and requires special equipment and experienced radiologists. MRI facilities should also be able to offer biopsies when suspicious findings are detected.

Scintimammography. In scintimammography, a radioactive chemical is injected into the circulatory system, which is then selectively taken up by the tumor and revealed on mammograms. This method is very accurate in detecting the presence or absence of breast cancer, and some doctors hope that it might eventually reduce the number of unnecessary invasive biopsies. It is used for women who have had abnormal mammograms or for women who have dense breast tissue. It is not used for regular screening or as an alternative to mammography.

A definitive diagnosis of breast cancer can be made only by a biopsy (a microscopic examination of a tissue sample of the suspicious area).

When a lump can be felt and is suspicious for cancer on mammography, an excisional biopsy may be recommended. This biopsy is a surgical procedure for removing the suspicious tissue and typically requires general anesthetic.

Click the icon to see an image of breast biopsy.

A core biopsy involves a small incision and the insertion of a spring-loaded hollow needle that removes several samples. The patient only requires local anesthetic.
A wire localization biopsy may be performed if mammography detects abnormalities but there is no lump. With this procedure, using mammography as a guide, the doctor inserts a small wire hook through a hollow needle and into the suspicious tissue. The needle is withdrawn, and the hook is used by the surgeon to locate and remove the lesion. The patient may receive local or general anesthetic.
A new vacuum-assisted device may be useful for some biopsies. This uses a single probe through which a vacuum is used to draw out tissue. It allows several samples to be taken without having to remove and re-insert the probe.

Final analysis of the breast tissue may take several days.

If breast cancer has been determined, the next diagnostic step is to find out how far it has spread. To do this, the doctor performs a procedure called an axillary lymphadenectomy, which partially or completely removes the lymph nodes in the armpit beside the affected breast (called axillary lymph nodes). It may require a hospital stay of 1 - 2 days.

Click the icon to see an image of the axillary lymph nodes.

Once the lymph nodes are removed, they are analyzed to determine whether subsequent treatment needs to be more or less aggressive:

If no cancer is found in the lymph nodes, the condition is referred to as node negative breast cancer. The chances are good that the cancer has not spread and is still local.
If cancer cells are present in the lymph nodes, the cancer is called node positive. Their presence increases the possibility that the cancer has spread microscopically to other areas of the body. In such cases, however, it is still not known if the cancer has metastasized beyond the lymph nodes or, if so, to what extent. The doctor may perform further tests to see if the cancer has spread to the bone (bone scan), lungs (x-ray or CT scan) or brain (MRI or CT scan).

Side effects of the procedure include increased risk for infection and pain, swelling in the arm from fluid build-up, and impaired sensation and restricted movement in the affected arm. Patients might ask their doctor about the availability of physical therapy or upper-body exercises after treatment. In two studies, such programs resulted in quicker recovery and no fluid build-up in the arm.

A technique known as a sentinel node biopsy is a less invasive alternative to axillary lymph node dissection. This procedure can help determine if cancer has spread beyond the nodes. If the doctor finds no evidence of cancer, the patient may not need to have a complete axillary lymphadenectomy.

Click the icon to see an image of a sentinel node biopsy.

Sentinel node biopsy involves:

The procedure uses an injection of a tiny amount of a tracer, either a radioactively-labeled substance (radioisotope) or a blue dye, into the tumor site.
The tracer or dye then flows through the lymphatic system into the sentinel node. This is the first lymph node to which any cancer would spread.
The sentinel lymph node and possibly one or two others are then removed.
If they do not show any signs of cancer, it is highly likely that the remaining lymph nodes will be cancer free, making further surgery unnecessary.

Patients who have a sentinel node biopsy tend to have better arm function and a shorter hospital stay than those who have an axillary node biopsy. The American Society of Clinical Oncology's 2005 guidelines recommend sentinel node biopsy instead of axillary lymph node dissection for women with early stage breast cancer who do not have nodes that can be felt during a physical exam. It is still not known if the sentinel node biopsy has any survival advantages compared to standard lymph node removal procedures.

Women often have to wait several days for results of sentinel node biopsies to learn whether they will require another surgery to remove additional lymph nodes. In 2007, the Food and Drug Administration approved the GeneSearch BLN Assay to help speed sentinel node biopsy testing. This molecular-based lab test can detect within 40 minutes whether cancer has spread to nearby lymph nodes. Because the test delivers rapid results while the patient is still on the operating table, it may help spare women the discomforts of a second surgical procedure and help them get treatment earlier.

Prognosis

In the U.S., about 40,460 women will die from breast cancer this year, making it the second most lethal cancer in women. (Lung cancer is the leading cancer killer in women.) The good news is that early detection and new treatments have improved survival rates. The 5-year survival rate for women diagnosed with cancer is 80%. About 88% of women diagnosed with breast cancer will survive at least 10 years. Unfortunately, women in lower social and economic groups still have significantly lower survival rates than women in higher groups.

Several factors are used to determine successful treatment and the possibility for a cure. They include:

The location of the tumor and how far it has spread
Whether the tumor is hormone receptor-positive or -negative
Genetic factors
Tumor size and shape
Rate of cell division
Biologic markers

The good news is that women are living longer with breast cancer, and at this time more than 2 million American women are survivors. Due to better treatment options, from 1990 - 2003, breast cancer mortality rates declined by 24%. However, survivors must live with the uncertainties of possible recurrent cancer and some risk for complications from the treatment itself.

Recurrences of cancer usually develop within 5 years of treatment. However, 25% of recurrences and half of new cancers in the opposite breast occur after 5 years. One study suggested that the risk factors for a first breast cancer do not necessarily place a woman at any higher risk for recurrence. (Women with a first cancer, however, do have a higher risk for a new cancer in the opposite breast. The outlook for such new cancers is independent from those of the first one.)

The location of the tumor is a major factor in outlook:

If the cancer is ductal carcinoma in situ (DCIS) or has not spread to the lymph nodes (is node-negative), the 5-year survival rates with treatment are up to 98%. However, cancer recurs in 9 - 30% of women with node-negative cancers. Recurrence is a potentially life-threatening problem, even if the disease relapses locally in the same breast. In one study of DCIS patients with locally invasive recurrence, 8-year mortality rates were only 12%.
If the lymph nodes contain cancer cells (are node positive) then survival rates fall. If the tumor is larger than 5 cm or there is widespread involvement in the lymph nodes, the cancer is sometimes referred to as locally advanced. In such cases, the survival rate drops to about 75% and below.
If the cancer has spread (metastasized) to other sites (most often the lung, liver, and bone), the average survival time is about 2 years (with some patients living for many years). New drug therapies, particularly aromatase inhibitors, have helped prolong survival for women with metastatic cancer.

The location of the tumor within the breast is an important predictor. Tumors that develop toward the outside of the breast tend to be less serious than those that occur more toward the middle of the breast.

Breast cancer cells may contain receptors, or binding sites, for the hormones estrogen and progesterone. Cells containing these binding sites are known as hormone receptor-positive cells. If cells lack these connectors, they are called hormone receptor-negative cells. About 75% of breast cancers are estrogen receptor-positive (ER-positive, or ER+). About 65% of ER-positive breast cancers are also progesterone receptor-positive (PR-positive, or PR+). Cells that have receptors for one of these hormones, or both of them, are considered hormone receptor-positive.

Hormone receptor-positive cancer is also called "hormone sensitive" because it responds to hormone therapy such as tamoxifen or aromatose inhibitors. Hormone receptor-negative tumors are referred to as "hormone insensitive" or "hormone resistant."

Women have a better prognosis if their tumors are hormone receptor-positive because these cells grow more slowly than receptor-negative cells. In addition, women with hormone receptor-positive cancer have more treatment options. (Hormone receptor-negative tumors can be treated only with chemotherapy.) A 2007 study in the Journal of Clinical Oncology indicated that recent declines in breast cancer mortality rates have been most significant among women with estrogen receptor-positive tumors, due in part to the widespread use of post-surgical tamoxifen therapy.

Determining a "genetic signature" for a tumor may prove to be a very powerful predictor of the aggressive nature of a breast cancer. Researchers have focused on 70 genes whose activity patterns may help make such predictions. In 2007, the Food and Drug Administration approved MammaPrint, a DNA microarray diagnostic test that profiles these 70 genes. The molecular test may help predict how likely it is that breast cancer will recur within 5 - 10 years. However, the accuracy of the test depends on a woman’s risk. It is more accurate when predicting a low risk for recurrence than a high risk.

The relevance of the inherited BRCA1 or BRCA2 mutations to survival is controversial. Some studies have suggested that these mutations offer a survival advantage. Others suggest that they make no difference or even worsen prognosis. Women with these genetic mutations do have a greater risk for a new cancer to develop. Patients with BRCA1 mutations tend to develop tumors that are hormone receptor negative, which can behave more aggressively.

Researchers are investigating numerous substances in tumor cells that may indicate whether or not a cancer is likely to spread. Such chemical markers may help doctors determine treatments, and some may even prove to be targets for future drugs. The following are only a few of the more well-researched markers.

HER2. The American Cancer Society recommends that all women newly diagnosed with breast cancer get a biopsy test for a growth-promoting protein called HER2/neu. HER2-positive cancer usually occurs in younger women and is more quickly-growing and aggressive than other types of breast cancer. The HER2 marker is present in about 20% of cases of invasive breast cancer. Two types of tests are used to detect HER2:

Immunohistochemistry (IHC)
Fluorescence in-situ hybridization (FISH)

Some doctors think that FISH is a more accurate test than IHC. According to 2006 HER2 testing guidelines from the American Society of Clinical Oncology and the College of American Pathologists, either test may be used as long as it is performed by an accredited laboratory. Tests that are not clearly positive or negative should be repeated. Treatment with trastuzumab (Herceptin) or lapatinib (Tykerb) may help women who test positive for HER2.

Angiogenesis Factors. Angiogenesis is the growth of new blood vessels. High levels of angiogenesis factors indicate that the tumor is developing its own supply of blood vessels, which enable the tumor to send colonies of cancer cells into the bloodstream and spread to other parts of the body. Specific angiogenesis factors, such as vascular endothelial growth factor (VEGF) and basic fibroblast growth factor (bFGF), may turn out to be important markers for determining treatment and prognosis. The monoclonal antibody bevacizumab (Avastin) targets VEGF. The drug is showing promise in clinical trials for prolonging progression-free survival in women with metastatic breast cancer.

Others. Many other markers are being investigated, including p53, cathepsin-D, protein c-erbB-2, bcl-2, Ki-67, telomerase, thymidylate synthase, CA 15-3, and carcinogenic embryonic antigen (CEA). The American Society of Clinical Oncology (ASCO) cautions, however, that the value of many of these factors has not yet been confirmed.

Tumor Size and Shape. Large tumors pose a higher risk than small tumors. Undifferentiated tumors, which have indistinct margins, are more dangerous than those with well-defined margins.

Rate of Cell Division. The more rapidly a tumor grows, the more dangerous it is. Several tests measure aspects of cancer cell division and may eventually prove to predict the disease. For example, the mitotic index (MI) is a measurement of the rate at which cells divide. The higher the MI, the more aggressive the cancer. Another test measures cells at a certain phase of their division.

Recent evidence has not supported early reports of survival benefits for women with metastatic breast cancer who engage in support groups. However, some studies have suggested that psychotherapy, group support, or both may relieve pain and reduce stress, particularly in women who are suffering emotionally.

Stress has been ruled out as a risk factor either for breast cancer itself or for its recurrence.

Treatment

The three major treatments of breast cancer are surgery, radiation, and drug therapy. No one treatment fits every patient, and combination therapy is usually required. The choice is determined by many factors, including the age of the patient, menopausal status, the kind of cancer (ductal vs. lobular), its stage, and whether or not the tumor contains hormone-receptors.

Breast cancer treatments are defined as local or systemic:

Local Treatment. Surgery and radiation are considered local therapies because they directly treat the tumor, breast, lymph nodes, or other specific regions. Surgery is usually the standard initial treatment.
Systemic Treatment. Drug treatment is called systemic therapy, because it affects the whole body.

Any or all of these therapies may be used separately or, most often, in different combinations. For example, radiation alone or with chemotherapy or hormone therapy may be beneficial before surgery, if the tumor is large or not easily removed at prevention. Surgery followed by radiation and hormone therapy is usually recommended for women with early-stage, hormone-sensitive cancer. There are numerous clinical trials investigating new treatments and treatment combinations. Patients, especially those with advanced stages of cancer, may wish to consider enrolling in a clinical trial.

Treatment strategies depend in part on the stage of the cancer.

Stage 0 (Carcinoma in Situ). Stage 0 breast cancer is considered non-invasive (‘in situ"), meaning that the cancer is still confined within breast ducts or lobules and has not yet spread to surrounding tissues. Stage 0 cancer is classified as either:

Ductal carcinoma in situ (DCIS). These are cancer cells in the lining of a duct that have not invaded the surrounding breast tissue.
Lobular carcinoma in situ (LCIS). These are cancer cells in the lobules of the breast. LCIS rarely develops into invasive breast cancer, but having it in one breast increases the risk of developing cancer in the other breast.

Treatment options for DCIS include:

Breast-conserving surgery and radiation therapy (followed by hormone therapy for women with hormone-sensitive cancer)
Total mastectomy (followed by hormone therapy for women with hormone-sensitive cancer)
Breast-conserving surgery without radiation therapy

Treatment options for LCIS include:

Regular exams and mammograms to monitor any potential changes (observation treatment)
Hormone therapy to prevent development of breast cancer (for women with hormone-sensitive cancer)
Mastectomy of both breasts was previously used as treatment, but is now rarely recommended

Stage I and II (Early-Stage Invasive). In stage I cancer, cancer cells have not spread beyond the breast, and the tumor is no more than 2 cm (about 3/4 of an inch) across.

Stage II cancer is classified as either stage IIA or stage IIb.

In stage IIA cancer the tumor is either:

No more than 2 centimeters and has spread to the underarm lymph nodes (axillary lymph nodes)
Between 2 - 5 centimeters and has not spread to the underarm lymph nodes

Treatment options for stage I and stage II breast cancer may include:

Breast-conserving surgery (such as lumpectomy) followed by radiation therapy
Modified radical mastectomy with or without breast reconstruction
Post-surgical therapy (adjuvant therapy), including radiation of lymph nodes, chemotherapy, or hormone therapy
Trastuzumab (Herceptin) given along with or following adjuvant chemotherapy for women with HER2-positive cancer

Stage III (Locally Advanced). Stage III breast cancer is classified into several sub-categories: Stage IIIA, stage IIIB, and stage IIIC (operable or inoperable).

In stage IIIA breast cancer, the tumor is usually confined to the underarm lymph nodes. Treatment options for stage IIIA breast cancer are the same as those for stages I and II.

In stage IIIB breast cancer, the tumor has spread to either:

Tissues near the breast (including the skin or chest wall)
Lymph nodes within the breast or under the arm

Stage IIIB treatment options may include:

Chemotherapy, and possibly hormone therapy (sometimes in combination with chemotherapy)
Chemotherapy followed by surgery (breast-conserving surgery or total mastectomy) with lymph node dissection followed by radiation therapy and possibly more chemotherapy or hormone therapy
Clinical trials

Stage IIIC breast cancer is classified as either operable or inoperable.

In operable stage IIIC, the cancer may be found in:

10 or more of the underarm lymph nodes
Lymph nodes beneath the collarbone and near the neck on the same side of the body as the affected breast
Lymph nodes within the breast as well as underarm lymph nodes

Treatment options for operable stage III breast cancer are the same as those for stage I and II breast cancers.

In inoperable stage III breast cancer, the cancer has spread to lymph nodes above the collarbone and near the neck on the same side of the body as the affected breast. Treatment options are the same as those for stage IIIB.

Stage IV (Advanced Cancer). In stage IV, the cancer has spread (metastasized) from the breast to other parts of the body. In about 75% of cases, the cancer has spread to the bone. The cancer at this stage is considered to be chronic and incurable, and the usefulness of treatments is limited. The goals of treatment for stage IV cancer are to stabilize the disease and slow its progression, as well as to reduce pain and discomfort.

Treatment options for stage IV cancer include:

Surgery or radiation for any localized tumors in the breast. A 2006 study indicated that surgical removal of the primary tumor immediately after metastatic cancer diagnosis can dramatically improve survival.
Chemotherapy, hormone therapy, or both. Targeted therapy with trastuzumab (Herceptin) or lapatinib (Tykerb) should be considered for women with HER2-positive cancer.
Cancer that has spread to the brain may require radiation and high-dose steroids.
Cancer that has spread to the bone may be helped by radiation or bisphosphonate drugs. Such treatments can relieve pain and help prevent bone fractures.
Clinical trials of new drugs or drug combinations, or experimental treatments such as high-dose chemotherapy with stem cell transplant.

In 2006, the American Society of Clinical Oncology (ASCO) released updated guidelines on follow-up care for patients who have been treated for breast cancer. ASCO recommends:

Visit your doctor every 3 - 6 months for the first 3 years after your first cancer treatment, every 6 - 12 months during the fourth and fifth year, and once a year thereafter.
Have a mammogram 1 year after the mammogram that diagnosed your cancer (but no earlier than 6 months after radiation therapy), and every 6 - 12 months thereafter.
Perform a breast self-exam every month (however, this is no substitute for a mammogram).
See your gynecologist regularly (women taking tamoxifen should be sure to report any vaginal bleeding).
A year after diagnosis, you can either continue to see your oncologist or transfer your care to your primary care physician.
If you are on hormone therapy, discuss with your oncologist how often to schedule follow-up visits for re-evaluation of your treatment.

ASCO does not recommend the use of laboratory blood tests (complete blood counts, carcinoembryonic antigen) or imaging tests (bone scans, chest x-rays, liver ultrasound, FDG-PET scan, CT scan) for routine breast cancer follow-up.

Genetic counseling may be helpful if you have:

Ashkenazi Jewish heritage
Personal or family history of ovarian cancer
Personal or family history of cancer in both breasts
Any first-degree female relative (mother, sister, daughter) diagnosed with breast cancer before age 50
Two or more first-degree or second-degree (grandparent, aunt, uncle) diagnosed with breast cancer
History of breast cancer in a male relative

Pregnancy after Breast Cancer Treatment. There are no definite recommendations on how long a woman should wait to become pregnant after breast cancer treatment. Because of the connection between estrogen levels and breast cancer cell growth, some experts recommend delaying pregnancy until 2 years after treatment in order to reduce the risk of cancer recurrence and improve odds for survival. However, a 2007 study indicated that conceiving 6 months after treatment does not negatively affect survival. Discuss with your doctor your risk for recurrence, and when it may be safe to attempt pregnancy.

Recurrent breast cancer is considered to be an advanced cancer. In such cases, the disease has come back in spite of the initial treatment. Most recurrences appear within the first 2 - 3 years after treatment, but breast cancer can recur many years later. Treatment options are based on the stage at which the cancer reappears, whether or not the tumor is hormone responsive, and the age of the patient. Between 10 - 20% of recurring cancers are local. Most recurrent cancers are metastatic. All patients with recurring cancer are candidates for clinical trials.

Because most breast cancer recurrences are discovered by patients in between doctor visits, it is important to notify your doctor if you experience any of the following symptoms. These symptoms may be signs of breast cancer recurrence:

New lumps in the breast
Bone pain
Chest pain
Abdominal pain
Shortness of breath or difficulty breathing
Persistent headaches or coughing
Rash on breast
Nipple discharge

Surgery

Surgery forms a part of nearly every patient's treatment for breast cancer. The initial surgical intervention is often a lumpectomy, the removal of the tumor itself. In the past, mastectomy (the removal of the breast) was the standard treatment for nearly all breast cancers. Now, many patients with early-stage cancers can choose breast-conserving treatment, or lumpectomy followed by radiation, with or without chemotherapy.

For invasive breast cancer, studies indicate that lumpectomy or partial mastectomy combined with radiation therapy works as well as a modified radical mastectomy.

Breast-conserving procedures are now appropriate and as successful as mastectomy in most women with early stage breast cancer. All women should discuss these options fully with their doctor. Recurrence rates with conservative surgery are highest in women under age 45. Some women choose mastectomy over breast-conserving treatment even if the latter is appropriate because it gives them a greater sense of security and allows them to avoid radiation therapy.

Lumpectomy. Lumpectomy is the removal of the tumor, often along with lymph nodes in the armpit. It serves as an opportunity for biopsy, a diagnostic tool, and a primary treatment for small local breast tumors. If invasive cancer is found, the doctor will decide to proceed with breast radiation therapy, to remove additional tissue (should the margins of the specimen show signs of cancer), or to perform a mastectomy. Lumpectomy followed by radiation therapy is appropriate and as effective as mastectomy in most women with Stage I or II breast cancers.

Click the icon to see an illustrated series detailing breast lump removal surgery.

Breast-Conserving Surgery (Quadrantectomy). Breast-conserving surgery (sometimes referred to as quadrantectomy) removes the cancer and a large area of breast tissue, occasionally including some of the lining over the chest muscles. It is less invasive than a full mastectomy, but the cosmetic results are less satisfactory than with a lumpectomy. Excellent studies have found that breast-conserving surgeries plus postoperative radiotherapy offer the same survival rates as radical mastectomy in women with early breast cancer. A new technology called partial breast radiation (MammoSite), approved by the Food and Drug Administration in 2002, confines radiation to the tumor site rather than delivering it to the whole breast, and reduces treatment time from 5 weeks to 5 days in women who undergo breast conserving surgery.

Surgery to remove the breast (mastectomy) is important for women with operable breast cancer who are not candidates for breast conserving surgeries. There are different variations on the procedure:

A total mastectomy involves removal of the whole breast and sometimes lymph nodes under the armpit.
A radical mastectomy removes the breast, chest muscles, all of the lymph nodes under the arm, and some additional fat and skin. (A modified radical mastectomy removes the entire breast and armpit lymph nodes, with the underlying chest wall muscle.) A 25-year study supported other research that observed no survival advantages from radical mastectomy compared to the less invasive mastectomies for the great majority of patients. It is rarely used anymore except when cancer is very advanced.

Click the icon to see an illustrated series detailing mastectomy surgery.

Complications and Side Effects of Surgery. Short-term pain and tenderness occur in the area of the procedure, and pain relievers may be necessary.

The most frequent complication of extensive lymph node removal is edema, or swelling, of the arm, which is usually mild and rarely painful but does increase the risk for infection. The likelihood of edema can be lessened by removing only some of the lymph nodes instead of all of them.

Infrequent complications include poor wound healing, bleeding, or a reaction to the anesthesia.

After mastectomy and lymph node removal, women may experience numbness, tingling, and difficulty in extending the arm fully. These effects can last for months or years afterward.

After a mastectomy, some women choose a breast prosthesis or opt for breast reconstruction, which can be performed during the mastectomy itself, if desired. Several studies have indicated that women who take advantage of cosmetic surgery after breast cancer have a better sense of well-being and a higher quality of life than women who do not choose reconstructive surgery. The breast is reshaped using a saline implant or, for a more cosmetic result, a muscle flap is taken from elsewhere in the body. Muscle flap procedures are more complicated, however, and blood transfusions may be required. (It should be noted that implants, including silicone implants, do not appear to put a woman at risk for breast cancer recurrence.) If the nipple is removed, it is rebuilt from other body tissues and color is applied using tattoo techniques. It is nearly impossible to rebuild a breast that is identical to its partner, and additional operations may be necessary to achieve a desirable effect.

Click the icon to see an illustrated series detailing breast reconstruction surgery.

Numerous studies are investigating minimally invasive techniques that use lasers, deep-freezing of cancer cells (cryosurgery), high-intensity ultrasound, and other experimental approaches to kill cancer cells and reduce severe complications of surgery. Radiofrequency ablation, for example, is an approach that uses an electrode inserted into the tumor. It emits radio waves that produce enough heat to destroy cancer cells. Early trials are promising. These procedures, however, are not considered standard at the present time.

Radiation

Radiation therapy uses high-energy x-rays to kill cancer cells or to shrink the size of a tumor in the breast or surrounding tissue. It is used for several weeks following lumpectomy or partial mastectomy, and sometimes after full mastectomy. Radiation therapy can help reduce the chance of breast cancer recurrence in the breast and chest wall. Radiation is also important in advanced stages of cancer for relief of symptoms and to slow progression. Research shows that radiation therapy is helpful for women of all ages, including those over age 65.

Radiation is generally administered in the following ways:

External Beam Radiation. This type of radiation is administered 4 - 6 weeks after surgery and delivered externally by an x-ray machine that targets radiation to the whole breast. It may be delivered to the chest wall in high-risk patients (large tumors, close surgical margins, or lymph node involvement). The treatment is generally given daily (except for weekends) for about 6 weeks. A follow-up boost of radiation therapy in patients with lumpectomies appears to reduce the risk for recurrence.

Brachytherapy. Less commonly, radiation is delivered in implants (called brachytherapy). Implants are most often used as a radiation boost after whole breast radiation. Studies suggest they improve survival in patients at high risk for local recurrence. Some evidence suggests that implants alone can reduce treatment time and may be as effective as external beam radiation in some patients with early stage breast cancer. A new technology for breast brachytherapy (MammoSite) was approved in 2002. The technique provides 5-year local tumor control rates similar to those of whole-breast radiation for selected patients, with much shorter treatment time and good cosmetic results.

Investigators are also testing other approaches to radiation treatment. One uses a combination of neutrons and protons (mixed-beam) or proton beams rather than the standard photon radiation therapy. Intensity-modulated radiation therapy is a promising technique that delivers different doses to multiple target areas using images of specific regions. Such an approach may improve the coverage of breast cancers while reducing the toxic effects to the heart and lungs.

Side effects of radiation include:

Fatigue is very common and increases with subsequent treatments, but most women are able to continue with normal activities. Exercise may be helpful.
Nausea and lack of appetite may develop and worsen as treatment progresses.
Skin changes and burns can occur on the breast skin. Using a cream that contains a corticosteroid, such as mometasone furoate (MMF), may be helpful. After repeated sessions, the skin may become moist and "weepy." Exposing the treated skin to air as much as possible helps healing. (Washing the affected skin with soap and water does not seem to be harmful and in one study was associated with a lower risk for this side effect.)
Uncommonly, the breast may change color, size, or become permanently firm.
Rarely, the nearest arm may swell and develop impaired mobility or even paralysis.

Future complications include:

Radiation to the left breast may increase the long-term risk for developing heart disease and heart attacks.
There is a very small risk (less than 1%) of lung irritation and scarring.
Some studies have reported a higher risk for future cancer in the opposite breast in younger women who have been given radiation to the chest wall.
Radiation therapy can increase the risk of developing other cancers, such as soft tissue malignancies known as sarcomas.

Current advanced imaging techniques use precise radiation that reduces exposure. These newer techniques are likely to reduce the risks for heart disease and other serious complications.

Medications

The most important advances in the cure of breast cancer have come through the use of drug therapy, also called systemic therapy. Surgery and radiation therapy are effective for treating tumors confined to the breast but not for cancer cells that have spread or are at risk of spreading. In such cases, drug therapy is needed.

Drug treatments for breast cancer include:

Chemotherapy. Chemotherapy drugs are "cytotoxic" (cell-killing) drugs. They are given orally or by injection. They work systemically by killing cancer cells throughout the body. (Unfortunately, they also kill normal cells, which accounts for many of their side effects.) Chemotherapy is always used for advanced breast cancer, but may also be used to treat types of early-stage breast cancer.
Hormone Therapy. The goal of hormone therapy is to prevent estrogen from stimulating breast cancer cells. It is recommended for women whose breast cancers are hormone-receptor positive (either estrogen or progesterone), regardless of the size of the tumor and whether or not it has spread to the lymph nodes. Like chemotherapy, hormone therapy works systemically.
Targeted Therapy. Newer biologic drugs target specific proteins involved in cancer. Because they do not work as systemically as chemotherapy or hormone therapy drugs, they tend to cause fewer widespread side effects. Currently, the monoclonal antibody trastuzumab (Herceptin) and the kinase inhibitor lapatinib (Tykerb) are the two targeted therapies approved for breast cancer. These drugs target the HER2/neu protein and are used to treat HER2-positive breast cancers. Bevacizumab (Avastatin) is a monoclonal antibody that targets vascular endothelial growth factor (VEGF), a protein involved in tumor blood vessel formation (angiogenesis). It is being studied in clinical trials for treatment of metastatic breast cancer.

Drug therapy may be used as:

Primary therapy for patients for whom surgery or radiation therapy is not appropriate.
Neoadjuvant therapy (before surgery or radiation) to shrink tumors to a size that can be treated with local therapy.
Adjuvant therapy (following surgery or radiation) to reduce the risk of cancer recurrence.

For metastatic cancer, drugs are used not to cure but to improve quality of life and prolong survival.

Chemotherapy

Chemotherapy needs to be tailored to the type of cancer involved. Women require different treatments depending on whether the tumor is node-negative or -positive, hormone receptor-positive or -negative, or HER2-positive or -negative. Different treatment approaches are also used for early-stage cancer and advanced cancer.

A 2006 study in the Journal of the American Medical Association indicated that women with hormone receptor-negative cancers respond better to chemotherapy than women with hormone receptor-positive cancer. However, some women with hormone receptor-positive cancer do benefit from chemotherapy, as well as from hormone therapy.

Adjuvant chemotherapy is administered following surgery and before radiation therapy. A 2007 study in the Journal of Clinical Oncology suggested that women with early-stage breast cancer can safely wait for up to 12 weeks after surgery before beginning chemotherapy. However, delaying chemotherapy until more than 12 weeks after surgery significantly increases the risk for breast cancer recurrence and can reduce the odds for survival by as much as 60%.

Many different types of chemotherapy drugs are used to treat breast cancer. Common types of chemotherapy drug classes include:

Anthracyclines include doxorubicin (Adriamycin) and epirubicin (Ellence). Anthracycline-based combination regimens are often used to treat early-stage breast cancer, as well as advanced cancer.
Taxanes include paclitaxel (Taxol) and docetaxel (Taxotere). Two 2003 studies suggested that taxane-based therapy is particularly helpful for node-positive breast cancer. A newer formulation of paclitaxel (Abraxane) is used as a secondary treatment for advanced breast cancer.
Platinum-based drugs include oxaliplatin (Eloxatin) and carboplatin (Paraplatin). These drugs may be used in combination regiments for advanced cancer or for cancers associated with BRCA genes.

Some of the abbreviations used for chemotherapy drug combinations (regimens) refer to drug classes rather than drug names. For example, regimens that contain an anthracycline drug (such as doxorubicin) use the letter "A," and regimens that contain a taxane drug (such as docetaxel) use the letter "T." Cyclophosphamide (Cytoxan), fluorouracil (5-FU), and methotrexate (MTX) are standard cancer drugs used in many breast cancer chemotherapy regimens.

Chemotherapy regimens usually consist of 4 - 6 cycles of treatment given over 3 - 6 months. Common chemotherapy regimens for early-stage breast cancer include:

AC (Doxorubicin and cyclophosphamide)
AC followed by T (Doxorubicin and cylophosphamide followed by paclitaxel)
CAF (Cyclophosphamide, doxorubicin, and 5-FU)
CMF (Cyclophosphamide, methotrexate, and 5-FU)
TAC (Docetaxel, doxorubicin, and cyclophosphamide)

Trastuzumab (Herceptin). Trastuzumab is a monoclonal antibody that targets the HER2 protein on cancer cells. HER2-positive cancers account for 15 - 25% of early-stage breast cancer and are associated with more aggressive disease. Younger women tend to be most affected. In November 2006, the Food and Drug Administration approved trastuzumab for treatment of HER2-positive, early-stage breast cancer (cancer confined to the breasts or lymph nodes that has been surgically removed). Trastuzumab is given along with other chemotherapy drugs following lumpectomy or mastectomy. Research indicates that trastuzumab can help prevent cancer recurrence and death among women with early-stage breast cancer, but it increases the risk of heart problems. Trastuzumab can cause heart failure. Women who have heart failure or weak heart muscle (cardiomyopathy) should not use this drug. Women who take trastuzumab need to have regular heart monitoring, especially if they have already have heart problems.

Patients who develop metastatic disease (cancer that spreads throughout the body) are generally not curable. New advances in drug therapies, however, can help shrink tumors, prolong survival, and improve quality of life.

Chemotherapy regimens for advanced cancer may use a single drug or a combination of drugs. Many chemotherapy regimens used for early-stage breast cancer are also used for advanced breast cancer. Some specific combinations for advanced cancer include:

Gemcitabine and paclitaxel. In 2004, the Food and Drug Administration approved the antimetabolite drug gemcitabine (Gemzar) for use in combination with paclitaxel (Taxol) as a first-line treatment option for women with metastatic breast cancer.
Capecitabine (Xeloda) and docetaxel (Taxotere). Capecitabine is an oral drug that is chemically related to 5-FU. It is also being studied in combination with many other drugs.

Numerous chemotherapy drugs and drug combinations are being tested in clinical trials. Patients with advanced breast cancer may also receive other types of drug treatments. Bisphosphonate drugs, such as zoledronic acid (Zometa) and pamidronate (Aredia), are important supportive drugs for preventing fractures and reducing pain in people whose cancer has spread to the bones.

Two targeted therapy drugs are approved for the treatment of HER2-positive advanced breast cancer

Trastuzumab (Herceptin) was approved in 1998 for treatment of metastatic breast cancer. It is used in adjuvant chemotherapy, along with drugs such as paclitaxel.
Lapatinib (Tykerb) was approved in March 2007 for patients who have not been helped by other cancer drugs, including an anthracycline, a taxane, or trastuzumab. Lapatinib is used in combination with capecitabine (Xeloda). Research suggests it may have fewer risks for heart problems than trastuzumab.

Promising new treatments for advanced breast cancer include:

Ixabepilone (BMS-247550). Ixabepilone is the first of a new class of cancer drugs called epothilones. It is showing encouraging results when combined with capecitabine, according to research presented at the 2007 annual meeting of the American Society of Clinical Oncology.
Bevacizumab (Avastin). Bevacizumab is a targeted therapy anti-angiogenesis drug approved for treatment of colorectal and lung cancers. It is being studied in combination with various chemotherapy drugs for treatment of advanced cancer.

Side effects occur with all chemotherapeutic drugs. They are more severe with higher doses and increase over the course of treatment.

Common side effects include:

Nausea and vomiting. Drugs known as serotonin antagonists, especially ondansetron (Zofran), can relieve these side effects. In one study, a combination of dexamethasone (a corticosteroid) with ondansetron taken within 24 hours of chemotherapy achieved either a major or complete reduction in nausea and vomiting. Aprepitant (Emend), a new drug for preventing chemotherapy-caused nausea and vomiting, was approved in 2006.
Diarrhea
Temporary hair loss
Weight loss
Fatigue
Depression

Serious short- and long-term complications can also occur and may vary depending on the specific drugs used. They include the following:

Anemia. The erythropoietins epoetin alfa (Epogen, Procrit) and darbepoetin alfa (Aranesp) stimulate red blood cell production and can help reduce or prevent anemia, resulting in significant improvement in quality of life. Aranesp persists longer in the blood than epoetin alfa and may therefore require fewer injections.
Increased chance for infection from severe reduction in white blood cells (neutropenia). The addition of a drug called granulocyte colony-stimulating factor (filgrastim and lenograstim) is very helpful in reducing the risk for severe infection.
Liver and kidney damage.
Abnormal blood clotting (thrombocytopenia).
Allergic reaction, particularly to platinum-based drugs.
Menstrual abnormalities and infertility. Premature menopause occurs in about 30% of women, particularly in those over 40. A natural hormone medication called a gonadotropin-releasing hormone analogue, which puts women in a temporary pre-pubescent state during chemotherapy, may preserve fertility in some women. Women may also wish to consider embryo cryopreservation -- the harvesting of eggs, followed by in vitro fertilization and freezing of embryos for later use. The American Society of Clinical Oncology recommends that women being treated for cancer see a reproductive specialist to discuss all available fertility preservation options.
Sexual dysfunction.
Rarely, secondary cancers such as leukemia.
A quarter to a third of women report problems in concentration, motor function, and memory, which can be long-term. In one study, women were having these symptoms 2 years after treatment, although by 4 years they had resolved.
Heart problems. Trastuzumab (Herceptin) may increase the risk for heart failure, particularly in women with pre-existing risk factors. Cumulative doses of anthracyclines (doxorubicin, epirubicin) can also damage heart muscles over time and increase the risk for heart failure.
Taxanes can cause a drop in white blood cells and possible problems in the heart and central nervous system. Allergic reactions can occur, more often in taxol than taxotere. Taking a steroid before taxane administration can help prevent such reactions. Taxane therapy may also cause severe joint and muscle pain in some patients, relievable with corticosteroids.

High-dose chemotherapy along with peripheral-blood stem cell rescue or bone marrow transplantation procedures have been used for cancer that has metastasized and, in some cases, for earlier stages of breast cancer in high-risk patients. The objective of this treatment is to be able to give patients very high toxic doses of cell-killing drugs.

Transplantation procedures are based on stem cells, which are produced in the bone marrow. Stem cells are the early forms for all blood cells in the body (including red, white, and immune cells). Cancer treatments can harm these growing cells as well as cancer cells.

Despite the initial enthusiasm over the use of high-dose therapy for treatment of high risk breast cancer, this approach can no longer be generally recommended and should not be used outside of a clinical trial setting. The results of several randomized studies have failed to show a convincing advantage for the use of high-dose therapy. Nevertheless, some experts believe this approach can still be useful in selected patients, and studies continue. In general, however, transplantation has a limited role in breast cancer management, and its use should be restricted to clinical trials.

Hormone Therapy

Hormone therapy works by blocking estrogen that causes cell proliferation. It is used only for patients with hormone receptor-positive tumors. Different types of hormone therapy work in different ways by:

Blocking estrogen receptors in cancer cells (Tamoxifen)
Suppressing estrogen production in the body (Aromatase inhibitors)
Destroying ovaries, which produce estrogen (Ovarian ablation)

Tamoxifen was the first widely used hormonal therapy drug, but it has been replaced by aromatase inhibitors for some women. Aromatase inhibitors are used only to treat postmenopausal women. Tamoxifen is mainly used as adjuvant therapy for premenopausal women with hormone-sensitive breast cancer.

Tamoxifen (Nolvadex) has been the standard hormonal drug used for breast cancer. It belongs to a class of compounds called selective estrogen receptor modulators (SERMs). SERMs chemically resemble estrogen and trick the breast cancer cells into accepting it in place of estrogen. Unlike estrogen, however, they do not stimulate breast cancer cell growth. Because SERMs block estrogen’s effects on cancer cells, they are sometimes referred to as "anti-estrogen" drugs.

Tamoxifen is used for all cancer stages in women of all ages with hormone receptor-positive cancers. In addition, it is used to prevent breast cancer in high-risk women. Another SERM drug, toremifene (Fareston), is an option for women with advanced cancer, but this drug is rarely used in the United States. A third drug, fulvestrant (Faslodex), works in a similar anti-estrogen way to tamoxifen but belongs to a different drug class. Fulvestrant is approved only for postmenopausal women with hormone-sensitive advanced breast cancer in which tamoxifen or aromatase inhibitors no longer work.

To prevent cancer recurrence, women should take tamoxifen for 5 years following surgery and radiation. Tamoxifen is an effective cancer treatment, but it can cause unpleasant side effects and has small (less than 1%) but serious risks for blood clots and uterine (endometrial) cancer. Immediately report any signs of vaginal bleeding to the doctor, as this may be a symptom of uterine cancer.

Less serious, but discomforting, side effects include hot flashes and mood swings. According to a 2007 study, nearly 25% of women stop taking tamoxifen within 1 year because of these symptoms. By 3.5 years, over 33% stop treatment. Taking tamoxifen for fewer than 5 years, however, increases the risk for cancer recurrence and death. Talk with your doctor about antidepressants or other therapies that may help you cope with tamoxifen’s side effects.

Many doctors now recommend that postmenopausal women switch to an aromatase inhibitor after 2 - 3 years of tamoxifen therapy. Several 2007 studies indicated that switching from tamoxifen to an aromatase inhibitor significantly improves survival rates and reduces the risk of death from breast cancer as well as other causes.

Endometrial cancer is a cancerous growth of the endometrium (lining of the uterus). It is the most common uterine cancer.

Aromatase inhibitors block aromatase, an enzyme that is a major source of estrogen in many major body tissues, including the breast, muscle, liver, and fat. Aromatase inhibitors work differently than tamoxifen. Tamoxifen interferes with tumors’ ability to use estrogen by blocking their estrogen receptors. Aromatase inhibitors reduce the overall amount of estrogen in the body.

Because these drugs cannot stop the ovaries of premenopausal women from producing estrogen, they are recommended only for postmenopausal women.

There are currently three aromatase inhibitors approved for treating early-stage, hormone receptor-positive breast cancer in postmenopausal women:

Anastrazole (Armidex) for treatment after surgery
Exemestane (Aromasin) for women who have taken tamoxifen for 2 - 3 years
Letrozole (Femara) for treatment after surgery or for women who have completed 5 years of tamoxifen therapy

All of these drugs are also approved for women with advanced (metastatic) hormone-sensitive breast cancer. Studies indicate that the introduction of aromatase inhibitors has helped greatly in prolonging survival for women with advanced cancer.

Compared to tamoxifen, aromatase inhibitors are less likely to cause blood clots and uterine cancer. However, these drugs are more likely to cause osteoporosis, which can lead to bone loss and fractures. In general, recent studies indicate that aromatase inhibitors are better than tamoxifen in improving survival and reducing the risk of cancer recurrence. Unfortunately, like tamoxifen, they can cause hot flashes, as well as joint pain.

Ovarian ablation literally shuts down estrogen production from the ovaries. Medications can accomplish ovarian ablation. Destroying the ovaries with surgery or radiation can also shut down estrogen production. (Osteoporosis is one serious side effect of this approach, but several therapies are available to help prevent bone loss.)

Chemical Ovarian Ablation. Drug treatment (non-chemotherapy drugs) to block ovarian production of estrogen is called chemical ovarian ablation. It is often reversible. The primary drugs used are luteinizing hormone-releasing hormone (LHRH) agonists, such as goserelin (Zoladex). (They are also sometimes called GnRH agonists). These drugs block the release of the reproductive hormones LH-RH, therefore stopping ovulation and estrogen production.

Studies suggest that women with estrogen-positive early stage cancer who take goserelin have similar survival rates to those who take standard chemotherapy. They also experience fewer serious side effects. A major analysis of four trials using LHRH agonists plus tamoxifen suggested that this combination should be the standard for patients with advanced breast cancers that are hormone-receptor positive, although this is an area of controversy. (Chemotherapy is still more effective in women with estrogen-negative tumors.)

Ovariectomy. Ovariectomy, the removal of the ovaries, has modestly improved breast cancer survival rates in some premenopausal women whose tumors are hormone receptor-positive. In these women, combining this procedure with tamoxifen may improve results beyond those of standard chemotherapies. Ovariectomy does not benefit women after menopause, and its advantages can be blunted in women who have received adjuvant chemotherapy. The procedure causes sterility and can have a major negative emotional impact on younger patients.

Resources

www.cancer.gov -- National Cancer Institute
www.cancer.org -- American Cancer Society
www.asco.org -- American Society of Clinical Oncology
www.oncolink.org -- Oncolink
www.womenshealth.gov -- National Women's Health Information Center
www.nccn.org -- National Comprehensive Cancer Network
www.plwc.org -- People Living With Cancer
www.cancer.gov/clinicaltrials -- Find clinical trials
www.breastcancer.org -- Find clinical trials

References

Bardia A, Hartmann LC, Vachon CM, Vierkant RA, Wang AH, Olson JE, et al. Recreational physical activity and risk of postmenopausal breast cancer based on hormone receptor status. Arch Intern Med. 2006 Dec 11-25;166(22):2478-83.

Barron TI, Connolly R, Bennett K, Feely J, Kennedy MJ. Early discontinuation of tamoxifen: a lesson for oncologists. Cancer. 2007 Mar 1;109(5):832-9.

Boccardo F, Rubagotti A, Aldrighetti D, Buzzi F, Cruciani G, Farris A, et al. Switching to an aromatase inhibitor provides mortality benefit in early breast carcinoma: pooled analysis of 2 consecutive trials. Cancer. 2007 Mar 15;109(6):1060-7.

Boehm JS, Zhao JJ, Yao J, Kim SY, Firestein R, Dunn IF, et al. Integrative genomic approaches identify IKBKE as a breast cancer oncogene. Cell. 2007 Jun 15;129(6):1065-79.

Boyd NF, Guo H, Martin LJ, Sun L, Stone J, Fishell E, et al. Mammographic density and the risk and detection of breast cancer. N Engl J Med. 2007 Jan 18;356(3):227-36.

Breen N, A Cronin K, Meissner HI, Taplin SH, Tangka FK, Tiro JA, et al. Reported drop in mammography : is this cause for concern? Cancer. 2007 Jun 15;109(12):2405-9.

Chia SK, Speers CH, D'Yachkova Y, Kang A, Malfair-Taylor S, Barnett J, et al. The impact of new chemotherapeutic and hormone agents on survival in a population-based cohort of women with metastatic breast cancer. Cancer. 2007 Jul 23;110(5):973-979 [Epub ahead of print]

Cho E, Chen WY, Hunter DJ, Stampfer MJ, Colditz GA, Hankinson SE, et al. Red meat intake and risk of breast cancer among premenopausal women. Arch Intern Med. 2006 Nov 13;166(20):2253-9.

Coombes RC, Kilburn LS, Snowdon CF, Paridaens R, Coleman RE, Jones SE, et al. Survival and safety of exemestane versus tamoxifen after 2-3 years' tamoxifen treatment (Intergroup Exemestane Study): a randomised controlled trial. Lancet. 2007 Feb 17;369(9561):559-70.

Fenton JJ, Taplin SH, Carney PA, Abraham L, Sickles EA, D'Orsi C, et al. Influence of computer-aided detection on performance of screening mammography. N Engl J Med. 2007 Apr 5;356(14):1399-409.

Geiger AM, Thwin SS, Lash TL, Buist DS, Prout MN, Wei F, et al. Recurrences and second primary breast cancers in older women with initial early-stage disease. Cancer. 2007 Mar 1;109(5):966-74.

Geyer CE, Forster J, Lindquist D, Chan S, Romieu CG, Pienkowski T, et al. Lapatinib plus capecitabine for HER2-positive advanced breast cancer. N Engl J Med. 2006 Dec 28;355(26):2733-43.

Ives A, Saunders C, Bulsara M, Semmens J. Pregnancy after breast cancer: population based study. BMJ. 2007 Jan 27;334(7586):194. Epub 2006 Dec 8.

Jatoi I, Chen BE, Anderson WF, Rosenberg PS. Breast cancer mortality trends in the United States according to estrogen receptor status and age at diagnosis. J Clin Oncol. 2007 May 1;25(13):1683-90. Epub 2007 Apr 2.

Kahlenborn C, Modugno F, Potter DM, Severs WB. Oral contraceptive use as a risk factor for premenopausal breast cancer: a meta-analysis. Mayo Clin Proc. 2006 Oct;81(10):1290-302.

Kerlikowske K, Miglioretti DL, Buist DS, Walker R, Carney PA; National Cancer Institute-Sponsored Breast Cancer Surveillance Consortium. Declines in invasive breast cancer and use of postmenopausal hormone therapy in a screening mammography population. J Natl Cancer Inst. 2007 Sep 5;99(17):1335-9. Epub 2007 Aug 14.

Khatcheressian JL, Wolff AC, Smith TJ, Grunfeld E, Muss HB, Vogel VG, et al.American Society of Clinical Oncology 2006 update of the breast cancer follow-up and management guidelines in the adjuvant setting. J Clin Oncol. 2006 Nov 1;24(31):5091-7. Epub 2006 Oct 10.

Lehman CD, Gatsonis C, Kuhl CK, Hendrick RE, Pisano ED, Hanna L, et al. MRI evaluation of the contralateral breast in women with recently diagnosed breast cancer. N Engl J Med. 2007 Mar 29;356(13):1295-303. Epub 2007 Mar 28.

Lin J, Manson JE, Lee IM, Cook NR, Buring JE, Zhang SM. Intakes of calcium and vitamin D and breast cancer risk in women. Arch Intern Med. 2007 May 28;167(10):1050-9.

Lohrisch C, Paltiel C, Gelmon K, Speers C, Taylor S, Barnett J, et al. Impact on survival of time from definitive surgery to initiation of adjuvant chemotherapy for early-stage breast cancer. J Clin Oncol. 2006 Oct 20;24(30):4888-94. Epub 2006 Oct 2.

Michels KB, Xue F, Colditz GA, Willett WC. Induced and spontaneous abortion and incidence of breast cancer among young women: a prospective cohort study. Arch Intern Med. 2007 Apr 23;167(:814-20.

Moss SM, Cuckle H, Evans A, Johns L, Waller M, Bobrow L. Effect of mammographic screening from age 40 years on breast cancer mortality at 10 years' follow-up: a randomised controlled trial. Lancet. 2006 Dec 9;368(9552):2053-60.

North American Menopause Society. Estrogen and progestogen use in peri- and postmenopausal women: March 2007 position statement of The North American Menopause Society. Menopause. 2007 Mar-Apr;14(2):168-82.

Perez EA, Lerzo G, Pivot X, Thomas E, Vahdat L, Bosserman L, et al. Efficacy and safety of ixabepilone (BMS-247550) in a phase II study of patients with advanced breast cancer resistant to an anthracycline, a taxane, and capecitabine. J Clin Oncol. 2007 Aug 10;25(23):3407-14. Epub 2007 Jul 2.

Pierce JP, Natarajan L, Caan BJ, Parker BA, Greenberg ER, Flatt SW, et al. Influence of a diet very high in vegetables, fruit, and fiber and low in fat on prognosis following treatment for breast cancer: the Women's Healthy Eating and Living (WHEL) randomized trial. JAMA. 2007 Jul 18;298(3):289-98.

Qaseem A, Snow V, Sherif K, Aronson M, Weiss KB, Owens DK; Clinical Efficacy Assessment Subcommittee of the American College of Physicians. Screening mammography for women 40 to 49 years of age: a clinical practice guideline from the American College of Physicians. Ann Intern Med. 2007 Apr 3;146(7):511-5.

Ravdin PM, Cronin KA, Howlader N, Berg CD, Chlebowski RT, Feuer EJ, et al. The decrease in breast-cancer incidence in 2003 in the United States. N Engl J Med. 2007 Apr 19;356(16):1670-4.

Saslow D, Boetes C, Burke W, Harms S, Leach MO, Lehman CD, et al. American Cancer Society guidelines for breast screening with MRI as an adjunct to mammography. CA Cancer J Clin. 2007 Mar-Apr;57(2):75-89.

Smith I, Procter M, Gelber RD, Guillaume S, Feyereislova A, Dowsett M, et al. 2-year follow-up of trastuzumab after adjuvant chemotherapy in HER2-positive breast cancer: a randomised controlled trial. Lancet. 2007 Jan 6;369(9555):29-36.

Terry KL, Willett WC, Rich-Edwards JW, Michels KB. A prospective study of infertility due to ovulatory disorders, ovulation induction, and incidence of breast cancer. Arch Intern Med. 2006 Dec 11-25;166(22):2484-9.

Wolff AC, Hammond ME, Schwartz JN, Hagerty KL, Allred DC, Cote RJ, et al. American Society of Clinical Oncology/College of American Pathologists guideline recommendations for human epidermal growth factor receptor 2 testing in breast cancer. J Clin Oncol. 2007 Jan 1;25(1):118-45. Epub 2006 Dec 11.

Review Date:
1/26/2008
Reviewed By:
A.D.A.M. Editorial Team: David Zieve, MD, MHA, Greg Juhn, MTPW, David R. Eltz, Kelli A. Stacy, ELS. Previously reviewed by Harvey Simon, MD, Editor-in-Chief, Associate Professor of Medicine, Harvard Medical School; Physician, Massachusetts General Hospital (11/01/07).

A.D.A.M. Copyright

adam.com

Herpes simplex

FitSugar — Wed, 08 Oct 2008 17:35:02 -0700

In This Report

Highlights
Introduction
Symptoms
Transmission
Risk Factors
Complications
Diagnosis
Similar Conditions
Home Remedies and Preventio...
Treatment for Genital Herpe...
Treatment for Oral Herpes...
Resources
References

HEALTH GUIDE REFERENCE FROM A.D.A.M

Highlights

Herpes Diagnosis

In 2006, the U.S. Centers for Disease Control (CDC) released updated guidelines for diagnosis and management of sexually transmitted diseases.

For diagnosis of genital herpes, the CDC recommends the use of both skin and blood tests.
Blood (or type-specific serologic) tests must be able to detect antibodies to glycoprotein G (gG). According to the CDC, gG serologic tests are much more accurate than other types of blood tests and are the only ones that should be used. These blood tests can help determine whether genital herpes is caused by herpes simplex virus-1 (HSV-1) or herpes simplex virus-2 (HSV-2).
Although HSV-1 has traditionally been the main cause of oral herpes, and HSV-2 the main cause of genital herpes, HSV-1 is now causing up to 50% of all cases of genital herpes. Prognosis may vary depending on the type of virus involved.

Herpes Treatment

Acyclovir (Zovirax), famiciclovir (Famvir), and valacyclovir (Valtrex) are used for episodic treatment (when herpes outbreaks occur) or suppressive treatment (preventing outbreaks). Valacyclovir may be a particularly good choice for reducing the risk of herpes transmission among heterosexual couples when only one partner is infected with HSV-2.
According to a 2007 review of studies involving over 6,000 patients, these drugs are very effective in reducing herpes recurrences.

Herpes and HIV

Treatment of HSV-2 can help reduce HIV levels in women who are infected with both viruses, indicates a study published in 2007 in the New England Journal of Medicine. In the trial, women who received twice-daily valacyclovir therapy for 12 weeks had reduced genital-track shedding of HIV and blood HIV levels compared to women who received placebo. Researchers are now focusing on the major question: Whether treatment of genital herpes can help prevent HIV transmission.

Introduction

Herpes simplex virus (HSV) commonly causes infections of the skin and mucous membranes. Sometimes it can cause more serious infections in other parts of the body. HSV is one of the most difficult viruses to control and has plagued mankind for thousands of years.

Herpes simplex is part of a group of other herpes viruses that include human herpesvirus 8 (the cause of Kaposi's sarcoma) and herpes zoster (the virus responsible for shingles and chicken pox). They differ in many ways, but the viruses share certain characteristics, notably the word "herpes," which is derived from a Greek word meaning "to creep." This refers to the unique characteristic pattern of all herpes viruses to "creep along" local nerve pathways to the nerve clusters at the end, where they remain in an inactive state for some indeterminate time.

There are two forms of the herpes simplex virus:

Herpes simplex virus 1 (HSV-1)
Herpes simplex virus 2 (HSV-2)

These viruses are distinguished by different proteins on their surfaces. They can occur separately, or they can both infect the same individual. Until recently, the general rule has been to assume that HSV-1 infections occur in the oral cavity (mouth) and are not sexually transmitted, while HSV-2 attacks the genital area and is sexually transmitted. It is now widely accepted, however, that either type can be found in either area and at other sites. In fact, HSV-1 is now responsible for up to half of all new cases of genital herpes.

For infection to occur, the following conditions must apply:

The herpes simplex virus passes moves through bodily fluids (saliva, semen, fluid in the female genital tract) or in fluid from herpes sores.
The virus must have direct access to the noninfected person through injuries in their skin or mucus surfaces (such as in the mouth or genital area).

When herpes simplex virus enters the body, the infection process typically takes place as follows:

The virus enters vulnerable cells in the lower layers of skin tissue and tries to reproduce in the cell nuclei. Scientists are close to decoding the genetic structure of herpes simples virus and to discovering how the virus works its way into specific cells. The virus may have specially shaped proteins called cell adhesion molecules that can allow the virus to enter healthy cells. For example, protein receptors on cells called nectin 1 and 2 may bind to some subtypes of the virus and help the infection move from cell to cell.
Even after it has entered the cells, the virus never causes symptoms in most cases.
However, if the virus destroys the host cells when it multiplies, inflammation and fluid-filled blisters or ulcers appear. Once the fluid is absorbed, scabs form, and the blisters disappear without scarring.
After the first time they multiply, the viral particles are carried from the skin through branches of nerve cells to clusters at the nerve-cell ends (the dorsal root ganglia).
Here, the virus lives in an inactive (latent) form. The virus does not multiply, but both the host cells and the virus survive.
At unpredictable times, the virus begins multiplying again. It then goes through a period called shedding. During those times, the virus can be passed into bodily fluids and infect other people. Unfortunately, a third to half of the times shedding occurs without any symptoms at all.
Eventually, the symptoms return in most cases, causing a new outbreak of blisters and sores.

This close-up view of early herpes outbreak shows small, grouped blisters (vesicles) and lots of inflammation (erythema).

Symptoms

Symptoms vary depending on the stage of the virus, the initial or primary outbreak, and recurrence. Both herpes simplex viruses 1 and 2 produce similar symptoms, but they can differ in severity depending on the site of infection. More than 60% of new herpes simplex virus 2 (HSV-2) infections and about a third of new herpes simplex virus 1 (HSV-1) infections do not produce symptoms.

Skin Eruptions and Pain. Skin eruptions will appear 2 - 12 days after the initial exposure to the virus.

The first sign of infection is fluid accumulation (edema) at the infection site, which is quickly followed by small, grouped blisters -- the characteristic herpes virus lesions.
These form on an inflamed skin base, which is more visible in dry skin areas.
The blisters then dry out and heal rapidly without scarring within 7 - 10 days. Blisters in moist areas heal more slowly than others. The lesions may sometimes itch, but itching decreases as they heal.
When the crust falls off, the lesions are no longer contagious. (Rarely, the virus may still be active in nearby tissue.)
Once the virus gains entry to a site in the body, it can also spread to nearby mucosal areas through nerve cells. This characteristic spreading can cause fairly large infected areas to erupt at some distance from the initial crop of sores.

The primary skin infection with either herpes simplex virus 1 (HSV-1) or herpes simplex virus 2 (HSV-2) lasts up to 2 - 3 weeks, but skin pain can last 1 - 6 weeks in the first (primary) virus attack.

Other Symptoms. Some patients experience other symptoms as well, which may occur before the actual outbreak (called a prodrome).

Fever rising to about 102°F, muscle aches, headache, and flu-like malaise. These general symptoms usually go away within a week.
Lymph glands near the site may be swollen as well.

It may be especially important to identify a first (primary) infection -- if possible -- and to treat it as soon as possible. Some preliminary research suggests that early treatment may limit the number of viruses that remain latent in the body and reduce the frequency of recurrent outbreaks.

Latency. After an outbreak, the herpes simplex virus goes into a stage known as latency. During that time, the virus does not produce symptoms and cannot be transmitted to other people.

Asymptomatic Shedding. At certain times, the virus undergoes shedding. During this phase the virus multiples and can be transmitted through fluids and infect other people. This occurs during an outbreak. However, in a third to half of cases shedding occurs without any symptoms at all (asymptomatic). One study reported that about 40% of all people infected with herpes simplex virus (HSV) had sheeding of the virus without symptoms more than 5% of the time. (Other evidence suggests shedding occurs much more often -- 9 - 28% of the time.) About half of shedding episodes without symptoms happen within a few days before or after an outbreak and can last about 1.5 days. Asymptomatic shedding is much more common with herpes simplex virus 2 (HSV-2) than with herpes simplex virus 1 (HSV-1).

Symptoms of Recurrence. Herpes simplex nearly always recurs. The site on the body and the type of virus influence how often it comes back. The virus usually takes the following course:

Prodrome. The outbreak of infection is often preceded by a prodrome, an early group of symptoms that may include itching skin, pain, or an abnormal tingling sensation at the site of infection. The patient may also have a headache, enlarged lymph glands, and flu-like symptoms. The prodrome, which may be as few as 2 hours or as many as 2 days, steps when the blisters develop. About 25% of the time, recurrence does not go beyond the prodrome stage.
Outbreak. Recurrent outbreaks of herpes simplex virus (HSV) feature most of the same symptoms at the same sites as the primary attack, but they tend to be milder and briefer. After blisters erupt, they typically heal in 6 - 10 days. Occasionally, the symptoms may not resemble those of the primary episode but appear as fissures and scrapes in the skin or as general inflammation around the affected area.

Triggers of Recurrence. It is not completely known what triggers renewed infection, but several different factors may be involved. These include sunlight, wind, fever, local physical injury, menstruation, suppression of the immune system, and emotional stress. Some studies link recurrence in genital herpes to persistent stress (lasting longer than a week) and high levels of anxiety. Oral herpes can be provoked within about 3 days of intense dental work, particularly root canal or tooth extraction, as well as after laser skin resurfacing, a popular form of cosmetic surgery.

Timing of Recurrences. Recurrent outbreaks may occur at intervals of days, weeks, or years. For most people, outbreaks recur with more frequency during the first year after an initial attack. During that period, the body mounts an immune response to HSV, and in most healthy people recurring infections tend to become progressively less severe and less frequent. The immune system, however, cannot kill the virus completely.

Oral herpes (herpes labialis) is most often caused by herpes simplex virus 1 (HSV-1) but can also be caused by herpes simplex virus 1 (HSV-2). It usually affects the lips and, in some primary attacks, the mucous membranes in the mouth. A herpes infection may occur on the cheeks or in the nose, but facial herpes is very uncommon.

Primary Oral Herpes Infection. If the primary (or initial) oral infection causes symptoms, they can be very painful, particularly in small children.

Blisters form on the lips but may also erupt on the tongue.
The blisters eventually rupture as painful open sores, develop a yellowish membrane before healing, and disappear within 3 - 14 days.
Increased salivation and foul breath may be present.
Rarely, the infection may be accompanied by difficulty in swallowing, chills, muscle pain, or hearing loss.

In children, the infection usually occurs in the mouth. In adolescents, the primary infection is more apt to appear in the upper part of the throat and cause soreness.

Recurrent Oral Herpes Infection. Most patients have only a couple of outbreaks a year, although up to 10% of patients experience more frequent recurrences. (HSV-2 oral infections recur less frequently than HSV-1.) Recurrences are usually much milder than primary infections and are known commonly as cold sores or fever blisters (because they may arise during a bout of cold or flu). They usually show up on the outer edge of the lips and rarely affect the gums or throat. (Cold sores are commonly mistaken for the crater-like mouth lesions known as canker sores, which are not associated with herpes simplex virus.)

Genital herpes, which typically affects the penis, vulva, or rectum, is usually caused by herpes simplex virus 2 (HSV-2), although the rate of simplex virus 1 (HSV-1) genital infection is increasing. Studies now report, in fact, that the cases of new symptomatic genital infections are equally split between HSV-1 and HSV-2. Some studies even report a higher incidence of genital HSV-1 cases. While there is no difference in treatment, there can be a difference in disease course. Initial genital infections due to HSV-1 may be more severe than those caused by HSV-2. Recurrences tend to be milder and less frequent than with HSV-2, however.

Primary Genital Herpes Infection. The first outbreak usually occurs in or around the genital area 3 - 14 days after exposure to the virus. If there is a long time between the initial infection and the first outbreak of symptoms, the episode may be quite mild because the immune system has already produced antibodies to the virus. These kinds of first infections are less transmissible, heal faster, and produce fewer symptoms.

In about 80% of initial outbreaks of genital herpes, patients develop symptoms such as flu-like discomfort and fever. The virus sheds for about 3 weeks. Symptoms in men and women are very different from each other.

In women, the pattern of a first infection is often more complicated and severe than in men:

In addition to general flu-like discomfort, women may experience nerve pain, itching, lower abdominal pain, urinary difficulties, and yeast infections before or during the eruption of the skin blisters.
When the outbreak occurs, blisters form raw sores (ulcers) almost immediately. Later they become crusted and fill with a grayish-white fluid. A new crop often occurs during the second week and is accompanied by swollen lymph glands in the groin. The symptoms may last as many as 6 weeks.
Lesions commonly appear around the vaginal opening, on the buttocks, in the vagina, or on the cervix. If lesions occur inside the vagina, they are not visible and pain may be minimal. Such women, then, may be unaware that they have genital herpes. In such cases, the blisters produce a discharge that is still highly infectious.
Lesions develop in places other than the genital region in 10 - 18% of primary HSV-2 infections. In most of these cases, outbreaks occur in the urethra (the channel that carries urine) where they can cause painful burning during urination. Inflammation of the internal reproductive organs, including the uterus lining (endometrium) and the fallopian tubes, is rare.

In men, about 6 - 10 blisters typically develop on the head or shaft of the penis. They rarely occur at the base. In some cases, they can occur on the buttocks, around the anus, or on the thighs.

Recurrent Genital Herpes Infection. In general, recurrences are much milder than the initial outbreak. The virus sheds for a much shorter period of time (about 3 days) compared to in an initial outbreak of 3 weeks. Women may have only minor itching, and the symptoms may be even milder in men.

On average, people have four recurrences a year, although this varies widely depending on the severity of the initial outbreak. Men, for example, have 20% more recurrences of genital herpes than women even though their symptoms are milder. There are also some differences in frequency of recurrence depending on whether HSV-2 or HSV-1 causes genital herpes:

HSV-2 Genital Herpes Recurrences. HSV-2 genital infections recur more often than HSV-1, and they tend to be more severe. Up to 90% of HSV-2 genital infections recur within the first year after primary infection. Many patients report 5 - 8 recurrences in the first year, but some have them as often as every 2 weeks. Some, though, have only one initial outbreak without any subsequent recurrences, a rate more typical of those with HSV-1.
HSV-1 Genital Herpes Recurrences. In one study, 38% of patients with HSV-1 genital infections had no recurrences in the first year after primary infection, 35% had one recurrence, and 27% had 2 or more recurrences. The average time to recurrence was about 7.5 months. Only 7% of those with genital HSV-1 had two or more recurrences annually for at least 2 years.

Patients with genital herpes usually notice a significant reduction in recurrence by the seventh year after infection. Some patients, however, particularly those with genital HSV-2, may actually face an increase in recurrence during the first 5 years.


Location and type	Symptoms	Treatments
*Eye (ocular herpetic infection).* Affects only one eye at a time. Usually caused by HSV-1, but acute cases in the retina are more likely to be due to HSV-2. The incidence has been highest in children, although it is increasing in older individuals.	Primary: Inflammation of the cornea (keratitis), causing sudden and severe pain, blurred vision, or corneal lesions. A cloudy layer can form over the cornea. Swelling may occur around the eyes. Heals within 2 - 3 weeks. Recurrence: About 40% of people have more than one recurrence, usually keratitis in a single eye, but symptoms may be present in the other eye as well. In the experience of some doctors, short, intense exposure to sunlight may trigger a recurrence, but there is no clear evidence concerning sunlight or any other potential triggers. Branching, ulcerous lesions of the cornea may occur later in the disease. Stromal keratitis, inflammation of inner layers of the cornea, occurs in about 25% of patients. It is a late immune response to the infection and can, in some cases, be very serious. In the U.S., it is the major cause of blindness in the cornea (which is still very uncommon).	Medications of Ocular HSV. Ocular HSV should be treated carefully since certain treatments may aggravate the condition. Artificial tears may be appropriate for mild cases. Treatments include trifluridine (Viroptic) eye drops or acyclovir or vidarabine (Vira A) ointments. Adding interferon, an immune system booster, to trifluridine may speed healing. Interferon in combination with debridement is also helpful. With treatment, most HSV ocular infections resolve within 5 - 9 days. Taking long-term oral acyclovir after an initial episode of ocular HSV reduces recurrences by about 45%. Medications for Stromal Keratitis. Oral acyclovir also protects against stromal keratitis in patients with a history of it. Trifluridine or cidofovir may also be protective against it. Neither drug, however, has any effect once stromal keratitis develops. Treatment includes artificial tears for mild cases and topical steroids for moderate-to-severe inflammation. Procedures. Patients with ocular HSV may also need debridement, in which the surgeon scrapes away the injured tissue with a cotton swab. The patient may wear a patch or soft contact lens afterward. Patients with HSV who show scarring in the cornea may need surgery. In rare cases, a corneal transplant may be necessary.
*Brain (HSV encephalitis).* Usually HSV-1, although HSV-2 is typically the cause in newborns. In about 25% of HSV-1 encephalitis cases, the infection may be caused by a new strain of the virus. About a third of cases occur in people under 20 years old, half over age 50, and the balance between ages 20 -50.	Fever, headache, stiff neck, seizures, partial paralysis, stupor, or coma. Other symptoms: smell and taste disturbances, double vision, odd mental states, bizarre or psychotic behavior, loss of the ability to speak or understand, memory loss, confusion, emotional volatility.	Intravenous acyclovir is the treatment of choice for encephalitis and should be started immediately if this complication is suspected. It must be administered for at least 10 days. In rare cases, surgical measures may be needed to relieve the buildup of pressure in the brain.
*Finger (herpetic whitlow)*. One finger, usually thumb or index finger in adults. Any finger in children. HSV-1 the cause in 60% of cases, and HSV-2 in 40% of cases. HSV-1 is usually caused by finger-sucking in children or as an occupational condition in adults (usually health care workers not using gloves). HSV-2 is usually acquired by touching infected genital areas.	Primary: Itching or pain, swelling, flushing of the skin, localized tenderness of the infected finger. Clear-yellowish or pus-filled blisters may appear on fingertip lasting 2 - 3 weeks. Soft tissue around fingernail may become painfully infected. Finger blisters may become secondarily infected with common bacteria, causing fever and swollen glands in the armpit. Recurrence: Sometimes intense burning, nerve pain, or excessive sensitivity.	Topical acyclovir for acute attack and oral acyclovir for prevention of recurrences.
Lower back. Usually caused by HSV-2 and typically occurs in bedridden patients or those with AIDS.	Numbness, tingling of the buttocks or the area around the anus, urinary retention, constipation, and impotence. Weakness or extreme skin sensitivity in the lower extremities, possibly persisting for months. Headaches, stiff neck, and, very rarely, paralysis in lower extremities caused by inflammation of the spinal cord.	Acyclovir, or foscarnet in patients resistant to acyclovir.
Peripheral nervous system. Affecting nerves other than in the brain and spine. Usually caused by HSV-1.	Portion of the face temporarily paralyzed (Bell's palsy). Other areas of the body may exhibit numbness or loss of feeling to the touch.	Acyclovir or similar drugs in combination with oral prednisone.
*Other skin areas (herpetic erythema multiforme).* May follow any form of recurrent HSV. Is relatively rare.	Circular or irregular eruptions on backs of arms and hands. Recurrence of erythema multiforme is common in the same areas. This is actually an allergic reaction that lasts 2 - 3 weeks.	Usually minor and resolves without complications. Acyclovir and symptom relievers (common pain relievers, cold compresses, topical steroids, saline gargles).
Esophagus. Usually caused by HSV-1. Typically occurs in immunocompromised patients or in those taking long-term steroids or other immunosuppressant drugs, but can occur in infected people with normal immune systems.	Difficulty swallowing or burning, squeezing throat pain while swallowing, weight loss, pain in or behind the upper chest while swallowing. Herpes lesions difficult to differentiate from other throat sores.	Intravenous acyclovir may be recommended. Recurrences are rare in patients with healthy immune systems, so preventive therapy is usually unnecessary in these patients.

Click the icon to see an image of herpetic esophagitis.

Transmission

To infect people, the herpes simplex viruses (both HSV-1 and HSV-2) must get into the body through broken skin or a mucous membrane, such as inside the mouth or on the genital area. Each virus can be carried in bodily fluids (saliva, semen, fluid in the female genital tract) or in fluid from herpes sores. The risk for infection is highest with direct contact of blisters or sores during an outbreak.

Once the virus has contact with the mucous membranes or skin wounds, it begins to replicate. The virus is then transported within nerve cells to their roots where it remains inactive (latent) for some period of time. During inactive periods, the virus cannot be transmitted to another person. However, at some point, it often begins to multiply again without causing symptoms (called shedding ). During shedding, the virus can infect other people through exchange of bodily fluids.

Sometimes, infected people can transmit the virus and infect other parts of their own bodies (most often the hands, thighs, or buttocks). This process, known as autoinoculation, is uncommon, since people generally develop antibodies that protect against this problem.

Oral herpes (usually HSV-1) has been detected in both the saliva and blood of patients with active oral infections. It is the most prevalent form of herpes simplex virus, and infection is most likely to occur during preschool years. Oral herpes is easily spread by direct exposure to saliva or even from droplets in breath. Skin contact with infected areas is enough to spread it. Transmission most often occurs through close personal contact, such as kissing. In addition, because herpes simplex virus 1 can be passed in saliva, people should also avoid sharing toothbrushes or eating utensils with an infected person.

Genital herpes is most often transmitted through sexual activity, and people with multiple sexual partners are at high risk. The virus, however, can also enter through the anus, skin, and other areas.

People with active symptoms of genital herpes are at very high risk for transmitting the infection. Unfortunately, evidence suggests about one-third of all herpes simplex virus 2 (HSV-2) infections occur when the virus is shedding but producing no symptoms. Most people either have no symptoms or don't recognize them when they appear.

In the past, genital herpes was mostly caused by HSV-2, but herpes simplex virus 1 (HSV-1) genital infection is increasing, most likely to due to oral sex. Shedding of genital HSV-1 is less common than with HSV-2, but transmission obviously still occurs, as evidenced by the rising prevalence of genital HSV-1. In fact, a person who carries both HSV-1 and HSV-2 poses a greater risk for sexually transmitting HSV-2 than a person who carries only HSV-2. A person who is infected with only HSV-1 has some protection against being infected by HSV-2.

Risk Factors

Everyone is at risk for herpes simplex virus. According to the latest U.S. data from 1999 - 2004, 57.7% of Americans ages 14 – 49 are infected with herpes simplex virus 1 (HSV-1). About 17% of Americans in the same age range test positive for herpes simplex virus 2 (HSV-2). Infection rates for both viruses have declined since the late 1980s. However, infection is lifelong.

Oral herpes is usually caused by HSV-1. The highest incidence of first infection occurs between 6 months and 3 years of age. The incidence in children varies among regions and countries, with the highest rates occurring in crowded and unsanitary regions. Studies suggest that by age 5 more than a third of children in low-income areas are infected compared to 20% of children in middle-income areas. However, by the time children in middle-income areas reach their 30s, about 60% have become infected with HSV-1. After age 40, socioeconomic differences in infection rates become even less pronounced.

The number of Americans with genital herpes increased by 30% from the late 1970s through the early 1990s. However, recent surveys indicate that prevalence is decreasing. A 2006 study in the Journal of the American Medical Association found that among Americans age 14 - 49, the prevalence of herpes simplex virus 2 (HSV-2) decreased by 19% from 1988 - 2004. The decrease was greatest among teenagers age 14 - 19.

The prevalence of herpes virus simplex 1 (HSV-1) also declined, but the percentage of genital herpes infections caused by HSV-1 more than tripled. Among people infected with HSV-1, but not HSV-2, 1.8% were diagnosed with genital herpes from 1999 to 2004 compared with 0.4% from 1988 to 1994. (HSV-2 still causes the majority of genital herpes infections.)

Although the prevalence of genital herpes is declining in the United States, it still remains in epidemic proportions. According to the U.S. Centers for Disease Control and Prevention, at least 45 million Americans age 12 and over have had genital herpes. About 1 in 5 teenagers and adults are infected with genital herpes.

Gender. Anyone who is sexually active is at risk for genital herpes. Studies indicate that around 22% of Americans are infected with HSV-2, with the risk higher in women (26%) than in men (18%). Men, however, have twice as many recurrent infections as women.

Women have an 80 - 90% chance of contracting HSV-2 after unprotected sexual activity with an infected partner and are 4 times more likely to be infected than men. In one study of sexually active American teenagers, 15% of the females had evidence of being infected with HSV-2, compared to none of the males. Having a drinking problem greatly increased the likelihood of infection in these young women.

Ethnicity. Although African-Americans are more likely to test positive for HSV-2, Caucasians have a higher risk for active genital symptoms. Over the past few years, the greatest increase in HSV-2 has occurred in Caucasian teenagers.

Compromised Immune Systems. People with compromised immune systems, notably patients with HIV, are at very high risk for HSV-2. Between 68 - 81% of patients with HIV are infected with HSV-2. These patients are also at risk for more severe complications from herpes. Other immunocompromised patients include those taking drugs that suppress the immune system and transplant patients.

The following are examples of people who are at particularly risk for specific forms of herpes.

Health care providers, including doctors, nurses, and dentists. This group is at higher than average risk for herpetic whitlow, herpes that occurs in the fingers.
Wrestlers, rugby players, and other athletes who participate in direct contact sports without protective clothing. These individuals are at risk for herpes gladiatorum, an unusual form of HSV-1 that is spread by skin contact with exposed herpes sores and usually affects the head or eyes.

Complications

The severity of symptoms depends on where and how the virus enters the body. Except in very rare instances and in special circumstances, the disease is not life threatening, although it can be very debilitating and cause great emotional distress.

Pregnant women who are infected with either herpes simplex virus 2 (HSV-2) or herpes simplex virus 1 (HSV-1) genital herpes have a higher risk for miscarriage, premature labor, retarded fetal growth, or transmission of the herpes infection to the infant while in the uterus or at the time of delivery. Recurrence in women previously infected with herpes is also common during pregnancy.

However, although about 1 million pregnancies occur each year in women who have been infected with HSV-2, complications occur in fewer than 4 in 1,000 infected pregnant women.

Approach to the Pregnant Herpes Patient. The approach to a pregnant woman who has been infected by either HSV-1 or HSV-2 in the genital area is usually determined by when the infection was acquired and the mother's condition around the time of delivery:

If lesions are present at the time of birth, Cesarean section is usually recommended. An important 13-year study confirmed that this approach helps prevent transmission. In the study, the baby became infected in only 1.1% of Cesarean sections compared to 7.7% of vaginal deliveries. (Even a Cesarean section is no guarantee that the child will be virus-free, and the newborn must still be tested.)
If lesions erupt shortly before the baby is due then samples must be taken and sent to the laboratory. Samples are cultured to detect the virus at 3 - 5-day intervals prior to delivery to determine whether viral shedding is occurring. If no lesions are present and cultures indicate no viral shedding, a vaginal delivery can be performed and the newborn is examined and cultured after delivery.

Some doctors now recommend anti-viral medication for pregnant women who are infected with HSV-2. Recent studies indicate that acyclovir (Zovirax) or valacyclovir (Valtrex) can help reduce the recurrence of genital herpes and the need for Cesarean sections. Women begin to take the drug on a daily basis beginning in the 36th week of pregnancy (last trimester).

Although 25 - 30% of pregnant women in the U.S. and Europe have a history of herpes simplex virus (HSV-2) infection, the risk of transmission to the newborn is low, occurring in between one in 3,500 - 20,000 births, depending on the population group.

The greatest danger to the baby is from an asymptomatic infection during a vaginal delivery in women who acquired the virus for the first time late in the pregnancy. In such cases, 30 - 50% of newborns become infected. Recurring herpes and a first infection that is acquired early in the pregnancy pose a much lower risk (less than 1%) to the infant.

The reasons for the higher risk with a late primary infection are:

During a first infection, the virus is shed for longer periods, and more viral particles are excreted.
An infection that first occurs in the late term does not allow the mother to develop antibodies that would help her baby fight off the infection at the time of delivery.

The risk for transmission also increases if infants with infected mothers are born prematurely, if there is invasive monitoring, or if instruments are required during vaginal delivery. Transmission can occur if the amniotic membrane of an infected woman ruptures prematurely, or as the infant passes through an infected birth canal. Very rarely, the virus is transmitted across the placenta, a form of the infection known as congenital herpes.

Infants may acquire congenital herpes from a mother with an active herpes infection at the time of birth. Aggressive treatment with antiviral medication is required, but may not help systemic herpes.

Unfortunately, only 5% of infected pregnant women have a history of symptoms, so in many cases herpes infection is not suspected, or symptoms are missed, at the time of delivery. Occasionally, lesions on the mother's buttocks may help indicate the presence of the virus.

Herpes infection in a newborn is a very serious and even-life threatening condition if it goes undiagnosed and untreated. Fortunately, since the introduction of acyclovir the outlook for these children has significantly improved. In general, there are three categories of herpes in the newborn.

Localized infection affects the skin, eyes, and mucous membranes. Herpes simplex virus 1 (HSV-1) usually causes this temporary. However, in some cases, most often herpes simplex virus 2 (HSV-2) infections, later complications develop in 5 - 10% of infants. If untreated, the virus may lead to very severe complications, notably disseminated or central nervous system infection.
Disseminated disease can affect internal organs, such as the liver, lungs, and adrenal glands. It is fatal in up to 80% of newborns if left untreated, and those who survive are at high risk for complications, particularly in the eyes. If infants are treated, however, survival rates are close to 90%.
Central nervous system infection can cause meningitis or encephalitis. This form is also highly fatal, and complications that affect learning and mental functions are common in surviving children.

Factors that Indicate a Higher Risk for Severe Complications. These may include:

Acute infection in the mother at delivery
Prematurity
Seizures in the infant
Disseminated intravascular coagulopathy, a blood-clotting disorder that can occur in response to infection

Factors that Indicate a Lower Risk for Severe Complications. These may include:

Newborn infection caused by a recurring HSV-2 infection in the mother. (Mothers with such infections appear to pass along protective antibodies to the newborn. However, antibodies to HSV-1 do not appear to offer similar protection to the newborn.)
Newborn infections that are confined to the skin and do not cause frequent outbreaks within the first 6 months.

Tests for the Newborn at Risk for Herpes. Any newborn with an infected or high-risk mother should be tested and checked carefully for symptoms. (Experts are divided, however, over whether the high cost of testing mothers specifically for HSV before delivery, even in high-risk groups, is worth the benefit for such a small group of mothers and infants.)

In the asymptomatic newborn delivered from an infected mother, cultures should be taken between 24 - 48 hours after birth. A culture taken right at the time of delivery may give a false indication of infection in the baby, simply because it can carry some of the mother's virus from the birth canal.
Testing specimens for viral DNA using a test called polymerase chain reaction is proving to be very important in newborns, particularly when central nervous system infection is suspected, since it eliminates the need for brain biopsies.
While results are pending, the baby should be checked regularly for rashes and blisters, particularly in areas where the skin is broken, along with any signs of illness including fever, lethargy, respiratory distress, and poor feeding.

Symptoms of Herpes in the Newborn. Although treatments have improved the outlook of infected newborns, there has been little change over the past 20 years in the time between the onset of symptoms and the initiation of treatments. Doctors and parents should be suspicious of any signs if there is any risk of infection to the newborn.

When symptoms occur in newborns, they usually become apparent within 5 - 17 days of life, but they may develop as early as 24 hours or as late as 34 days.

An unstable temperature can be the first indication of the infection.
About half of infected infants develop a rash. Lesions may range from raised spots to large isolated blisters. They can be anywhere on the skin or eyes or in the mouth.
The other half of infected infants develop no lesions until later in the course of the infection. The absence of lesions, therefore, in high-risk infants should not be considered a guarantee that HSV has not been transmitted.
Other symptoms to watch for include irritability, blotchy skin, discharge in the eyes, sensitivity to light, tearing, lethargy, jaundice, pallor, coughing, rapid breathing, a swollen abdomen (enlarged spleen), seizures, or tremors. Doctors should suspect infection in any infant with fever, irritability, lethargy, or poor feeding at 1 week of age.

Treatment of Herpes in the Newborn. If doctors suspect herpes virus infection in a newborn, intravenous acyclovir treatment should begin immediately, since the potential dangers of the condition far outweigh any risks associated with the drug.

The following are recommendations for treating infants who have been infected or are at risk for infection:

If disseminated or central nervous system infection has developed or is suspected, intravenous acyclovir treatment should continue for 21 days.
If the infection is limited to the skin, eyes, or mouth and the infant is at low risk for more serious complications, treatment may be given for 10 - 14 days.

The American Academy of Pediatrics Committee on Infectious Diseases now recommends higher-than-standard doses to improve outcome in infants who have any of these infections. Investigators are studying whether giving long-term acyclovir by mouth to newborns following the initial infection will improve the outcome.

Herpes Encephalitis. Each year in the U.S., herpes accounts for 2,100 cases of encephalitis, a rare but extremely serious brain disease. Herpes simplex virus 1 (HSV-1) is usually the cause, except in newborns. In about 70% of cases of infant herpes encephalitis, the disease occurs when a latent herpes simplex virus 2 (HSV-2) is activated. Untreated, herpes encephalitis is fatal over 70% of the time. Respiratory arrest can occur within the first 24 - 72 hours. Fortunately, rapid diagnostic tests and treatment with acyclovir have both significantly improved survival rates (up to about 80%) and reduced complication rates (to nearly 40%). For those who recover, nearly all suffer some impairment, ranging from very mild neurological changes to paralysis. Recovery from herpes encephalitis depends on the patient's age, the level of consciousness, duration of the disease, and the promptness of treatment. The best chances for a favorable outcome occur in patients who are treated with acyclovir within 2 days of becoming ill.

Herpes Meningitis. Herpes meningitis, an inflammation of the membranes that line the brain and spinal cord, occurs in up to 10% of cases of primary genital HSV-2. Women are at higher risk than men for herpes meningitis. Symptoms include headache, fever, stiff neck, vomiting, and sensitivity to light. Fortunately, herpes meningitis usually resolves without complications, lasting for up to a week, although recurrences have been reported.

Click the icon to see an image of the meninges of the brain.

Alzheimer's Disease. Some studies indicate a higher risk for Alzheimer's in people who have both HSV-1 and a gene called ApoE4, a known risk factor for Alzheimer's. Furthermore, a protein found in HSV-1 has been shown to mimic beta amyloid, a protein that is critical in the development of Alzheimer's disease.

Other Neurologic Diseases. Other neurologic syndromes that have been linked to HSV infection include epilepsy, multiple sclerosis, atypical pain syndromes, ascending or transverse myelitis (inflammation of the spinal column), and neuralgia (severe stabbing pain along a nerve or group of nerves).

A form of herpes infection called eczema herpeticum, also known as Kaposi's varicellum eruption, can affect patients with skin disorders and immunocompromised patients. The disease tends to develop into widespread skin infection that resembles impetigo. Symptoms appear abruptly and can include fever, chills, and malaise. Clusters of dimpled blisters emerge over 7 - 10 days and spread widely. They can become secondarily infected with staphylococcal or streptococcal organisms. When treated, lesions heal in 2 - 6 weeks. Untreated, this condition can be extremely serious and possibly fatal.

Herpetic infections of the eye (ocular herpes) occur in about 50,000 Americans each year. In most cases it causes inflammation and sores on the lids or outside of the cornea that go away in a few days.

Click the icon to see an image of the eye.

Stromal Keratitis. Stromal keratitis occurs in up to 25% of cases of ocular herpes. In this condition, deeper layers of the cornea are involved, possibly as an abnormal immune response to the original infection. In these rare cases, scarring and corneal thinning develop, which may cause the eye's globe to rupture, resulting in blindness. Although rare, it is the major cause of corneal blindness in the US.

Iridocyclitis. Iridocyclitis is another serious complication of ocular herpes, in which the iris and the area around it become inflamed.

Herpes can cause multiple painful ulcers on the gums and mucous membranes of the mouth, a condition called gingivostomatitis. This condition usually affects children 1 - 5 years of age. It nearly always subsides within 2 weeks.Rarely, it can lead to a viral infection. Children with gingivostomatitis commonly develop herpetic whitlow (herpes of the fingers).

A herpetic whitlow is an infection of the herpes virus around the fingernail. In children, this is often caused by thumbsucking or finger sucking while they have a cold sore. It is seen in adult health care workers, such as dentists, because of increased exposure to the herpes virus. The use of rubber gloves prevents herpes whitlow in health care workers.

Not least among the damaging effects of genital herpes is its impact on the social and emotional life of patients. In one survey of patients with herpes, 82% felt depressed, and 75% were worried about rejection. Over 25% had suicidal thoughts. In nearly 80% of the respondents, the disease had a profound effect on their sexual lives. The patient must notify sexual partners, past and present, about their condition, a deeply humiliating experience. Guilt and anger are common emotions, and relationships may be shattered. It is important to note that the condition is often dormant for many years and may not have been transmitted by a current sexual partner. Support groups or couple therapy can be very helpful.

Herpes simplex is particularly devastating when it occurs in immunocompromised patients and, unfortunately, coinfection is common. People infected with herpes have a three-fold increased risk for contracting HIV. Furthermore, studies have reported that 68 - 81% of patients with HIV are also infected with herpes simplex virus 2 (HSV-2).

Patients with HIV are particularly vulnerable to complications. When a person has both viruses, there appears to be a synergy between them, with each virus increasing the severity of the other. HSV-2 infection increases HIV levels in the genital tract, which makes it easier for the HIV virus to be transmitted to sexual partners. In addition, episodes of herpes recurrence increase, at least temporarily, HIV viral load. An important 2007 study in the New England Journal of Medicine indicated that treatment of HSV-2 with valacyclovir can help reduce plasma and genital levels of HIV in women who are infected with both viruses. Researchers are continuing to investigate whether treatment of HSV-2 may help reduce the risk of HIV transmission.

Herpes simplex in any patient with a seriously compromised immune system can cause serious and even life-threatening complications, including:

Pneumonia
Inflammation of the esophagus
Encephalitis (inflammation of the brain)
Destruction of the adrenal glands
Disseminated herpes (spread of infection throughout the body)
Liver damage, including hepatitis

Hepatitis caused by primary or recurrent herpes can sometimes develop into a life-threatening condition called fulminant liver failure. This condition is treatable with medications, or even a liver transplant, when diagnosed promptly. Early symptoms may include nausea, vomiting, and abdominal pain. (This is an uncommon complication in HSV-infected people with healthy immune systems, but cases have been reported, such as after surgical procedures.)

Less serious conditions include stomach and anal ulcers, inflammation in the colon, and eczema herpeticum.

Several conditions have been linked to herpes infections, although the association has not been substantiated in most cases.

Arthritis, usually in a single joint, has been sporadically reported as a result of herpes infection.
People with herpes simplex virus 2 (HSV-2) may be more likely to get sexually transmitted hepatitis C.
Some evidence suggests that herpes simplex virus 1 (HSV-1) may slightly increase the risk for certain cancers of the mouth or throat in people who are already at higher risk because of cigarette smoking or infection with another microorganism called human papillomavirus.
Some studies have reported associations between herpes simplex and heart disease, including lower survival rates. Such infections may produce persistent inflammation in the arteries leading to heart trouble. Research is ongoing.
Other rare complications of herpes simplex include erosion or ulcers in the lining of the esophagus and stomach. Certain kidney and blood diseases have also been reported in conjunction with HSV infection. These are very uncommon, however, particularly in people with healthy immune systems.

Diagnosis

The herpes simplex virus is usually identifiable by its characteristic lesion: A thin-walled blister on an inflamed base of skin. However, other conditions can resemble herpes, and doctors cannot base a herpes diagnosis on visual inspection alone. In addition, some patients who carry the virus may not have visible genital lesions. Laboratory tests are essential for confirming herpes diagnosis. These tests include virologic tests (which examine samples of skin taken from the lesion) and serologic tests (blood tests that detect antibodies).

In its 2006 guidelines for sexually transmitted diseases, the U.S. Centers for Disease Control (CDC) recommends that both virologic and serologic tests be used for diagnosing genital herpes. Patients diagnosed with genital herpes should also be tested for other sexually transmitted diseases.

According to the CDC, up to 50% of first-episode cases of genital herpes are now caused by herpes simplex virus 1 (HSV-1). However, recurrences of genital herpes, and viral shedding without overt symptoms, are much less frequent with HSV-1 infection than herpes simplex virus 2 (HSV-2). It is important for doctors to determine whether the genital herpes infection is caused by HSV-1 or HSV-2, as the type of herpes infection influences prognosis and treatment recommendations.

Viral culture tests are made by taking a fluid sample, or culture, from the lesions as early as possible, ideally within the first 3 days of appearance. The viruses, if present, will reproduce in this fluid sample but may take 1 - 10 days to do so. If infection is severe, testing technology can shorten this period to 24 hours, but speeding up the timeframe during this test may make the results even less accurate. Viral cultures are very accurate if lesions are still in the clear blister stage, but they do not work as well for older ulcerated sores, recurrent lesions, or latency. At these stages the virus may not be active enough to reproduce sufficiently to produce a visible culture.

Polymerase chain reaction (PCR) tests are much more accurate than viral cultures, and the CDC recommends this test for detecting herpes in spinal fluid when diagnosing herpes encephalitis (see below). PCR can make many copies of the virus’ DNA so that even small amounts of DNA in the sample can be detected. PCR is much more expensive than viral cultures and is not FDA-approved for testing genital specimens. However, because PCR is highly accurate, many labs have used it for herpes testing.

An older type of virologic testing, the Tzanck smear test, uses scrapings from herpes lesions. The scrapings are stained and microscopically examined for the virus. Findings of specific giant cells with many nuclei or distinctive particles that carry the virus (called inclusion bodies) indicate herpes infection. The test is quick but accurate 50 - 70% of the time. It cannot distinguish between virus types or between herpes simplex and herpes zoster. The Tzanck test is not reliable for providing a conclusive diagnosis of herpes infection and is not recommended by the CDC.

Serologic (blood) tests can identify antibodies that are specific to the virus and its type, herpes virus simplex 1 (HSV-1) or herpes virus simplex 2 (HSV-2). When the herpes virus infects someone, their body’s immune system produces specific antibodies to fight off the infection. If a blood test detects antibodies to herpes, it’s evidence that you have been infected with the virus, even if the virus is in a non-active (dormant) state. The presence of antibodies to herpes also indicates that you are a carrier of the virus and might transmit it to others.

Newer “type-specific” assays test for antibodies to two different proteins that are associated with the herpes virus:

Glycoprotein gG-1 is associated with HSV-1
Glycoprotein gG-2 is associated with HSV-2

Although glycoprotein (gG) type-specific tests have been available since 1999, many of the older nontype-specific tests are still on the market. The CDC recommends only type-specific glycoprotein (gG) tests for herpes diagnosis.

Serologic tests are most accurate when administered 12 - 16 weeks after exposure to the virus. Recommended tests include:

HerpeSelect. This includes two tests: ELISA (enzyme-linked immunosorbent assay) or Immunoblot. They are both highly accurate in detecting both types of herpes simplex virus. Samples need to be sent to a lab, so results take longer than the in-office Biokit test.
Biokit HSV-2 (also marketed as SureVue HSV-2). This test detects HSV-2 only. Its major advantages are that it requires only a finger prick and results are provided in less than 10 minutes. It is very accurate, although slightly less so than the other tests. It is also less expensive.
Western Blot Test. This is the gold standard for researchers with accuracy rates of 99%. It is costly and time consuming, however, and is not as widely available as the other tests.

False-negative (testing negative when herpes infection is actually present) results can occur if tests are done in the early stages of infection. False-positive results (testing positive when herpes infection is not actually present) can also occur, although more rarely than false-negative. Your doctor may recommend that you have the test repeated.

Experts recommend serologic herpes tests especially for:

People who have had recurrent genital symptoms but no negative herpes viral cultures
Confirming infection in people who have visible symptoms of genital herpes
Determining if the partner of someone diagnosed with genital herpes has acquired herpes
People who have multiple sex partners and who need to be tested for different types of STDs

At this time, doctors do not recommend screening for HSV-1 or HSV-2 in the general population.

It make take a number of test to diagnose herpes encephalitis.

Imaging Tests. Electroencephalography traces brain waves and can identify about 80% of cases. Computed tomography or magnetic resonance imaging scans may be used to differentiate encephalitis from other conditions.

Brain Biopsy. Brain biopsy is the most reliable method of diagnosing herpes encephalitis, but it is also the most invasive and is generally performed only if the diagnosis is uncertain.

Polymerase Chain Reaction (PCR). The polymerase chain reaction (PCR) assay looks for tiny pieces of the DNA of the virus, and then replicates them millions of times until the virus is detectable. This test can identify specific strains of the virus and asymptomatic viral shedding. PCR identifies HSV in cerebrospinal fluid and gives a rapid diagnosis of herpes encephalitis in most cases, eliminating the need for biopsies. The CDC recommends PCR for diagnosing herpes central nervous system infections.

Similar Conditions

Canker Sores (Aphthous Ulcers). Common canker sores (known medically as aphthous ulcers) are often confused with the cold sores of herpes simplex virus 1 (HSV-1). Canker sores frequently crop up singly or in groups on the inside of the mouth or on or under the tongue. They are usually white or grayish crater-like ulcers with a sharp edge and a red rim. They usually heal in 2 weeks without treatment.

Canker sores (Aphthous ulcers) are very common. Typically, they are a shallow ulcer with a white or whitish/yellow base surrounded by a reddish border. This ulcer is seen in an individual with AIDS and is located in front and just below the bottom teeth.

Thrush (Candidiasis). Candidiasis is a yeast infection that causes a whitish overgrowth in the mouth. It is most common in infants but can appear in people of all ages, particularly those with impaired immune systems.

Click the icon to see an image of thrush.

Other conditions that may be confused with oral herpes include herpangina (a form of the Coxsackie A virus), sore throat caused by strep or other bacteria, and infectious mononucleosis.

Conditions that may be confused with herpes simplex virus 2 (HSV-2) include bacterial and yeast infections, genital warts, herpes zoster (shingles), molluscum (a virus disease which produces small rounded swellings), scabies, syphilis, and certain cancers.

In a few cases, HSV-2 may occur without lesions and resemble cystitis and urinary tract infections.

Simple corneal scratches can cause the same pain as herpetic infection, but these usually resolve within 24 hours and don't exhibit the corneal lesions characteristic of herpes simplex.

Skin disorders that may mimic herpes simplex include shingles and chicken pox (both caused by varicella-zoster, another herpes virus), impetigo, and Stevens-Johnson syndrome, a serious inflammatory disease usually caused by a drug allergy.

Click the icon to see an image of the shingles.

Click the icon to see an image of chickenpox.

Home Remedies and Prevention

Patients can manage most herpes simplex infections that develop on the skin at home with over-the-counter painkillers and measures to relieve symptoms.

Several simple steps can produce some relief:

Hygiene is important. Avoid touching the sores. Wash hands frequently during the day. Fingernails should be scrubbed daily. Keep the body clean.
Drink plenty of water.
Keep blisters or sores clean and dry with cornstarch or similar product. (Women should not use talcum powder because it may increase their risk for ovarian cancer.)
Some people report that drying the genital area with a blow dryer on the cool setting offers relief.
Avoid tight-fitting clothing, which restricts air circulation and slows healing of the sores.
Choose cotton underwear, rather than synthetic materials.
Local application of ice packs may alleviate the pain and help reduce recurrences by suppressing the virus.
Lukewarm baths may be helpful. (For people who have pain on urination, some experts recommend urinating in the bath water at the end of the bathing time. This dilutes the urine and prevents burning the sores. Urinating in a cool shower is also helpful and is less offensive to many people. )
Wearing sun block helps prevent sun-triggered recurrence of herpes simplex virus 1 (HSV-1).
Avoid sex during both outbreaks and prodromes (the early symptoms of herpes), which include tingling, itching, or tenderness in the infected areas.
Over-the-counter medications such as aspirin, acetaminophen (Datril, Panadol, Tylenol), or ibuprofen (Advil, Medipren, Motrin, Nuprin), can be used to reduce fever and local tenderness. Children should take acetaminophen. Never give children aspirin.

In one study, stress management techniques developed using cognitive-behavioral methods not only were effective in reducing depression in those with hepres simplex virus 2 (HSV-2) but blood test results also revealed lower levels of HSV-2 antibodies, a possible sign of decreased viral activity. In any case, reducing stress using relaxation techniques does no harm.

Many herbal and dietary supplement products claim to help fight herpes infection by boosting the immune system. There has been little research on these products, and little evidence to show that they really work. Some are capsules taken by mouth. Others come in the form of ointment that is applied to the skin. Popular herbal and supplement remedies for herpes simplex include:

Echinacea (Echinacea purpurea )
Siberian ginseng (Eleutherococcus senticosus )
Aloe (Aloe vera )
Bee products that contain propolis, a tree resin collected by bees
Lysine
Zinc

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

The following are special concerns for people taking natural remedies for herpes simplex:

Echinacea can lower white blood cell levels when taken for long periods of time. This herb can also interfere with drugs that are used to treat immune system disorders.
Siberian ginseng can raise blood pressure levels.
Bee products (like propolis) can cause allergic reactions in people who are allergic to bee stings.
Do not take Lysine with certain types of antibiotics.
'Taking zinc in large amounts (more than 200 mg/day) can cause stomach upset.

Infected people should take several steps to avoid transmitting the virus to others. It is almost impossible to defend against the transmission of oral herpes simplex virus 1 (HSV-1) since it can be transmitted by very casual contact.

Preventing Transmission During an Outbreak. When an outbreak of herpes occurs, the following precautions are useful:

Persons carrying any herpes virus should carefully wash their hands and nails after contact with the infected area so as not to transmit the virus to other sites on the body.
Although transmission from objects such as toilet seats and towels is unlikely, keeping personal items separate during an active infection may help to reduce transmission to other household members. The virus can live for up to 2 hours on cloth and for 4 hours on plastic.
If genital lesions are present, infected persons should abstain from sexual intercourse.

Preventing Sexually Transmitted Disease. Any infected man or a partner of an infected woman should wear a condom during any sexual activity, even when symptoms are not present. Condoms are also important during oral sex, as an increasing number of new genital herpes cases are due to HSV-1, particularly among younger people.

The use of condoms for preventing the transmission of herpes simplex virus 2 (HSV-2) is not foolproof. Even a small tear can permit passage of the virus. However, studies show that regular condom use can significantly reduce the risk of HSV-2 infection.

Condoms made of latex are less likely to slip or break than those made of polyurethane. “Natural” condoms made from animal skin do not protect against HSV infection because herpes viruses can pass through them.

Women appear to be better protected than men are by male condoms. The reason may be that men shed HSV-2 from the skin of the penis, which is covered by the condom. However, in women the virus is often shed from skin areas around the genital area, which can have contact to skin areas in the male outside the condom.

The female condom is another option for infected women or partners of infected men. The female condom covers a large area and is an effective barrier to sexually transmitted viruses.

Note on Lubricants and Spermicides. Only water-based lubricants (K-Y Jelly, Astroglide, AquaLube, glycerin) should be used. Oil-based lubricants (petroleum jelly, body lotions, cooking oil) can weaken latex.

Some condoms come prelubricated with sperm-killing substances called spermicides, which are no longer recommended. The standard active ingredient in spermicides is nonoxynol-9, which attacks the surface of the sperm cell. Nonoxynol-9 does not provide any additional protection against sexually transmitted diseases (STDs). It can cause yeast and urinary tract infections in women. In addition, it can cause irritation around the genital areas, which makes it easier for herpes and other STDs to be transmitted. In fact, research indicates that it actually increases the risk for HIV in women.

Treatment for Genital Herpes

No drug can cure herpes simplex virus. The infection may recur after treatment has been stopped, and, even during therapy, a patient can still transmit the virus to another person. Drugs can, however, reduce symptoms and improve healing times.

Antiviral drugs called nucleosides or nucleotide analogues are the main drugs used to treat genital herpes. They are taken by mouth. (Acyclovir is also available as an ointment, but the oral form is much more effective.) These drugs limit herpes viral replication and its spread to other cells. They are not cures, however.

Three drugs are approved to treat genital herpes:

Acyclovir (Zovirax or generic)
Valacyclovir (Valtrex)
Famiciclovir (Famvir)

When a patient has herpes for the first time, the drug is taken several times a day for 7 -10 days. Then the drugs are used either to suppress the virus or to treat outbreaks.

To treat outbreaks, regimens depend on the medication and dosage prescribed:

Acyclovir: 400 mg three times a day for 2 days or 800 mg twice a day for 5 days
Valacyclovir: 500 mg twice a day for 3 days or 1 g once a day for 5 days
Famiciclovir: 125 mg twice a day for 5 days or 1000 mg twice a day for 1 day. (In 2006, famiclovir was approved as the first one-day treatment for recurrent genital herpes.)

To suppress outbreaks, treatment requires taking pills daily on a long-term basis. (Acyclovir and famiciclovir are taken twice a day, valacyclovir once a day.) Suppressive treatment can reduce outbreaks by 70 – 80%. It is generally recommended for patients who have frequent recurrences (6 or more outbreaks per year). Valacyclovir may work especially well for preventing herpes transmission among heterosexual patients when one partner has herpes simplex virus 2 (HSV-2) and the other partner does not. However, valacyclovir may not be as effective as acyclovir or famiciclovir for patients who have very frequent recurrences of herpes (more than 10 outbreaks per year).

Because the frequency of herpes recurrences often diminishes over time, patients should discuss annually with their doctors whether they should stay with drug therapy or discontinue it. Studies suggest that daily drug therapy is safe and effective for up to 6 years with acyclovir, and up to 1 year with valacyclovir or famciclovir.

Side Effects. Nausea and headache are the most common side effects, but in general these drugs are safe. Although there is some evidence these drugs may reduce shedding, they probably do not prevent it entirely. The use of condoms during asymptomatic periods is still essential, even when patients are taking these medications.

Risk for Resistant Viruses. As with antibiotics, doctors are concerned about signs of increasing viral resistance to acyclovir and similar drugs, particularly in immunocompromised patients (such as those with AIDS). Some experts believe, however, that the prevalence of drug-resistant viruses will be low for many years. They feel that widespread use of antiviral drugs will prevent many cases of herpes from developing and will slow the spread of the disease. Even patients on long-term suppressive drug therapy show few signs of drug resistance. However, patients who do not respond to standard regimens should be monitored for emergence of drug resistance.

Some doctors believe that developing an effective herpes vaccine is the only practical way to control the disease and the spread of infection. Furthermore, if such a vaccine becomes available, then universal immunization may be the best approach. Vaccines also hold the potential for eliminating latent, lifelong infections.

In 2002, the National Institute of Allergy and Infectious Diseases (NIAID) launched the Herpevac Trial for Women. The NIAID seeks to enroll 7,500 women between the ages of 18 and 30 who test negative for both herpes simplex virus 1 (HSV-1) and herpes simplex virus 2 (HSV-2) infection. The trial is being conducted at more than 40 sites in the United States and Canada. Participants are randomly assigned to receive either three doses of the experimental herpes vaccine or an investigational hepatitis A vaccine. The women will be observed for 20 months following the initial vaccination to determine if they contract genital herpes (or, for the control group, hepatitis A) during this time. The vaccine used in the trial does not contain live virus and will not itself cause infection.

The premise for the Herpevac trial is based on results from two studies published in the New England Journal of Medicine in 2002. In these studies, a glycoprotein D vaccine was effective in preventing genital herpes in women who were not infected with HSV-1 or HSV-2. For uninfected women, the risk of contracting genital herpes was reduced by nearly 75 percent. The vaccine was not useful, however, for women already infected with HSV-1 and was ineffective in men regardless of their virus status.

Treatment for Oral Herpes

Acyclovir (Zovirax), valacyclovir (Valtrex), and famciclovir (Famvir) -- the anti-viral pills used to treat genital herpes -- can also treat the cold sores associated with oral herpes. In addition, acyclovir is available in topical form, as is penciclovir (a related drug).

These ointments or creams help shorten healing time and duration of symptoms. However, none are truly effective in eliminating outbreaks.

Penciclovir (Denavir) heals herpes simplex virus 1 (HSV-1) sores on average about half a day faster than without treatment, stops viral shedding, and reduces the duration of pain. Ideally, the patient should apply the cream within the first hour of symptoms, although benefits have also been noted with later application. It is continued for 4 consecutive days, and should be reapplied every 2 hours while awake.
Acyclovir cream (Zovirax) works best when applied early on (at the first sign of pain or tingling).
Docosanol cream (Abreva) is the only FDA-approved non-prescription ointment for oral herpes. The patient applies the cream five times a day, beginning at the first sign of tingling or pain. Studies have been mixed on the cream’s benefits.
Over-the-counter topical anesthetics may provide modest relief. They include Anbesol gel, Blistex lip ointment, Campho-phenique, Herpecin-L, Viractin, and Zilactin.

Resources

www.ashastd.org -- American Social Health Association
www.niaid.nih.gov -- National Institute of Allergy and Infectious Diseases
www.cdc.gov/std/herpes -- Centers for Disease Control and Prevention
www.herpesdiagnosis.com -- Herpes Diagnosis
www.herpesalliance.org -- International Herpes Alliance
www.gotherpes.com -- Herpes support site
www.niaid.nih.gov/dmid/stds/herpevac -- Herpevac (herpes vaccine) clinical trial information

References

Centers for Disease Control and Prevention, Workowski KA, Berman SM. Sexually transmitted diseases treatment guidelines, 2006. MMWR Recomm Rep. 2006 Aug 4;55(RR-11):1-94.

Lebrun-Vignes B, Bouzamondo A, Dupuy A, Guillaume JC, Lechat P, Chosidow O. A meta-analysis to assess the efficacy of oral antiviral treatment to preventgenital herpes outbreaks. J Am Acad Dermatol. 2007 Aug;57(2):238-46. Epub 2007 Apr 9.

Nagot N, Ouedraogo A, Foulongne V, Konate I, Weiss HA, Vergne L, et al. Reduction of HIV-1 RNA levels with therapy to suppress herpes simplex virus. N Engl J Med. 2007 Feb 22;356(:790-9.

Review Date:
9/9/2007
Reviewed By:
Harvey Simon, MD, Editor-in-Chief, Associate Professor of Medicine, Harvard Medical School; Physician, Massachusetts General Hospital.

A.D.A.M. Copyright

adam.com

CaringBridge: Social Networking For Sick Loved Ones

FitSugar — Tue, 31 Mar 2009 03:30:00 -0700

If you've ever had a family member in the hospital, you know that keeping everyone informed about the patient's progress can be as exhausting as the nights spent in the waiting room. We rely on everything from phone trees to mass emails to get updates or find out where to send flowers, but I just discovered a website called CaringBridge that makes this very difficult task easier.

Sort of like Facebook for tough times, the free service lets you easily create a website to share updates on a loved one's illness, surgery, hospital stay, and progress. When a friend of mine was recently hospitalized, her family set up a page on CaringBridge, and I've been really impressed by how extensive it is. To find out how it works, read more.

CaringBridge lets you post explanations about a patient's illness, plus photos and updates on test results or overall mood. Friends and family can sign up for email notifications when new info is posted and leave their thoughts and messages on the guestbook page. The site even lets you make a donation along with a tribute to the patient in question. It seems like a great solution in what can be a very challenging time. Have you ever used one of these sites? Tell me what you thought.

Scoliosis

FitSugar — Wed, 08 Oct 2008 17:35:13 -0700

In This Report

Highlights
Introduction
Causes
Risk Factors
Prognosis
Symptoms
Diagnosis
Treatment
Managing Scoliosis
Braces
Surgery
Treatment for Adult Scolios...
Resources
References

HEALTH GUIDE REFERENCE FROM A.D.A.M

Highlights

Diagnosing Scoliosis

Scoliosis is diagnosed typically in children 10 - 15 years of age. However, only about 1% of cases actually require treatment. There is a large female preponderance for larger curves that do require treatment.

Defining Scoliosis

Nonstructural scoliosis is a simple side-to-side curve of the spine. Structural scoliosis adds to that simple curve a rotation of the vertebrae, resulting in a twisting of the spine.

Causes

In about 80% of scoliosis cases, the cause is unknown (idiopathic scoliosis). Research has not been able to identify any genetic abnormality that would make a person susceptible to developing scoliosis.

Treatment with Bracing

Bracing has long been the standard treatment to prevent progression of the curvature of scoliosis. However, patient compliance has been a problem, especially for younger patients. Newer braces are now more comfortable and can be worn discretely under the clothing, thus improving patient compliance and treatment results.

Introduction

Scoliosis is the abnormal curvature of the spine. While the normal spine has gentle natural curves that round the shoulders and make the lower back curve inward, scoliosis typically involves a three-dimensional deformity of the spinal column and rib cage. To varying degrees, the spine curves from side-to-side, and some of the spinal bones may rotate slightly, making the hips or shoulders appear uneven. It may develop in the following way:

As a single primary side-to-side curve (resembling the letter C), or
As two curves (a primary curve along with a compensating secondary curve that forms an S shape).

Scoliosis most commonly develops in the area between the upper back (the thoracic area) and lower back (lumbar area). It may also occur only in the upper or lower back. The doctor attempts to define scoliosis by the following characteristics:

The shape of the curve
Its location
Its direction
Its magnitude
Its causes, if possible

Click the icon to see an image of scoliosis.

The severity of scoliosis is determined by the extent of the spinal curvature and the angle of the trunk rotation (ATR) and is usually measured in degrees. Curves of less than 20 degrees are considered mild and account for 80% of scoliosis cases. Curves that progress beyond 20% require medical attention. Such attention, however, usually involves periodic monitoring to make sure the condition is not becoming worse.

Scoliosis affects about 2 - 3% of the population (about 6 million people in the United States). It can occur in adults but is more commonly diagnosed for the first time in children aged 10 - 15 years. About 10% of the adolescent population has some degree of scoliosis, but less than 1% develops scoliosis that requires treatment. The condition also tends to run in families. Among persons with relatives that have scoliosis, about 20% develop the condition.

Among adults, previous reports have indicated a prevalence of scoliosis of up to 32%. But a recent study of 75 healthy adults aged 60 years and older with no known history of scoliosis or prior spine surgery suggested a rate of 68%. However, scoliosis was not linked to physical or social impairment in this population.

Scoliosis is often categorized by the shape of the curve, usually as either structural or nonstructural.

Structural scoliosis. In addition to the spine curving from side to side, the vertebrae rotate, twisting the spine. As it twists, one side of the rib cage is pushed outward so that the spaces between the ribs widen and the shoulder blade protrudes (producing the rib-cage deformity, or hump). The other half of the rib cage is twisted inward, compressing the ribs.
Nonstructural scoliosis. The curve does not twist but is a simple side-to-side curve.

Other abnormalities of the spine that may occur alone or in combination with scoliosis include hyperkyphosis (an abnormal exaggeration in the backward rounding of the upper spine) and hyperlordosis (an exaggerated forward curving of the lower spine, also called swayback).

Click the icon to see an image of kyphosis.

The location of a structural curve is defined by the location of the apical vertebra. This is bone at the highest point (the apex) in the spinal hump. This particular vertebra also undergoes the most severe rotation during the disease process.

The direction of the curve in structural scoliosis is determined by whether the convex (rounded) side of the curve bends to the right or left. For example, a doctor will diagnose a patient as having right thoracic scoliosis if the apical vertebra is in the thoracic (upper back) region of the spine, and the curve bends to the right.

The magnitude of the curve is determined by taking measurements of the length and angle of the curve on an x-ray view.

Vertebrae. The spine is a column of small bones, or vertebrae, that support the entire upper body. The column is grouped into three sections of vertebrae:

Cervical (C) vertebrae are the 7 spinal bones that support the neck.
Thoracic (T) vertebrae are the 12 spinal bones that connect to the rib cage.
Lumbar (L) vertebrae are the 5 lowest and largest bones of the spinal column. Most of the body's weight and stress falls on the lumbar vertebrae.

Each vertebra can be designated by using a letter and number; the letter reflects the region (C=cervical, T=thoracic, and L=lumbar), and the number signifies its location within that region. For example, C4 is the fourth bone down in the cervical region, and T8 is the eighth thoracic vertebra.

Below the lumbar region is the sacrum, a shield-shaped bony structure that connects with the pelvis at the sacroiliac joints. At the end of the sacrum are 2 - 4 tiny, partially fused vertebrae known as the coccyx or "tail bone."

The Spinal Column and its Curves. Altogether, the vertebrae form the spinal column. In the upper trunk the column normally has a gentle outward curve (kyphosis) while the lower back has a reverse inward curve (lordosis).

The Disks. Vertebrae in the spinal column are separated from each other by small cushions of cartilage known as intervertebral disks. Inside each disk is a jelly-like substance called the nucleus pulposus, which is surrounded by a tough, fibrous ring called the annulus fibrosis. The disk is 80% water. This structure makes the disk both elastic and strong. The disks have no blood supply of their own, relying instead on nearby blood vessels to keep them nourished.

Processes. Each vertebra in the spine has a number of bony projections, known as processes. The spinal and transverse processes attach to the muscles in the back and act like little levers, allowing the spine to twist or bend. The particular processes form the joints between the vertebrae themselves, meeting together and interlocking at the zygapophysial joints (more commonly known as facet or z joints).

Spinal Canal. Each vertebra and its processes surround and protect an arch-shaped central opening. These arches, aligned to run down the spine, form the spinal canal, which encloses the spinal cord, the central trunk of nerves that connects the brain with the rest of the body.

Click the icon to see an image of the spine.

Click the icon to see an image of the sacrum.

Click the icon to see an image of the curves of the spine.

Click the icon to see an image of an intervertebral disk.

Click the icon to see an image of the spinal canal.

Causes

In 80% of patients, the cause of scoliosis is unknown. Such cases are called idiopathic scoliosis. (Idiopathic means without a known cause.) Idiopathic scoliosis may be due to multiple, poorly understood inherited factors, most likely from the mother's side. However, the severity often varies widely among family members who have the condition, suggesting that other factors must be present.

Researchers have not been able to identify the specific genetic abnormalities that make a young person susceptible to spinal distortion. Inherited physical abnormalities, problems in coordination, abnormalities in the central nervous system, and other inherited factors may play some role either alone or in combination with other conditions to produce scoliosis.

Physical Abnormalities. Researchers are investigating possible physical abnormalities that may cause imbalances in bones or muscles that would lead to scoliosis. Among them are the following:

Imbalances in Muscles around the Vertebrae. Some research suggests that imbalances in the muscles around the vertebrae may make children susceptible to spinal distortions as they grow.
High Arches. One study showed a higher incidence of abnormally high arches in the feet in people with idiopathic scoliosis, suggesting that altered balance may be a factor in certain cases.

Problems in Coordination. Some experts are looking at inherited defects in perception or coordination that may cause asymmetrical growth in the spine of some children with scoliosis.

Genetic Abnormalities in the Central Nervous System. Genetic defects that cause altered processing in the brain may play a role in producing abnormalities in the growing spine. For example, research has implicated low levels of melatonin, a hormone secreted in the pineal gland in brain. Melatonin is involved with sleep and growth. Researchers speculate that genetic factors that cause reduced blood levels of melatonin may adversely affect muscle tone and development during sleep, perhaps contributing to scoliosis.

Other Biologic Factors. Several other biologic factors are being investigated for some contribution to scoliosis:

Abnormalities in collagen, the critical structural protein found in muscles and bones. Enzymes known as matrix metalloproteinases are involved in the repair and remodeling of collagen. Researchers have found high levels of the enzymes in the disks of patients with scoliosis, which suggests that the enzymes may contribute to curve progression. Elevated levels of the enzymes can cause abnormalities in components in the spinal disks, contributing to disk degeneration.
A possible defective gene responsible for production of fibrillin, an important component of connective tissue, which makes up bones and muscles.
Abnormalities in a protein called platelet calmodulin that binds to calcium. This protein acts like a tiny muscle and pulls clots together. Measuring levels of this protein may eventually help predict whether scoliosis will worsen.

Congenital scoliosis is caused by inborn spinal deformities that may result in the development of absent or fused vertebrae. Kidney problems, particularly having only one kidney, often coincide with congenital scoliosis. The condition usually becomes evident at either age 2 or between ages 8 and 13 as the spine begins to grow more quickly, putting additional stress on the abnormal vertebrae. It is essential to diagnose and monitor such curvatures as early as possible, since they can progress quickly. Early surgical treatment -- before age 5 -- may be important in many of these patients to prevent serious complications.

Adult scoliosis has two primary causes:

Progression of childhood scoliosis.
Degenerative lumbar scoliosis. Degenerative lumbar scoliosis is a condition that typically develops after age 50. With this condition, the lower spine is affected, usually due to disk degeneration. Osteoporosis, a serious problem in many older adults, is not a risk factor for new-onset scoliosis, but it can be a contributing factor. In most cases, however, it is not known why scoliosis occurs in adults.

Scoliosis may be a result of various conditions that affect bones and muscles associated with the spinal column. They include the following:

Muscle paralysis.
Muscle deterioration from diseases such as muscular dystrophy, polio, or cerebral palsy.
Injury to the spinal cord.
Tumors, growths, or other small abnormalities on the spinal column. For example, syringomyelia, a disorder in which cysts form along the spine, can cause scoliosis. These spinal abnormalities may play a larger role in causing some cases of scoliosis than previously thought.
Familial dysautonomia, a rare disorder in Jewish children of Ashkenazi descent. (Only about 500 cases have been reported.)
Stress fractures and hormonal abnormalities that affect bone growth in young, competitive athletes.
Birth defects, including spina bifida (an open spinal cord) and myelomeningocele (a hernia of the central nervous system).
Turner syndrome, a genetic disease in females that affects physical and reproductive development.
Other diseases that can cause scoliosis are Marfan syndrome, Aicardi syndrome, Friedreich ataxia, Albers-Schonberg disease, rheumatoid arthritis, Cushing syndrome, and osteogenesis imperfecta.

Spina bifida is a congenital disorder (birth defect) in which the backbone and spinal canal do not close before birth. In severe cases, this can result in the spinal cord and its covering membranes protruding out of an affected infant's back. Spina bifida may also be nearly inconsequential, or may be repairable through surgery.

Nonstructural scoliosis is usually not a serious problem, since the curve is side to side. It can develop from a number of physical problems, including the following:

Unequal leg length. Injury, a shortened Achilles tendon, or other structural in-born problems can cause this very common condition. Unequal leg length rarely causes any problems and in most cases requires no treatment other than a lift in one of the shoes to equalize the length.
Muscle spasms.

Risk Factors

Risk Factors for Initial Scoliosis. Idiopathic scoliosis, the most common form, occurs most often during the growth spurt right before and during adolescence. (Between 12 - 21% of idiopathic cases occur in children ages 3 - 10 years, and less than 1% in infants.) Mild curvature (under 20 degrees) occurs about equally in girls and boys, but curve progression is 10 times more likely to occur in girls. Being taller than average at earlier ages may put some girls at risk, but other factors must be present to produce scoliosis. A risk factor that affects females is a delayed onset of menstruation, which can prolong the growth spurt period, thus increasing the possibility for the development of scoliosis.

Risk Factors for Curvature Progression. Once scoliosis is diagnosed, it is very difficult to predict who is at highest risk for curve progression. About 2 - 4% of all adolescents develop curvature of 10 degrees or more, but only about 0.3 - 0.5% of teenagers have curves greater than 20 degrees, which requires some medical attention.

People with certain medical conditions that affect the joints and muscles are at higher risk for scoliosis. These conditions include rheumatoid arthritis, muscular dystrophy, polio, and cerebral palsy. Children who receive organ transplants (kidney, liver, heart) are also at increased risk.

In one study, idiopathic scoliosis occurred in about 5% of close family members of children with the condition.

Scoliosis may be evident in young athletes, with a prevalence of 2 - 24%. The highest rates are observed among dancers, gymnasts, and swimmers. The scoliosis may have been due in part to loosening of the joints, delay in puberty onset (which can lead to weakened bones), and stresses on the growing spine. There have also been other isolated reports of a higher risk for scoliosis in young athletes who engage vigorously in sports that put an uneven load on the spine. These include figure skating, dance, tennis, skiing, and javelin throwing, among other sports. In most cases, the scoliosis is minor, and everyday sports do not lead to scoliosis. Exercise has many benefits for people both young and old and may even help patients with scoliosis.

Prognosis

In general, the severity of the scoliosis depends on the degree of the curvature and whether it threatens vital organs, specifically the lungs and heart.

Mild Scoliosis (less than 20 degrees). Mild scoliosis is not serious and requires no treatment other than monitoring.
Moderate Scoliosis (between 25 and 70 degrees). It is still not clear whether untreated moderate scoliosis causes significant health problems later on. Some studies have found no difference in either back pain or survival rates in adult untreated patients versus the general population. In one study, adults with moderate scoliosis had normal lung function, although they had difficulty exercising. (This low exercise tolerance might have been because many patients with scoliosis do not engage in regular physical activity.)
Severe Scoliosis (over 70 degrees). If the curvature exceeds 70 degrees, the severe twisting of the spine that occurs in structural scoliosis can cause the ribs to press against the lungs, restrict breathing, and reduce oxygen levels. The distortions may also affect the heart and possibly cause dangerous changes.
Very Severe Scoliosis (Over 100 degrees). Eventually, if the curve reaches over 100 degrees, both the lungs and heart can be injured. Patients with this degree of severity are susceptible to lung infections and pneumonia. Curves greater than 100 degrees increase mortality rates, but this problem is very uncommon in America.

Some experts argue that simply measuring the degree of the curve may not identify patients in the moderate and severe groups who are at greatest risk for lung problems. Other factors (spinal flexibility, the extent of asymmetry between the ribs and the vertebrae) may be more important in predicting severity in this group.

Scoliosis is associated with osteopenia, a condition characterized by loss of bone mass. About 27 - 38% of adolescent girls who have scoliosis also have osteopenia. Some experts recommend measuring bone mineral density when a patient is diagnosed with scoliosis. The amount of bone loss may help predict how severely the spine will curve. Preventing and treating osteopenia may help limit further curve progression.

If not treated, osteopenia can later develop into osteoporosis. Osteoporosis is a more serious loss of bone density that is common among postmenopausal women. Adolescents who have scoliosis are at increased risk of developing osteoporosis later in life. [See In-Depth Report#18: Osteoporosis.]

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

After 20 years or more, scoliosis patients who were previously treated with surgery experience small but significant physical impairment, (mainly mild back problems), compared to their peers without scoliosis. In one study, 65% of patients reported some low back pain compared to 47% of people without a history of scoliosis. In general it was mild, although 45% of patients reported having to take days off from work compared to 19% of nonscolosis patients. In another study, only 1.5% of the scoliosis group had severe debilitating back pain. In general, the quality of life was similar, however. Pain also did not play a major role in social limitations.

The following are some possible causes of later back problems in people with a history of treated scoliosis:

Spinal fusion disease. Patients who are surgically treated with fusion techniques lose flexibility and may experience weakness in back muscles due to injuries during surgery.
Disk degeneration and low back pain. With disk degeneration, the disks between the vertebrae may become weakened and rupture. In some patients, years after the original surgeries, particularly with the first generation of the Harrington rods, the weight of the instrumentation can cause disk and joint degeneration severe enough to require surgery. Treatment may involve removal of the old instrumentation and extension of the fusion into the lower back. Still, most patients do not experience significant back pain from these problems.
Height loss.
Scarred regions. Pain can occur from old scars in the incision areas.
Lumbar flatback. This condition is most often the result of a scoliosis surgical procedure called the Harrington technique, which eliminated lordosis (the inward curve in the lower back). Adult patients with flatback syndrome tend to stoop forward. They may experience fatigue and back and even neck pain.
Rotational trunk shift (uneven shoulders and hips).

Evidence suggests that previous treatment with braces may also cause mild back pain and more days off, but problems appear to be less than with surgery. In one study, dysfunction was comparable to people without a history of scoliosis.

Pain in adult-onset or untreated childhood scoliosis often develops because of posture problems that cause uneven stresses on the back, hips, shoulders, necks, and legs. In one study conducted 20 years after growth had stopped, two-thirds of adults who had lived with curvatures of 20 - 55 degrees reported they experienced back pain. Other studies have reported that adults with a history of scoliosis tend to have chronic and more back pain than the general population.

Nearly all individuals with untreated scoliosis at some point develop spondylosis, an arthritic condition in the spine. The joints become inflamed, the cartilage that cushions the disks may thin, and bone spurs may develop. If the disk degenerates or the curvature progresses to the point that the spinal vertebrae begin pressing on the nerves, pain can be very severe and may require surgery. Even surgically treated patients are at risk for spondylosis if inflammation occurs in vertebrae around the fusion site.

Emotional Impact in Childhood. The emotional impact of scoliosis, particularly on young girls or boys during their most vulnerable years, should not be underestimated. Adults who have had scoliosis and its treatments often recall significant social isolation and physical pain. Follow-up studies of children who had scoliosis without having strong family and professional support often report significant behavioral problems. Fortunately, current treatments are solving many of the problems that previous generations had to deal with, including unsightly bracing and extremely painful surgeries with little pain control.

Emotional Effects in Adults. Of some concern are growing numbers of adults with scoliosis. This group experiences considerable problems in general health, social functioning, emotional and mental health, as well as pain.

Older people with a history of treated scoliosis may carry negative emotional events into adulthood that have their roots in their early experiences with scoliosis. Many studies have reported that patients who were treated for scoliosis have limited social activities and a poorer body image in adulthood. Some patients with a history of scoliosis have reported a slight negative effect on their sexual life. Pain appears to be only a minor reason for such limitation.

Women who have been successfully treated for scoliosis have only minor or no additional risks at all for complications during pregnancy and delivery. A history of scoliosis also does not endanger the child. Pregnancy itself, even multiple pregnancies, does not increase the risk for curve progression. Women who have severe scoliosis that restricts the lungs, however, should be monitored closely.

Some evidence suggests a slightly higher risk for breast cancer and leukemia in patients who had multiple x-rays. Risks are highest in patients who had the largest radiation exposure, such as those who had been surgically treated.

Patients who simply received x-ray series for untreated idiopathic scoliosis or scoliosis caused by uneven length legs or hip abnormalities have a very low risk for future complications.

Click the icon to see an image of an x-ray.

Symptoms

Scoliosis is usually painless. The curvature itself may often be too subtle to be noticed, even by observant parents. Some parents may notice abnormal posture in their growing child that includes:

A tilted head that does not line up over the hips
A protruding shoulder blade
One hip or shoulder that is higher than the other, causing an uneven hem or shirt line
An uneven neckline
Leaning more to one side than the other
In developing girls, breasts appearing to be of unequal size
One side of the upper back being higher than the other when the child bends over, knees together, with the arms dangling down

Scoliosis may be suspected when one shoulder appears to be higher than the other, there is a curvature in the spine, or the pelvis appears to be tilted. The treatment of scoliosis can involve the use of a brace or surgery. Treatment is determined by the cause of the scoliosis, the size and location of the curve, and the stage of bone growth of the patient.

With more advanced scoliosis, fatigue may occur after prolonged sitting or standing. Scoliosis caused by muscle spasms or growths on the spine can sometimes cause pain. Nearly always, however, mild scoliosis produces no symptoms, and the condition is usually detected by the pediatrician or during a school screening test.

Diagnosis

The severity of scoliosis and need for treatment is usually determined by two factors:

The extent of the spinal curvature. (Scoliosis is diagnosed when the curve measures 11 degrees or more.)
The angle of the trunk rotation (ATR).

Both are measured in degrees. These two factors are usually related. For example, a person with a spinal curve of 20 degrees will usually have a trunk rotation (ATR) of 5 degrees. These two measurements, in fact, used to be the cutoff for recommending treatment. However, the great majority of 20-degree curves do not get worse. Patients do not usually need medical attention until the curve reaches 30 degrees, and the ATR is 7 degrees.

Adam's Forward Bend Test. The screening test used most often in schools and in the offices of pediatricians and primary care doctors is called the Adam's forward bend test.

The child bends forward dangling the arms, with the feet together and knees straight. The curve of structural scoliosis is more apparent when bending over. In a child with scoliosis, the examiner may observe an imbalanced rib cage, with one side being higher than the other, or other deformities.

The forward bend test is used most often in schools and doctor's offices to screen for scoliosis. During the test, the child bends forward with the feet together and knees straight while dangling the arms. Any imbalances in the rib cage or other deformities along the back could be a sign of scoliosis.

The forward bend test, however, is not sensitive to abnormalities in the lower back, a very common site for scoliosis. Because the test misses about 15% of scoliosis cases, many experts do not recommend it as the sole method for screening for scoliosis.

Other Physical Tests.

The patient walks on the toes, then the heels, and then jumps up and down on one foot. Such activities indicate leg strength and balance.
The doctor will check leg length and look for tight tendons in the back of the leg, which may cause an uneven leg length or other back problems.
The doctor will also check for neurologic impairment by testing reflexes, nerve sensation, and muscle function.

Proper diagnosis is important. A misjudgment can lead to unnecessary x-rays and stressful treatments in children not actually at risk for progression. Unfortunately, although measurements of curves and rotation are useful, no test exists yet to determine whether a curve will progress.

Inclinometer (Scoliometer). An inclinometer, also known as a Scoliometer, measures distortions of the torso. The procedure is as follows:

The patient bends over, arms dangling and palms pressed together, until a curve can be observed in the upper back (thoracic area).
The Scoliometer is placed on the back and measures the apex (the highest point) of the upper back curve.
The patient continues bending until the curve can be seen in the lower back (lumbar area). The apex of this curve is also measured.
Measurements are repeated twice, with the patient returning to a standing position between repetitions.
If results show a deformity, x-rays probably need to be performed to determine the extent.

Some experts believe the Scoliometer would make a useful device for widespread screening. Scoliometers, however, indicate rib cage distortions in more than half of children who turn out to have very minor or no sideways curves. They are therefore not accurate enough to guide treatment.

Currently, x-rays are the most cost-effective method for diagnosing scoliosis. Experts hope that accurate, noninvasive diagnostic techniques will eventually be developed to replace some of the x-rays used to monitor the progression of scoliosis. To date, imaging techniques under investigation appear to be fairly accurate for detecting scoliosis in the upper back (the thoracic region), but not scoliosis in the lower back (the lumbar region).

X-Rays. If screening indicates scoliosis, the child may be sent to a specialist who takes an initial x-ray and monitors the child every few months using repeated x-rays. X-rays are essential for an accurate diagnosis of scoliosis in that they:

Reveal the degree and severity of scoliosis.
Identify any other spinal abnormalities, including kyphosis (hunchback) and hyperlordosis (swayback).
Help the doctor determine whether skeletal growth has reached maturity.
X-rays taken when patients are bending forward can also help differentiate between structural and nonstructural scoliosis. Structural curves persist when a person bends over, and nonstructural curves tend to disappear. (Muscle spasms or spinal growths may sometimes cause nonstructural scoliosis that shows a curve on bending.)
Children and young adolescents who have mild curves and in older adolescents who have more severe curvatures but whose growth has stopped or slowed need x-rays every few months to detect increasing severity. Young people who are diagnosed with scoliosis should keep their x-rays indefinitely in case they develop back problems later in adulthood and need to be re-examined.

Magnetic Resonance Imaging. Magnetic resonance imaging (MRI) is an advanced imaging procedure that does not use radiation, as x-rays do. It is expensive, however, and not generally used for an initial diagnosis. MRI can, nevertheless, identify spinal cord and brain stem abnormalities, which some studies indicate may be more prevalent than previously believed in children with idiopathic scoliosis. It also may be particularly useful before surgery for detecting defects that could lead to potential complications.

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

Because frequent x-rays may be required for young children with scoliosis, parents should be sure that x-ray technicians take all necessary protective measures. Experts are concerned about the long-term effects of radiation on sensitive young organs, particularly about a possible increase in the risk for cancer. Studies have reported an increased risk for cancer in women and men who, because of scoliosis, had been exposed to diagnostic x-rays in their childhood and adolescence.

X-ray techniques have become safer in recent years, and technicians can reduce the hazards with the following simple measures:

Directing x-ray beams through the patient from back to front, rather than the reverse.
Using x-ray filters that absorb some of the beam.
Using fast film to reduce exposure by two to six times.
Placing lead aprons or shields over parts of the body that are not being x-rayed.

There are various methods for determining and classifying the extent of the curve.

Cobb Method. The technique known as the Cobb method nearly always calculates the degree of the curve.

On an x-ray of the spine, the examiner draws two lines: One line extends out and up from the edge of the top vertebrae of the curve. The second line extends out and down from the bottom vertebrae.
The technician then draws a perpendicular line between the two lines.
Measuring the intersecting angle determines the degree of curvature.

The Cobb method is limited because it cannot fully determine the flexibility or the three-dimensional aspect of the spine. It is not as effective, then, in defining spinal rotation or kyphosis. It also tends to over-estimate the curve. Other diagnostic tools are needed then to make a more accurate diagnosis.

Classifying the Curve.Classification of the curve allows the doctor to identify patterns that can help determine treatments, particularly specific surgical techniques. The following are examples:

King Classification. The King classification classifies scoliotic curves as one of five patterns, which can help determine surgical treatments. It has limitations, however, and is not very useful for advanced surgical techniques.
Lenke Classification. Lenke classification takes more features of the curve into consideration and is proving to be more reliable. This includes six curve patterns plus additional factors that modify each of these curves.

Three-Dimensional Modeling Techniques. Advanced computer modeling techniques are able to create three dimensional images using x-rays or other two-dimensional images. They allow doctors to observe the spinal distortions and eventually could reduce the number of x-rays currently needed to monitor scoliosis and help surgeons determine optimal surgical procedures.

Even if the curve is accurately calculated, it still remains difficult to predict whether the scoliosis will progress. A recent report indicates that measuring the nerve conduction activity of the muscles supporting the spine may help predict subsequent progression in children with scoliosis. In addition, computer models are being used to better predict risk. One approach requires measuring 21 radiographic and clinical indicators and entering them into a computer program. The technique takes less than 20 minutes per patient, and studies found it to be up to 80% accurate in determining progression of curvature.

One way of predicting whether or not the curvature will progress is knowing when the child will stop growing:

If the child has years to grow, then the spine has more time to progress.
If the child will stop growing within a year, then progression should be very slight. (However, some progression continues in nearly 70% of curves even after the spine has matured.)

Knowing the child's age is, of course, the first step in estimating the end of growth. In addition, other methods can help predict the end of the growth stage. One method is called the Risser sign, which grades the amount of bone in the area at the top of the hipbone. A low grade indicates that the skeleton still has considerable growth; a high grade means that the child has nearly stopped growing and the curve is unlikely to progress much further. The Risser scale differs between genders, and, in boys, a high grade does not always signify the end of progression.

Screening programs for scoliosis, which began in the 1940s, are now mandatory in middle or high schools in many states, but there is considerable debate over whether screening should be routine.

Arguments Against Routine Screening. The U.S. Preventive Services Task Force does not recommend routine screening to detect adolescent scoliosis for the following reasons:

Screening tests are not accurate and depend too much on the skill of the examiner.
Schools often refer children with minor curves who are not at any risk for a progressive or serious condition to doctors, and such over-referrals add considerably to the costs of the health system. In one major study, 94% of the children referred to a doctor by the school did not require treatment. (Over 2,000 children were screened in order to find only 5 children who did need treatment.)
A long-term study of untreated patients with late-onset scoliosis indicates that these patients are productive and functional at a high level at 50-year follow-up. Patients with scoliosis have no greater danger for significant lung problems than the general population until their curves reach 60 - 100 degrees, making early screening unnecessary.

Experts against screening argue that such programs result in early treatments that either will not prevent curve progression and surgery or are unnecessary in the first place since curvatures often do not progress at all.

Arguments for Routine Screening. The American Academy of Orthopaedic Surgeons recommends that girls be screened twice, at ages 10 and 12, and that boys be screened once, at 13 or 14. The American Academy of Pediatrics recommends, however, scoliosis screening at ages 10, 12, 14, and 16 years. (In one study, over 40% of high school sophomores with newly diagnosed scoliosis had shown no signs of the disorder in earlier screening tests.) Other experts make the following arguments for universal screening:

Universal screening is useful for producing information on scoliosis that may eventually lead to knowledge of its cause and ways to prevent it.
Braces have proven to be effective, and early treatment can be important.
Without screening, the chances are slim that children with scoliosis will be diagnosed at an early stage if parents rely only on examinations by a family doctor or pediatrician. Such doctors often do not even look at backs and, if they do, they tend to use only the forward bend test, which is not accurate.

Some experts argue that widespread screening would be cost effective if schools had reasonable guidelines for determining which children should see a doctor for further testing. The following are some suggested guidelines for determining the need for a doctor referral:

Children should be sent to a doctor only if they have a 30-degree curve. (A 20-degree curve with a 5-degree trunk rotation has been the criteria for recommending treatment, although up to 80% of 20-degree curves do not get worse.)
Children with curves between 20 and 30 degrees should be screened every 6 months.

Such guidelines would detect about 95% of all genuinely serious cases while referring only 3% of all children tested for follow-up, thereby cutting costs without jeopardizing children.

Treatment

The treatments for scoliosis are not always straightforward. Some young people do not need treatment at all -- only careful observation. When treatment is warranted, several options, including braces and different surgical procedures, can help.

The general rule of thumb for treating scoliosis is to monitor the condition if the curve is less than 20 degrees. Curves greater than 25 degrees, or those that progress by 10 degrees while being monitored, may require treatment. Whether scoliosis is treated immediately or simply monitored is not an easy decision, however. The percentage of cases that will progress more than 5 degrees can be as low as 5% in certain cases or as high as 50 - 90%, depending on the severity of the curve or other predisposing factors:

Age. In general, the older the child the less likely the curve will progress. Scoliosis in a child under 10, for example, is more likely to progress than scoliosis in an adolescent. Experts estimate that curves less than 19 degrees will progress 10% in girls ages 13 - 15 years and 4% in children older than 15. (In some rare, severe cases, a curve may worsen even after a child has received treatment and stopped growing because of the weight of the body pressing against the abnormal curve.)

Gender. Girls have a higher risk for progression than boys.

Location of the Curvature. Thoracic curves, those in the upper spine, are more likely to progress than thoracolumbar curves or lumbar curves, those of the middle to lower spine.

Severity of the Curvature. The higher the degree of curvature the more likely the chance of progression and the more likely the lungs will be affected. Some experts argue that the degree of the curve alone may not identify patients with moderate and severe scoliosis who are at greatest risk for complications and therefore need treatment. For example, spinal flexibility and the extent of asymmetry between the ribs and the vertebrae may be more important than the curve degree in predicting severity in this group.

Presence of Other Health Conditions. Children in poor health may suffer more from stressful scoliosis treatments than other children. On the other hand, children who have existing conditions and are predispose to lung and heart problems may warrant immediate, aggressive treatment.

For example, a young man of 18 who has a curvature of 30 degrees may require no treatment because his growth has probably almost stopped, and his gender puts him at lower risk. A young girl of 10, however, with the same curvature requires immediate treatment.

In general, the following criteria are used to determine whether a patient should receive braces and conservative therapies or surgery:

Braces tend to be used in children with curvatures between 25 - 40 degrees who still will be growing significantly.
Surgery is suggested for patients with curvatures over 50 degrees, in untreated patients, or when braces have failed. In adults, scoliosis rarely progresses beyond 40 degrees, but surgery may be required if the patient is in a great deal of pain or if the scoliosis causes neurologic problems.

The choice may not be so straightforward in certain cases, and patients should discuss all options with their doctor.

In Children and Adolescents. After a mild curve is detected, a more difficult step is required: predicting whether the curve will progress into a more serious condition. Although as many as 3 in every 100 teenagers have a condition serious enough to need at least observation, progression is highly variable and individual.

In a study of patients whose curves did progress after diagnosis, 34% progressed more than 10 degrees, 18% progressed more than 20 degrees, and 8% progressed more than 30 degrees. Doctors cannot rely on any definitive risk factors for curve progression to predict with any certainty which patients will need aggressive treatment. Some evidence suggests the following factors may help determine patients at lower or higher risk:

Being female, particularly if taller than average.
Being younger at the onset of scoliosis.
Having a greater angle of curvature. For example, at 20 degrees, only about 20% of curves progress. Young people diagnosed with a 30-degree curve, however, have a risk for progression of 60%. With a curve of 50 degrees, the risk is 90%.
Curvatures caused by congenital scoliosis (spinal problems present at birth). These may progress rapidly.
Treatment with growth hormone. (Studies are mixed on whether this treatment poses any significant risk, although strict monitoring is still essential in young patients being given growth hormone.)

Curvatures may be less likely to progress in girls whose scoliosis was low in the back and whose spine was out of balance by more than an inch. Height also comes into play. For example, a shorter-than-average girl of 14 with low-back scoliosis of 25 - 35 degrees but whose spine is imbalanced by over an inch would have almost no risk. The same degree of curvature in the chest region of a tall 10-year old girl whose spine was in balance, however, would almost certainly progress.

In Adults. In rare cases, unrecognized or untreated scoliosis in youth may progress into adulthood, with the following curvatures posing low to high risk:

Curvatures under 30 degrees almost never progress
Predicting progression at curves around 40 degrees is not clear
Curvatures over 50 degrees are at great risk for progression

Managing Scoliosis

Exercise has many health benefits and is important for maintaining strength and muscle tone and stabilizing weight. Stretching exercises may be beneficial in children whose scoliosis is due to uneven leg lengths or a shortened tendon.

Strengthening the Muscles That Turn the Torso. A promising approach focuses on training and strengthening the muscles that turn the torso. Studies using specific equipment (MedX Torso Rotation machine) are showing promise. In a 2003 study, 16 of the 20 patients experienced curve reduction, and no curves progressed. In an earlier study, patients increased strength from 12 - 40%. One girl with a severe lumbar curve required surgery, but the remaining 11 patients had no progression of curvature, and 4 of the patients experienced a reduction in their curvature. Treatment did not involve braces. Clinical trials using this approach are underway. Exercising the torso to build muscle strength is important, in any case, in conjunction with braces.

ASCO Scoliosis Treatment Method. ASCO Scoliosis Treatment Method is a Russian approach that consists of isometric and stretching exercises, vibration, spinal manipulation, and electrical muscle stimulation. Some U.S. centers are reporting success in halting curve progression, but more research is needed to determine possible benefits.

Biofeedback. Researchers have investigated biofeedback on the premise that people receiving a signal to improve posture when slumping may, in some cases, reduce their spinal deformities. (Some experts believe that braces work only because the young patients self-correct their curves by retraining their posture to avoid the discomfort of the brace.)

Chiropractic Care. Several case reports suggest that chiropractic manipulation of the spine may help stop progression of mild curves. However, no rigorous studies have proved this. One small study reported no benefits from chiropractic in girls with spinal curves less than 20 degrees. (About 80% of such curves will not progress significantly without any treatment.)

Airway Ventilation at Night. Some research has focused on the use of airway systems, such as nasal continuous positive airflow pressure, for patients with severe scoliosis and reduced lung capacity. Patients use such systems during the night to force air into the upper airways and into the lungs. In one study, the use of these devices reduced hospitalization and improved lung function, shortness of breath, and fatigue. Such systems also can treat sleep apnea, a common sleep disorder.

Breathing Exercises. Breathing exercises may help improve lung function in children with scoliosis, and signs of lung problems.

When a difference in leg lengths causes secondary scoliosis, adding lifts to the heels may decrease a mild curvature. In one study, this practice reduced the curvature by an average of 5.3 to 7.5 degrees. (Curvatures were all less than 20 degrees.) Patients with the greatest curvature experienced some muscle pain, fatigue, and even nausea during the first few days they were using the lifts, but these symptoms eased within 10 days.

Braces

A brace can prevent further progression of moderate curves of (24 - 40 degrees). However, a brace will almost never reverse an existing curve and is only used to stop progression. One study reported overall success rates of around 74%, but results vary widely depending on the length of time the brace is worn, the type of brace, and the severity of the curve. The great majority of subjects in scoliosis studies are girls. Limited data suggest that in boys compliance rates are low, and braces are not effective.

Compliance with wearing a brace correlates strongly with success rate. In analysis of 34 patients, the compliance rate for the patients whose curve progressed by more than 5 degrees was 62%, while the compliance rate for the patients who did not progress was 85%.

In overweight patients with adolescent idiopathic scoliosis, braces appear to be less effective than in those who are not overweight. In one 10-year multicenter retrospective study, overweight patients were about three times more likely to have an unsuccessful result with braces than were people of normal weight.

A brace is one type of treatment for scoliosis. The brace works by exerting pressure on the back and ribs to push the spine in a straighter position. The brace usually fits snugly around the torso and can come in many styles. In a child who is still growing, bracing is usually recommended to help slow the progression of the curve. The brace is usually worn full-time until the growth of the bones has stopped.

Many experts have questioned whether a brace is any better than nature in halting curvature progress. Early studies found that braces were successful in halting progression in only half of cases (the same rate as no treatment at all). In recent years, however, braces have improved. Many now fit under the arms and can be worn under clothing, so that patients are much more likely to use them for longer periods during the day, which greatly affects their success rates.

Wearing the brace for the prescribed time is difficult but essential for any success. A team approach, with several health professionals involved, is beneficial and often necessary to support the patient through the bracing process. An orthopedic surgeon interprets the x-rays, assesses the potential progression of the scoliosis, and plans the treatment with the patient and family. If a brace is used, an orthotist measures and fits the patient with the device. A physical therapist tailors an exercise program best suited for the patient. A nurse may also coordinate the treatment plans and provide physical and emotional support.

Milwaukee Brace. A full torso brace called the Milwaukee brace was the standard treatment until a decade ago. It is still used particularly for high curves.

The device contains a wide flat bar in front and two smaller ones in back. These bars attach to a ring around the neck that has rests for the chin and back of the head. One study determined that correcting the curve occurs best if the patient lies on their chest when wearing the brace. Some researchers suggest that increasing the tension on the chest straps might add benefit. The brace is also periodically adjusted for growth.

The brace needs to be worn 23 hours a day, with relief during bathing and exercise only. Compliance is a major problem. In one study, only 15% of patients wore the Milwaukee brace as directed. It is a particularly difficult brace to endure wearing; one woman who had worn it for 7 years during adolescence remembered being invisible during her school years, ignored and shunned by other children.

The Boston and TLSO Braces. Molded braces called thoracolumbar-sacral orthoses (TLSOs), most often the Boston brace, come up to beneath the underarms and can be fitted close to the skin so they do not show beneath clothing. It appears to be effective for mid-back and lower curves. In one study, treatment was judged successful in 61% of adolescents who wore Boston braces, and success correlated with wearing the brace more than 18 hours a day. Wearing the brace for 16 hours a day may still be beneficial, although the risk for curve progression is significantly higher the less time the brace is worn. These braces have problems; they are hot, reduce lung capacity by nearly 20%, and cause mild, temporary changes in kidney function.

The Charleston Bending Brace. The Charleston Bending Brace is worn only at night. Some doctors question its value, although it appears to be suitable for small, flexible curves. In a 2002 study, it was equally effective as the Boston brace. Other studies have reported success rates of 56 - 66% in patients who wore the brace as directed. Still, more than 10% of the patients using either brace eventually needed surgery.

Additional Braces in Development. New braces are being developed in an attempt to improve compliance and results. Some examples are:

The Providence brace is a computer-fitted device that is worn only at night. It is specifically designed for the individual curvature abnormalities, and early studies are showing promise.
A bracing method called the SpineCor uses adjustable bands and a cotton vest that allows flexibility. A 2003 study reported that after 2 years, the brace corrected the curve by 5 degrees in more than half the patients, while 38% were stabilized and only 7% had curvature that worsened by more than 5 degrees. A recent trial of 24 girls with idiopathic scoliosis compared the SpineCor with a TLSO-type brace. The study indicated that the SpineCor did not halt curvature progression associated with idiopathic scoliosis during the pubertal growth spurt whereas the TLSO device did.
The custom-fitted TriaC brace exerts pressure in specific areas of the back to allow greater comfort and flexibility. It may be less conspicuous than some of the older braces.

Studies are needed to determine if these or other new braces provide any additional value.

According to a 2003 study, compliance in wearing the brace averages 65% (although it varied from 8 - 90%). Patients were apt to wear them at night but often wore them sporadically during the day. The quality of life can vary by the type of brace worn. In one study, patients who had the Milwaukee brace reported greater impairment than patients with the Boston, TSLO, or Charleston braces. The choice of brace should be one that will be the most effective for a particular patient with the lowest impact on quality of life. Young people often refuse to wear braces, even the newer models, and emotional support from the family and professionals is extremely important to help a child accept the process and sustain compliance. On a positive note, one study reported that brace treatment did not negatively affect the self images of the adolescents who had to wear them.

For children who require braces, an exercise program helps boost well being, improves compliance with treatment, and keeps muscles in tone so that the transition period after brace removal is easier.

An exercise and physical therapy program is important to maintain or achieve the following:

Chest mobility.
Proper breathing. In one study, young girls who wore the Boston brace and performed aerobic exercises for 30 minutes four times a week experienced improved lung function, whereas lung function declined in girls who did not exercise.
Muscle strength (especially in the abdominal muscles).
Flexibility in the spine. One small study showed that patients who performed exercises improving flexibility in the torso experienced less spinal twisting and had improved curvature.
Correct posture. Practicing correct posture, especially in front of a mirror, is an extremely important part of any physical therapy program. A patient who is accustomed to a curved spine may have the sensation of being crooked when first taught to properly align the spine. Practicing in front of a mirror provides a reality check.
Patients must also learn to conduct daily activities while wearing the brace. Patients tend to comply with physical therapy in the period when the brace is first being used. They typically stop exercising when they have gotten used to the brace, however, and resume exercising only near the time the brace is being removed. Patients who don't stay with the program throughout the duration of brace use experience a weakening in the back at the time of removal.

Surgery

The goals of scoliosis surgery are threefold:

Straighten the spine as much as possible in a safe manner
Balance the torso and pelvic areas
Maintain correction

It takes a two-part process to accomplish these goals:

Fusing (joining together) the vertebrae along the curve
Supporting these fused bones with instrumentation (steel rods, hooks, and other devices) attached to the spine

There are many surgical variations that use different instruments, procedures, and surgical approaches to treat scoliosis. All of the operations require meticulous skill. In most cases, success depends less on the type of operation than on the skill and experience of the surgeon. The cause of scoliosis often determines the type of procedure. Parents of patients or adult patients should not be shy in asking the surgeon and hospital about their experience with the specific procedures being considered.

Surgery is usually recommended for the following children and adolescents with idiopathic scoliosis:

All young people whose curve exceeds 50 degrees.
Growing children whose curve has gone beyond 40 degrees. (There is still some debate, however, about whether all children with curves of 40 degrees should have surgery.)
Older children who have surgery tend to experience improved well-being from the changes in their appearance, even if they have no actual improved physical functioning.

Surgery may be required for the following children at as early an age as possible.

Those whose scoliosis is due to inborn abnormalities. (The younger they are when surgery is performed the better their chances for success.)
Children with multiple physical handicaps.

Procedures will differ depending on whether a child has idiopathic scoliosis, or scoliosis due to muscle and nerve disorders (such as muscular dystrophy or cerebral palsy). In the latter cases, children also need a team approach to reduce their risks for serious complications.

Before the operation, a doctor conducts a complete physical examination to determine leg lengths, muscle strength, lung function, and any postural abnormalities. The patient receives training in deep breathing and effective coughing to avoid lung congestion after the operation. The patient should also receive training in turning over in bed in a single movement (called log-rolling) before the operation. Psychologic intervention using cognitive-behavioral methods that help young patients cope may be very helpful in reducing anxiety and pain after surgery.

Patients are encouraged to donate their own blood before the operation for use in possible transfusions. The patient should have no sunburn, rashes, or sores on the back before the operation, which could increase the risk for infection.

Most scoliosis operations involve fusing the vertebrae. The instruments and devices used to support the fusion vary, however.

In the fusion procedure, the surgeon will:

Slice flaps to expose the backs of the vertebrae that lie along the curve.
Remove the bony outgrowths along the vertebrae that allow the spine to twist and bend.
Lay matchstick-sized bone grafts vertically across the exposed surface of each vertebra, being careful that they touch adjoining vertebrae.
Fold the flaps back to their original position, covering the bone grafts.
These grafts will regenerate, grow into the bone, and fuse the vertebrae together.

Depending upon the severity and responsiveness to other treatment, a doctor may recommend surgery for scoliosis. Surgery involves correcting the curve (although not all the way) and fusing the bones in the curve together. The surgeon lays bone grafts across the exposed surface of each vertebra. These grafts will regenerate, grow into the bone, and fuse the vertebrae together. The bones are held in place with one or two metal rods held down with hooks and screws, helping to support the fusion of the vertebrae.

Graft Materials. A surgeon takes bone grafts from the patient's hip, ribs, spine, or other bones (called autografts). This is the best quality bone. However, because autografts are taken directly from the scoliosis patient, the operation is longer and the patient experiences more pain afterward. Researchers are investigating allografts, bone grafts taken from another person or a cadaver. This would reduce the pain and duration of the operation. Allografts, however, pose an increased risk for infection from the donor.

Some surgical centers now perform spinal fusions in adults using a biologically-manufactured human bone protein instead of bone grafts. RhBMP-2 (INFUSE Bone Graft) contains a bone morphogenetic protein (BMP) that helps the body grow its own bone. A surgeon inserts the protein into a pair of thimble-like cages, which are implanted between the spinal vertebrae. The cages help stabilize the spine, while the protein prompts new bone growth. Doctors hope that this new procedure can eliminate the pain of autografts and the risk of infection of allografts. Results from preliminary studies have been promising. BMP treatments are currently approved only for adults.

Healing. The healed fusions harden in a straightened position to prevent further curvature, leaving the rest of the spine flexible. It takes about 3 months for the vertebrae to fuse substantially, although 1 - 2 years are required before fusion is complete. Fusion stops growth in the spine, but most growth occurs in the long bones of the body (such as in the legs), anyway. Patients will most likely gain height from both growth in the legs and from the straighter spine. Patients may walk at a slightly slower pace after fusion, but balance may improve, and sports activities are not restricted after the procedure.

Harrington Procedure. Until 10 years ago, the standard instruments used in fusion procedures were those of the Harrington procedure, first developed in the 1960s:

To support the fusion of the vertebrae, the surgeon uses a steel rod, extending from the bottom to the top of the curve. (More than one rod may be used depending on the type of curve and whether outward curvature of the spine is present.)
The rod is attached by hooks that are suspended from pegs inserted into the bone.
Similar to changing a tire, the steel rod is jacked up and then locked into place to support the spine securely. The surgeon is then ready to fuse the vertebrae together.
After this operation, patients must wear a full body cast and lie in bed for 3 - 6 months until fusion is complete enough to stabilize the spine.
After 1 - 2 years, the steel rod is not really necessary, but it is almost always left in place unless infection or other complications occur.

The Harrington procedure is very difficult to undergo, particularly for young people, and although the operation can achieve a correction of the curve of over 50%, studies have reported a loss in this correction of between 10 - 25% over time. The procedure does not correct the rotation of the spine and, therefore, does not improve an existing rib hump that was caused by the rotation. The operation does not interfere with normal pregnancies and deliveries later in life.

Certain complications may occur from this procedure:

About 40% of Harrington patients have a condition called the flat back syndrome, because the procedure eliminates normal lordosis (the inward curving of the lower back). Flat back syndrome from the Harrington procedure does not cause any immediate pain. In later years, however, the disks may collapse below the fusion, making it difficult to stand erect, and the condition can cause significant pain and emotional distress.
Studies have reported that 5 - 7 years after their surgery, between a fifth and a third of patients who had the Harrington procedure experienced low back pain. (In one study, only 3% had experienced back pain before surgery.) In such cases, however, the pain was not severe enough to interfere with normal activities and did not require additional surgery.
Children younger than age 11 whose skeleton is immature and who have the Harrington procedure have a fairly high risk for a specific curve progression called the crankshaft phenomenon. This condition occurs when the front of the fused spine continues to grow after the procedure. The spine cannot grow longer, so it twists and develops a curvature. In one study that followed patients for 5 - 16 years, crankshaft curve progression was moderate, however, with the Cobb angle averaging 9 degrees and rotation averaging 7 degrees.

Cotrel-Dubousset Procedure. The Cotrel-Dubousset procedure not only corrects the curve but also may help correct rotation, and it does not cause flat back syndrome.

With this procedure, a surgeon cross links parallel rods for better stability in holding the fused vertebrae. Improvement in correction averaged 66% in one study, with a later correction loss reported to be 5%. (Other studies have reported loss of curvature correction at less than 2%.) Over 95% of patients reported the results to be good or very good (only 86% of patients who had the Harrington procedure experienced the same levels of satisfaction). Patients often go home in 5 days and may be back in school in 3 weeks.

Complication rates are similar to the Harrington procedure but with some differences:

Operation time and blood loss are greater than with the Harrington procedure.
Cotrel-Dubousset and other procedures that are designed to reverse the rotation of the spine have less risk for flat back syndrome, but they have a higher risk for spinal imbalance than the Harrington procedure.
Failure rates are about 25% after 10 years, which is very high. Experts hope that the advances in current scoliosis procedures will help reduce the long-term adverse effects.

The Texas Scottish-Rite Hospital (TSRH) Instrumentation. The Texas Scottish-Rite Hospital (TSRH) instrumentation is similar to the Cotrel-Dubousset procedure in that it uses parallel rods and other devices that reverse rotation as well as improve curvature. TSRH, however, uses smooth rods and hooks that are designed to make removal or adjustment easier later on if complications arise. Complications are similar to the Cotrel-Dubousset procedure.

Additional Forms of Instrumentation. Other instrumentation procedures have refined the hardware used in the Harrington and Cotrel-Dubousset operations.

After surgeons developed Luque instrumentation to help maintain normal lordosis, experts hoped that bracing would not be needed afterward. Several studies showed, however, that without braces, correction was lost after this operation, and the procedure may have a higher risk for spinal cord injury than other standard procedures. Luque instrumentation is used primarily in people whose scoliosis is due to problems of nerves and muscles, such as in children with cerebral palsy.
Wisconsin segmental spine instrumentation (WSSI) is as safe as the Harrington rod and nearly as strong as the Luque instrumentation.
The Dorsal Dynamic Spondylodesis (DDS) system, under testing in Germany, is a semirigid system that allows for greater flexibility of the spine.

Instrumentation for Anterior Approach. The anterior approach, in which the surgeon performs the operation by opening the chest wall, requires specific hardware. Halm-Zielke instrumentation, for example, uses TSRH instrumentation with bone grafts constructed from ribs to prop open the spaces between the disks. It allows true three-dimensional curve correction. However, it does not solve specific problems with this approach -- higher risks for kyphosis (an outward curve) and pseudoarthrosis (a false joint at the fusion site). Variants using two rod systems, fusion cages, or other instruments appear to improve this procedure.

Posterior Approach (Through the Back). Many surgeons use a posterior approach for scoliosis, which reaches the surgical area by opening the back of the patient. It has been the gold standard for decades and is generally used with Harrington instrumentation. The posterior approach has advantages and disadvantages:

Advantages. Surgeons are familiar with it, so fusion rates are excellent, curve correction is good, and it has few complications.
Disadvantages. Preadolescent children are at risk for the crankshaft phenomenon (a worsening of the curve) later on. (Newer posterior instrumentation, such as the Isola instrumentation, may prevent this occurrence.) The posterior approach also does not always correct hypokyphosis (the loss of normal outward curvature) in the thoracic (upper) spine. The procedure is not always effective for curves in the thoracolumbar region (where the upper and lower spine meet) and may cause spinal abnormalities there.

Anterior Approach (Through the Front). Increasingly, surgeons are using the anterior approach, in which the surgeon performs the operation through the chest wall (called a thoracotomy). With the anterior approach, the surgeon makes an incision in the chest, deflates the lung, and removes a rib in order to reach the spine. This rib can be used during the operation as a strut to support the spine. It also may be repositioned within the patient until it is used for bone grafting during fusion.

The anterior approach also has its advantages and disadvantages:

Advantages. Because the frontal approach allows the procedure to be performed higher up in the spine than with standard procedures, the patient may have a lower risk for lower-back injury later on. In addition, transfusion rates are much lower with the anterior approach. With increasing experience, the anterior approach is as effective as the posterior approach.
Disadvantages. It is a more recent procedure than the posterior approach, and, among inexperienced surgeons, carries a higher risk for complications than in the more standard posterior approach. One study noted poorer lung function 2 years after surgery than with the posterior approach, possibly because the wide chest incision impairs the chest muscles, which can affect lung function afterward. Anterior instrumentation poses a risk for hyperkyphosis (exaggerated outward curvature) and a higher risk for pseudoarthrosis, a painful condition in which a false joint develops at the fusion site. Hardware failure rates may also be higher in the anterior approach than in the posterior approach. Increasing experience and newer hardware designs are reducing many of these problems.

The Combined Anterior-Posterior Approach. The combination approach uses an anterior approach first, which allows better correction of the problems. The fusion part of the operation is done with the posterior approach. This is a very long and complex procedure. It appears to be safe, however, and is proving to be useful, even in very young patients, for preventing the crankshaft phenomenon. It also may correct large rigid curves and specific severe curves in the thoracic spine.

Researchers are evaluating new approaches to treating thoracic scoliosis in adolescents and children. Researchers in Germany are studying the effects of implanting a vertical expandable prosthetic titanium rib. This implant expands the thoracic cavity, thereby correcting the curvature and allowing spinal, thoracic, and lung growth. Early experience with 15 children showed improvement of thoracic insufficiency syndrome and ability to sit, in addition to greatly improvement cosmetic appearance.

Researchers in the U.S. recently compared the radiographic and clinical outcomes and pulmonary function in patients treated with either anterior thoracoscopic or traditional posterior surgery. The anterior thoracoscopic surgery uses a video-assisted anterior approach and recently developed spinal instrumentation. There were 28 patients in the thoracoscopic group (average, 14.6 years of age) and 23 patients in the posterior fusion group (average, 14.3 years of age). The researchers found no significant differences between the groups in terms of kyphosis, coronal balance, or tilt angle. Advantages of the anterior thoracoscopic approach include the need for fewer vertebral levels fused, less blood loss, and lower transfusion rate, yet the operative time was nearly 2 times longer than for the posterior approach.

While both of these new treatments have shown some early positive results, more research will be needed to determine their true value.

Complication rates are high (nearly 10%) with any of these procedures, including the standard Harrington method and the newer Cotrel-Dubousset procedure.

Complications for all procedures include allergic reactions to anesthesia and the following:

Bleeding. Standard procedures increase the risk for major blood loss during the procedure. Patients are encouraged to donate blood before the operation for use in possible transfusions. Children sometimes require more than one transfusion following surgery. Researchers are investigating various methods for reducing the need for transfusions.

In one study, patients received erythropoietin (rhEPO) before the procedure. RhEPO is a hormone that acts in the bone marrow to increase the production of red blood cells. Patients who received this hormone, particularly those with idiopathic scoliosis, needed fewer transfusions and spent less time in the hospital than those who did not receive rhEPO.

Newer endoscopic techniques are reducing the need for transfusions.

Postoperative Pain. Some pain always follows these procedures, requiring intravenous administration of potent painkillers right after the operation (endoscopic procedures may require only mild pain relievers). Of some concern is a study suggesting that the use of NSAIDs, or nonsteroidal anti-inflammatory drugs (aspirin, Motrin, Advil), for pain relief right after fusion may increase the risk for fusion failure. Until more research is conducted, these common painkillers should not be routinely used immediately after surgery.

Infection. Infection is always a risk with any operation. One study reported changes in the immune system for about 3 weeks after surgery, which indicated a greater risk for infection. Researchers recommended being very vigilant for signs of infection, including in the pancreas and urinary tract. Doctors also recommend antibiotics, given by injection for 2 - 5 days after surgery and by mouth for 1 - 2 weeks longer.

Nerve Damage. Patients often worry about neurologic injuries, but the risk is actually very low. In general, nerve injury occurs in 1% of patients, with the risk highest in adults. If neurologic damage occurs, it most often causes muscle weakness. Paralysis is very rare and can be prevented using monitoring techniques during the operation. Nearly all monitoring procedures use a so-called wake-up test, in which the patient is brought out of anesthesia during or at the end of the procedure and assessed for sensations to be sure no injury has occurred. One simple method is to wake patients up in the middle of their operations and ask them to wiggle their toes. More sophisticated methods measure the electrical activity of the spinal cord; if the monitor indicates a fall in electrical response and possible injury, the surgeon adjusts his techniques to avoid further damage to the spinal cord.

Pseudoarthrosis. If the fusion fails to heal, pseudoarthrosis, a painful condition in which a false joint develops at the site, may develop. In one study, teenagers who smoked and heavier adolescents (over 154 pounds) who had hyperkyphosis (hunchback) were at higher risk for this complication. The anterior approach may pose a higher risk for pseudoarthrosis. One study reported that pseudoarthrosis may be undiagnosed, and rates may average 20% after surgery, therefore acting as a major contributor to post-surgery pain.

Disk Degeneration and Low Back Pain. Fusion in the lumbar area produces great stress on the lower back and eventually can cause disk degeneration. Loss of trunk mobility, balance, and muscle strength from surgical treatments can also cause lower back pain and chronic problems in future years. Patients who are surgically treated with fusion techniques lose flexibility; their back muscles may be weakened if they were injured during surgery. In most cases, however, the consequences are mild to moderate.

Lung Function. Some patients may develop serious lung problems after surgery. These complications are highest in children whose scoliosis is due to neuromuscular problems, such as spina bifida, cerebral palsy, or muscular dystrophy. Lung problems can occur up to 1 week after surgery. Lung function may not become completely normal until 1 - 2 months after surgery.

Other Complications. Other problems can include, but are not limited to, the following:

Hooks dislodging or a fused vertebra fracturing
Gallstones
Pancreatitis (inflammation of the pancreas). Among adolescents, this complication tends to occur more often among those who are older or who have a lower body mass index.
Intestinal obstruction

Click the icon to see an image of gallstones.

Patients must perform breathing and coughing exercises shortly after the procedure and continue them through the recovery process to rid the lungs of congestion. The patient is usually able to sit up the day after the operation, and most patients can move on their own within a week. A brace may be necessary, depending on the procedure. With the anterior approach in the upper back, patients may have some trouble with activities involving the arms and hands -- such as tying shoes and cutting food. In one study, however, occupational therapy using stretching and strengthening exercises allowed for full resumption of daily activities, including dressing, bathing, and grooming, within 3 months.

Patients are often concerned that surgery will stiffen their backs, but most cases of scoliosis affect the upper back, which has only limited movement, so that patients do not notice much difference. It may take a year or more for muscle strength to return. In some cases, the operation cannot completely correct the curve, and one leg may be shorter than the other. Heel lifts may help in this case.

Patients may need a corrective procedure called revision or salvage surgery, usually for one of these reasons:

Failure of the previous procedure
Curvature progression around the fusion site
Disk degeneration
Poor posture alignment

Minimally invasive surgery is an alternative to spinal fusion. These types of surgeries use a few small incisions and cause less scarring than standard open approaches that require wide cuts. However, these surgeries are limited to certain patients and are not yet as frequently performed as spinal fusion surgeries.

Endoscopy. In endoscopy, the surgeon makes small incisions and inserts tubes that contain tiny instruments and cameras through the incisions in order to view and execute the procedure. In most cases, the procedure occurs in two stages:

First, the surgeon uses the anterior approach to remove disk material and loosen the spine.
They follow with a posterior for fusion and instrumentation.

Recovery after surgery is rapid. Most patients are out of bed 2 days after surgery. Endoscopy causes fewer and smaller scars, and an easier recovery, than more invasive surgical approaches.

However, the endoscopic procedure for scoliosis is complicated, and few surgeons are trained to perform it. The surgery is generally used only for single curves in the upper back or for patients with a curve in the upper back and a compensating curve in the lower back. Some surgeons are now able to operate on areas below the diaphragm, including the lumbar spine. The patients must still wear a brace for 3 months after surgery. Long-term studies are required to compare results to those of standard procedures.

Growing Rod Technique. This technique is used for very young children in whom bracing has not helped. Instead of doing spinal fusion, doctors surgically insert a rod into the patient’s back. Additional surgeries are performed every 6 months to extend the rod so that the spine can continue to grow. Some growing rod techniques use a single rod, while others use two rods. Studies suggest that dual rods are stronger than single rods, which may help provide better spinal stability and correction.

Vertebral Body Stapling. Vertebral body stapling is an experimental technique that may prevent curve progression in some young patients with curves less than 50 degrees. It involves stapling the convex (outer) curve of the anterior spine (the side of the spine facing the chest), which helps stabilize and reduce progression of the inner (concave) curve. The procedure uses a special metal device that is clamp-shaped at body temperature but can be straightened when subjected to cold temperatures and inserted into the spine. When warmed up, the staple returns to its clamp shape and supports the spine.

Treatment for Adult Scoliosis

Adults who were surgically treated for scoliosis in their youth are at risk for disk degeneration and spinal fusion failure. In most adults with previous scoliosis, moderate exercise is not harmful and is extremely important for maintaining healthy supportive muscles and preventing disk degeneration. However, people who have only one or two mobile lumbar vertebrae below the area that was fused during surgery should avoid activity or exercise that causes excessive twisting on the spine. Some experts believe this may accelerate spinal degeneration.

In most cases of adult scoliosis, nonsurgical care is preferred if possible. This can include patient education, exercises, and medical treatments. Braces are not useful.

One center reported that epidural steroid injections were a beneficial alternative to surgery in patients with degenerative lumbar scoliosis.

Candidates for Surgery. In general, pain is the most common reason for surgery in adult scoliosis. Surgery may be recommended in the following cases:

Curvatures over 50 degrees with persistent pain.
Surgery is almost always recommended for adults with curvatures over 60 degrees.
Progressive mid and low back curve or low back curve with persistent pain.
Reduced heart and lung function. Most surgeons, however, will not operate on adults with severely impaired lung function and heart failure. Once this has occurred, surgery will not help improve lung capacity and may cause the condition to worsen, at least temporarily.
Significant deformity is present. Adults should not expect to achieve a completely straight spine, however. There is a high risk for nerve damage if the spine is over-corrected, and adult spines are less flexible than children's are. Usually, however, the correction achieves an acceptable cosmetic improvement.

Surgeons prefer to operate on adults under 50 years old, although surgery may be appropriate in some older people.

Standard Scoliosis Procedures in Adult Scoliosis. The procedures involve the following depending on whether the patient had been treated previously or not:

In patients who have not had previous treatment and who have degenerative lumbar scoliosis, the procedure is often a diskectomy (removal of the diseased disks) followed by scoliosis procedures (instrumentation and fusion).
In patients with previously treated scoliosis, the only remedy is removal of the old instrumentation, extension of the fusion, and implementation of new instrumentation and bone grafts.

Surgical procedures in adult scoliosis are complex and undertaken only after careful consideration and all nonsurgical methods have been exhausted. Adults have a much higher risk than children for complications, including pneumonia, infection, poor wound healing, and persistent pain. In addition, procedures in adults often involve fusion in lumbar and sacral areas (the low back), which can cause several complications. Some experts believe that the risks of operations in this area nearly always outweigh any benefits in adults. Most studies on adults have also reported low success rates.

Others argue that without an operation, the back will become unstable and painful. In addition, most studies on adults report on procedures using the old Harrington instrumentation techniques. Advances in instrumentation are increasing success rates in adults.

In a recent study, for example, adults who underwent anterior fusion and instrumentation had excellent results. In another study of newer generation instrumentation, 87% of adult patients reported satisfaction.

Wedge Osteotomy. Researchers are investigating wedge osteotomy in patients with mature spines, as corrective surgery and as an alternative to braces. In this procedure, a surgeon cuts wedges of bone from the concave side of the curve. The surgeon then straightens the spine by inserting a temporary rod and closing the cut sections. The patient needs to wear a brace and restrict activity for about 12 weeks or until the bone has healed. The patient can resume normal activities when a surgeon removes the rod, and the spine is mobile.

Resources

www.scoliosis.org -- National Scoliosis Foundation
www.srs.org -- Scoliosis Research Society
www.scoliosis-assoc.org - - Scoliosis Association
www.aaos.org -- American Academy of Orthopaedic Surgeons
www.niams.nih.gov -- National Institute of Arthritis and Musculoskeletal and Skin Diseases
www.ispine.com -- Information on the spine

References

Akbarnia BA, Marks DS, Boachie-Adjei O, Thompson AG, Asher MA. Dual growing rod technique for the treatment of progressive early-onset scoliosis: a multicenter study. Spine. 2005;30(17 Suppl):S46-S57.

Helenius I, Jalanko H, Remes V, Sairanen H, Salminen S, Holmberg C, et al. Scoliosis after solid organ transplantation in children and adolescents. Am J Transplant. 2006;6(2):324-330.

Hell AK, Campbell RM, Hefti F. The vertical expandable prosthetic titanium rib implant for the treatment of thoracic insufficiency syndrome associated with congenital and neuromuscular scoliosis in young children. J Pediatr Orthop B. 2005;14:287-293.

Hung VW, Qin L, Cheung CS, Lam TP, Ng BK, Tse YK, et al. Osteopenia: a new prognostic factor of curve progression in adolescent idiopathic scoliosis. J Bone Joint Surg Am. 2005;87(12):2709-2716.

Lee WT, Cheung CS, Tse YK, Guo X, Qin L, Lam TP, et al. Association of osteopenia with curve severity in adolescent idiopathic scoliosis: a study of 919 girls. Osteoporos Int. 2005;16(12):1924-1932.

Lonner BS, Kondrachov D, Siddiqi F, Hayes V, Charf C. Thoracoscopic spinal fusion compared with posterior spinal fusion for the treatment of thoracic adolescent idiopathic scoliosis. J Bone Joint Surg. 2006;88A:1022-1034.

Luhmann SJ, Bridwell KH, Cheng I, Imamura T, Lenke LG, Schootman M. Use of bone morphogenetic protein-2 for adult spinal deformity. Spine. 2005;30(17 Suppl):S110-S117.

Thompson GH, Akbarnia BA, Kostial P, Poe-Kochert C, Armstrong DG, Roh J, et al. Comparison of single and dual growing rod techniques followed through definitive surgery: a preliminary study. Spine. 2005;30(18):2039-2044.

Yuan N, Fraire JA, Margetis MM, Skaggs DL, Tolo VT, Keens TG. The effect of scoliosis surgery on lung function in the immediate postoperative period. Spine. 2005;30(19):2182-2185.

Review Date:
4/6/2007
Reviewed By:
Harvey Simon, MD, Associate Professor of Medicine, Harvard Medical School; Physician, Massachusetts General Hospital.

A.D.A.M. Copyright

adam.com

Non-small cell lung cancer

FitSugar — Wed, 08 Oct 2008 17:35:06 -0700

In This Report

Highlights
Introduction
Causes
Symptoms
Risk Factors
Lifestyle Changes
Diagnostic Tests
Staging Systems
Surgical Procedures
Radiation Treatments
Treatment Options by Stages...
Chemotherapy Treatments
Investigative Agents
Resources
References

HEALTH GUIDE REFERENCE FROM A.D.A.M

Highlights

Research News:

About 3,000 nonsmokers die each year of lung cancer resulting from exposure to secondhand smoke, according to a 2006 Surgeon General report.
Advexin, a genetic therapy that contains the p53 tumor-suppressor gene, is showing promise. A 2006 study in Japan found that out of 13 patients with advanced NSCLC receiving Advexin, 10 had stabilized. Advexin is in Phase II clinical trials for NSCLC.
Studies are finding that NSCLC tumors in people who never smoked have a much higher rate of epithelial growth-factor receptor (EGFR) mutations. EGFR helps new blood vessels grow to feed tumors. This discovery may help tailor future treatments to specific patient populations. It also helps explain why some newer treatments seem effective mostly in patients who never smoked.

Treatment News:

Video-assisted thoracic surgery (VATS) is a new, less-invasive surgical technique that uses a thin tube containing a miniature camera and surgical instruments. Though the procedure is not appropriate in all cases, it offers significant advantages, especially in older or frail patients, in the treatment of early stage non-small cell lung cancer (NSCLC).
Bevacizumab, a monoclonal antibody, was approved in October 2006 as a first-line treatment (in combination with carboplatin and paclitaxel) for inoperable, locally advanced, metastatic, or recurrent non-squamous, non-small cell lung cancer.
Gefitinib (Iressa), a drug that targets EGFR, proved disappointing in final clinical trials. However, erlotinib (Tarceva), a drug that targets a different part of the EGFR molecule, has shown benefits. Erlotinib is now approved as a second-line chemotherapy to treat patients with locally advanced or metastatic NSCLC after a previous course of chemotherapy failed.

Introduction

Although lung cancer accounts for only 13% of all cancers, it is among the most lethal, accounting for over 28% of all cancer deaths. It is more deadly than colon, breast, and prostate cancers combined. An estimated 160,390 people will die from lung cancer in 2007. Death rates have been declining in men over the past decade, and they have now stabilized in women.

The lungs are two spongy organs 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. About 90% of the lung is filled with air; only 10% is solid tissue.

Air is carried from the trachea (the windpipe) into the lung through flexible airways called bronchi.
Like the branches of a tree, the bronchi in turn divide into over a million smaller airways called bronchioles.
The bronchioles lead to grape-like clusters of microscopic sacs called alveoli.
In each adult lung, there are about 300 million of these tiny alveoli. A thin membrane makes up the alveoli sacs. Oxygen and carbon dioxide pass through this membrane to and from capillaries.
Capillaries, the smallest of our blood vessels, carry blood throughout the body.

The major features of the lungs include the bronchi, the bronchioles, and the alveoli. The alveoli are the microscopic blood vessel-lined sacks in which oxygen and carbon dioxide gas are exchanged.

Lung cancer develops when genetic mutations (changes) occur in a normal cell within the lung. As a result, the cell becomes abnormal in shape and behavior, and reproduces endlessly. The abnormal cells form a tumor that, if not surgically removed, invades neighboring blood vessels and lymph nodes and spreads to nearby sites. Eventually, the cancer can spread (metastasize) to locations throughout the body.

The two major categories of lung cancer are small cell lung cancer and non-small cell lung cancer. Most lung cancers are non-small cell cancer, the subject of this report. Less common cancers of the lung are known as carcinoids, cylindromas, and certain sarcomas (cancer in soft tissues).

Some experts believe all primary lung cancers come from a single common malignant (cancerous) stem cell that, as it copies itself, can develop into any one of these cancer types in different individuals.

In addition, cancers in the lung may have spread from other primary sites, such as the breast, thyroid, or colon. In these cases, doctors name the cancer after its original location; for example, "breast cancer with lung metastases."

Non-small cell lung cancers are categorized into three types: squamous cell carcinoma (also called epidermoid carcinoma), adenocarcinoma, and large cell carcinoma. These separate types are grouped together because, in early stages before the cancers have spread, they all can be treated surgically.

Squamous Cell Carcinoma. Squamous cells are formed from reserve cells, which are round cells that replace injured or damaged cells in the lining (the epithelium) of the bronchi, the major airways. Tumors formed from squamous cells are usually found in the center of the lung, either in a major lobe or in one of the main airway branches. They may grow to large sizes and form cavities in the lungs.

Click the icon to see an image of squamous cell carcinoma.

When squamous cell cancer metastasizes, it may travel to the bone, adrenal glands, liver, small intestine, and brain.

Squamous cell carcinoma is nearly always caused by smoking and used to be the most common cancer. It still makes up 25 - 40% of all lung cancers.

Adenocarcinoma. Adenocarcinomas usually arise from the mucus-producing cells in the lung. About two-thirds of adenocarcinomas develop in the outer regions of the lung, while one-third develop in the center of the lung. In 1965, 12% of lung cancers were adenocarcinomas. They are now estimated to account for 30 - 50% of all lung cancers and are the most common lung cancers in many countries. They are also the most common lung cancers in women. In fact, a 2000 European study showed that nearly 34% of the women with lung cancer under investigation had adenocarcinoma, compared to 26.4% who had squamous cell carcinoma, and 22.3% with small cell lung cancer. Adenocarcinoma is also increasing dramatically in men. Until recently, adenocarcinoma was only weakly linked to smoking. Experts now suggest, however, that the dramatic increase in recent decades in this lung cancer type may be due to low-tar, filtered cigarettes. People who smoke them draw tiny particles deeper into the lungs, thereby possibly increasing the risk for adenocarcinoma.

The course of this cancer varies widely. Most often, it develops slowly and causes few or no symptoms until it is far advanced. In some cases, however, it can be extremely aggressive and rapidly fatal. In 50% of cases in which this cancer spreads, it spreads only to the brain. Other common locations it spreads to include the other lung, the liver, the adrenal glands, and bone.

Click the icon to see an image of adenocarcinoma.

Bronchoalveolar Lung Cancer. Bronchoalveolar lung cancer is actually a subtype of adenocarcinoma. It develops as a layer of column-like cells on the lung and spreads through the airways, causing great volumes of sputum. This cancer also is increasing in incidence.

Large Cell Carcinoma. Large cell carcinoma, which makes up about 10 - 20% of lung cancers, includes cancers that cannot be identified under the microscope as squamous cell cancers or adenocarcinomas.

Click the icon to see an image of large cell carcinoma.

Small cell lung cancer may, like squamous cells, be derived from reserve cells or other cells in the epithelium. It causes 15 - 25% of all lung cancers; without chemotherapy, it is very aggressive and usually rapidly fatal. It requires a different treatment approach from non-small cell lung cancer, so it is not discussed in this report.

Click the icon to see an image of small cell carcinoma.

Causes

Cigarette Smoke. Smoking causes 87% of lung cancer deaths, accounting for 30% of all cancer deaths. Cigarettes, nicotine, or both may contribute to lung cancer in one or more of the following ways:

In general, chronic exposure to nicotine may cause an acceleration of coronary artery disease, peptic ulcer disease, reproductive disturbances, esophageal reflux, hypertension, fetal illnesses and death, and delayed wound healing.

The smoke is the most dangerous component of the cigarette. Chemicals formed during smoking trigger genetic mutations that lead to cancer. When people inhale cigarette smoke, they bring into their lungs tar that includes over 4,000 chemicals, some of which are carcinogenic (cancer-causing). Other inhaled chemicals in cigarette smoke that may increase the risk for cancer include cyanide, benzene, formaldehyde, methanol (wood alcohol), acetylene (the fuel used in torches), and ammonia. Smoke also contains nitrogen oxide and carbon monoxide, both of which are harmful gases.
Nicotine itself may be a hazard. A 2000 laboratory study suggested that the human body might be converting inhaled nicotine into a chemical called aminoketone, which has been linked to the formation of tobacco-related lung cancer. A 2001 study reported that nicotine triggered new blood vessel growth, which could, in theory, promote growth of any existing tumors. A study published in 2005 found that nicotine was responsible for disabling a gene that induces the death of cancer cells in lung tumors. Whether or not these studies apply to long-term use of nicotine replacement products (such as patches), or to cigarette smoking, is still unclear. The studies should certainly not discourage people from using nicotine replacement methods for quitting. However, these studies may indicate that people should not use these devices on a long-term basis.

Radon. Radon is a gas produced naturally by the breakdown of uranium. It is often present in the soil and in water and can seep into any dwelling. Radon may be responsible for between 10% and 14% of lung cancer deaths, making it, after smoking, the second leading cause of this cancer.

Other Contributors. Toxic particles leading to precancerous changes in the lung are also found in marijuana. In one study, 53.8% of cigarette smokers, 66.7% of marijuana smokers, and all of those subjects who smoked both substances showed evidence of precancerous changes in the lungs.

There is considerable debate over the lung cancer risk posed by depleted uranium used in military weapons (such as in the Gulf and Balkan conflicts). A 2001 study estimated that it would cause an additional 8 deaths from lung cancer out of every 10,000 people or soldiers who were highly exposed to this substance. The study was based on a mathematical model, however, and the issue is not settled.

Other lung carcinogens include asbestos, arsenic, certain petrochemicals (materials made from crude oil or natural gas), and other airborne (carried through the air) byproducts of various mining and manufacturing processes.

Click the icon to see an image of the tobacco plant.

Genetic mutations that cause cancer generally occur in two types of genes:

Tumor-suppressor genes, which prevent cells from endlessly copying themselves
Proto-oncogenes, which encourage cells to keep making copies of themselves [when a proto-oncogene changes (becomes mutated), it is then called an oncogene]

Damage to either type of gene can cause a mutation that results in an uncontrolled division of cells. This uncontrolled division forms tumors.

It is unlikely that a single specific abnormality causes all lung cancer. It probably takes a variety of mutations to start the devastating chain of events leading to cancer. The following mutations are among those under investigation:

BPDE-caused mutations: The chemical BPDE, a byproduct of tobacco smoke, is involved with a number of genetic mutations, including those to an oncogene called K-ras and to three tumor-suppressor genes known as p53, PPP2R1B, and p16. When normal, the tumor-suppressor genes are involved in cell repair and healthy copying of the cell. When they are damaged or blocked, out of control cell production can occur, leading to cancer. About 10% of the population may carry a gene that protects against lung cancer, by reducing levels of BPDE.
Chemotherapy resistance genes: Tumors that contain the p53 mutation may also be more resistant to chemotherapy.
Rb Mutations: Another important contributor to lung cancer is a genetically defective protein called retinoblastoma (Rb), which is associated with very aggressive tumors. Low levels of the normal Rb gene may sometimes predict aggressive cancer, especially in patients with small cell lung cancer.
Mutations to the FHIT gene: Another potentially important mutation may be an abnormality in the FHIT gene. This mutation causes the cells lining the lung to become more vulnerable to the effects of tobacco smoke and other carcinogens.

Symptoms

Lung cancer is unlikely to produce symptoms until the disease is advanced. When symptoms develop, they may result from the lung tumor itself, from its effects on tissues outside the lung, or from the spread of malignant cells to other organs.

Early symptoms may include the following:

Frequent bouts of pneumonia, or pneumonia that does not clear up in a normal period of time
Coughing (particularly coughing up blood)
Weight loss
Fever
Shortness of breath
Chest pain

Later-stage symptoms include the following:

Shortness of breath: This common symptom is the result of cancer that has spread in the lung and the pleura, the membrane covering the lung.
Superior vena cava syndrome: In some cases, tumor growth or spreading of the cancer presses against the superior vena cava, a large vein that returns blood from the upper part of the body to the heart. When this happens, a condition called superior vena cava syndrome may occur, leading to obvious swelling in the arms and face.
Trouble swallowing: The esophagus is the pipe that takes food from the mouth to the stomach. The cancer may spread to or press against the esophagus, interfering with swallowing and nutrition.
Hoarseness: Cancer can damage the nerves that control the voice box, causing hoarseness.
Pancoast syndrome: Damage to the brachial plexus, a group of nerves branching from the neck, can cause pain, weakness, or numbness in the arm or hand (Pancoast syndrome).
Bronchoalveolar lung cancer may produce very large amounts of mucus.
Hypercalcemia: Some lung cancers produce substances that remove calcium from bone and release it into the bloodstream, causing a condition called hypercalcemia. Patients with this disorder can experience nausea, vomiting, constipation, weakness, and fatigue.

Other lung cancers (usually small cell cancer) cause the body to retain water, lowering the blood's sodium levels. This condition, called hyponatremia, can produce confusion, weakness, and even seizures.

Risk Factors

Before cigarettes became popular in the beginning of the 20th century, lung cancer was rare. In 2007, lung cancer is expected to strike up to 213,380 Americans, and about 160,390 are expected to die from it.The disease usually occurs in people over 50 years old. Men have a significantly greater incidence of lung cancer compared to women. On the encouraging side, the rate of lung cancer in men has been declining significantly over the past decade. While lung cancer rates have been increasing dramatically in women (by 600% from 1950 to 2000), they now appear to be stabilizing.

Smoking appears to be the primary risk factor in 85 - 90% of lung cancers. About 15% of all people who smoke develop lung cancer. The risk depends on the duration of the addiction and the number of pack years. (One pack year equals the number of packs of cigarettes smoked per day, multiplied by the number of years that the person has smoked.) Genetic damage in the lung occurs in nearly all chronic smokers, even if cancer has not developed.

An elevated risk for lung cancer can persist for more than 20 years after quitting smoking, although the risk drops significantly even in the first year after quitting. And, there are benefits to quitting smoking even for people who are well into middle age.


Quitting Age	Percentage
30	2%
40	3%
50	6%
60	10%

Second-Hand Smoke. The Environmental Protection Agency has classified second-hand smoke as a carcinogen (cancer-causing chemical). Exposure to second-hand tobacco smoke increases the risk of lung cancer in the nonsmoker by about 20 - 30%. A 2006 Surgeon General report found that about 3,000 nonsmokers die each year of lung cancer resulting from exposure to secondhand smoke.

There may be some ethnic differences in lung cancer risk. For example, African-Americans face a risk that is two to four times higher than that in Caucasians, regardless of smoking status. It is not clear what factors are responsible for this higher risk. Some African-Americans appear to have a genetic vulnerability to the harmful chemicals in cigarette smoke.

In China, an estimated one third of all young male smokers will eventually die because of tobacco-related illnesses. Their risk for lung cancer, however, is much less than it is for chronic lung disease, the opposite of the Western trend. A 2001 study reported that the lower rate of lung cancer among Chinese people might be due to a slow rate of clearing nicotine, which results in smoking fewer cigarettes.

People with High Exposure to Radon. Studies have shown that radon raises the risk of lung cancer in underground miners by 40%. It is unclear whether the results of these studies would apply to people exposed to radon in their homes One study suggests that people with intense or prolonged exposure to radon in their homes do indeed face the same risk as miners exposed to similar levels of radon. A cumulative long-term exposure to radon and smoking also increases the danger. Most people move an average of 10 or 11 times over their lifetime, so the risk of developing lung cancer through radon exposure is very low in most individuals, even for those who lived for awhile in areas with high radon levels. People with homes that have high radon levels and those who sleep or spend many hours to days in basements with detectable but moderate levels should consider taking protective measures.

Workers Highly Exposed to Carcinogens. An estimated 9,000 - 10,000 men and 900 - 1,900 women develop lung cancer each year because of occupational exposure to carcinogens. More than half of these cases are attributable to past exposure to asbestos, which has long been known to be a risk factor for mesothelioma (cancer of the pleura, the lining around the lung) and can increase the risk of lung cancer in smokers. With better protective measures, these rates are expected to fall in the future.

Other chemicals that put workers at risk for lung cancer include:

Arsenic (insecticide and herbicide sprayers, tanners, oil refinery workers)
Chloromethyl methyl ether (workers exposed to certain polymers, water repellents, or products using chloride and formaldehyde)
Chromium compounds (workers using certain alloys, paints, pigments, and preservatives)
Depleted uranium (soldiers exposed to weapons during battlefield conditions)
Crystalline silica

By contrast, agricultural workers seem to have a lower lung cancer rate, despite their possible occupational exposures to risky chemicals. While this rate has traditionally been attributed to good health habits, including low tobacco use, a 2000 study suggests that agricultural workers' exposure to endotoxin may be responsible. Endotoxin is a component of common bacteria found in soil and animals and may have cancer-preventing effects on the immune system.

Exposure to Smoke from Grills. Grilling and high-heat frying emit chemicals called heterocyclic amines, which are known to be carcinogenic. A 2000 study of Chinese women found that smokers who stir-fried meat daily and inhaled cooking fumes had a higher risk of lung cancer than did those who stir-fried meat less frequently. No higher risk was found among nonsmokers.

Air Pollution. Although any risk from air pollution is very small, it nevertheless may be a contributor to those lung cancers not obviously related to smoking. Some studies, including a major analysis of vital statistics in 2002, have found an association between increased risk for lung cancer and long-term exposure to very small particulates, especially sulfates, present in polluted air. The risk, if any, is very small.

A family history of lung cancer may play a role in increasing susceptibility to this disease. In one study, people who had parents or siblings with respiratory tract cancers had a 30% higher risk for lung cancer, compared to people without a family history. Women with mothers or sisters with lung cancer had triple the risk. A higher risk occurred in both smokers and nonsmokers. There was no association between a history of other cancers and lung cancer. Both genetic factors and secondhand smoke appeared to contribute to the danger in these individuals.

Smokers with emphysema or chronic inflammatory lung diseases, such as asthma, are at increased risk for lung cancer. Both smokers and nonsmokers whose lungs are scarred from recurrent lung diseases, such as pneumonia or tuberculosis, are also at increased risk, particularly for bronchoalveolar lung cancer.

Lifestyle Changes

Quitting improves lung function almost immediately. Some evidence suggests that the benefits for the lungs are even more significant for women who quit than for men. It should be noted, however, that it can take 20 years or longer, particularly in heavy smokers, for the lungs to be restored to a fully healthy condition in which the risk for lung cancer is as low as for nonsmokers. Quitting is extremely difficult. No one should be discouraged if they relapse. Everyone should keep trying to quit. With continued efforts, many people succeed.

The many methods of quitting smoking include counseling and support groups, nicotine patches, gums and sprays, and incremental reduction.

At this time perhaps the most effective method for quitting is a combination of the following:

Nicotine replacement products that reduce withdrawal symptoms and cravings.
The antidepressants bupropion (Zyban) or nortriptyline (Pamelor, Aventyl), which reduce emotional effects and cravings associated with withdrawal, and improve abstinence rates.
Professional counseling or support organizations that may be effective, in addition to the medication, in helping people maintain abstinence.

[See In-Depth Report #41: Smoking.]

While people are in the process of quitting (and afterwards), they should maintain as healthy a lifestyle as possible.

Phytochemicals. Some data suggest that diets rich in fresh fruits and vegetables may be protective against lung cancer in both smokers and non-smokers. Some studies have reported protection from specific plant chemicals (phytochemicals), such as the following:

Isothiocyanates. These chemicals are found in cruciferous vegetables (broccoli, cauliflower, and Brussels sprouts). They may help block the effects of carcinogens in smoke, suppress tumor growth, and inhibit growth-promoting steroid hormones.
Flavonoids. Major sources are apples, grapefruit, onions, red wine, and tea. In one study on flavonoids, apple eaters had the lowest cancer risk, 68% less than those who ate fruit infrequently. In another, those who ate relatively more onions, apples, and white grapefruit had less than half the lung cancer risk as people who ate relatively small amounts of these foods. Flavonoids are also found in soybeans, berries, broccoli, carrots, citrus fruits, eggplant, peppers, squash, and tomatoes. Specific flavonoids in dark chocolate may be protective against lung cancer (but not other cancers).
Lycopene. Lycopene is found in tomatoes, which have been associated with a lower risk for lung cancer. Cooking the tomatoes appears to increase the potency of lycopene.
Cryptoxanthin. Some studies suggest that eating foods rich in cryptoxanthin, a yellow-orange pigment, reduces the risk for lung cancer. Foods with high amounts of cryptoxanthin include pumpkin, corn, papaya, red bell peppers, tangerines, oranges, and peaches. More research is needed in this area, however.
Isoflavones. Isoflavones, found in soy beans and flax seed, behave like estrogen in some ways and not in others. Some evidence suggests the genistein (a type of isoflavone) in soy may have properties that are protective against lung cancer.

Click the icon to see an image of phytochemicals.

Note: Studies on these chemicals are not consistent. It is unlikely that individual phytochemicals offer protection, but rather that the benefits come from a collection of vitamins and plant chemicals contained in fruits and vegetables. Fruit, especially, appears to be protective.

Fats and Oils. Some studies have indicated that diets high in animal fats increase the risk for lung cancer. Others have suggested some protection from cod liver oil, which contains omega-3 fatty acids (found in fatty fish), omega-6 fatty acids (found in flax and in soybean and canola oils), and monounsaturated oils (found in olive and canola oils). Of interest was a 2002 study reporting that women who had a high intake of cheese had a lower risk of lung cancer. Despite these intriguing pieces of information, the ability of these substances to protect against lung cancer remains controversial, and discontinuation of smoking remains the best advice.

Click the icon to see an image of fats and oils.

Vitamin Supplements. Even with a healthful diet, smoking reduces the levels of a number of vitamins, importantly vitamin C. There is no evidence, however, to support any protection from antioxidant supplements, including vitamins E, A, or beta carotene.

In fact, evidence is now suggesting that high doses of vitamin C, vitamin E, and beta carotene supplements may have harmful effects. A 2000 study, for example, reported a higher risk for cancer in male smokers who took multivitamins plus A, C, or E. The strongest studies to date on negative effects of antioxidant supplements have reported 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. In other words, antioxidants may actually be harmful in people who already harbor cancer cells. This is particularly important information for smokers, who may carry precancerous or cancerous cells for years prior to developing the disease. The best way of achieving healthy levels of important nutrients is from healthy foods.

Click the icon to see the benefits of vitamin A.

Click the icon to see dietary sources of vitamin A.

Trace Element Supplements. Trace elements may be important in cancer risk and prevention.

Selenium appears to inhibit cell production and may have other anti-cancer properties. A few studies have reported some protection with selenium. However, a major 2002 analysis supports previous work, indicating that taking selenium helps only people who are deficient to begin with.

Click the icon to see the benefits of selenium.

Zinc may prove to be more important than selenium. Some research suggests that zinc may help protect smokers by blocking cadmium. Smokers have higher levels of cadmium in their body, and there may be a link between cadmium and a higher risk for lung cancer. Some laboratory studies have indicated that zinc might help protect against tumor progression. There is no evidence that taking zinc supplements will reduce the risk for lung cancer, however.

A 2003 study reported a lower risk in lung cancer in men and women who were physically active. Both moderate and intensive exercises were associated with protection.

People concerned about radon in their home or area can purchase a test approved by the Environmental Protection Agency. Methods for removing radon include installing a soil suction system. It should be noted, however, that home prevention measures rarely reduce radon levels to zero. Simply sleeping by an open window reduces the risk.

Nonsteroidal anti-inflammatory drugs (NSAIDs) and COX-2 inhibitors (coxibs) both block cyclooxygenase (COX) enzymes. NSAIDs block COX-1 and 2, and coxibs selectively block COX-2. Evidence now strongly suggests that the COX-2 enzyme plays a role in blood vessel growth (angiogenesis) that can feed lung cancers.

NSAIDs. NSAIDs include aspirin, ibuprofen (Advil), and naproxen (Aleve, Naprosyn, Naprelan, Anaprox). These agents inhibit COX-2, but they also target another COX enzyme. Studies are now reporting an association between regular use of aspirin or other NSAIDs and a reduced risk for non-small cell lung cancer.

COX-2 Inhibitors. The COX-2 inhibitors are more recent forms of NSAIDs. Currently, only celecoxib (Celebrex) is still on the market. Rofecoxib (Vioxx) and valdecoxib (Bextra) were withdrawn from the market due to their high risk of causing strokes and heart attacks. Because they target the COX-2 enzyme specifically, researchers are focusing on these drugs for a possible role in treating lung cancer and preventing recurrence.

Diagnostic Tests

Chest X-Rays. In a small percentage of cases, a routine chest x-ray reveals the first signs of lung cancer. Usually, however, symptoms of existing lung cancer, such as coughing, chest pain, and blood in the sputum, will lead to a chest x-ray. If non-small cell lung cancer is present, chest x-rays may show lesions (damaged or abnormal tissue) in the center of the lung, cavities formed by squamous cell carcinoma, or lace-like pattern of cells spreading through the lungs. By the time lung cancer is diagnosed by chest x-rays, however, it has often spread so far that it cannot be surgically cured. Four major studies found no survival benefits in early detection from chest x-rays and sputum screening. Regular screening for lung cancer using x-rays is therefore not currently recommended.

Computed Tomography. Computed tomography (CT), particularly the specific technique called low-dose spiral (or helical) CT, is more effective than x-rays for detecting cancer in patients with suspected lung cancer. It is the standard imaging procedure for determining if and where the cancer has spread (metastasized). Surgeons also use CT scans to evaluate patients before lung surgery.

CT stands for computerized tomography. In this procedure, a thin x-ray beam is rotated around the area of the body to be visualized. Using very complicated mathematical processes called algorithms, the computer is able to generate a 3-D image of a section through the body. CT scans are very detailed.

The use of helical CT for early screening is still controversial. Studies of CT scans in smokers suggest that early screening will detect about 2% of lung cancers, most of these in early stages. In the studies, 62 - 82% of the patients with stage 1A cancer (when the tumor has not spread yet) were still alive at 5 years. Neither study, however, was controlled (compared with other groups, such as non-smokers). The survival figures were likely to be higher than in actual practice.

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

Evidence regarding the survival benefits of early detection is not clear. Many experts are highly opposed to widespread screening for lung cancer. Some evidence, for example, suggests that lung cancer cells in non-small cell lung cancer are often very aggressive at microscopic levels (before a tumor is formed). If this were true, the cancer would be highly likely to have already spread, long before it was visible with CT scans. Moreover, some studies have found no association between tumor size at the time of diagnosis and survival times. On the other hand, some suspicious areas detected by CT scans may actually be innocent, and these patients might be more likely to die from aggressive treatments than from the disorder itself.

It should also be noted that about 98% of suspicious areas seen on CT scans turn out to be benign. Even after rescreening, many scans will show suspicious areas that turn out to be harmless but will require invasive and expensive biopsies. Additional experience with CT scans, however, may allow experts to better determine which abnormalities are likely to be benign.

High-risk individuals who are still interested in early screening with CT scans should ask their doctor about available clinical trials.

Computed tomography is the standard imaging procedure for determining if and where the cancer has spread (metastasized). Other imaging tests, however, may be useful for staging and tracking lung cancers (staging means finding out how advanced the cancer is).

Positron Emission Tomography. Positron emission tomography (PET), specifically a technique known as FDG/PET, is the most accurate noninvasive test for detecting early lung cancer. It is also the best imaging technique for staging lung cancers, not only those located in the lungs, but also those that have spread, particularly into the space between the two lungs (the mediastinum). With this imaging test, the patient is first injected with a specially formulated liquid sugar (called FDG), and then viewed with a machine that records energy given off by tumor cells.

PET is expensive and not widely available. However, its supporters suggest that it may prevent many unnecessary surgeries by identifying patients whose cancer has advanced past the stage at which surgery is helpful. There is some evidence that FDG/PET scan can detect a metabolic (processing) response to treatments that may help predict the outlook for the patient.

Scintigraphy. Scintigraphy is an imaging procedure in which patients are administered low-level radioactive agents that bind to cancer cells, which then can be tracked by special cameras to reveal the cancer cells' location and intensity. Agents selected are those that can best bind successfully with specific tumor types. For example, a 2001 study of the binding agent 111In-DOTA-LAN demonstrated excellent results in identifying non-small cell lung tumors. This study further suggests the possibility of using such highly-targeted binding agents as lung cancer treatments.

Magnetic Resonance Imaging. Magnetic resonance imaging (MRI), an imaging procedure that uses radio wave energy, is frequently used instead of CT scanning to locate brain and bone metastases that can be associated with lung cancer.

Biopsies of lung tissue are needed to confirm lung cancer. This requires invasive procedures that may vary from simple needle aspiration to chest surgery.

Needle Aspiration. Sometimes, a biopsy specimen is obtained by inserting a needle between the ribs, and then guiding it with the use of computed tomography scans, ultrasound, or fluoroscopy (a device allowing an x-ray view). Specific techniques include transbronchial or transthoracic needle aspiration (TBNA or TTNA) or endoscopic ultrasound-guided needle aspiration (EUS-NA). Their use depends on how much of the area can be observed with less invasive imaging methods. There is a 5 -10% risk for bleeding or collapsed lung with needle aspiration.

Thoracoscopy. Thoracoscopy is usually very effective for diagnosing cancer in the outer areas of the lungs, or those involving the pleura (membrane surrounding the lungs). This is a surgical procedure that uses a fiber-optic tube to view the area:

The procedure requires general anesthesia.
The surgeon passes surgical instruments and a fiber-optic tube through a small incision in the chest. The tube has a camera in it, which allows the surgeon to look at the lungs on a video screen.

Bronchoscopy. To locate cancer that develops in the central areas and major airways of the lung (usually squamous or small cell cancer), bronchoscopy is typically performed. The procedure is done as follows:

The patient is given a local anesthetic, supplementary oxygen, and sedatives.
The doctor inserts a bronchoscope, a hollow flexible tube often containing a fiber-optic light source, into the lower respiratory tract through the nose or mouth.
The tube acts like a telescope into the body, allowing the doctor to see the windpipe and major airways. In a procedure called fluorescence bronchoscopy, the doctor injects the patient with a drug that makes cancer tissue appear red when exposed to laser light from the bronchoscope.
The surgeon removes specimens for biopsy, ideally combining techniques to include cutting tissue, brushings, and a washing process called bronchoalveolar lavage (BAL). BAL involves injecting saline through the bronchoscope into the lung and then immediately suctioning the fluid back through the hollow tube of the bronchoscope; the fluid is then analyzed in the laboratory. Both brushing and washing procedures may be very valuable additions.

Advances in this procedure, such as laser-induced fluorescence endoscopic bronchoscopy, may improve early detection of cancer.

Bronchoscopy 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.

Click the icon to see an image of bronchoscopy procedure.

Click the icon to see an image of a bronchoscope.

Mediastinoscopy. Mediastinoscopy uses a tube inserted between the lungs to locate the appropriate areas for biopsy. It is performed if the physician suspects that cancer has spread to nearby lymph nodes but has not yet metastasized.

Sputum Analysis for Presence of Cancer Cells. Some experts are now recommending an analysis of coughed-up sputum as a useful and cost-effective measure for identifying cancer cells, particularly those located in central areas of the lung. However, although sputum analysis appears to be as accurate as any other screening test currently conducted, it may miss cancers such as adenocarcinoma, which form in mucus-producing cells typically in the outer portion of the lungs. If a sputum analysis does not show cancer cells, but other signs of lung cancer are present, including blood in the sputum and suspicious areas on x-rays, other tests are performed.

Biomarkers. Biologic markers, called biomarkers, are high levels of substances that are released by tumors and indicate the presence of specific cancers. Biomarkers can be found in sputum, blood, and tissue samples. They can include enzymes, hormones, amino-acid compounds, antigens (identified by antibodies that specifically target them), growth factors, and other chemicals. Some biomarkers may prove to reveal the presence of cancer cells before they are evident on CT scans or other imaging tests. For example, genetic mutations, notably K-ras and p53, can now be detected in cells found in sputum, or cells taken during bronchoscopy. Such mutations occur only with cancerous changes and may enable early detection. Other markers that prove to be important for predicting aggressive cancers are high levels of matrix metalloproteinase (MMP9) and vascular endothelial growth factor (VEGF), which are compounds involved with angiogenesis (the process in which blood vessels serving the tumor develop).

As part of the doctor's initial examination, patients may have a pulmonary function test to evaluate lung health and capacity. In addition, since the heart and lungs are often involved in complications following lung cancer surgery, the doctor may be especially interested in taking a complete history of those systems in patients who might need surgery.

Staging Systems

Tests to Determine Cancer Stage. After diagnosing non-small cell lung cancer, the doctor makes treatment choices by determining the cancer's stage (how large the tumor is and how far the cancer has spread). To stage the cancer and determine other aspects of the disease, a number of tests are conducted:

The cancer cells are examined microscopically for size, shape, and other configurations.
Computer tomography (CT), magnetic resonance imaging (MRI), or both, are used to scan the lung and perhaps other locations, such as the liver, upper abdomen, and brain, to determine the extent of the disease.

Physical Examination. A detailed physical examination of the whole body is very important to identify or rule out the spread of cancer to other areas, and to determine the general condition of the patient. For example, questions about dizziness or headaches can help the doctor determine if the cancer has spread to the brain, while bone or joint pain might suggest that the cancer has spread to the bone. The doctor will also look for head and neck symptoms that might reveal the presence of other tumors. Also, according to a 2000 review, the patient's weight loss and ability to function are two very important factors for predicting survival following treatment. Patients who are mobile and have lost less than 10% of their pre-treatment weight tend to have better survival rates.

In lung cancer, the stage of the disease at the time of diagnosis is a major factor in determining how to treat the cancer, and how long the patient can expect to live. In general, survival is longest for patients with very early-stage disease and shortest for patients with very advanced disease that has spread to several regions of the body. Staging is based on the results of physical and surgical examinations, and laboratory and imaging tests, including biopsies.

To determine the stage, medical professionals first categorize each tumor by size and by how far it has extended. This identification method is called the TNM system.

The TNM categories then determine the stage (numbered 0 to IV), indicating how advanced the cancer is.

TNM stands for Tumor, regional lymph Nodes, and Metastasis (cancer spread beyond the original tumor).

T refers to the size and extension of the tumor itself. In TX and T0, the tumor is indicated by cancer cells in sputum or lung samples but cannot be seen. Tis: Carcinoma in situ. The cells are cancerous, but the tumor does not show evidence of spreading. In T1, the tumor is 3 cm or less in size, is still contained in the lung or the membrane covering the lung, and has not reached the main airway.

In T2, the tumor has one or more of the following features:

It is greater than 3 cm
It involves the main airway
It is 2 cm or more away from the ridge (the carina) at the lowest part of the windpipe
It has invaded the pleura
It is associated with collapsed lung tissue (atelectasis) or swelling that blocks part (but not all) of the lung

In T3, a tumor of any size has directly invaded any of the following:

Chest wall
Diaphragm
The membrane covering organs and structures in the chest
The outer wall of the membrane around the heart (pericardium)

In addition, one or more of the following conditions are present:

The tumor is in the main airway, less than 2 cm away from the carina, but is not in the trachea (windpipe).
The tumor is associated with a collapsed lung or swelling that blocks the entire lung.

In T4, the tumor has invaded any of the following:

The area between the lungs (mediastinum)
The heart
The great vessels (the blood vessels that carry blood from the heart)
Carina, trachea, or esophagus
Main portion of the spine

In addition, one or both of the following occurs: separate tumors are present in the same lobe; the tumor is accompanied by an increased amount of fluid between the pleural membrane and the lung.

N followed by a number from 0 to 3 refers to whether the cancer has reached regional (in the area of tumor) lymph nodes. In stage N0, the regional lymph nodes are still cancer-free.

In N1, the cancer has spread to the nearest lymph nodes around the airways, to the hilum (a central zone in the lung where blood and lymph vessels enter), or both. The tumor has extended directly into lymph nodes within the lung. In N2, the cancer has spread to lymph nodes in the middle of the chest that are still next to the affected lung, to the nodes below the carina, or to both regions.

In N3 the cancer has spread to lymph nodes in the middle of the chest that are next to the opposite lung, to the hilum in the opposite lung, to lymph nodes in nearby or opposite muscle tissue, or to lymph nodes above the collar bone.

M Stages refer to metastasis. In M0, metastasis has not occurred.

In M1 distant metastasis has occurred. This includes the presence of a separate tumor in a different lobe.

Staging factors are used to help determine treatment and outlook. The following suggest a more aggressive disease:

The presence of respiratory symptoms
A tumor larger than 3 cm
High numbers of blood vessels in the tumor

Researchers are always looking for more accurate ways to determine a treatment and outlook for lung cancer. For example, some research involves specific biomarkers and related blood vessel development within tumors. These markers might eventually help determine how aggressive a cancer is likely to be, and what the best treatment approach is.

If the cancer is still localized, surgery can produce 5-year survival rates of up to 75% in stage I patients and up to 50% in stage II patients. Unfortunately, very few patients are diagnosed at such early stages. In locally advanced stages, the standard treatment is concurrent radiation and chemotherapy. However, even with this approach average survival times are less than 2 years. Even if an initial tumor has been surgically removed or irradiated, cancer recurrence rates are very high. The risk for recurrence is lower in smokers who quit after treatment.

On an encouraging note, advances in therapies for later stage lung cancer are now offering some hope for improving survival. Still at this time, the mortality rate for lung cancer is still extremely high, and reports of improved response or survival rates using drugs or combinations of therapies do not mean cures. Ultimately, the patient must weigh a diminished quality of life using aggressive treatments against a chance for a modestly prolonged life.

Surgical Procedures

Surgery is performed in the following circumstances:

The surgical removal of an entire lobe or parts of a lung is the primary treatment for eligible patients in early stages of cancer. Recurrence is high after surgery, although the new tumor is often operable.
Some patients with stage IIIA cancer may also benefit from surgery. The intent at this stage is to extend survival time, rather than cure the disease.
Surgery is not out of the question in rare cases of metastasis when the cancer appears in a single operable location, such as the brain.

Unfortunately, lung surgery may be too risky for patients with other lung diseases or serious medical conditions, and because lung cancers tend to occur in smokers over 50, such health problems are likely to be present. Long-term survival rates appear to be better in patients treated at hospitals that perform large numbers of lung cancer surgeries, and when surgeries are performed by thoracic surgeons, who specialize in chest procedures.

The type of surgery depends on the amount of lung or other tissue that needs to be removed.

Wedge Resection or Segmentectomy. Wedge resection and segmentectomy remove only a small part of the lung; consequently, they preserve almost normal breathing function after the operation.

Lobectomy. Removal of one of the lobes of the lung is called lobectomy. The patient's lung function must be adequate before undergoing this procedure. The operation carries an overall mortality rate of 3 - 5%, with older patients having the highest risk.

Click the icon to see an illustrated series detailing surgery to remove diseased lobes of the lung.

Pneumonectomy. Pneumonectomy removes the entire lung. The procedure itself carries a mortality rate of 5 - 8%, with the oldest patients having the greatest risk. In such patients, recurrence almost always occurs.

Surgical advances are allowing a wider range of options, including minimal surgeries for early cancers and surgeries that relieve cancer symptoms in late stages of the disease.

Thoracoscopy. Thoracoscopy, also known as video-assisted thoracic surgery (VATS), is a less-invasive technique that employs a thin tube containing a miniature camera and surgical instruments. It requires much smaller incisions than open surgery and speeds recovery to the point that patients are up within hours. Though the procedure is not appropriate in all cases, it offers significant advantages, especially in older or frail patients. The death and complication rates following VATS are lower than those following conventional surgeries. Pain is reduced, and patients are released from the hospital quicker. Several studies found that the 5-year survival and recurrence rates in patients with stage I NSCLC treated with VATS were comparable to those in patients treated with traditional open chest surgeries.

Laser Surgery. Laser surgeries allow removal of minimal amounts of lung tissue and are proving useful for improving symptoms in stage II and IIIA patients. They may also be beneficial in treating cancers that have spread to the throat, obstructing it.

Photodynamic Therapy. Photodynamic therapy uses bronchoscopy and special laser light beams combined with a light-sensitive drug, called porfimer sodium (Photofrin), to kill cancer cells. The most common side effect is sun sensitivity. Serious side effects include bleeding in the lungs. Photodynamic therapy may be considered for patients in early-stage disease who are not candidates for other surgical procedures. It may also be used to reduce symptoms in late-stage disease.

Cryosurgery. Cryosurgery uses a probe chilled to below freezing to destroy the tumor cells on contact and is being investigated in combination with radiation therapy. It may also be an alternative in early stage cancer for patients who cannot have surgery.

Electric Cauterization. Electric cauterization, the use of electricity to produce heat that destroys tissue, is also under investigation as a treatment for early-stage disease.

Back Surgery. Spinal cord compression is a common cause of pain in patients with advanced lung cancer. Because such patients can live for a year or longer, some research indicates that back surgery followed by radiation therapy can significantly improve the quality of life for many of these patients.

Radiation Treatments

In addition to surgery, radiation is the other primary treatment for early-stage lung cancer. Doctors are also studying the benefits of radiation treatment in advanced lung cancer.

Radical Radiation in Early-Stage Cancer. Radical radiation is used as the sole procedure in stage I and some stage II patients who have adequate lung function but, for medical or other reasons, cannot be treated with surgery. In these cases, the 5-year survival rate is about 20%, and the cancer is likely to recur. Survival rates may be higher or lower, depending on the tumor size. In general, treatment with radiation therapy alone shows less benefit with larger tumors. A 2002 analysis suggested that the use of radiotherapy after surgery in patients whose tumors had been completely removed might be associated with reduced survival rates. Nevertheless, a recent study confirmed earlier results that show that radiation therapy by itself is as effective as surgery in patients who are unable or unwilling to have surgery for early stage non-small cell lung cancer.

Combined Treatments for Improving Survival in Advanced Cancer. Radiation is also being investigated in various combinations with chemotherapy, surgery, or both. At this time, concurrent radiation treatment plus platinum-based chemotherapy may extend survival times in advanced lung cancer. Other combinations are showing promise.

Palliative Radiation. Doctors use palliative radiation to shrink tumors and reduce pain and symptoms. Palliative radiation is appropriate for patients with advanced disease and poor lung functions, or in those with metastasized cancer. In up to 85% of patients with advanced disease, palliative radiation therapy helps relieve pain, shortness of breath, the superior vena cava syndrome, coughing up blood, and symptoms caused by brain metastases. Radiation, in these cases, is not generally used with the intention of reducing mortality rates, although it may increase survival in some patients, such as those with excellent lung function whose tumors are small.

Delaying radiation therapy until symptoms develop does not appear to reduce survival times or impair quality of life compared to starting it right away, in patients with minimal or no symptoms.

Radiation Therapy in Metastasis to the Brain. Radiation is the primary treatment when cancer has spread to the brain unless the cancer is small enough to be treated surgically. When radiation is used, a technique called stereotactic radiosurgery may be used to deliver powerful, highly targeted radiation to specific areas in the brain. Some trials are investigating using radiation to the head to prevent metastasis to the brain.

The goal of radiation treatment is to administer doses as high as possible to kill as many cancer cells as possible, without destroying surrounding healthy tissues or causing a dangerous reaction. Doctors may try different procedures for the same patient. The exact radiation procedure depends on the site of the cancer or how far it has spread:

External-Beam Radiation. External-beam radiation therapy focuses a beam of radiation directly on the tumor. It is generally used for metastasized cancer.
Brachytherapy. Brachytherapy involved the implantation of radioactive seeds through thin tubes directly into the cancer sites. Brachytherapy may be used for lung cancers that have spread to the throat and caused obstruction. High-dose-rate brachytherapy may also have some value for patients with inoperable tumors in the central region of the lung.

Hyperfractionated radiotherapy gives smaller than standard doses a number of times a day (usually two or three). This allows doctors to use a higher cumulative dose over the whole course of treatment. It is not as useful as therapy by itself, but should be combined with chemotherapy to have any survival benefits.

Hyperfractionated Accelerated Radiotherapy. Continuous hyperfractionated accelerated radiotherapy (CHART) administers multiple doses per day but uses standard doses. This allows the total dose of radiation to be administered over a shorter time period than the standard 6 weeks. CHART is proving to extend survival rates of patients with localized cancer over that of standard radiotherapy or non-accelerated hyperfractionated radiation. It can cause severe swallowing problems. A modification in which treatment is suspended for 2 days out of 7 may help reduce this effect.

Three-dimensional (3-D) conformal radiotherapy delivers external-beam radiation designed to closely match the specific targeted organs or tissues. This allows significantly higher doses to attack the cancer while reducing the risk to healthy cells. In a 2003 report, 3-year survival rates in stage IIIA patients were nearly 60%, and nearly half the patients experienced no side effects.

Stereotactic body radiotherapy, an advance on conformal radiation, uses a body frame and an abdominal press to immobilize the patient's body and limit breath movement. This allows a more accurate delivery of high-energy radiation. The technique is still investigational.

Radiation can have significant side effects when used as part of intensive treatments, such as hyperfractionated radiotherapy or radiotherapy in combination with chemotherapy. Among the most serious problems is severe inflammation in the esophagus (esophagitis) or the lungs (pneumonitis). Infection is also a danger.

The use of targeted approaches, such as conformal radiotherapy, may help reduce these complications. Investigators are also studying drugs, notably amifostine, which appear to help reduce throat and lung inflammation caused by radiation, without reducing its cancer-fighting effects.

Treatment Options by Stages

In the occult stage (TX, N0, M0), cancer cells are found in a sample of a patient's coughed-up sputum, but no cancer cells have yet been detected in the lung.

Treatment Options. Surgical removal of the tumor, if one can be located, allows identification of its stage and often results in cure.

Stage 0 or carcinoma in situ (Tis, N0, M0) are noninvasive cancers and only a few layers of cancer cells are detected within one local area. The cancer has not grown through to the top lining in the lung and can be surgically removed. There is a high risk for development of a second tumor, however.

Treatment Options:

Surgery, often a limited procedure, where only part of a lobe is removed from the lung.
In patients who cannot be treated surgically, consider photodynamic therapy, cryotherapy, or brachytherapy.

In stage I, the cancer has reached higher layers of the lung but has not spread into the lymph nodes or beyond the lung.

General Treatment Options. The primary treatment is surgery, such as lobectomy (removal of a whole lobe), if possible. Patients with poor lung function should undergo partial lobectomy, if possible. Radiation treatments may be appropriate and beneficial for patients who cannot have surgery. It is not clear if early-stage lung cancer patients, who have radiation or chemotherapy in addition to surgery, have higher survival rates. A 2002 analysis suggested that the use of radiotherapy after surgery in patients whose tumors had been completely removed might be associated with reduced survival rates. An analysis of studies using chemotherapy in addition to surgery or radiotherapy, however, indicated benefits in survival. The overall 5-year survival rates for early stage-cancer are in the range of 30 - 50%. Patients should consider clinical trials for prevention of recurring (returning) cancer after the initial treatment. The risk for recurrence is highest in patients who continue to smoke.

Stage IA (T1, N0, M0). The 5-year survival rates for stage IA patients after successful treatment can be as high as 80%. Treatment options are:
- Lobectomy or sometimes pneumonectomy (removal of one lung)
- Wedge or segment removal, particularly in patients with poor lung function who cannot withstand lobectomy
- Radiation in selected patients whose condition is inoperable (for example, frail patients with T1 tumors); 5-year survival rates can be equal to those with surgery, between 32 - 60%
- Clinical trials of adjuvant chemotherapy following surgery

Stage 1B (T2, N0, M0). Stage IB survival rates after treatment can be better than 60%. Treatment options are:
- Lobectomy or sometimes pneumonectomy; wedge or segment removal, particularly patients with poor lung function
- Clinical trials of chemotherapy following surgery
- Clinical trials of chemotherapy before surgery (induction therapy; studies are promising)
- Clinical trials for radiation treatments in selected patients whose condition is inoperable
- Clinical trials of chemotherapy before, after, or during radiation treatments

In stage II the cancer cells have spread to nearby lymph nodes.

General Treatment Options. Surgery, usually removal of a lobe (lobectomy) or one lung (pneumonectomy), is the treatment of choice. Five-year survival rates associated with stage II surgery can vary. A 2000 review of existing research places the numbers as high as 40 - 50%, but notes that they can drop to 25% and below if the cancer has spread beyond the immediate lymph nodes.

Patients whose cancer is inoperable may consider radiation treatments. In patients who can complete treatment, 5-year survival rates average 20 - 30%, with higher rates for stage IIA. Patients should consider clinical trials for prevention of recurring cancer after primary treatment. To date, however, supplementing surgical treatment with radiation or chemotherapy does not appear to prolong survival rates.

Stage IIA (T1, N1, M0). Survival rates can be as high as 60%. Treatment options are:
- Surgery
- Radiation
- Clinical trials of chemotherapy following surgery
- Clinical trials of chemotherapy before, after, or during radiation treatments
- Clinical trials of chemotherapy to reduce tumor size before surgery (induction therapy)
Stage IIB (T2, N1, M0) or (T3, N0, M0). Survival rates can be over 40%. Treatment options are:
- Surgery
- Radiation
- Clinical trials of chemotherapy following surgery
- Clinical trials of chemotherapy before surgery (induction therapy)
- Clinical trials of chemotherapy before, after, or given at the same time as radiation treatments

In stage III, the cancer cells have spread beyond the lung to the chest wall, diaphragm, or further lymph nodes, such as those in the neck.

General Treatment Options. Generally, the treatment of choice for stage III tumors is radiation and sometimes surgery, chemotherapy, or combinations of all three.

Combination approaches may be significantly more effective than single treatments. For example, of particular interest is a treatment approach that starts with chemotherapy and radiation, given at the same time, followed by surgery. In one study, 5-year survival in stage III patients treated this way was nearly 50%.

Stage IIIA (T1, N2, M0) or (T2, N2, M0) or (T3, N1, M0) or (T3, N2, M0).
- Surgery, if the tumor and affected lymph nodes can be completely removed. Consider platinum-based chemotherapy or radiation therapy after surgery.
- Radiation treatment plus platinum-based chemotherapy, given at the same time, is an option for those in otherwise good health. This regimen should be followed by surgery, if possible.
- Consider clinical trials using advanced radiation techniques, including continuous hyperfractionated accelerated radiation, or 3-D conformal radiation.
- Consider other clinical trials, including those of various combination treatments, preventive radiation therapy to the brain, and new second-line drugs.
Stage IIIB (Any T, N3, M0) or (T4, Any N, M0). Some patients may consider surgery if there is no lymph node involvement (T4, N0), and tumor can be removed. Surgery is not an option for other patients with stage IIIB cancer. Treatment options are:
- Radiation alone, usually for symptom control; it may improve survival in certain patients, such as those with lymph node involvement above the collar bone
- Chemotherapy alone
- Concurrent (given at the same time) cisplatin-based chemotherapy plus radiation, sometimes followed by surgery if possible
- Clinical trials using induction chemotherapy alone to shrink tumors, which may then be treated with surgery or radiation
- Clinical trials using advanced radiation techniques, including continuous hyperfractionated accelerated radiation, or 3-D conformal radiation
- Other clinical trials, including those of various combination treatments, preventive radiation therapy to the brain, and new second-line drugs

In stage IV (any T, any N, M1), the cancer has spread (metastasized) to other parts of the body.

Treatment Options are:

Combination of two- or three-drug chemotherapies that include platinum-based drugs and newer agents; the best patient candidates are those in otherwise good health, who have a limited number of distant metastasized sites. Chemotherapy is not recommended for patients who are too ill
External-beam radiation for symptom relief
Paclitaxel or gemcitabine as a single medication
Other clinical trials
If metastasized cancer involves only one or two areas in the brain, it may respond to surgery followed by radiation to the brain

Recurring or additional new tumors occur, usually in the lung again, in half of treated patients. Research shows that a single tumor in the lung is more often a new tumor that, in many cases, may be operable.

Treatment Options are:

Radiation for symptom control
Chemotherapy with or without bevacisumab (Avastin)
If the cancer spread to only one site in the brain, it may respond to surgery, followed by whole-brain radiation. Extended disease-free survival is possible. If the brain tumor is not operable, it is treated with radiation. Even if cancer returns in the brain (in 50% of cases), treating it again is possible in many patients, if the disease has not spread elsewhere
Laser therapy or interstitial radiation for tumors inside the airways
Stereotactic radiosurgery (in a few selected patients)

Chemotherapy Treatments

Chemotherapy is the use of drugs given by mouth or by injection to destroy cancer cells that may have spread beyond the tumor. Until recently, there has been some doubt about the effectiveness of chemotherapy for lung cancer. A major 2002 analysis of 52 trials supported its use, particularly with platinum-based regimens, and with the use of supportive care.

Chemotherapy in early stages: Chemotherapy is proving to be beneficial in many patients as an additional (adjuvant) treatment with surgery or radiation.
Chemotherapy in advanced disease: Chemotherapy may be used as first-line treatment in patients with inoperable or metastasized lung cancer. It is typically used in late stages to reduce symptoms and, in some cases, extend survival. Since 2006, the combination of bevacizumab (Avastin, a monoclonal antibody) and platinum-based chemotherapy is also a first line treatment choice for such patients, if the cancer is the non-squamous type

Powerful platinum compounds, either cisplatin (Platinol) or carboplatin (Paraplatin), are the basis for most chemotherapy regimens. Two-drug combinations, with one drug being a platinum-based agent, are currently the preferred regimens. Reasonable combinations include paclitaxel (Taxol) and carboplatin or cisplatin. This regimen can also include gemcitabine, docetaxel, or vinblastine or its derivative (vindesine or vinorelbine). There does not seem to be any significant differences in effectiveness among them. Gemcitabine and vinorelbine combination might be a good option for patients who cannot tolerate platinum compounds. Chemotherapy for lung cancer may have reached its peak. Still, investigative chemotherapeutic drugs may yet improve response. Many experts are pinning their hope on agents called biologic response modifiers, such as gefitinib (Iressa) or LY900003 (Affinitak). To date, however, they have not achieved better results than standard platinum-based chemotherapies. Gefitinib (Iressa), a second-line therapy for non-small cell lung cancer (NSCLC), is now available only for a limited group of patients. These patients have benefited from gefitinib in the past, or they are enrolled in a clinical study with the drug. While this medicine initially showed great promise in clinical trials, results from a newer study failed to show that it prolonged survival in advanced lung cancer patients who failed other treatments.

If you are currently taking gefitinib, do not stop taking it without talking to your doctor.

Erlotinib (Tarceva) is in the same medication class as gefitinib. It is approved for patients with locally advanced or metastatic NSCLC, who have failed one type of chemotherapy treatment in the past (it is a second-line treatment). Unlike gefitinib, erlotinib shows survival and progression-free benefits compared to placebo. However, it should not be combined with platinum-based chemotherapy.

Chemotherapy treatments are usually performed in an outpatient setting and in regular cycles for several months. How many chemotherapy cycles to administer in late-stage cancers, the timing of those cycles, and the sequences of the drugs are still matters of investigation. For instance, research suggests that a three- or four-course cycle may achieve the same survival times and better quality of life than the standard of six or more course cycles. Changing even one day in a drug sequence can sometimes significantly affect outcome. Such fine-tuning of chemotherapy regimens is likely to have the most effect on patients with advanced-stage disease, which requires more tailored treatment than early-stage disease.

Treatment for lung cancer depends on the type of cancer and the stage of the disease. Chemotherapy is a form of treatment for lung cancer that may cure, shrink, or keep the cancer from spreading.

Side effects of chemotherapy treatments are common, and they are more severe with higher doses. Side effects increase over the course of treatment. Some trials suggest that they can be reduced by giving the drugs for shorter durations, without loss of cancer-killing effects. Common side effects include the following:

Diarrhea
Temporary hair loss
Weight loss
Fatigue
Depression
Nausea and vomiting: Drugs known as serotonin antagonists, especially ondansetron (Zofran), can relieve these two side effects. Serotonin antagonists work well in nearly all patients given moderate drugs, and in most patients who take drugs that are more powerful. In one study, a combination of dexamethasone (a steroid) with ondansetron, taken within 24 hours of chemotherapy, achieved either a major or complete reduction in nausea and vomiting.
Anemia: Anemia, an abnormally low number of red blood cells, is common in lung cancer. Treatments include transfusions or injections of erythropoietin, an agent that causes more red blood cell production. Erythropoietin is available as epoetin alfa (Epogen, Procrit) and darbepoetin alfa (Aranesp), which requires fewer injections. These agents improve well-being and quality of life. Trials are in progress to determine if they may have survival benefits as well.

These side effects are nearly always temporary. Most patients are able to continue with normal activities for all but perhaps 1 or 2 days per month.

Serious complications of chemotherapy can also occur and may vary depending on the specific drugs. They include the following:

Increased chance for infection from suppression of the immune system.
Severe drops in white blood cells (neutropenia): Certain chemotherapy drugs, such as taxanes, pose a higher risk for this complication than other drugs. White blood cell count can improve with the addition of a type of drug called granulocyte colony-stimulating factor (filgrastim and lenograstim).
Liver and kidney damage: Amifostine (Ethyol) reduces the risk for kidney damage in patients taking repeated regimens of cisplatin-based therapy. It is also a radioprotector; that is, it helps prevent severe effects in the esophagus from radiotherapy, with or without chemotherapy.
Abnormal blood clotting (thrombocytopenia).
Allergic reaction, particularly to platinum-based agents: A simple skin test is under investigation that may identify people with a potential allergic response.

Second-line chemotherapy is used for patients whose cancers have recurred after first-line chemotherapy. Some experts believe that the longer survival rates for advanced lung cancer seen for the past 5 years may be due to these drugs. Because platinum-based agents are most often used first, they are not beneficial for second-line therapy. The following are commonly used second-line agents.

Docetaxel (Taxotere). Docetaxel is the drug of choice at this time for cancers that do not respond to initial chemotherapy. Studies have reported that it achieves longer survival times than supportive care alone. It is usually given every 21 days. This regimen causes more side effects than pemetrexed, the newer major second-line drug. Weekly doses of docetaxel are effective and less toxic than the 3-week schedule. It is not clear if survival rates are comparable to those of pemetrexed with that schedule, however.

Pemetrexed (Alimta). Pemetrexed, known as an anti-folate, is another promising new agent for second-line therapy and possibly for first-line treatment as well. The drug targets a number of enzymes that play a role in how cancer cells increase. Some research suggests that it is as effective as docetaxel. Pemetrexed does have some serious toxic effects, but they can be significantly reduced with folic acid and vitamin B12 supplements. It is then less toxic than docetaxel, when docetaxel is given every 21 days, but not when it is given weekly.

Gefitinib (Iressa) and Other Tyrosine Kinase Inhibitors. Much research is focusing on drugs that block small molecules involved with the growth of blood vessels that feed the tumor (a process called angiogenesis). Compounds called growth factors, which may be important in cancer cell production, control the growth of these new blood vessels. Researchers, then, are interested in medications that literally turn off these growth factors or their receptors, such as epidermal growth factor receptor (EGFR). In so doing, the agents may be able to cut off cancer's lifeblood. Gefitinib and erlotinib are angiogenesis inhibitors that target receptors of an epidermal growth factor called tyrosine kinase. Interestingly, studies are finding that NSCLC tumors in people who have never smoked have a much higher rate of EGFR mutations. This helps to explain why gefitinib and erlotinib are more effective in treating NSCLC in people who have never smoked.

Gefitinib (Iressa) was approved in 2003 as a second-line therapy for non-small cell lung cancer. Many patients report significant improvement in symptoms and quality of life, and the drug initially showed great promise. In one study, gefitinib reduced tumor size by 50% in about 10% of the patients. However, recent large-scale clinical trial results have failed to confirm any survival advantage for most patients. At this time, gefitinib is available only for patients who have benefited from it in the past.
Erlotinib (Tarceva) was approved as a single agent second-line therapy in November 2004. Study results show that the drug prolonged survival by several more months than placebo (6.7 versus 4.7 months). Erlotinib is administered orally and has very low toxicity (rash and diarrhea are common).

Chemotherapy Following Surgery (Adjuvant Chemotherapy). Chemotherapy is being evaluated in combination with surgery, radiation therapy, or both. Fairly strong evidence is now supporting the use of platinum-based chemotherapy as adjuvant treatment after surgery in patients with lung cancers in stages Ib-IIIa, with some research indicating a 5% improvement in five-year survival rates. Not all studies confirm survival benefits, however, and trials are ongoing.

Chemotherapy before Surgery (Induction Chemotherapy). Some researchers are testing induction chemotherapy, which is used to shrink potentially operable tumors before surgery. Studies have been mixed in reporting any survival benefits in patients with advanced lung cancer.

Combined and Multi-Modal Therapy. In stage III cancers, investigators are researching very intensive treatments that use two or more combinations of chemotherapy, radiation, and surgery.

For example, radiation plus chemotherapy may be helpful in patients whose tumors are surgically removable.

In inoperable lung cancer, combining radiation with chemotherapy is proving to extend the time to recurrence, the overall duration of survival, or both, compared to radiation alone. Evidence also suggests that giving radiation treatments at the same time as chemotherapy (instead of in separate cycles) improves 5-year survival rates, compared to a sequential approach (separate cycles following each other). Chemotherapy and radiation treatments given at the same time are more toxic, however.

Other approaches use even more intensive multi-modal therapy. For example, some trials use radiation therapy with chemotherapy, followed by surgery. Patients are then sometimes given additional chemotherapy or radiation. In other promising regimens, patents are given concurrent radiation and chemotherapy followed by chemotherapy alone. Such approaches are very toxic but appear to improve survival in selected patients.

Severe inflammation in the esophagus is the most common severe side effect of the radiation and chemotherapy combination. There is also a very high risk of serious infections, including pneumonia, herpes zoster, and cytomegalovirus. Long-term antibiotic therapy may be needed.

Although patients over 70 may suffer more from toxic effects than younger patients, studies now suggest that they can achieve survival rates with combined treatments that are equal to those in younger patients.

There are many painkilling medications available. Research shows that aggressive pain relief can help patients manage cancer treatment symptoms (in addition to pain) better. For example, a 2001 study suggested that reducing pain in elderly cancer patients markedly lowered their fatigue levels, and improved other symptoms as well.

Opioids are the most potent painkillers. The correct use of these strong medications is very important for reaching acceptable pain relief, and preventing a toxic response. For example, the long-lasting version of oxycodone (OxyContin) must be swallowed whole; chewing, inhaling, or injecting it can create a deadly overdose.

Investigative Agents

According to a 2001 article, of the nearly 500 cancer drugs currently in development, 58 of them (about 13%) are aimed at fighting lung cancer. Only the number of breast cancer drugs exceeded that percentage. Unfortunately, none to date have shown any real benefit in terms of patient survival. However, some drugs are showing promise, and at this time, these agents are the best hope for improving lung cancer survival rates.

Monoclonal antibodies (MAbs) are genetically designed immune factors. MAbs mark foreign compounds called antigens for attack by the immune system. Trastuzumab (Herceptin) and cetuximab (Erbitux) are MAbs under investigation for lung cancer. Bevacizumab (Avastin) was approved in October 2006 as a first-line treatment (in combination with carboplatin and paclitaxel) for inoperable, locally advanced, metastatic, or recurrent non-squamous, non-small cell lung cancer.

All three of these MAbs block epidermal growth factor. These agents are of particular interest for patients who have cancers that produce too much of the protein called HER2. These agents show great promise in combination with chemotherapies and newer drugs, such as the tyrosine kinase inhibitors. For example, the disease-free survival time in patients with advanced NSCLC is longer when adding bevacizumab to platinum-based chemotherapy.

Antisense oligonucleotides are drugs being used to block molecules that result in too many cells that cause cancers. LY900003 (Affinitak), for example, targets an enzyme called PKC-alpha, which promotes tumor growth. Early studies with Affinitak showed some promising results. However, a 2003 study found no difference in survival when patients received Affinitak in combination with platinum-based chemotherapy, compared to patients receiving chemotherapy alone.

Genasense (G3139, oblimersen) blocks Bcl-2. Bcl-2 is a protein that is expressed in abnormally high amounts in some cancers. This antisense drug is also under investigation.

Advexin, a genetic therapy that contains the p53 tumor-suppressor gene, is showing promise. In one early study, 60% of patients experienced partial or total tumor shrinkage when the agent was used in combination with radiation therapy. A 2006 study in Japan found that out of 13 patients with advanced NSCLC receiving Advexin, 10 had stabilized. Three of the stabilized patients remained stable for over 9 months. One patient had a partial response to Advexin. The only side effect of the multiple doses given was a passing fever that disappeared within 24 hours. Advexin is in Phase II clinical trials for NSCLC.

Vaccines use inactivated genetic materials from cancer cells, such as defective p53 or ras genes, to cause a highly targeted immune response to attack the cancer.

Retinoids are vitamin A-like antioxidant chemicals that help repair cell damage and appear to support growth of lung cells. A number of retinoid-like agents (retinal palmitate, TAC-101, 23-cis-retinoic acid, N-acetyl-cysteine) are being studied for the treatment or prevention of lung cancer.

Resources

www.cancer.gov -- National Cancer Institute
www.cancer.org -- American Cancer Society
www.cancercare.org -- Cancer Care
www.lungusa.org -- The American Lung Association
www.asco.org -- American Society of Clinical Oncology
www.alcase.org -- Alliance for Lung Cancer
www.lungcancer.org -- Joint project of Cancer Care and the Oncology Nursing Society
www.nccn.org -- National Comprehensive Cancer Network
www.lungcanceronline.org -- Lung cancer information
www.epa.gov/iaq/radon -- National radon information
www.clinicaltrials.gov -- Find clinical trials
www.cancer.gov/clinicaltrials -- Find clinical trials

References

Abeloff MD, Armitage JO, Niederhuber JE, Kastan MB, McKena WG. Clinical Oncology. 3rd ed. Orlando, Fl: Churchill Livingstone; 2004:1690-1701.

American Cancer Society. Cancer Facts and Figures 2006. Atlanta, Ga: American Cancer Society; 2006.

American Cancer Society. Cancer Facts and Figures 2007. Atlanta, Ga.: American Cancer Society; 2007:34.

Janne PA. Non-small Cell Lung Cancer in Never-smokers: A Biologically and Clinically Distinct Type of Lung Cancer. In: ASCO 2007 Educational Book. Meeting of the American Society of Clinical Oncology, Chicago, Ill.: June 1-5, 2007.

Kagawa S, Fujiwara T, Saijo Y, et al. A multicenter phase I study of adenoviral p53 (ADVEXIN) in Japanese patients with advanced non-small cell lung cancer. Journal of Clinical Oncology. 2006 ASCO Annual Meeting Proceedings Part I. Vol 24, No. 18S (June 20 Supplement), 2006: 2564.

Mehra R, Moore BA, Crothers K, Tetrault J, Fiellin DA. The association between marijuana smoking and lung cancer: a systematic review. Arch Intern Med. 2006 Jul 10;166(13):1359-67.

National Cancer Institute. Lung Cancer Home Page. Bethesda, Md.: U.S. National Institutes of Health. Available online.

National Comprehensive Cancer Network. NCCN Clinical Practice Guidelines in Oncology: Non-Small Cell Lung Cancer. Version 1.2007. Available online.

Tarceva [Package Insert]. Melville, NY: OSI Pharmaceuticals; 2005.

U.S. Department of Health and Human Services. The Health Consequences of Involuntary Exposure to Tobacco Smoke: A Report of the Surgeon General. Atlanta, Georgia: U.S. Department of Health and Human Services, Centers for Disease Control and Prevention, Coordinating Center for Health Promotion, National Center for Chronic Disease Prevention and Health Promotion, Office on Smoking and Health, 2006.

U.S. Food and Drug Administration, Center for Drug Evaluation and Research. List of Approved Oncology Drugs with Approved Indications. In: Oncology Tools. Available online.

U.S. Preventive Services Task Force. Lung cancer screening. Ann Int Med. 2004;140:738-739.

Xin M, Deng X. Nicotine Inactivation of the Proapoptotic Function of Bax through Phosphorylation. J Biol Chem. 2005 Mar 18;280(11):10781-9.

Review Date:
8/3/2007
Reviewed By:
Harvey Simon, MD, Associate Professor of Medicine, Harvard Medical School; Physician, Massachusetts General Hospital.

A.D.A.M. Copyright

adam.com