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The Most Active States in America

FitSugar — Thu, 11 Oct 2007 08:45:00 -0700

Are people in your state active?

The Centers for Disease Control and Prevention, or CDC, has put together a list of the most active states, as well as the least active states in the nation. Each state is ranked based on the percentage of people in each state meeting physical activity recommendations. Does your state make the top ten?

Alaska: 56.7%
Vermont: 55.9%
Wisconsin: 55.6%
Wyoming: 54.8%
Montana: 54.7%
New Hampshire: 54.4%
Oregon: 54.3%
Washington: 52.9%
Maine and Utah: 52.8%
California: 52.7%

Yay California - woot, woot!

To see the most sedentary states, just read more

The following ranks states by the percentage of people who are physically inactive, defined as those who report being physically active for less than 10 minutes per week.

Puerto Rico: 37.3%
Kentucky: 28.8%
Louisiana: 25.3%
Tennessee: 24.3%
West Virginia: 24%
U.S. Virgin Islands: 22.3%
Mississippi: 21.9%
Alabama: 20.1%
North Carolina: 19.5%
Georgia: 19%

To see the full list, visit the CDC website.

The State of Eating Veggies in the US

FitSugar — Wed, 30 Sep 2009 17:35:55 -0700

When it comes to eating enough veggies and fruits, Americans are failing miserably. The CDC estimates that only 14 percent of adults and fewer than 10 percent of teenagers in the US eat three servings of vegetables and two servings of fruit on a daily basis.

And you know, five servings of fruit and veggies is the minimum suggestion. Many health advocates believe we should be eating nine servings of produce daily. The percentages above represent the national average; in some states only nine percent of the adults eat enough produce. The CDC published this first state-by-state report to help us all understand how far off the mark we are when it comes to nutrition.

Here's the CDC list, ranking states from lowest to highest percentage of folks meeting the recommended servings of fruit and veggies.

1. Mississippi: 8.8%

2. Oklahoma and South Carolina: 9.3%

3. Alabama: 9.8%

4. South Dakota: 10.1%

5. West Virginia: 10.3%

Didn't see your state in the bottom five? Then keep on reading.

"F as in Fat" 2009 Finds Mississippi Heaviest State

FitSugar — Tue, 07 Jul 2009 03:45:17 -0700

The Trust For America's Health compiles a report every year, detailing how our nation's obesity policies are failing. The report, titled F as in Fat, doesn't mince words, but it does break down the rates of obesity by state.

For the fifth year in a row, Mississippi has the unfortunate distinction of topping the list with 32.5 percent of its adult population considered obese. The magnolia state also ranks number one for childhood weight woes; just over 44 percent of the population of 10- to 17-year-olds are considered overweight or obese.

This report does much more than finger-point; it examines state and federal policy and how it relates to the obesity epidemic. It looks at the relationship between obesity and the economy - cheap food is often unhealthy. There is even a section on how Summer break affects childhood obesity, titled "The Summer Slide." The report also makes recommendations for policy reform, changes in infrastructure (more sidewalks and bike paths, for one), and personal responsibility. You can find the entire 108-page report online in PDF format.

See how your state ranked.

The Geography of Stress in the USA

FitSugar — Thu, 16 Apr 2009 03:00:00 -0700

The state that created the concept of hanging loose is unsurprisingly the least stressed-out state in the union. According to a CDC phone survey, involving 2.4 million Americans, fewer Hawaiians experience "frequent mental distress" than anywhere else in the US.

Participants were asked the total days, out of the previous 30, they would describe their mental health as being "not good." The term mental health includes stress, depression, and emotional problems. If they answered 14 days, participants were classified as having "frequent mental distress." According to the survey, only 6.6 percent of the folks living in the island state were considered frequently stressed, followed closely by South Dakotans - where only 6.7 percent of respondents reported experiencing two weeks of not-so-good mental health days.

Learn how stressed your state is when you read more.

Here's the ranking of states according to the percentage of adults experiencing frequent mental distress, and states that "tied" with the same percentage are listed together.

1. Hawaii: 6.6%
2. South Dakota: 6.7%
3. Washington DC: 7.4%
4. Kansas, Nebraska, and North Dakota: 7.5%
5. Arizona: 7.6%
6. Iowa and Montana: 7.7%
7. Illinois: 7.9%
8. Connecticut: 8%
9. Wisconsin: 8.1%
10. Minnesota: 8.2%
11. North Carolina: 8.4%
12. Alaska, Maryland, Vermont: 8.5%
13. Ohio, Wyoming: 8.6%
14. New Jersey: 8.7%
15. New Hampshire, Oklahoma: 8.8%
16. Maine, Virginia: 9%
17. Washington: 9.2%
18. Colorado, Louisiana, Pennsylvania, South Carolina: 9.3%
19. Idaho, Tennessee: 9.4%
20. Massachusetts, Georgia, Utah: 9.5%
21. New York: 9.6%
22. New Mexico, Rhode Island, Texas: 9.7%
23. Delaware: 9.8%
24. Missouri: 9.9%
25. Oregon: 10%
26. Arkansas, Florida, California: 10.1%
27. Indiana: 10.3%
28. Michigan: 10.5%
29. Alabama, Mississippi: 10.8%
30. Nevada: 10.9%
31. West Virginia: 11.2%
32. Kentucky: 14.4%

I find it sad to see that so many of the residents of my golden state are frequently stressed. How did your state fare in the survey?

Source

Start Your Running Resolution at Midnight New Year's Eve

FitSugar — Wed, 17 Dec 2008 08:00:00 -0800

So you say you're going to get fit in 2009, eh? Why not put your resolution in motion by running to ring in the New Year? Yep, you can celebrate in the New Year by participating in a fun run or race.

If you're going to be in the NYC area to celebrate the New Year, then you may want to skip the crowds in Times Square and join the Emerald Nuts Midnight Run in Central Park. This four-mile fun run features a costume parade, dancing, and fireworks. It really is more of a party than a race, so you'll burn tons of calories while ringing in 2009.

If you don't live in the big apple, there are plenty of races and fun runs to be found. Active.com has a listing that includes 137 New Year's runs around the nation. You can run in Alaska or Georgia, in Idaho or Tennessee. Some races are on New Year's Eve and some on New Year's Day, with a few races on the Sunday following all the festivities. I would sign up ahead of time to really solidify your intentions.

Source

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.

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A.D.A.M. Copyright

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

adam.com

Allergic rhinitis

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

In This Report

Highlights
Introduction
Causes
Symptoms
Risk Factors
Prognosis
Diagnosis
Treatment
Other Treatments
Decongestants
Antihistamines
Corticosteroids
Immunotherapy
Prevention
Resources
References

HEALTH GUIDE REFERENCE FROM A.D.A.M

Highlights

Drug Approval

Ciclesonide (Omanaris), a corticosteroid nasal spray, has been approved for treatment of seasonal and perennial allergic rhinitis (hay fever) in adults and children age 12 years and older.

FDA Drug Warnings

The antihistamine promethazine (Phenergan) should not be given to children younger than age 2 because it may cause serious breathing problems.
Omalizumab (Xolair) may cause a life-threatening allergic reaction (anaphylaxis). This drug is used to treat allergy-related asthma, but is also being investigated as an allergy treatment.

Cough and Cold Medicines for Children

In 2007, the FDA began reviewing the safety and effectiveness of cough and cold medicines for children. These medicines contain antihistamines, decongestants, expectorants, and cough suppressants. The FDA is particularly concerned about the use of these medicines in children younger than 2 years of age. Overdoses can cause serious heart problems and death. However, many experts are concerned that the currently recommended dosages are themselves not safe.

Immunotherapy (Allergy Shots)

Immunotherapy is safe and effective for patients with allergic rhinitis, particularly those who have not been helped by other treatments, indicates a 2007 review in the Cochrane Database.
An experimental DNA-based ragweed vaccine is showing promise in early clinical trials. In a 2006 pilot study published in the New England Journal of Medicine, six weekly injections of the vaccine helped improve symptoms with benefits lasting into the following ragweed season.

Allergic Rhinitis and Sleep

Allergic rhinitis can cause sleep disorders and interfere with sleep quality, indicates a 2006 study in the Archives of Internal Medicine. In the study of nearly 600 patients with allergic rhinitis, patients with severe allergic rhinitis experienced worse sleep problems than those with mild allergic rhinitis.

Allergic Rhinitis and Parkinson’s Disease

Allergic rhinitis may be associated with the later development of the neurological disorder Parkinson’s disease, suggests a 2006 study in Neurology. Both conditions are associated with an inflammatory response.

Introduction

The nose is separated into two passages by a wall of cartilage called the septum. The nasal passages are lined with a membrane that produces a clear liquid called mucus. Mucus is a one of the body's defense systems:

The mucus traps small particles and bacteria, which may enter the nose as a person breathes.
The trapped bacteria usually do not cause harm in healthy individuals.
However, the bacteria can lead to a daily cycle of congestion and decongestion.
When one side of the nose is congested, air passes through the open (decongested) side. The sides alternate between being wide-open and partly or completely blocked.

If the congestion becomes severe or other changes occur that irritate the nasal passage, rhinitis develops. To be diagnosed with rhinitis, the patient must experience at least two of the following symptoms for an hour or more on most days:

Runny nose
Obstruction in the nasal passage
Nasal itching
Sneezing

Click the icon to see an image showing symptoms of allergic rhinitis.

These symptoms may occur as a result of colds or environmental irritants, such as allergens, cigarette smoke, chemicals, changes in temperature, stress, exercise, or other factors.

Infectious Rhinitis. If symptoms last less than 6 weeks, the condition is referred to as acute rhinitis and is usually caused by a cold or infection, or temporary overexposure to environmental chemicals or pollutants. [See In-Depth Report #94: Colds and the flu.]

Chronic Rhinitis. When rhinitis lasts for a longer period, the condition is called chronic rhinitis. Allergies are often the cause, but structural problems or chronic infections could also be to blame.

Aging Process. The elderly are at risk for chronic rhinitis as the mucous membranes become dry with age. In addition, the cartilage supporting the nasal passages weakens, causing changes in airflow. In such cases, therapy involves avoiding possible allergens and airborne irritants as well as measures to keep the nasal passages moist. Decongestants are not helpful.

Irritative Rhinitis. Irritative rhinitis is caused by an overreaction to irritants, such as cigarette smoke, dozens of other air pollutants, strong odors, alcoholic beverages, and exposure to cold. The nasal passages become red and engorged. This reaction is not the same as an allergic reaction, although both are associated with increased numbers of white blood cells called eosinophils.

Vasomotor Rhinitis. Vasomotor rhinitis, also sometimes called idiopathic or irritant rhinitis, is congestion and stuffy nose that is produced by the changes in blood vessels and nerve cells in the nasal passages. It occurs in response to irritants, including smoke, environmental toxins, changes in temperature and humidity, stress, and even sexual arousal. This over-reaction is not associated with any immune response. The biologic causes are unknown. Some research has found an association between vasomotor rhinitis and gastroesophageal reflux disorder (GERD, a common cause of heartburn), which some experts think may be due to a common defect in the nervous system that controls muscle action. Symptoms of vasomotor rhinitis are similar to most of those caused by allergies. Usually, however, they are more severe and occur predominantly on one side of the nose.

Foreign Objects. Blockage in young children is very often caused by foreign objects that they have pushed up their nose. If they are left in place, they may eventually cause infection and nasal discharge, (usually in one side of the nose), which may be yellow or green and foul smelling.

Blockage in the Nose from Polyps or Structural Abnormalities. A number of conditions may block the nasal passages. Surgery may be helpful for certain cases.

Polyps. These are soft, gray, fluid-filled sacs that develop off stalk-like structures on the mucus membrane. They impede mucus drainage and restrict airflow. Polyps usually develop from sinus infections that cause overgrowth of the mucus membrane in the nose. They do not regress on their own and may multiply and cause considerable obstruction.
Deviated Septum. A common structural abnormality that causes rhinitis is a deviated septum. The septum is the inner wall of cartilage and bone that separates the two sides of the nose. When deviated, it is not straight but shifted to one side, usually the left.
Other Causes of Blockage. Rarely, cleft palates, overgrowth of bones in the nose, or tumors cause rhinitis.

Nonallergic Rhinitis in Children. Chronic nasal congestion in children often accompanies a susceptibility to ear, sinus, or adenoid infections. Adenoids are spongy tissue masses located between ends of the nasal passages and the soft tissue in the back of the throat. Enlarged adenoids may also cause ear problems. The bacteria that cause these other infections, however, are not usually the cause of this chronic rhinitis.

Medications and Illegal Drugs. A number of drugs can cause rhinitis or worsen it in people with conditions such as deviated septum, allergies, or vasomotor rhinitis:

Overuse of decongestant sprays used to treat nasal congestion can, over time (3 - 5 days) cause inflammation in the nasal passages and worsen rhinitis.
Many people with allergies and asthma are sensitive to common painkillers known as nonsteroidal anti-inflammatory drugs (NSAIDs). These include aspirin, ibuprofen (Motrin, Advil, Nuprin, Rufen), and naproxen (Aleve), among many others. Aspirin and products containing aspirin can even cause life-threatening asthma attacks in some highly susceptible individuals. NSAIDs vary, however, and some patients may not have a reaction to all of them. For minor pain, acetaminophen (Tylenol), which is not an NSAID, is usually recommended for patients with intolerance to NSAIDs. A pharmacist should be consulted if the ingredients of any over-the-counter preparations are not known.
Other medications that may cause rhinitis include oral contraceptives, hormone replacement therapy, anti-anxiety drugs (particularly alprazolam), some antidepressants, and some blood pressure medications, including beta-blockers and vasodilators.
Sniffing cocaine damages nasal passages and can cause chronic rhinitis.

Estrogen in Women. Elevated levels of estrogen appear to increase mucus production and swelling in the nasal passages and can cause congestion. This effect is most apparent in women during pregnancy. In such cases the condition usually clears up after delivery. Oral contraceptives and hormone replacement therapies that contain estrogen have also been associated with nasal congestion in some women.

Medical Conditions. Hypothyroidism is associated with chronic rhinitis. People with certain genetic or other medical conditions that specifically affect the mucous membranes are at also risk, although rhinitis in such people is apt to be only one of many more serious conditions, including chronic sinusitis and respiratory problems. Wegener's granulomatosis, for example, is a serious but very rare illness that causes long-term swelling and tumor-like masses in air passages.

Rare genetic disorders that cause chronic rhinitis include the following:

Cystic fibrosis, in which the mucus is very thick.
Kartagener's syndrome. With this condition the body's major internal organs are located in the mirror-image position of their normal location. In addition, the body's cilia (hair-like-projections on many body tissues that help to move mucus and other fluids) are impaired or motionless.

In both disorders, mucus build-up also produces an environment favorable to infection-causing organisms.

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

Click the icon to see an image of the adenoids.

Causes

The allergic process, called atopy, and its connection to asthma is not completely understood. It involves various airborne allergens or other triggers that set off a cascade of events in the immune system leading to inflammation and hyperreactivity in the airways.

The conductor in an orchestra of immune factors that contribute to allergies and asthma appears to be a category of white blood cells known as helper T cells, in particular a subgroup called Th2 cells.
Th2 cells overproduce interleukins (ILs), immune factors that are molecular members of a family called cytokines, which are involved in the inflammatory process.

Interleukins 4, 9, and 13 may be responsible for a first-phase asthma attack. These interleukins stimulate the production and release of antibody groups known as immunoglobulin E (IgE). People with both asthma and allergies appear to have a genetic predisposition for overproducing IgE.
During an allergic attack, these IgE antibodies bind to special cells in the immune system called mast cells, which are generally concentrated in the lungs, skin, and mucous membranes. This bond triggers the release of a number of active chemicals, importantly potent molecules known as leukotrienes. These chemicals cause airway spasms, overproduce mucus, and activate nerve endings in the airway lining.
Another cytokine, interleukin 5, appears to contribute to a late-phase inflammatory response. This interleukin attracts white blood cells known as eosinophils. These cells accumulate and remain in the airways after the first attack. They persist for weeks and mediate the release of other damaging particles that remain in the airways.

One theory blames the dramatic increase in asthma and allergies on the reductions in childhood infections that have occurred with modern hygiene and antibiotic use. The basic theory rests on the idea that infections stimulate production of specific immune factors called Th1 cells. As these cells build up, they replace other immune factors called Th2 cells, which react to allergens -- a less serious threat to the body. Without infections to stimulate the production of the Th1 infection fighters, the Th2 allergen fighters are not replaced, and they persist at high levels, making the growing child more susceptible to allergies and asthma.

A number of different studies support this theory:

Some studies suggest that being part of a large family or attending day care increases the risk for early respiratory infections but reduces the risk of childhood asthma. The occasional cold, then, may be protective.
In a 2002 study, researchers measured levels of bacterial byproducts called endotoxins in the mattress dust of 812 children. Those with the highest levels had an 80% lower rate in allergies and asthma.
Another study further found a strong association between allergy development and the absence of certain beneficial bacteria (called probiotics) in infants' intestines. Infants who were born in more hygienic environments tended to lack these bacteria. Antibiotic overuse and modern hygiene may reduce these helpful organisms. (Probiotics are available in active yogurt cultures and in supplements, which are being studied for protection.)

According to many studies, the standard vaccinations against serious childhood infections pose no risk for developing asthma or hay fever. Some studies have even reported lower risk for asthma and allergies in the second and third years after vaccinations.

Some evidence suggests that the increase in allergies and asthma may be due to overexposure to indoor allergens. These may include wall-to-wall carpeting, cats, and mold produced by dampness in homes. Children who spend hours indoor each day may become overexposed to indoor allergens. This exposure is intensified by the recent trend of making homes more energy-efficient, which may result in more dust mites being trapped inside. However, other studies suggest that early exposure to allergens may actually prevent the development of allergies in children.

Seasonal allergic rhinitis occurs only during periods of intense airborne pollen or spores. It is commonly, although inaccurately, called hay fever or rose fever, depending on whether it occurs in the late summer or spring. No fever accompanies this condition, and the allergic response is not dependent on either hay or roses. In general, triggers of seasonal allergy in the U.S. include:

Ragweed. Ragweed is the most dominant cause of allergic rhinitis in the U.S., affecting about 75% of allergy sufferers. One plant can release 1 million pollen grains a day. Ragweed occurs everywhere in the U.S., although it is less common in western coastal states, southern Florida, northern Maine, Alaska, and Hawaii. The effects of ragweed in the northern states are first felt in middle to late August and last until the first frost. Ragweed allergies tend to be most severe before midday.
Grasses. Grasses affect people in mid-May to late June. Grass allergies are experienced more in the late afternoon.
Tree Pollen. Small pollen grains from certain trees usually produce symptoms in late March and early April.
Mold Spores. Mold spores that grow on dead leaves and release spores into the air are common allergens throughout the spring, summer and fall. Mold spores may peak on dry windy afternoons or on damp or rainy days in the early morning.

Click the icon to see an animation about allergies.

Major weather changes, such as El Nino, can affect the timing of allergy seasons. For example, in 1998, when the effects of El Nino were very strong, allergy attacks were markedly increased, and maximum tree pollen counts occurred 2 - 4 weeks earlier and mold counts 2 - 3 months earlier than the previous year.

Allergens in the House. Allergens in the house can trigger attacks in people with year-long allergic rhinitis, called perennial rhinitis. Household allergens may include the following:

House dust and mites. Dust mites, specifically mite feces, are coated with enzymes that contain a powerful allergen.
Cockroaches
Pet dander
Molds growing on wallpaper, house plants, carpeting, and upholstery

However, some studies are suggest that early exposure to some of these allergens, including dust mites and pets, may prevent allergies from developing in the first place in children.

Fossil Fuels. There may be an association between traffic-related air pollution and allergic rhinitis. Some experts believe that refined fossil fuels, such as diesel fuel and particularly kerosene, are important triggers for allergic rhinitis. In people who already have allergies or asthma, exposure to such fossil fuels may worsen symptoms.

Symptoms

The general symptoms of rhinitis are congestion, runny nose, and postnasal drip, in which mucous drips into the throat from the back of the nasal passage, especially when lying on the back. Symptoms may vary depending on the cause of rhinitis. Symptoms of influenza and sinusitis must also be differentiated from allergies and colds.

Symptoms of allergic rhinitis occur in two phases, early and late.

Early Phase Symptoms. The early phase occurs within minutes of exposure to the allergens and includes:

Runny nose
Frequent or repetitive sneezing
Itching in the nose, eyes, throat, or roof of the mouth

Late-Phase Symptoms. The late phase occurs 4 - 8 hours later and may include one or more of these symptoms:

Nasal congestion and possibly plugged ears. Children may push their nose upward with the palm of their hand or twitch their nose rabbit-like to clear the obstruction.
Fatigue.
Mental changes can include irritability, a slight decrease in attention span, worsened memory, and slower thinking.
Other common physical symptoms include a decreased sense of smell, plugged ears, sinus headache, postnasal drip or some combination. In severe allergies, dark circles may develop under the eye. The lower eyelid may be puffy and lined with creases.

Risk Factors

Allergic rhinitis affects between 20 - 40 million Americans of all ages. As with asthma and many upper respiratory infections, the incidence in allergic rhinitis is increasing. Allergies most often appear first in childhood, and allergic rhinitis is the most common chronic condition in childhood, although it can develop at any age. About 20% of allergic rhinitis cases are due to seasonal allergies, 40% to perennial (chronic) rhinitis, and the rest are mixed.

Genetic factors are the major determinants of allergies.

If both parents have an allergy, the child's risk is 75%.
If one parent is allergic, the child's risk is 50%.

Having other allergies increases the risk for allergic rhinitis. Here are some examples:

Young children who have eczema (an allergic skin reaction) have a later risk for allergic rhinitis and asthma. In fact, a family history of eczema increases the risk.
Food allergies are associated with allergic rhinitis and asthma. (Early feeding patterns, time of weaning, and introduction of solid food do not appear to affect this risk.)
Asthma, especially in patients who develop it as adults, may increase allergic sensitivity to ragweed and other allergens. Patients who have asthma and a genetic tendency towards allergies (atopy) are also at risk for rhinitis.

Birth Month. Some studies report a higher risk of allergies and asthma in children born in winter months and lower risk in those born during the summer.

Breastfeeding. Some researchers suggest that the dramatic increase in asthma and allergies may be due to fewer women breastfeeding their infants. In a number of studies, breastfeeding has been associated with a lower risk for allergies and asthma -- at least until age 2. Breastfeeding can also help prevent other upper respiratory infections. The American Academy of Pediatrics recommends feeding infants exclusively breast milk for the first 6 months of life.

Prognosis

Seasonal allergic rhinitis tends to diminish as a person ages. The earlier the symptoms start, the greater the chances for improvement. People who develop hay fever in early childhood tend not to have the allergy in adulthood. In one study, over half of allergic subjects reported that by 40 years of age their symptoms had decreased, and a quarter were symptom-free. In some cases, allergies go into remission for years and then return later in life. People who develop allergies after age 20, however, tend to continue to have hay fever at least into middle age.

People with allergic rhinitis may be at higher risk for other allergies, including potentially serious food or latex allergies.

Although allergic rhinitis is not considered a serious condition, it nonetheless can interfere with many important aspects of life. A 2006 survey of nasal allergy sufferers reported that symptoms made patients feel tired (80%), miserable (65%), irritable (62%), and interfered with work performance (52%).

People with allergic rhinitis, particularly those with perennial allergic rhinitis, may experience sleep disorders and daytime fatigue. Often they attribute this to medication, but studies suggest congestion may be the culprit in these symptoms. In addition, a 2002 study indicated that patients with seasonal allergies experience hundreds of brief, subtle awakenings, called "microarousals," each night. In such cases, people are not aware that they wake up, but such events can cause fatigue the next day. A 2006 study of nearly 600 patients with allergic rhinitis found that sleep disorders and poor sleep quality were prevalent. Patients who had severe allergic rhinitis had worse sleep problems than those with mild allergic rhinitis.

Asthma and allergies often coexist, and the allergic response plays a strong role in childhood asthma. About 70 - 85% of children with asthma have allergies. Aggressive treatment of allergies in children with asthma can lower the risk for asthma attacks. Treating allergies in children may also help prevent the onset of asthma.

Any chronic rhinitis, whether allergic or nonallergic, can cause swelling in the turbinate, which may become persistent (turbinate hypertrophy). The turbinate is a tiny shelf-like bony structure that protrudes in the nasal passageways. It helps warm, humidify, and clean the air that passes over it. If turbinate hypertrophy develops, it causes persistent nasal congestion and, sometimes, pressure and headache in the middle of the face and forehead. This condition requires surgery.

Children with severe allergies may have a higher risk for behavioral problems than those without allergies. Some research suggests that allergic rhinitis is responsible for 2 million missed school days each year.
There have been reports that 30 - 45% of people with allergic rhinitis also suffer from ear infections (otitis media).
Chronic nasal obstruction from year-round allergies can affect a child's appearance. If a child can only breathe through the mouth, the continual force of air passing through the oral cavity can change facial development. Such changes may include an elongated face and an overbite from teeth coming in at an abnormal angle.
Chronic rhinitis can cause headaches and also affect a child's sleep, concentration, hearing, appetite, and growth.

Depression. Some evidence has linked depression with allergies. A 2002 study, for example, found that people with depression reported a higher rate of allergic disorders (71%) compared to nondepressed individuals (43%). During allergy season, patients with allergies were more likely to experience mood changes, including sadness, lethargy, and mental fatigue, than at other times. Some evidence suggests that specific immune factors in the allergic response can cause depressive symptoms. Other research indicates that both may have a common cause.

Parkinson’s Disease. A 2006 study suggested that allergic rhinitis may be associated with the later development of the neurological disorder Parkinson’s disease. The researchers think that the inflammatory response may be the link between the two conditions. However, there is not yet any evidence that treating allergic rhinitis can prevent Parkinson’s disease.

Chronic Fatigue Syndrome (CFS). Some, although not all, studies have reported that a majority of patients with CFS also have allergies to foods, pollen, metals (such as nickel or mercury), or other substances. One theory is that allergens, like viral infections, may trigger a harmful overreaction of the immune system that can cause fatigue, joint aches, and fever as well as hormone and brain chemical disturbances. (However, most people with allergies do not have CFS.)

Diagnosis

To determine the cause of allergic rhinitis, the doctor will ask a number of questions about:

Time of day and year of rhinitis episodes. Rhinitis that appears seasonally is typically due to pollens and outdoor allergens. If symptoms occur throughout the year, the doctor will suspect perennial allergic or non-allergic rhinitis.
Family history of allergies.
History of medical problems.
In women, if they are pregnant or taking drugs that contain estrogen (oral contraceptives, hormone replacement therapy).
Use of other medications including decongestants, which can cause a rebound effect.
Pets.
Any additional unusual symptoms. As examples, bloody nasal discharge and obstruction in only one nasal passage could suggest a tumor. Fatigue, sensitivity to cold, weight gain, and depression may be signs of hypothyroidism.

The doctor will examine the inside of the nose with an instrument called a speculum. This is a painless examination allowing the doctor to check for redness and other signs of inflammation. The doctor will also usually check the eyes, ears, and chest.

A skin test is a simple method for detecting common allergens. Patients are usually tested for a panel of common allergens. Skin tests are rarely needed to diagnose mild seasonal allergic rhinitis, since the cause is usually obvious. The skin test is not appropriate for children younger than age 3.

The procedure is as follows:

Patients should not take antihistamines for at least 12 - 72 hours before the test. Otherwise an allergic reaction may not show up.
Small amounts of suspected allergens are applied to the skin with a needle prick or scratch or are injected a few cells deep into the skin. The injection test may be more sensitive than the standard prick test.
If an allergy is present, a hive (a swollen reddened area) forms within about 20 minutes.

The test is not completely accurate. For instance, a 2001 study reported that testing detected allergies in less than half of children with rhinitis. Furthermore, about 15 - 20% of people may have a skin reaction without actually having an allergy.

Nasal Smear. The doctor may take a nasal smear. The nasal secretion is examined microscopically for factors that might indicate a cause, such as increased numbers of white blood cells, indicating infection, or high counts of eosinophils. High eosinophil counts indicate an allergic condition, but low counts do not rule out allergic rhinitis.

Tests for IgE. Blood tests for IgE immunoglobulin production may also be performed. One test is called the radioallergosorbent Test (RAST), used to detect increased levels of allergen-specific IgE in response to particular allergens. Blood tests for IgE may be less accurate than skin tests. They should be performed only on patients who cannot undergo skin testing or when skin test results are uncertain.

In people with chronic rhinitis, the doctor may also check for sinusitis. Imaging tests may be useful if other tests are ambiguous.

A test called transillumination, in which a doctor shines a bright light against the patient's cheek or forehead, is an inexpensive method for checking for abnormalities in the sinus cavities, although it is not highly accurate.
CT scans may be useful for some cases of sinusitis.

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

In certain cases of chronic or unresponsive seasonal rhinitis, a doctor may use endoscopy to examine for any irregularities in the nose structure. Endoscopy uses a tube inserted through the nose that contains a miniature camera to view the passageways.

Treatment

If rhinitis is caused by non-allergic conditions, particularly if there are accompanying symptoms indicating a serious problem, the doctor should treat any underlying disorders. If rhinitis is caused by medications, such as decongestants, the patient may need to stop taking them or find alternatives.

Patients with chronic allergic rhinitis may require daily medications. Patients with severe seasonal allergies should start medications a few weeks before the pollen season and continue taking them until the season is over. Effective medications include:

Drugs that reduce the inflammatory response are important for preventing severe allergic rhinitis. Nasal corticosteroids (commonly called steroids) are now considered to be the most effective measure for preventing allergy attacks. Other anti-inflammatory drugs include leukotriene-antagonists and nasal cromolyn.
Antihistamine tablets relieve sneezing and itching and can prevent nasal congestion before an allergy attack. Many brands are available by prescription and over-the-counter.
Immunotherapy ("allergy shots") may be considered for patients with severe seasonal allergies that do not respond to treatment. It may also prevent asthma and the development of new allergies in children. Many experts now recommend immunotherapy for people with both asthma and allergies. Newer immunotherapeutic approaches using specially designed antibodies and vaccines are also showing promise.

All drug treatments have side effects, some very unpleasant and, in rare cases, serious. Patients may need to try different drugs until they find one that relieves symptoms without producing excessively distressing side effects.

Because seasonal allergies generally last only a few weeks, most doctors do not recommend the more potent prescription treatments for children. It is important for parents to determine if the child is actually under severe distress and that the parent is not simply responding to their own anxiety when they hear the child snorting or snoring. Prescription drugs are required only in severe cases. However, in children with both asthma and allergies, treatments for allergic rhinitis may also improve asthmatic symptoms.

Treating Mild Allergy Attacks. Mild allergy attacks usually require little more than reducing exposure to allergens and using a nasal wash. Dozens of treatments are available for allergic rhinitis. Many are available over-the-counter, but some require a prescription. They include the following:

Nasal washes
Decongestants that relieve nasal congestion and itchy eyes
Decongestant/antihistamine combinations

Due to side effects, decongestants should not be used in children ages 14 years or younger. Also, overuse of nasal decongestions can actually worsen sinus congestion.

Treating Severe Allergic Rhinitis. Patients with chronic allergic rhinitis, particularly if they also have asthma, may require daily medications. These drugs include:

Antihistamines. The newer non-sedating antihistamines -- such as cetirizine (Zyrtec), loratadine (Claritin), fexofenadine (Allegra), or desloratadine (Clarinex) -- cause less drowsiness than older antihistamines, such as Benadryl. Some of the newer drugs, such as Zyrtec and Clarinex, may also relieve nasal congestion.
Anti-inflammatory drugs. Nasal corticosteroids are now considered to be the most effective measure for preventing allergy attacks. They are recommended for patients with very severe allergies that do not respond to antihistamines.
Leukotriene-antagonists and nasal cromolyn may be beneficial in specific cases of allergies
Immunotherapy ("allergy shots") works well for many patients with severe allergies. It is also proving to reduce asthma symptoms and the use of asthma medications in patients with known allergies.

Itching and redness in the eyes sometimes respond to oral antihistamines. Eye drops, however, provide faster relief, and a combination of the two may be best. The following are eye drops for itchy eyes. Others are also available. Individual responses vary, and patients need to find which specific treatment works best for them.

Antihistamine eye drops: azelastine (Optivar), olopatadine (Patanol), ketotifen (Zaditor), levocabastine (Livostin) for relief of both nasal symptoms and itchy red eyes
Decongestant eye drops: phenylephrine (Allergan Relief), naphazoline (Naphcon, Opcon-A, VasoClear), tetrahydrozoline (Murine Plus, Visine)
Combination decongestant/antihistamine: Visine A.
Corticosteroids: loteprednol (Lotemax, Alrex), pemirolast (Alamast).

General Side Effects and Warning.

All eye drops can cause stinging, and some may result in headache and congestion.
No one should continue taking eye drops if they experience pain, changes in vision, worsened redness, or irritation, or if the condition lasts more than 3 days.
Do not touch the tip of the device to the eye or touch other surfaces with it. Replace the cap after using. Discard any solution that changes color or becomes cloudy.
People who have heart disease, high blood pressure, an enlarged prostate gland, or glaucoma should talk to their doctor before taking these types of eye drops.

Other Treatments

For mild allergic rhinitis, a nasal wash can be helpful for removing mucus from the nose. You can purchase a saline solution at a drug store or make one at home (one cup of warm water, half teaspoon salt, pinch of baking soda). Over-the-counter saline nasal sprays that contain benzalkonium chloride as a preservative may actually worsen symptoms and infection.

Simple method for administering a nasal wash:

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

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

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

Nearly half of asthma or allergy sufferers resort to alternative treatments. To date, however, little evidence supports treatments such as high-dose vitamins, homeopathic remedies, and most herbal remedies. Some relaxation methods, such as massage therapy, may be beneficial in reducing stress related to allergy symptoms. According to research presented at a 2004 allergy conference, acupuncture is now the most popular alternative treatment among allergy sufferers. The following are examples of recent areas of research:

Acupuncture may provide symptom relief for persistent allergic rhinitis in children, according to results published in a 2004 pediatrics journal. The study compared the effects of active versus sham acupuncture. Larger trials are needed to confirm these results.
Butterbur (also known as Petasites hybridus, butter dock, blatterdock, bog rhubarb, and exwort) is a plant found in Europe, North American, and parts of Asia. It is a traditional herbal remedy used for seasonal allergies and asthma. In a 2002 study, it was as effective and less sedating than a commonly prescribed antihistamine for treating seasonal allergies over a 2-week period.
Probiotics are beneficial bacteria that may help protect against allergies and asthma. Probiotics are available in active yogurt cultures and in supplements, which are being studied for protection.

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

The following are special concerns for people with allergic rhinitis:

Grapeseed extract is sometimes touted as a natural antihistamine. A 2002 study, however, reported no benefits from it.
A 2002 study found no benefits with homeopathy immunotherapy for asthmatic patients allergic to dust mites.
Some patients have reported worse symptoms after drinking herbal teas, which may contain leaves or pollens the patient is sensitive to. Herbal remedies themselves can trigger an allergic reaction. For example, echinacea is of special concern. This herbal remedy actually boosts the immune system. People with nasal congestion may mistakenly take it because it is often used to treat colds. In the case of allergies, however, echinacea may worsen symptoms or even trigger them in people who haven't experienced them. People with autoimmune diseases or who have plant allergies should particularly avoid it.
A Chinese herbal cold and allergy remedy sold as Aller Relief contains trace amounts of aristolochic acid, a chemical that is toxic to the kidneys and a carcinogen. Products containing aristolochic acid have been associated with several reports of kidney failure in Europe. Of specific concern are studies suggesting that up to 30% of herbal patent remedies imported from China have been laced with potent pharmaceuticals such as phenacetin and steroids. Asian herbal remedies may also contain toxic metals.
Aromatherapy is often used for relaxation. Some of the exotic plant extracts in these formulas have been associated with a wide range of skin allergies.

Decongestants

For mild allergic rhinitis, a nasal wash can be helpful for removing mucus from the nose. Decongestants may help dry nasal congestion. They work by shrinking vessels in the nose. By reducing blockage, they decrease the risk of developing sinusitis caused by viruses or bacteria. Many over-the-counter decongestants are available, either in tablet form or as nasal or inhaled decongestants that are applied directly into the airways as sprays, drops, or vapors.

Nasal-delivery decongestants are applied directly into the nasal passages with a spray, gel, drops, or vapors. Nasal decongestants come in long-acting or short-acting forms. The effects of short-acting decongestants last about 4 hours; long-acting decongestants last 6 - 12 hours. The active ingredients in nasal decongestants include oxymetazoline, xylometazoline, and phenylephrine. Nasal forms work faster than oral decongestants and may not cause as much drowsiness. However, they can cause dependency and rebound.

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

With prolonged use (more than 3 - 5 days), nasal decongestants lose effectiveness and can cause swelling in the nasal passages.
The patient then increases the frequency of the dose. As the congestion worsens, the patient may respond with even more frequent doses.
This causes dependency and increased nasal congestion.

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

When using a nasal spray, spray each nostril once. Wait a minute to allow absorption into the mucosal tissues, and then spray again.
Do not share droppers and inhalators with other people.
Discard sprayers, inhalators, or other decongestant delivery devices when the medication is no longer needed. Over time, these devices can become reservoirs for bacteria.
Discard the medicine if it becomes cloudy or unclear.

Oral decongestants also come in many brands, which have similar ingredients. The most common active ingredient is pseudoephedrine (Sudafed, Actifed, Drixoral), sometimes in combination with an antihistamine. [The alternative decongestant, phenylpropanolamine (PPA) was taken off the market.] A small 2006 study reported that over-the-counter pseudoephedrine works just as well as the prescription drug montelukast (Singulair) in controlling allergic rhinitis symptoms. Patients in the study received a once-daily morning dose (240 mg) of ephedrine. Researchers suggest that taking pseudoephedrine in the morning, as opposed to later in the day or before bedtime, can help patients avoid side effects such as insomnia and nervousness.

Decongestants have certain adverse effects, which are more apt to occur in oral than nasal decongestants. These side effects include:

Agitation and nervousness
Drowsiness (particularly with oral decongestants and in combination with alcohol)
Changes in heart rate and blood pressure
Avoid combinations of oral decongestants with alcohol or certain drugs, including monoamine oxidase inhibitors (MAOI) and sedatives.

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

Heart disease
High blood pressure
Thyroid disease
Diabetes
Prostate problems that cause urinary difficulties
Migraines
Raynaud's phenomenon
High sensitivity to cold
Emphysema or chronic bronchitis. (Individuals with these conditions should particularly avoid high-potency, short-acting nasal decongestant.)
Medications that increase serotonin levels, such as certain antidepressants, anti-migraine drugs, diet pills, St. John's wort, and methamphetamine. The combination of these medicines and decongestants can cause blood vessels in the brain to narrow suddenly, causing severe headaches and even stroke.

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

Pregnant women
Children. The American College of Chest Physicians advises against the use of over-the-counter decongestants and other cold medications in children ages 14 years or younger. Children are at particular risk for side effects that depress the central nervous system. Such symptoms cause changes in blood pressure, drowsiness, deep sleep, and, rarely, coma. In 2007, the FDA began reviewing the safety and effectiveness of cough and cold remedies for children.

In 2000, the Food and Drug Administration (FDA) took action to ban oral decongestants containing phenylpropanolamine (PPA) from the U.S. market. This action was in response to reports of an increased risk of stroke in young women who took products containing this ingredient. All major brands that previously contained PPA have now substituted other active ingredients (usually pseudoephedrine) and are safe to use.

Anyone with old forms of decongestant should check the labels and discard them if they contain phenylpropanolamine.

Antihistamines

Histamine is one of the chemicals released when antibodies overreact to allergens. It is the cause of many symptoms of allergic rhinitis. Antihistamines can help relieve:

Itching, sneezing, and nasal discharge
Other allergy symptoms unrelated to rhinitis, including hives and some rashes
Nasal congestion, for some of the newer antihistamines, such as cetirizine (Zyrtec) and desloratadine (Clarinex)

If possible, patients should take antihistamines before an anticipated allergy attack.

Many antihistamines are available. They include short-acting and long-acting forms and are available as tablets, nasal-inhalers, eye drops, and syrups. Antihistamines are generally categorized as first- and second-generation. First-generation antihistamines may cause more side effects than newer second-generation ones.

There are some notes of caution when taking any antihistamine:

Antihistamines may thicken mucus secretions and can worsen bacterial rhinitis or sinusitis.
Antihistamines can lose their effectiveness over time, and a different one may need to be tried.

First-Generation Antihistamines Ingredients and Brand Names. The older, so-called first generation antihistamines include:

Diphenhydramine (Benadryl)
Carbinoxamine (Clistin)
Clemastine (Tavist)
Chlorpheniramine (Chlor-Trimeton). Some health professionals recommend this drug if antihistamines are required during pregnancy. It may be as effective as the second generation antihistamines and much less expensive.
Brompheniramine (Dimetane)
Promethazine (Phenergan). This antihistamine should never be used for children younger than age 2 because it may cause life-threatening breathing problems.

First-generation antihistamines contain compounds called anticholinergics, which tend to produce more side effects than second-generation antihistamines.

Side Effects

Drowsiness and impaired thinking
Dry mouth
Dizziness
Agitation
Insomnia or nightmares
Sore throat
Rapid heart beat and chest tightness (uncommon and should be reported)
Men with enlarged prostate glands may experience difficulty urinating

Drowsiness and First-Generation Antihistamines. Drowsiness is the most distressing side effect reported from first-generation antihistamines, and is potentially serious. It may pose a higher than average risk for work-related and automobile accidents than alcohol, narcotics, or prescription sedatives. However, some studies have not found any strong differences in sedation between the first- and second-generation antihistamines. Still, experts caution against the first-generation antihistamines for people most at risk from sedative effects, particularly elderly individuals. To reduce risks, take the antihistamine at home a few hours before bedtime, and do not combine it with alcohol or tranquilizers. Do not drive or operate heavy machinery.

The newer second-generation antihistamines do not contain anticholinergics, so they do not usually cause drowsiness to the extent that the first generation antihistamines do. They are sometimes referred to collectively as nonsedating antihistamines.

A major 2003 analysis reported that although Benadryl, the most common first-generation antihistamine, had a more negative effect on daily activities than the newer antihistamines, the differences were modest. Researchers in the study concluded that no clear distinction exists between the first- and second-generation antihistamines.

Brand Names. The second-generation drugs include:

Loratadine (Claritin). Claritin is available over-the-counter and is approved for children ages 2 and older. Desloratadine (Clarinex) is similar to Claritin but stronger and longer-lasting. It is available only by prescription.
Cetirizine (Zyrtec). Zyrtec is approved for both indoor and outdoor allergies. It is the only antihistamine to date approved for infants as young as 6 months. It is available over-the-counter.
Fexofenadine (Allegra) is also available over-the-counter.
Acrivastine (Semprex)
Ebastine, norastemizole, levocetirizine, and mizolastine are other second-generation antihistamines under investigation in the U.S. and Europe. Some may prove to be useful for specific populations.

For nonprescription antihistamines, some studies suggest that cetirizine (Zyrtec) is more effective than Allegra or Claritin in improving symptoms, including those in children. However, cetirizine can cause drowsiness when taken at high doses.

Zyrtec and Claritin are approved for children younger than 5 years, although most antihistamines appear to be safe in children. Zyrtec is the only antihistamine approved for both indoor and outdoor allergies and for infants as young as 6 months. Both are available in syrup form. Studies with Zyrtec have reported fewer symptoms in children allergic to dust mites, and one study reported that infants with allergies who were given Zyrtec were much less likely to develop asthma later on than untreated infants. Claritin, at this time, is generally the preferred drug for young people, however, because it has the least negative effect on concentration and learning. Women who are pregnant or nursing should avoid these medications unless recommended by a doctor.

Side Effects and Precautions

Common side effects include headache, dry mouth, and dry nose. (These are often only temporary and go away during treatment.)
Drowsiness occurs in about 10% of adults and between 2 - 4% of children.
Uncommon side effects include rapid heart beat and chest tightness. Tell your doctor if these effects occur.
Extended-release forms of Claritin and Zyrtec have other ingredients that can cause other symptoms, including nervousness, restlessness, and insomnia. Some patients taking Claritin-D 24 Hour Extended Release tablets have reported obstruction in the upper gastrointestinal tract, including difficulty swallowing.

Drug and Food Interactions. Two earlier second generation drugs, terfenadine (Seldane) and astemizole (Hismanal), in rare cases, caused dangerous heart rhythm abnormalities, particularly in high doses or in people who had liver disease. They also caused interactions with certain other medications and grapefruit juice. Both Seldane and Hismanal have been taken off the market. Allegra, Zyrtec, and Claritin do not appear to pose any of the dangers associated with Seldane.

Until more is known, however, anyone who takes a second-generation antihistamine should probably avoid or use with caution combinations with grapefruit juice or the drugs that caused problems with Seldane and Hismanal. Such medications include:

The antibiotics clarithromycin (Biaxin) and troleandomycin
Certain HIV protease inhibitors
Antidepressant serotonin-reuptake inhibitors (Prozac, Paxil, and Serzone)

Azelastine (Astelin) and levocabastine (Livostin) are available in nasal spray form. They can reduce nasal congestion as well as allergy symptoms. Both reduce symptoms, although azelastine may be more effective in some patients. Their disadvantages are a bitter taste, drowsiness, and expense. They are not as effective as steroid nasal sprays.

Many prescription and non-prescription products that combine antihistamines and decongestants are available. Combinations sold over-the-counter include Allerest, Sudafed Severe Cold Formula, Vicks DayQuil, Benadryl Allergy/Sinus, Contac Day/Night Allergy & Sinus. Prescription combinations include Claritin-D, Allegra D, and Zyrtec-D. Symptoms may improve within 60 minutes, with congestion clearing up first.

Corticosteroids

A number of drugs are available for reducing the inflammatory response in allergies. These drugs can help prevent an allergy attack from occurring.

Nasal-spray corticosteroids (commonly called steroids) are considered the most effective drugs for treating severe allergic rhinitis. Corticosteroids suppress important stress and other hormones in a region of the brain called the HPA axis. The suppression of these hormones blocks the inflammatory response that triggers an allergic attack. Steroids do not relieve symptoms immediately. It may take several hours before their effects are felt. Nasal spray steroids benefits include:

Reducing inflammation and mucus production
Improving night sleep and daytime alertness in patients with perennial allergic rhinitis
Treating polyps in the nasal passages

Comparison studies report that nasal steroid sprays work better than second generation antihistamines, such as loratadine (Claritin) and cetirizine (Zyrtec), and are possibly even more effective than allergy shots. They have no effect on itchy eyes, however.

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

Triamcinolone (Nasacort). Approved for children over age 6.
Mometasone furoate (Nasonex). Approved for use in patients age 3 and older.
Fluticasone (Flonase, Flounce, generic). Approved for children over age 4.
Beclomethasone (Beconase, Vancenase), flunisolide (Nasalide), and budesonide (Rhinocort). Approved for children over age 6.
Ciclesonide (Omnaris). Approved for patients age 12 and older.

Side Effects. Corticosteroids are powerful anti-inflammatory drugs. Although oral steroids can have many side effects, the nasal-spray form affects only local areas and has less risk for widespread side effects unless the drug is used excessively. Side effects of nasal steroids may include:

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

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

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

Cromolyn serves as both an anti-inflammatory drug and a specific blocker for allergens. The standard cromolyn nasal spray (Nasalcrom) is not as effective as steroid nasal sprays but does work well for many people with mild allergies. It is one of the preferred first-line therapies for pregnant women with mild allergic rhinitis. It may take up to 3 weeks to experience full benefit.

Side Effects. Cromolyn has no major side effects, but minor ones include nasal congestion, coughing, sneezing, wheezing, nausea, nosebleeds, and dry throat. The spray can cause burning or irritation.

Leukotriene-antagonists are oral drugs that block leukotrienes, powerful immune system factors that are important in causing airway constriction and mucus production in allergy-related asthma. Leukotriene-antagonists include zafirlukast (Accolate), montelukast (Singulair), zileuton (Ziflo), and pranlukast (Ultair, Onon). These drugs are mainly used to treat asthma. Montelukast was approved in 2003 to treat seasonal allergies, and in 2005 to treat indoor allergies.

Immunotherapy

Immunotherapy (commonly referred to as "allergy shots") is a safe and effective treatment for patients with allergies. It is based on the premise that people who receive injections of a specific allergen will lose sensitivity to that allergen. The most common allergens for which shots are given are house dust, cat dander, grass pollen, and mold.

Immunotherapy benefits include:

Targeting the specific allergen.
Reducing sensitivity in airways in the lungs as well as in the upper airways.
Preventing the development of new allergies in children.
Reducing asthma symptoms and the use of asthma medications in patients with known allergies. Research suggests it may also help prevent the development of asthma in children with allergies.

Candidates for Immunotherapy. Immunotherapy may be given to anyone over age 7 whose allergies are severe and who do not respond to medication. Many experts agree that immunotherapy should be considered as soon as possible for children with asthma and allergies. Immunotherapy is safe for pregnant women who are already receiving it, although half-strength doses are generally recommended, and it should not be started during pregnancy.

Individuals at Risk for Complications. People who should probably avoid immunotherapy include those who have:

An extreme response to skin tests (this may predict an allergic reaction).
Wheezing.
Uncontrolled severe asthma or lung disease.
Patients taking certain medications (such as beta-blockers).
The health status of anyone should be determined before starting treatment.

The major downside to immunotherapy is that it requires a prolonged course of weekly injections. The process generally includes:

Injections of diluted extracts of the allergen are given on a regular schedule, usually twice a week to weekly at first, then in increasing doses until a maintenance dose has been reached. It usually takes several months and may take up to 3 years to reach a maintenance dose.
At that time, intervals between shots can be 2 - 4 weeks, and the treatment is continued for another 3 - 5 years.
Patients can experience some relief within 3 - 6 months. If there is no benefit within 12 - 18 months, discontinue the shots.

After stopping immunotherapy, about a third of allergy sufferers no longer have any symptoms, a third have improved symptoms, and a third relapse.

The use of an injection series is effective, but patients often fail to comply with the regimens. Some other schedules and delivery methods are being investigated that might make the program easier and less distressing.

Rush Immunotherapy. Investigators are studying "rush immunotherapy," in which patients achieve the full maintenance dose with several shots a day over a period of 3 - 5 days. Rush therapy uses modifications that reduce the risk of severe reactions to excessive doses. Studies suggest that it is effective and safe, with few side effects other than itching. Patients must be monitored closely during this period, however, for severe reactions.

Oral Forms. Trials are underway to test oral forms of immunotherapy as an alternative to allergy shots. These methods include using a pill taken by mouth or a sublingual (under-the-tongue) tablet. Although oral and sublingual immunotherapy is prescribed in many countries in Europe and South America, it is not approved in the United States and is not considered accepted therapy at this time.

Injections for ragweed and, sometimes, dust mites have higher risks for side effects than other allergy shots. If complications or allergic reactions develop, they usually occur within 20 minutes, although some can develop up to 2 hours after the shot is given.

Side effects of immunotherapy include:

General itching, swelling, red eyes, hives, soreness at the injection site.
Less common side effects are low blood pressure, asthma worsening, or difficulty breathing. This is due to an extreme hypersensitivity response called anaphylaxis. It can also occur if excessive doses are given.
In rare cases, particularly because of excessive doses or if a patient has a serious lung problem, severe reactions can occur, which can be life threatening.
Premedicating patients with antihistamines and corticosteroids may help reduce the risk of reactions to immunotherapy, although this could mask early warning signs.

In a 10-year study, the incidence of any adverse effect was less than two-tenths of 1%, and the great majority of events were mild. The risk for a fatal response is estimated to be 1 in 63 million injections. (As a comparison, the risk for a fatal reaction to penicillin is much higher, 1 in 7.5 million injections.)

Vaccines. Of particular interest is the development of immunotherapeutic vaccines that use more specific targets to produce an insensitivity to allergens. One such vaccine uses a small protein from the allergen, which is injected into the patient. Other vaccines under investigation are those that use the allergen's genetic material (its DNA) to promote tolerance to the allergen. In a promising 2006 pilot study, patients who received 6 weekly injections of a DNA-based experimental ragweed vaccine had symptom reductions that lasted a year later into a second ragweed season. Researchers will be testing this vaccine in further clinical trials.

Monoclonal Antibodies. Monoclonal antibodies (MAb) are genetically-developed antibodies that are designed to target and attack very specific factors. A MAb known as omalizumab (Xolair) prevents the antibody immunoglobulin E (IgE) from triggering the inflammatory events that lead to allergies. Studies in recent years have suggested that omalizumab may help reduce symptoms and improve quality of life for patients with non-seasonal allergic rhinitis. A 2006 study suggested that treatment with omalizumab before and during ragweed allergy shots may help reduce immunotherapy side effects. The drug is currently approved for asthma. In 2007, the FDA warned that omalizumab may cause a life-threatening allergic reaction (anaphylaxis) in some patients.

Prevention

People with existing allergies should avoid irritants or allergens. These triggers include:

Pollen. This is the primary cause of allergic rhinitis.
Dust mites, specifically mite feces, which are coated with enzymes that contain a powerful allergen. These are the primary allergens inside the home.
Animal dander (flakes of skin) and hair from cats, house mice, and dogs. House mice are proving to be significant sources of allergens, particularly in urban children.
Molds.
Fungi.
Cockroaches are major asthma triggers and may reduce lung function even in people without a history of asthma.
Some research suggests that alcohol intake may influence allergy severity. One study found that as little as one drink a day is enough to worsen dust mite allergies.
Some studies suggest that early exposure to some of these allergens, including dust mites and pets, may actually prevent allergies from developing in children.

Controlling Pets. People who already have pets and are not allergic to them are probably at low risk for developing such allergies later on. When children are exposed to more than one dog or cat during their first year, they have a much lower risk for not only pet allergies but also seasonal allergies and asthma. (Pet exposure does not protect them from other allergens, notably dust mites and cockroaches).

In children who have an existing allergy to pets, however, the pets should be given away or kept outside. If this isn't possible, they should at least be confined to carpet-free areas outside the bedroom. Cats harbor significant allergens, which can even be carried on clothing. Dogs usually present fewer problems. Washing animals once a week can reduce allergens. Dry shampoos, such as Allerpet, that remove allergens from skin and fur and are now available for both cats and dogs and are easier to use than wet shampoos.

For small children, stuffed animals might serve as a comforting replacement, although they might harbor dust mites. Putting stuffed animals in the freezer for 24 hours before washing them kills the dust mites. For best effect, this process should be done weekly.

Preventing Exposure to Cigarette and Cooking Smoke. Parents who smoke should quit. Studies show that exposure to second-hand smoke in the home increases the risk for asthma and asthma-related emergency room visits in children. [For help in quitting, see In-Depth Report # 41: Smoking.]

Controlling Dust. Spray furniture polish is very effective for reducing both dust and allergens. Air cleaners, filters for air conditioners, and vacuum cleaners with High Efficiency Particulate Air (HEPA) filters can help remove particles and small allergens found indoors. Neither vacuuming nor the use of anti-mite carpet shampoo, however, is effective in removing mites in house dust. Vacuuming actually stirs up both mites and cat allergens. People with these types of allergies should avoid having carpets or rugs in their homes.

Bedding and Curtains. Many experts recommend reducing exposure to dust mites by enclosing mattresses and pillows in semipermeable coverings. (Vinyl mattress covers limit airflow and may worsen, or even cause, asthma in children.) However, several 2005 studies suggested that such covers do not prevent allergies or asthma. Curtains should be replaced with shades or blinds and bedding washed using the highest water temperature setting.

Reducing Humidity in the House. Dust mites thrive in humidity, and damp houses increase the risk for mold. On-going humidifiers can worsen the problem. If they are used, humidity levels should not exceed 40%, and humidifiers should be cleaned daily with a vinegar solution.

Exterminating Pests (Cockroaches and Mice). Use professional exterminators to eliminate cockroaches. (One study reported that ridding a home of cockroaches and cleaning the house using standard housecleaning techniques failed to eliminate the cockroach allergens themselves.) Exterminate mice and attempt to remove all dust, which might contain mouse urine and dander.

Avoiding Outdoor Allergens. The following are some recommendations for avoiding allergens outside:

Start taking allergy medications 1 - 2 weeks before ragweed season begins. Be sure to take allergy medications before going outside. If regular medications do not work, ask your doctor about allergy shots.
Camping and hiking trips should not be scheduled during times of high pollen count (May and June for grass pollen and September to October for ragweed).
Patients who are allergic should avoid barns, hay, raking leaves, and mowing grass. (A mask can be worn during outdoor chores to help reduce pollen exposure.)
Sunglasses can help prevent pollen from getting into eyes.
After being outdoors, clean off pollen residue by bathing, washing hair and clothes, and using a nasal salt water rinse.

Some evidence suggests that people with allergic rhinitis and asthma may benefit from a diet rich in omega-3 fatty acids (found in fish, almonds, walnuts, pumpkin, and flax seeds) and fruits and vegetables (at least five servings a day). Some studies also suggest reducing sodium, trans fatty acids (hydrogenated fats found in commercial products and baked goods), and omega-6 fatty acids (found in most vegetable oils). Investigators are also studying probiotics -- so-called good bacteria, such as lactobacillus and bifidobacterium, which can be obtained in supplements.

Resources

www.aaaai.org -- American Academy of Allergy, Asthma & Immunology
www.acaai.org -- American College of Allergy, Asthma & Immunology
www.niaid.nih.gov -- National Institute of Allergy and Infectious Diseases
www.njc.org -- National Jewish Medical and Research Center
www.lungusa.org -- The American Lung Association

References

Bower JH, Maraganore DM, Peterson BJ, Ahlskog JE, Rocca WA. Immunologic diseases, anti-inflammatory drugs, and Parkinson disease: a case-control study. Neurology. 2006 Aug 8;67(3):494-6.

Calderon M, Alves B, Jacobson M, Hurwitz B, Sheikh A, Durham S. Allergen injection immunotherapy for seasonal allergic rhinitis. Cochrane Database Syst Rev. 2007 Jan 24;(1):CD001936.

Creticos PS, Schroeder JT, Hamilton RG, Balcer-Whaley SL, Khattignavong AP, Lindblad R, et al. Immunotherapy with a ragweed-toll-like receptor 9 agonist vaccine for allergic rhinitis. N Engl J Med. 2006 Oct 5;355(14):1445-55.

Leger D, Annesi-Maesano I, Carat F, Rugina M, Chanal I, Pribil C, et al. Allergic rhinitis and its consequences on quality of sleep: An unexplored area. Arch Intern Med. 2006 Sep 18;166(16):1744-8.

Review Date:
3/22/2007
Reviewed By:
Harvey Simon, MD, Associate Professor of Medicine, Harvard Medical School; Physician, Massachusetts General Hospital.

A.D.A.M. Copyright

adam.com

Viral encephalitis

FitSugar — Wed, 08 Oct 2008 17:35:12 -0700

HEALTH GUIDE REFERENCE FROM A.D.A.M

Highlights

West Nile Virus

In 2007, 3,510 cases of West Nile virus were reported to the U.S. Centers for Disease Control. States with the highest number of reported cases included Colorado, California, and North Dakota. Of the reported cases, two-thirds were in the form of West Nile fever, and one-third were diagnosed as West Nile neuroinvasive disease (encephalitis and meningitis). However, the high proportion of neuroinvasive disease cases is due to the fact that serious cases of West Nile virus are more likely to be reported to health authorities than mild cases. In general, less than 1% of people who become infected with West Nile virus develop encephalitis.

West Nile Virus Symptoms and Diagnosis

Most people (80%) who are infected with West Nile virus do not have any symptoms. About 20% of people develop mild symptoms that include fever, headache, body aches, and nausea and vomiting. These symptoms can last from a few days to a few weeks. For the minority of people who develop neuroinvasive disease, symptoms can include high fever, headache, neck stiffness, muscle weakness, and convulsions. While West Nile neuroinvasive disease is rare, its neurological complications such as paralysis can be permanent.

Prevention

West Nile virus is carried by mosquitoes and is most common during the summer and early fall. The best way to prevent becoming infected with West Nile virus is to avoid being bitten by a mosquito. Use insect repellant when you go outside, especially during the peak mosquito hours of dusk and dawn. Remove mosquito-breeding environments (such as standing water in flower pots) from your property. Scientists are testing several different vaccines to protect against West Nile virus, but it will be many years before they are commercially available.

Introduction

Encephalitis is a rare but potentially life-threatening inflammation of the brain that can occur in people of all ages. The most common cause of encephalitis is infection by a virus. In very rare cases, encephalitis can also be caused by bacterial infection, parasites, or complications from other infectious diseases. This report focuses on viral encephalitis.

Many viruses can cause encephalitis. The West Nile virus, for example, has been responsible for high-profile outbreaks in the U.S. Most people exposed to encephalitis-causing viruses have no symptoms. Others may experience a mild flu-like illness, but do not develop full-blown encephalitis.

In severe cases, the infection can have devastating effects, including:

Swelling of the brain (cerebral edema)
Bleeding within the brain (intercerebral hemorrhage)
Nerve damage

The damage may cause long-term cognitive or physical problems, depending on the specific areas of the brain affected.

Other Viral Infections of the Central Nervous System. Viral infection and inflammation can affect multiple areas of the central nervous system, and is categorized by its location:

Meningitis: infection of the meninges (the membranes that surround the brain and spinal cord)
Meningoencephalitis: infection of both the brain and meninges
Encephalomyelitis: infection of the brain and spinal cord

Encephalitis caused by viruses in the United States generally fall into the following groups:

Arboviruses are the primary cause of acute encephalitis (sudden-onset encephalitis caused by direct infection). Arboviruses, short for "arthropod-borne viruses," are spread by mosquitoes and ticks.
Enteroviruses, such as coxsackievirus.
Herpes viruses are the other major cause of encephalitis in the U.S. This virus family includes herpes simplex, Epstein-Barr, cytomegalovirus, and varicella-zoster.
In rare cases, secondary encephalitis can develop following childhood viral diseases such as measles, mumps, and rubella.

[For more information, see the Causes section in this report.]

Encephalitis can develop shortly after an initial viral infection, or it can develop when a virus that was lying dormant in the body suddenly reactivates. Viruses are simple, but powerful infectious organisms.

The virus infects a person (host) by penetrating a cell membrane and ejecting its genetic material (its DNA or RNA) into the cell.
The viral DNA or RNA takes control of important cell processes, telling the cell to make more viruses.
The cell ruptures, releasing new viral particles that infect other cells.

There are two ways that viruses can infect brain cells:

The virus silently invades the body. There are no initial symptoms. The virus is carried by the bloodstream to the nerve cells of the brain, where they gather and multiply. Viruses that enter the brain in this manner are often widely scattered throughout the brain. This is called diffuse encephalitis.
A virus first infects other tissue and then invades brain cells. Viruses that are transmitted from other tissues usually cause focal infection, meaning they produce extensive damage in only a small area of the brain.

The brain and spinal cord comprise the central nervous system. The adult human brain weighs about 3 pounds (1.4 kilograms). There are two major parts of the brain:

The higher and larger forebrain (the cerebrum)
The lower and smaller brain stem

The cerebrum is the uppermost and largest part of the brain. It is the most highly developed section of the brain. There cerebrum has several components:

The Cerebral Cortex. The cortex is the outermost layer of the cerebrum. It is made of gray and white matter:

Gray matter is a thin sheet of nerve cells that cover the surface of the brain.
White matter is a bundle of insulated nerve fibers that underlies the cortex and makes up the core of the cerebral hemispheres.

The Hemispheres. The two hemispheres control higher brain functions, such as memory, learning, decision making, and processing input from the senses. They are each divided into four lobes, which regulate different brain functions:

Frontal lobe: This is the brain's "gatekeeper." It controls higher motor functions, including speech, and governs concentration, attention, inhibition, judgment, and personality traits.
Parietal lobe: Processes information from the senses and controls walking, posture, and head and eye movements.
Occipital lobe: Responsible for interpreting visual input from the eyes.
Temporal lobe: Responsible for interpreting auditory input from the ears. Also regulates how language is interpreted and retrieves information for memory storage.

The Basal Ganglia. The basal ganglia are clusters of gray matter within each of the lobes. They are important for coordinating voluntary muscle movement, balance, and posture.

The Limbic System. The limbic system is located deep in the cerebrum and controls interpretation of smell, instinctive behavior, emotions, and drives.

The brain stem is responsible for all vital functions. It is divided into the following areas, which are responsible for specific functions:

Medulla: sleep, breathing, heartbeat, digestion, activation of higher forebrain functions
Pons: sleep, breathing, motor control, activation of higher forebrain functions
Cerebellum: movement coordination
Midbrain: walking, posture, head, eye movement
Hypothalamus: body temperature, appetite, sexual behavior, reproductive hormones
Thalamus: communication with higher forebrain

The spinal cord extends out of the base of the skull through the vertebrae of the spinal column. It is continuous with the brain. Thirty-one pairs of nerves extend from the sides of the spinal cord to other parts of the body (the peripheral nervous system).

The meninges are three membranes that enclose the brain and spinal cord. They contain cerebrospinal fluid, which protects the central nervous system from pressure and injury.

Causes

Arboviruses

Arboviruses, including the West Nile virus, are transmitted by blood-sucking insects such as mosquitoes and ticks. Most of the time, the viral infections initially develop in birds. Insects that feed on the infected blood from a diseased bird (or reservoir ) carry the virus, and transmit it when they bite a susceptible host (such as an animal or a human). Because these insects play a role in the disease-transmission process, they are referred to as vectors.

Arboviruses multiply in blood-sucking vectors, nearly always mosquitoes. There is no evidence that these infections can be transmitted casually from one infected person or animal directly to another uninfected person without passing through a mosquito (or tick) first. (Although, a small number of West Nile virus cases have occurred through blood transfusions, organ transplantation, and possibly breast-feeding.) It should be stressed that only about 10% of people who are infected by an arbovirus develop encephalitis and that only about 1% of those infected show symptoms.

Arboviruses that cause encephalitis are primarily found in three virus families: Togaviridae, Bunyaviridae, and Flaviviridae. In the United States, the main mosquito-borne encephalitis strains are: Eastern equine, Western equine, St. Louis, La Crosse, and West Nile. Equine encephalitis causes disease in both humans and, as its name implies, horses. Powassan encephalitis is a less common tick-borne flavivirus that occurs primarily in the northern United States. Japanese encephalitis is the most common form of viral encephalitis to occur outside of the United States. It is endemic in rural areas in east, south, and southwest Asia, especially China and Korea. Venezuelan equine encephalitis is found in South and Central America.

Different arboviruses cause different forms of encephalitis. Although the overall disease is the same, there are subtle differences in symptoms and the type of brain damage they produce.


Eastern Equine Encephalitis
Virus Family	Togaviridae (genus Alphavirus)
U.S. Geographic Areas	Atlantic and Gulf coasts, in New England, and around the Great Lakes. States most affected are Florida, Georgia, Massachusetts, and New Jersey.
Symptom Onset	Symptoms appear 4 - 10 days following infection and can range from mild flu-like symptoms to full-blown encephalitis.
Incidence and Mortality Rates	The most serious of the U.S. arboviruses are fortunately rare. About 220 cases have been confirmed since 1964 with an average rate of 5 cases per year. About a third of people who contract EEE die from it. Children are more likely to survive but also to suffer complications afterward.
Age Risk Groups	Adults over age 50 and children under age 15.
Western Equine Encephalitis
Virus Family	Togaviridae (genus Alphavirus)
U.S. Geographic Areas	Farming areas in western and central Plains and Rocky Mountain states west of the Mississippi.
Symptom Onset	5 - 10 days following infection.
Incidence and Mortality Rates	Very rare. There was only one case reported between 1995 and 2000. Mortality rate is 3 - 4%; 30% of survivors have complications afterward. Most severe in children, especially those younger than 1 year. Infants may suffer permanent neurological damage.
Age Risk Groups	Infants younger than 12 months.
St. Louis Encephalitis
Virus Family	Flaviviridae (genus Flavivirus)
U.S. Geographic Areas	Takes its name from an epidemic in St. Louis, but outbreaks have occurred in wider geographic areas, especially in midwestern and southeastern states, and can occur in rural or urban areas. As of 2000, the highest numbers of total cases have been reported in Texas (970), Illinois (695), Ohio (440), Indiana (368), and Florida (379).
Symptom Onset	7 - 10 days following infection.
Incidence and Mortality Rates	Although over 4,500 cases have been reported since 1964, the average number of cases has been declining with a yearly average of only 11 cases between 1995 and 2000. Mortality rate of between 3 - 30%, with about 5% of survivors suffering complications afterward.
Age Risk Groups	Elderly adults (over age 60) are at highest risk, and the disease is most severe in this age group. Younger people usually experience mild, flu-like symptoms.
La Crosse Encephalitis
Virus Family	Bunyaviridae (genus Bunyavirus)
U.S. Geographic Areas	Occurs most frequently in upper Midwestern, southeastern (Appalachia), and mid-Atlantic states. Most cases have occurred in Ohio and Wisconsin. Unlike other encephalitis viruses which originate in birds, La Crosse encephalitis is transmitted to mosquitoes from infected chipmunks and squirrels.
Symptom Onset	5 - 10 days following infection.
Incidence and Mortality Rates	An average of 70 - 100 cases reported per year. Mortality rates are less than 1%. More common and severe in children under age 16.
Age Risk Groups	Children younger than 16 years.
West Nile Encephalitis
Virus Family	Flaviviridae (genus Flavivirus).
U.S. Geographic Areas	Cases have been reported throughout the mainland United States. In 2007, the majority of West Nile encephalitis cases occurred in Colorado, California, and North Dakota.
Symptom Onset	3 - 14 days following infection.
Incidence and Mortality Rates	In 2007, 3,510 cases of WNV were reported to the CDC, with 109 deaths. Of all the reported cases, 65% were due to West Nile fever. A third of those who contracted WNV had more severe conditions, such as meningitis and encephalitis. However, most cases of West Nile virus do not produce symptoms, and are not reported, so these numbers imply a more worrisome picture than actually exists. In fact, fewer than 1% of people who are infected with WNV go on to develop neurological disease.
Age Risk Groups	Adults over age 50.

West Nile Virus (WNV). Until 1999, the West Nile virus was generally restricted to Africa, the Middle East, southwestern Asia, eastern Europe, and Australia. It emerged in the United States with the first outbreak in New York City in 1999. WNV is now found in birds and mosquitoes in every state except Alaska and Hawaii. Human cases of West Nile encephalitis have been reported throughout the continental United States.

How WNV Is Transmitted. WNV, discovered in Uganda in 1937, circulates primarily between birds and mosquitoes and can be carried long distances by migrating birds. In a given geographic area, the appearance of the virus among birds and mosquitoes generally precedes infection in humans. WNV has infected over 110 species of birds. In addition to mosquito-to-human transmission, other causes of human infection have included blood transfusions and organ transplantation. The U.S. now uses screening tests to detect West Nile virus in donated blood and organs. There have also been cases of mother-to-child transmission during pregnancy. However, a 2006 study reported that most pregnant women who are infected with WNV deliver healthy babies. It is still not clear if WNV can be transmitted through breast milk.

Severity of WNV. About 80% of people infected with WNV will not have any symptoms. Twenty percent will develop West Nile fever (which includes fever, headache, and occasional skin rash). Less than 1% of infected people will develop neuroinvasive disease, the most severe form of WNV.

Neuroinvasive disease affects the nervous system and includes encephalitis, meningitis, and poliomyelitis. People over age 50 and those with weakened immune systems are at the greatest risk for neuroinvasive disease. The fatality rate for those afflicted ranges from 3 - 15%. Neuroinvasive disease symptoms include high fever, headache, stiff neck, stupor, disorientation, coma, tremors, convulsions, muscle weakness, and paralysis. Preliminary research is currently being conducted on vaccines to prevent WNV and antiviral drugs to treat it.

Although West Nile fever is considered to be less serious than West Nile neuroinvasive disease, an important 2006 study found that both conditions can cause long-term health complications. Researchers found that more than a year after being diagnosed with WNV, half of patients complained of neurological and psychological symptoms, including fatigue, memory problems, headaches, depression, and tremors. Patients who had West Nile fever were as likely to experience these problems as those who had WNV-associated encephalitis or meningitis.

Tick-borne encephalitis (TBE) is commonly found in many countries throughout Europe, Asia, and the former Soviet Union, but it is reported only rarely in the U.S. Powassan encephalitis is the main tick-borne encephalitis found in the United States and Canada. Cases of tick-borne encephalitis have also been reported from Rocky Mountain spotted fever, but this is a bacterial (not viral) infection.

Enteroviruses include various viruses that enter the body through the gastrointestinal tract. They account for between 10 - 20% of viral encephalitis cases. The group A coxsackievirus has been detected in infants and children with encephalitis and is among the important viruses in the class. (It should be noted that the enteroviruses are nearly as common as cold viruses and are rarely serious.) Enteroviruses can be spread through food or water contaminated by trace amounts of fecal material and through sneezing and coughing.

The herpes virus group includes a number of common infections, including herpes simplex, varicella-zoster (the cause of chickenpox and shingles), cytomegalovirus, herpes virus 6, and Epstein-Barr (EB) virus (the cause of mononucleosis). About 2,100 people are hospitalized each year from herpes-associated encephalitis. These viruses share certain features, including the capacity to cause an infection and then to go into hiding. They can lie dormant for periods of time as short as months or as long as a lifetime. In a few cases, when the viruses reactivate, they cause encephalitis. In fact, some evidence suggests that varicella-zoster, cytomegalovirus, and Epstein-Barr (EB) virus may be more common causes of encephalitis than previously thought. In most cases, however, encephalitis from these viruses occurs in people with impaired immune systems, such as people with HIV or organ transplant patients.

Herpes Simplex Virus. Herpes simplex virus (HSV) is the most common cause of encephalitis in developed countries and is responsible for about 10 - 20% of all adult cases of viral encephalitis. There are two distinct types of the herpes simplex virus: HSV-1 (commonly associated with oral herpes) and HSV-2 (which usually causes genital herpes, although HSV-1 can also cause this form). HSV-2 causes 70 - 90% of encephalitis cases in neonatal infants; the virus is transmitted through the mother's genital secretions. Although HSV-1 is the primary culprit in most adult cases of herpes encephalitis, HSV-2 may also cause a small number of these cases.

Herpes simplex encephalitis is the only effectively treatable form of encephalitis, but treatment (typically intravenous acyclovir) must be administered within the first few days of symptom onset. If left untreated, the mortality rate for patients with HSV-1 is about 70%; if treated, the mortality rate declines to 30%. The mortality rate for neonatal HSV-2 encephalitis ranges from 15 - 57%. [For more information, see In-Depth Report #52: Herpes simplex.]

Varicella-Zoster Virus. The varicella-zoster virus is responsible for both chickenpox (when the virus is called varicella) and shingles (when it is referred to as herpes zoster ). Chickenpox is the initial infection, after which the virus remains dormant, often for a lifetime. If it erupts, usually years later, is does so in the form of shingles. Encephalitis caused by varicella can occur in both children and adults and be very serious. If it occurs as a result of herpes zoster in adults, the brain inflammation tends to be mild, except in immunocompromised patients. In such cases, symptoms can appear weeks to months after an attack of shingles and resemble those of a stroke. Fortunately, encephalitis is rare with both varicella and zoster. [For more information, see In-Depth Report #82: Shingles and chickenpox (varicella-zoster virus).]

Epstein-Barr Virus. Epstein-Barr virus is the cause of infectious mononucleosis, which is most common in children and young adults. Symptoms of the disease are severe fatigue, headache, sore throat, and fever. In 1% of cases, neurological complications occur about 1 - 3 weeks after the onset of the infection. If encephalitis develops, it is almost always mild with full recovery.

Cytomegalovirus Encephalitis. Cytomegalovirus is also very common and usually mild. In immunocompromised patients, such those with AIDS, it can be dangerous, with severe complications including encephalitis.

Rabies. The rabies virus is transmitted from the saliva of an infected animal. The encephalitis it causes is virtually always fatal but is very rare in the U.S. Only one or two cases are typically reported each year, often from contact with bats.

Encephalitis Associated with Childhood Diseases. Encephalitis occurs rarely after common childhood infections, such as rubella, measles, and mumps. Immunizations have almost completely eliminated these infections in developed countries. Measles encephalitis still sometimes occurs in immunocompromised children. Rarely, influenza has caused acute encephalitis, usually in children. (Flu vaccinations are important in preventing these events.) Although there used to be concern that diphtheria-pertussis-tetanus and measles-mumps-rubella vaccines could cause encephalitis, recent research indicates that these childhood vaccines are very safe and do not increase encephalitis risk.

Adenoviruses. Adenoviruses were first identified in 1953 from infected tonsils and adenoids. The viruses can cause respiratory or gastrointestinal infections that are usually mild. In rare cases, adenoviruses can cause encephalitis or meningoencephalitis, which can be fatal in 30% of patients. Symptoms include lethargy, confusion, coma, and symptoms of meningitis (stiff neck, headache, and vomiting).

Toxoplasmosis. Encephalitis from toxoplasmosis, which is transmitted in a cat's fecal matter, results in 2,100 hospitalizations a year, which rivals herpes as the most common infectious cause of encephalitis. However, this condition causes very mild symptoms in most people. People with HIV and impaired immune systems are at risk for more severe forms. In addition, the effects on the fetus in a pregnant women infected with toxoplasmosis can be devastating. It can be treated with antibiotics, particularly those that treat parasites.

Raccoon Roundworm. Raccoon roundworm (Baylisascaris procyonis) is a large parasitic worm that lives in the intestines of raccoons. In one Wisconsin study, half the raccoons tested were infected. Humans usually become infected by ingesting the worm's eggs through accidental contact with soil, wood chips, or tree bark contaminated with raccoon feces. The worm is harmless in raccoons but can produce severe central nervous system disease, including encephalitis, in people. At least 12 severe cases have been reported in the U.S. since 1981, most in children younger than 6 years of age (who are at higher risk because of their tendency to put their fingers or other objects into their mouths). Prompt treatment with larvae-killing drugs, such as albendazole, or anti-inflammatory drugs is not consistently effective, so it is extremely important to avoid infection. Raccoons should not be kept as pets. Eliminate access to food sources, like garbage cans and bird feeders, which will attract raccoons. Raccoon nests should be sealed off while raccoons are absent. Burning any contaminated materials is the most effective method of disposal. If burning is not feasible, contaminated substances should be buried deeply in a location remote from human activity. Wearing disposable gloves, boots, and a dust mask is important. Decks, woodpiles, and other surfaces can be decontaminated with boiling water.

Other Parasitic Infections. Encephalitis may be caused by other parasitic infections, such as toxocariasis (from roundworms found in dogs and cats) or cysticercosi (from food or water contaminated with pork tapeworm eggs). These infections usually cause only chills, fever, and swelling of lymph nodes, though seizures and headaches can occur.

In very rare circumstances, encephalitis may be caused by bacterial or fungal organisms.

Acute disseminated encephalomyelitis (ADEM), also called noninfectious encephalitis, constitutes one-third of all known cases of encephalitis. It is not caused by a virus, although it most often develops in patients 2 - 3 weeks after recovery from a viral illness. (It does not affect children under 2 years old.) Damage to nerve cells in such cases is caused not by the viral infection, however, but most likely by an autoimmune reaction, in which the body's immune system attacks its own brain tissue.

Acute disseminated encephalomyelitis has been reported as a rare complication of childhood illness, including chickenpox, mumps, or measles. Vaccination reduces these risks to nearly insignificant levels. It is a complication of the rabies vaccine in one out of 30,000 cases. Nonspecific respiratory infections are now the most common causes of ADEM, but such cases are also extremely rare.

The inflammation occurs predominantly in the white matter of the brain rather than the gray matter (the usual target of infectious encephalitis). The nerve cells do not die as they do in a viral infection. Rather, the nerve cell coating (called a myelin sheath) is partially destroyed in much the same way as it is in multiple sclerosis. Indeed, the two conditions may at first be difficult to distinguish. Recurrences may occur several months to years after the initial episode.

Symptoms

Symptoms of encephalitis usually appear within 2 days to 2 weeks of exposure to the virus. In milder cases, symptoms may resemble the flu. In severe cases of full-blown encephalitis, symptoms may include:

Behavioral and personality changes
Sensitivity to light
Fever
Headache
Vomiting
Lethargy and reduced consciousness
Seizures -- uncommon with West Nile virus
Memory loss
Stiff neck and back -- accompanied by fever and headache would indicate meningitis
Confusion
Speech, hearing, and vision problems
Muscle weakness
Seizures
Partial paralysis
Loss of consciousness
Coma

Patients experiencing these types of symptoms (especially if they may have recently been bitten by a mosquito or tick of if they have lesions on the lips or genitals) should immediately seek medical treatment.

Symptoms in Infants. Infants with herpes virus encephalitis may develop lesions in the mouth, in the eye, or on the skin 1 - 45 days after birth. Other symptoms include lethargy, seizures, and changes in temperature. Their fontanels, the soft spots on their head where the skull has not yet closed, may bulge outward.

Risk Factors

Encephalitis is a rare disease, extremely uncommon in the U.S. even for people in the risk groups discussed below. Many people fall into the following categories; very few of them will ever contract encephalitis.

Encephalitis can occur at any age; increased age-associated risks depend on the type of encephalitis virus. Newborn infants are particularly at risk for herpes virus. For arboviruses, infants are most vulnerable to Western equine encephalitis. Older children and teenagers are more susceptible to Eastern equine and La Crosse encephalitis. Older and elderly adults are at higher risk for Eastern equine, St. Louis, and West Nile encephalitis.

Immunocompromised Patients

Patients whose immune systems are compromised by conditions such as HIV-AIDS, cancer therapies, or organ transplantation are more susceptible than other individuals to any form of encephalitis. Of particular concern are varicella and cytomegalovirus encephalitis which tend to be more common and deadly in these patients than in the normal population.

U.S. Geographic Regions. The primary risk factor for arbovirus encephalitis is living in areas of possible exposure to virus-carrying mosquitoes. Most viral outbreaks occur in rural or farming areas, but they can also occur in cities. While some forms of arbovirus encephalitis are limited to specific geographical regions, the West Nile virus has become endemic throughout the mainland United States. [See Common Forms of Mosquito-Borne Encephalitis table for more detailed regional information.]

Seasonal Risks. Transmission of arboviruses correlates with the mosquito season and is highest during the months of July through September (late summer through early fall). The ideal conditions for mosquito breeding are a wet spring followed by a hot, dry summer.

Few people in the world have not been infected with at least one of the herpes viruses. Most of these viruses are easily transmitted in body fluids, including from saliva or droplets after people exhale or sneeze. Infants can contract herpes simplex virus from an infected mother during delivery, which can have very serious consequences. [For more information, see In-Depth Report #52: Herpes simplex.]

Prognosis

In most cases of arbovirus infection, symptoms are mild, last 3 - 5 days, and resolve without becoming serious. In fact, the infection is generally unrecognized as anything other than a mild flu.

Prognosis for severe encephalitis depends on many factors, including the following:

Age of the patient -- worse outcomes for infants under age 12 months and adults over age 55
Immune status
Preexisting neurological conditions
Virulence of the virus

In severe cases of encephalitis, the swelling of the brain inside the skull places downward pressure on the brain stem. The brain stem controls vital functions, such as respiration and heartbeat, and if the pressure becomes too severe, these vital functions can cease and cause death.

Coma is a common symptom in patients with severe encephalitis, but does not necessarily predict a fatal or severe outcome. In one study of Eastern equine encephalitis, some survivors averaged 5 days in a coma and had no or only mild-to-moderate complications afterward. One patient was in a coma for 9 days and had only mild complications afterward.

Survivors of encephalitis commonly experience neurologic consequences, which can be long-term and even permanent. The degree and type of brain damage can vary from mild-to-severe and from focal (in one part of the brain) to multifocal (several parts of the brain) to diffuse (throughout the brain).

The location and severity of the infection largely determines the pattern of brain damage and therefore its effects, which can be:

Physical (muscle control)
Behavioral and emotional (personality changes)
Cognitive (memory, speech)
Sensory (vision, hearing)
Some patients who have memory problems and personality changes afterward describe their condition as being an "invisible disease." They appear to be normal to others, but they are plagued with forgetfulness and lapses in attention that have a considerable effect on the quality of their daily lives. Helpful support groups are now available on the Internet.

Diagnosis

In many cases, the symptoms of encephalitis are too similar to aid the doctor in differentiating among the many causes of brain inflammation. The primary objective in diagnosing viral encephalitis is to determine if it is caused by:

Arboviruses or other viruses that can be managed only by relieving symptoms
Herpes simplex or other conditions that are potentially treatable

If the doctor suspects encephalitis, a scanning technique is often the first diagnostic step. Computerized tomography (CT) or magnetic resonance imaging (MRI) scans may show the extent of the inflammation in the brain and help differentiate encephalitis from other conditions. MRI can detect injuries in parts of the brain that suggest infection with herpes virus at the onset of the disease, while CT scans cannot.

Electroencephalogram (EEG), which records brain waves, may reveal abnormalities in the temporal lobe that are indicative of herpes simplex encephalitis.

When encephalitis is suspected, a sample of cerebrospinal fluid is taken using a lumbar puncture, which involves inserting a needle between two vertebrae in the patient's lower back. The sample is taken to count white blood cells and identify specific blood cell types, to measure proteins and blood sugar levels, and to determine spinal fluid pressure. Doctors use cerebrospinal fluid to test for herpes simplex encephalitis and to look for the presence of antibodies to the West Nile virus. While cerebrospinal fluid tests may help diagnose encephalitis, they cannot provide information on how severe the disease will be.

Blood tests are used to test for West Nile virus and other arbovirus infections.

If necessary, tiny samples of brain tissue are surgically removed for examination and testing for the presence of the virus. Tissue is prepared using staining techniques and then viewed under an electron microscope. In a few cases, the viruses in brain cells are able to be cultured; that is, the viruses can actually be made to replicate in samples. A brain biopsy is the gold standard for diagnosing rabies.

Treatment

With the exception of herpes simplex and varicella-zoster encephalitis, the viral forms of encephalitis are not treatable. The primary objective is to diagnose the patient as soon as possible so they receive the right medicines to treat the symptoms. It is very important to lower fever and ease the pressure caused by swelling of the brain.

Patients with very severe encephalitis are at risk for body-wide (systemic) complications including shock, low oxygen, low blood pressure, and low sodium levels. Any potentially life-threatening complication should be addressed immediately with the appropriate treatments.

Since it is difficult to determine the cause of encephalitis, and rapid treatment is essential, it is common to give the patient medication for the symptoms that respond to therapy without waiting to determine the cause of the illness.

Some experts advise immediately administering intravenous acyclovir, the standard treatment for herpes simplex encephalitis, to all patients whose symptoms indicate encephalitis.
Corticosteroids, which reduce inflammation, may also be administered immediately.
Antibiotics, which attack bacteria but not viruses, are used in case the cause of the symptoms is bacterial meningitis.

All encephalitis treatments are aimed at reducing symptoms.

Seizures may be prevented by using fosphenytoin (Cerebyx).
Seizures may be treated with intravenous lorazepam (Ativan).
Sedatives may be prescribed for irritability or restlessness.
Simple pain relievers may be used for fever and headache.
In patients who are otherwise stable, the only other treatment measures are to keep the head elevated and monitor the patient's status.

Intravenous acyclovir is the treatment of choice for encephalitis caused by herpes simplex virus (HSV) or varicella-zoster virus. Treatment must be initiated within 2 days of symptoms for the best outcome. In nearly all cases, the virus clears within 2 weeks of treatment. If it does not, medications are continued for another 2 weeks. In rare cases, surgical measures may be needed to relieve the buildup of pressure in the brain.

Acyclovir is usually administered in the hospital. However, some patients may be safely treated with intravenous medications at home after the first few days with close monitoring by a health professional. Valacyclovir and famciclovir may be used for the treatment of non-life-threatening HSV infection.

About 25% of patients who have been successfully treated for herpes encephalitis have a relapse. Early diagnosis and treatment may help reduce this risk. Doctors are investigating if a 3-month course of oral valacyclovir will improve remission rates after a patient completes treatment with intravenous acyclovir. Foscarnet (Foscavir), another powerful antiviral drug known as a pyrophosphate analogue, may be useful for herpes simplex viral strains that have become resistant to acyclovir.

No other drugs have been effective for treating arboviruses, including West Nile virus. A number of drugs used to treat other virus infections are being investigated. They include ribavirin (an antiviral drug used to treat influenza), interferon alfa 2a (Roferon-A) and other interferons, immunoglobulin G, and glycyrrhizin (a compound in licorice root with anti-viral activity). Researchers with the U.S. National Institutes of Health are investigating Omr-IgG-am, a blood-derived product that contains WNV antibodies, which can be given intravenously.

ADEM is usually treated with high-dose intravenous methylprednisolone, a powerful anti-inflammatory drug known as a corticosteroid. Intravenous immunoglobulin (IVIG), alone or in combination with methylprednisolone, is also showing promise in certain patients, including children with severe ADEM.

Vaccinations

Certain vaccinations can help prevent the diseases that can lead to encephalitis.

Measles used to be a very common childhood disease. In about 1 in 1,000 patients it can lead to encephalitis or death. The risk for these severe complications is highest in the very young and very old. Aggressive vaccination programs have reduced the incidence of measles in the U.S. to fewer than 100 cases a year. Rarely, patients who receive the live-measles vaccine develop encephalopathy (brain damage), but the risk is far lower than brain problems occuring from the disease itself.

Herpes zoster, or shingles, is a reactivation of the varicella virus, which causes chickenpox. Children (and adults who do not have a history of infection and who lack evidence of immunity) should receive 2 doses of the chickenpox vaccine. In 2006, a vaccine for shingles became available for adults age 60 years and older. [For more information, see In-Depth Report #82: Shingles and Chickenpox.]

Researchers are investigating a number of vaccines against the flavivirus family of arboviruses.

A vaccine (JE-VAX) is currently available for Japanese encephalitis. In travelers, it is only recommended for those visiting rural areas in high-risk Asian countries for more than 30 days. These countries include China, Korea, India and neighboring areas, and Southeast Asia. The disease may occur with lower frequency in Japan, Taiwan, Singapore, Hong Kong, and eastern Russia. A new type of Japanese encephalitis virus vaccine is currently in clinical trials.

Another type of vaccine (FSME-IMMUN) is used to prevent tick-borne encephalitis (TBE) in travelers visiting regions where this type of encephalitis is prevalent. TBE is found mainly in Eastern Europe, China, North Africa, and Russia. This vaccine is available in many European countries, but it is not yet approved in the United States.

Two types of vaccines, chimeric and DNA, are under investigation for West Nile virus, but it will be several years before these vaccines could become commercially available.

Anyone exposed to bats, or the secretions of an animal suspected of having rabies, should be evaluated for post-exposure rabies vaccine. Exposed individuals may also receive immune globulin unless they were previously vaccinated. Local health authorities are generally consulted. When the saliva of a potentially infected animal is exposed to an open wound or mucous membrane, treatment is generally warranted. However, the need to administer rabies immunization or immune globulin after saliva exposure to intact skin is not as clear. 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 of these shots include:

Pain
Redness
Headache
Stomach pain
Nausea
Dizziness
Muscle aches
Swelling at the injection site

Allergic response can occur after the first shot and as many as 21 days after a booster shot. Rare cases of neurological disorders have been reported that cause pain and paralysis in the legs and arms, which clear up in about 12 weeks.

Prevention

The risk for mosquito-born infections is highest between dusk and dawn, when mosquitoes feed. A good insect repellent is very helpful in reducing the risk for vector-borne disease. The most complete personal protection program for adults and most children is to apply the insect repellant DEET to the skin, and also permethrin to clothing and other surfaces.

DEET. Most insect repellents contain the chemical DEET (N,N-diethyl-meta-toluamide), which remains the gold standard of currently available mosquito and tick repellents. DEET has been used for more than 40 years and is safe for most children when used as directed. Comparison studies suggest that DEET preparations are the most effective insect repellents now available.

Concentrations range from 4% to almost 100%. The concentration determines the duration of protection. Experts recommend that most adults and children over 12 years old use preparations containing a DEET concentration of 20 - 35% (such as Ultrathon), which provides complete protection for an average of 5 hours. (Higher DEET concentrations may be necessary for adults who are in high-risk regions for prolonged periods.)

Never use DEET products should on infants younger than 2 months. According to the Environmental Protection Agency (EPA), DEET products can safely be used on all children age 2 months and older. The EPA recommends that parents check insect repellant product labels for age restrictions. If there is no age restriction listed, the product is safe for any age. The American Academy of Pediatrics recommends that children use concentrations of 10% or less; 30% DEET is the maximum concentration that should be used for children. When deciding what concentration is most appropriate, parents should consider the amount of time that children will be spending outside, and the risk of mosquito bites and mosquito-borne disease.

When applying DEET, take the following precautions:

Do not use on the face, and apply only enough to cover exposed skin on other areas.
Do not over apply, and do not use under clothing.
Do not apply over any cuts, wounds, or irritated skin.
Only parents or an adult should apply repellent to a child. They should first put DEET on their own hands and then apply it to the child. They should avoid putting DEET not only near the child's eyes and mouth but also on the hands (since children frequently touch their faces).
Wash any treated skin after going back inside.
If using a spray, apply DEET outdoors -- never indoors. Spray repellents should not be applied directly on anyone's face.

Other Insect Repellent Products. In 2005, the U.S. Centers for Disease Control (CDC) added two new mosquito repellents to its list of recommended products: Picaridin and oil of lemon eucalyptus.

Picaridin, also known as KBR 3023 or Bayrepel, is an ingredient that has been used for many years in repellents sold in Europe, Latin America, and Asia. A product containing 7% picaridin is now available in the United States. Picaridin can safely be applied to young children and is also safe for women who are pregnant or breast-feeding. According to the CDC, insect repellents containing DEET or picaridin work better than other products.

In scientific tests, oil of lemon eucalyptus, also known as PMD, worked as well as low concentrations of DEET. However, oil of lemon eucalyptus is not recommended for children under the age of 3 years.

Permethrin is an insect repellent used as a spray for clothing and bed nets, which can repel insects for weeks when applied correctly. Electric vaporizing mats containing permethrin may be very helpful. A permethrin solution is also available for soaking items, but it should never be applied to the skin. Side effects from direct exposure may include mild burning, stinging, itching, and rash. In general, however, permethrin is very safe and its use may even reduce child mortality rates from malaria. People allergic to chrysanthemum flowers or who are allergic to head-lice scabicides should avoid using permethrin.

Eliminate Sources of Standing Water. Currently, the only proven method for reducing mosquito populations is to eliminate sources of standing water.

Look for any source of standing water, where mosquitoes can breed. For example, discard any rubbish with standing water, such as old tires, cans, and bottles. (Even bottle caps can breed mosquitoes.) Turn over wading pools and wheelbarrows when not in use. Change bird bath water every 3 - 4 days. A product called Mosquito Dunk can be used to prevent breeding in standing water.
Swimming pools and hot tubs should be clean and chlorinated or drained and covered if not in use.
Clean vegetation and debris from the edges of ponds.
Keep gutters clean and unclogged.

Mosquito Traps. Mosquito traps use various methods for repelling or attracting and trapping the insects. Effective traps are expensive, and they usually require electricity or propane, which adds to the cost. Use mosquito trap machines only outdoors. While many traps can draw in significant numbers of mosquitoes, they have limitations. Do not rely on them for sole protection.

All baits should aim to attract the female mosquito, which is the primary transmitter of the viruses. However, different baits may be more or less effective. Some may even attract one species and not others. For example, a comparative study of three traps that used similar attractants found that after 20 hours, the Magnet Liberty and Mosquito Trap MK01 attracted 75% of mosquitoes in a single area, while the Sonic Web had attracted only 25%. However, all three traps tended to attract twice as many Aedes mosquitoes (which carry La Cross and Eastern Equine encephalitis) as the Culex (which transmits West Nile and St. Louis Encephalitis).

Bug Zappers. Insect light traps (commonly called bug zappers), which attract and electrocute insects, may actually spread viruses and bacteria that are on the insects. They are also not very effective for killing female mosquitoes.

Encouraging Natural Defenders. Some attempts have been made to control mosquito populations with natural defenders, including building bat and bird houses to attract natural predators or growing certain insect-repellent plants.

Citronella Candles. Burning citronella candles reduces the likelihood of bites. (Indeed, burning any candle helps to some extent, perhaps because the generation of carbon dioxide diverts mosquitoes toward the flame.)

Your home environment, personal hygiene, and what you wear can also help reduce your risk for mosquito bites:

Wear trousers and long-sleeved shirts, particularly at dusk. One survey suggested that this measure may significantly reduce the incidence of mosquito-born disease.
Sleep only in screened areas.
Air-conditioning may reduce mosquito infiltration. Where air-conditioning is not available, fans may be helpful. Mosquitoes appear to be reluctant to fly in windy air.
Don't wear perfumes.
Cover up bare skin after dusk.
Wash your hair at least twice a week.

Public health measures are the best methods for controlling mosquitoes.

Spraying. Local areas that experience outbreaks of encephalitis from mosquitoes usually have a spraying program.

Insecticides containing synthetic pyrethroids (permethrin, resmethrin, and sumithrin) are generally recommended by consumer groups as being the most effective and the least toxic to people (although they are toxic to fish and bees).
Malathion and naral -- another pesticide -- are organophosphates and approved for spraying mosquitoes. Malathion specifically has been widely used in a number of areas. Organophosphates, however, can have toxic effects on the nervous system. Some people, for example, have reported being sick after exposure to Malathion. In addition, there is a risk that mosquitoes will develop resistance to it.

Report Dead Birds. Dead birds may be indicators that the West Nile virus has reached a specific region. Report any dead birds to your local public health authorities. You should never touch a dead bird with your bare hands.

Resources

www.cdc.gov -- The U.S. Centers for Disease Control (CDC)
www.cdc.gov/ncidod/dvbid/arbor -- CDC website for arboviruses
www.cdc.gov/ncidod/dvbid/westnile -- CDC West Nile virus website
www.ninds.nih.gov -- National Institute of Neurological Disorders and Stroke
www3.niaid.nih.gov -- National Institute of Allergy and Infectious Diseases
www.mosquito.org -- American Mosquito Control Association
www.npic.orst.edu/wnv -- National Pesticide Information Center's West Nile virus resource guide

References

Bleck TP. In: Goldman L and Ausiello DA, eds. Cecil Medicine. 23rd edition. Saunders; 2007.

Modlin JF. In: Goldman L and Ausiello DA, eds. Cecil Medicine. 23rd edition. Saunders; 2007.

Nath A, Berger JR. In: Goldman L and Ausiello DA, eds. Cecil Medicine. 23rd edition. Saunders; 2007.

Whitley RJ. In: Goldman L and Ausiello DA, eds. Cecil Medicine. 23rd edition. Saunders; 2007.

Review Date:
1/26/2008
Reviewed By:
Harvey Simon, MD, Editor-in-Chief, Associate Professor of Medicine, Harvard Medical School; Physician, Massachusetts General Hospital. Also reviewed by David Zieve, MD, MHA, Medical Director, A.D.A.M., Inc.

A.D.A.M. Copyright

adam.com

Colon and rectal cancers

FitSugar — Wed, 08 Oct 2008 17:35:05 -0700

In This Report

Highlights
Introduction
Causes
Symptoms
Risk Factors
Dietary Factors
Prevention
Diagnosis
Staging
Prognosis
Surgery
Medications
Radiation Treatment
Follow-up Testing
Treatment for Metastasized ...
Resources
References

HEALTH GUIDE REFERENCE FROM A.D.A.M

Highlights

Drug Approval

In September 2006, the Food and Drug Administration approved panitumumab (Vectibix) for the treatment of patients with colorectal cancer that has spread to other parts of the body following chemotherapy. Like cetuximab (Ertibux), panitumumab targets the epidermal growth factor receptor (EGFR) on cancer cells. Panitumumab is the first new colorectal cancer drug approved since 2004. The FDA granted accelerated approval to panitumumab based on a clinical trial of patients with metastatic cancer. The average time to disease progression or death was 96 days in patients treated with panitumumab compared to 60 days in patients who received standard care.

Diet and Colorectal Cancer Recurrence

Evidence indicates that diet plays a role in colorectal cancer prevention. Now, a 2007 study in the Journal of the American Medical Association (JAMA) suggests that dietary factors also affect the risk of cancer recurrence. Patients with stage III colorectal cancer who ate lots of red meat, refined grains, and sweets had a higher risk of cancer recurrence and death than patients whose diets were high in fruits and vegetables, poultry, and fish.

Folic Acid No Good for Prevention?

Many experts have long believed that folic acid supplements may help protect against colorectal cancer. But according to a 2007 JAMA study, high-dose folic acid supplements may not prevent colorectal cancer and may actually increase the risk for adenomatous polyp formation. Adenomatous polyps are benign colorectal tumors that can potentially become cancerous. In the study, patients who took folic acid supplements had a greater risk of developing new, more numerous, and larger adenomatous polyps than patients who did not take the supplements.

NSAIDS Not Recommended for Colorectal Cancer Prevention

In March 2007, the U.S. Preventive Services Task Force (USPSTF) recommended against the routine use of aspirin and nonsteroidal anti-inflammatory drugs (NSAIDs) to prevent colorectal cancer in people who are at average risk for this disease. Several recent studies have indicated that aspirin, and NSAIDs such as celecoxib (Celebrex), can help prevent colorectal cancer. But the USPSTF notes that the risks of these drugs outweigh the benefits. Long-term daily use of NSAIDs increases the risk for gastrointestinal bleeding, kidney function problems, and heart attack and stroke.

Introduction

Cancers of the colon and rectum, often referred to collectively as colorectal cancer, are life-threatening tumors that develop in the large intestine.

More than 80% of colorectal tumors evolve from adenomatous polyps. These gland-like growths develop on the mucous membrane that lines the large intestine. They are usually either:

Tubular polyps, which protrude mushroom-like
Villous adenomas, which are flat and spreading and are more apt to become malignant (cancerous)

Polyps are very common and almost always benign. Their numbers increase with age. Polyps are found in about 25% of people by age 50, and 50% of people by age 75. Fewer than 1% of polyps under 1 centimeter (slightly less than half an inch) become cancerous. About 10% of larger polyps become cancerous within 10 years, and about 25% of these larger polyps become cancerous after 20 years. Certain inherited polyps can become cancerous more rapidly.

Digestion takes place in the gastrointestinal (GI) tract, essentially a long tube that extends from the mouth to the anus. It is a complex organ system that first carries food from the mouth down the esophagus to the stomach. Food then travels through the small and large intestines before being excreted through the rectum and out the anus.

The esophagus, stomach, large and small intestine -- aided by the liver, gallbladder, and pancreas -- convert the nutritive components of food into energy and break down the non-nutritive components into waste to be excreted.

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

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

Click the icon to see an image of stomach anatomy.

The small intestine, despite its name, is the longest part of the gastrointestinal tract, extending for about 20 feet. Food passes from the stomach through its three parts: first the duodenum, then the jejunum, and finally the ileum. Most of the digestive process occurs in the small intestine.

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

Undigested material, such as plant fiber, is passed next to the large intestine, mostly in liquid form. The large intestine is wider than the small intestine but only about 6 feet long. It is the final portion of the digestive tract and includes the cecum, the appendix, the colon, and the rectum, which extends to the anus.

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

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

Click the icon to see an image of large intestine anatomy.

The first section, the ascending colon, extends upward from the cecum on the right side of the abdomen.
The second section, the transverse colon, crosses the upper abdomen to the left side.
The third section extends downward on the left side of the abdomen toward the pelvis and is called the descending colon.
The final section is the sigmoid colon.

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

Causes

In most cases of colon or rectal cancers, the cause or causes are unknown. Defects in genes that normally protect against cancer play the major role in causing polyp cells to continuously spread and become cancerous. Some of these cases are caused by inherited genetic defects, and such patients usually have family histories of colorectal cancer. Most of the genetic mutations involved in colon cancers, however, appear to arise spontaneously (no strong family history) rather than being inherited. In such cases, environmental or other factors trigger genetic changes in the intestine that lead to cancer.

About 6% of cases of colon cancer are due to inherited factors.

APC Gene and Familial Adenomatous Polyposis (FAP). When the adenomatous polyposis coli (APC) gene is normal, it helps suppress tumor growth. In its defective form, it permits high levels of the protein beta-catenin to accumulate, which accelerates cell growth leading to polyps. Various genetic mutations that affect the APC gene directly or indirectly have been identified:

Familial adenomatous polyposis (FAP) is a rare and serious disorder in which the patient inherits an adenomatous polyposis coli (APC) mutation from either parent. It occurs in about 1 in 8,000 people. During early adulthood, hundreds to thousands of polyps grow in the colon. FAP causes less than 1% of all cases of colorectal cancer, but if untreated, virtually everyone who inherits this condition develops cancer before the age of 40. Many of the deaths attributed to FAP can be prevented with early and aggressive surgical treatment.
Non-inherited mutations of the APC gene have been detected in nearly all patients with spontaneous colon cancers.

Hereditary Nonpolyposis Colorectal Cancer (HNPCC). Hereditary nonpolyposis colorectal cancer (HNPCC), also known as Lynch syndrome, accounts for at least half of colorectal cancers that run in families. (However, only 3% or less of all colorectal cancers are due to this problem). About 50 - 80% of people who inherit the abnormal gene will develop colon cancer. HNPCC tends to develop in the right side of the colon, often in young individuals. (Left-sided cancers can still occur as well.)

People who inherit HNPCC and other defects are prone to other cancers, including uterine and ovarian cancers, as well as cancers of the small intestine and kidney system (very rare). HNPCC is highly associated with genes containing an abnormality called microsatellite instability (MSI), which is a sign of defective DNA repair. Testing tumors for MSI in people with newly diagnosed colon cancer who also have a family history of the disease may prove to be an effective method for identifying patients with hereditary nonpolyposis colorectal cancer. Tests are being developed that can detect the actual HNPCC genetic abnormality (mutation) that was inherited from a father or mother. The two most commonly affected genes are MSH2 and MLH1.

Cyclooxygenases and Prostaglandins. Cyclooxygenase 1 and 2 (COX-1 and COX-2) are enzymes involved in the production of prostaglandins, substances produced by the body that cause inflammation, widen and narrow blood vessels, control muscle contractions, and inhibit hormones that regulate fat metabolism. COX-2, but not COX-1, appears to play a role in the development and spread of colorectal tumors. COX-2 increases the levels of prostaglandin E2 (PGE2), which, in turn, stimulates factors that inhibit apoptosis, the natural process whereby all cells, including cancerous ones, self-destruct. It also activates interleukin-6 (IL-6), a factor in the immune system that is associated with cancer cell invasion.

C-Reactive Protein (CRP). CRP is another indicator of inflammation. In a 2004 study published in the Journal of the American Medical Association, elevated CRP levels predicted the development of colon -- but not rectal -- cancer.

Bile Acid Salts. Deoxycholic acid, which is found in the fat-digesting bile salts released by the gallbladder, appears to have carcinogenic properties. Its effects are now believed to play a role in some cases of colon cancer. Levels of the acid can rise as a result of high-fat diets or certain diseases.

Growth Factors. Chronically higher circulating levels of growth factors, including insulin-like growth factor, have been associated with colorectal cancer.

Inflammatory bowel diseases include Crohn's disease and ulcerative colitis. These chronic disorders cause persistent injuries in the intestinal tract that can, in some cases, produce cancerous changes.

Symptoms

It is possible to have colon or rectal cancer without symptoms. Many patients are free of symptoms until their tumors are quite advanced.

Weight loss and changes in bowel movements are general symptoms for colon cancer, but these symptoms also occur in many other diseases.

Blood in the stools is a common sign of many intestinal cancers. It may appear red if it is fresh or black if it is old. It should be reported to a doctor immediately, even though it is often caused by conditions other than cancer, including:

Hemorrhoids
Minor tears around the rectal or anal areas
Diverticulosis

In addition, stool can change color by:

Eating certain red foods, such as beets or red licorice (red)
Taking iron supplements and medications that have bismuth subsalicylate, most commonly Pepto-Bismol (black)

Nevertheless, blood in the stools is an abnormal finding that should never be ignored. Always report it to your doctor for further advice.

Symptoms of colorectal cancer vary widely depending on the location of the cancer within the large intestine.

Tumors in the Cecum and Ascending Colon (Right Colon). The waste matter in the first portion of the colon is in liquid or semi-liquid form. Tumors that develop here do not change bowel habits or stool formation, but they may cause intermittent or chronic bleeding. Although the stools look normal, patients may develop symptoms of anemia from iron deficiency. Such symptoms include weakness, fatigue, heart palpitations, shortness of breath, and exercise intolerance.

Tumors in the Transverse Colon. As waste material passes across the upper quadrants of the abdomen (the transverse colon), the intestine absorbs water, and the waste matter becomes more solid. In addition to bleeding, tumors here may cause cramps, gas, partial or complete obstruction, and even perforation of the bowel. Anemia can also occur.

Tumors in the Descending Colon and Rectum (Left Colon). When tumors partially block the lower intestine, thin, pencil-shaped stools may form. Bowel habits can change. Tumors in the rectum and lowest part of the intestine can cause pain and a feeling of fullness. Defecation may be painful, or patients may feel the urge to defecate but nothing happens. Bleeding from these locations may be brisk and bright red or maroon, but cancer is often detected before symptoms of chronic anemia develop.

Risk Factors

Colorectal cancer is the third most common cancer in the U.S., with Americans facing a lifetime chance of 5.5 - 6% for this cancer. In 2007, colorectal cancer was expected to cause 153,760 new cases and 52,180 deaths in the United States. About 73% of cancers occur in the colon and 27% in the rectum.

The lifetime risk of cancer of the colon or rectum is 5.9% for men and 5.5% for women.

Colorectal cancer risk increases with age. More than 90% of these cancers occur in people over age 50. The rate of colorectal cancer in patients under 20 years is less than 1 in 100,000 per year. At age 50 about 1 in 2,000 people per year will develop colorectal cancer. After age 65, this rate increases to almost 3 in 1,000.

African-Americans have the highest risk of being diagnosed with, and dying from, colorectal cancer. Among Caucasians, Jews of Eastern European (Ashkenazi) descent have an elevated rate of colorectal cancer. Asian Americans/Pacific Islanders, Hispanics/Latinos, and American Indians/Alaska Natives have a lower risk than Caucasians.

About 20 - 25% of colorectal cancers occur among people with a family history of the disease. (Seventy-five percent of cases are due to other causes.) People who have more than one first-degree relative (sibling or parent) with the disease are especially at high risk. The risk is even higher if the relative was diagnosed with colorectal cancer before the age of 60.

About 5 - 10% of patients with colorectal cancer have an inherited genetic abnormality that causes the disease. Genetic mutations associated with colorectal cancer include familial adenomatous polyposis and hereditary nonpolyposis colorectal cancer.

The risks for colon cancer are far higher in industrialized nations than less developed countries. A Western lifestyle, being sedentary, smoking, and having excess weight have all been associated with increased risk for colorectal cancer. (However, about 75% of cases occur without a known predisposing factor.)

Dietary Factors. Eating a lot of red meat increases the risk for colorectal cancer. Other types of animal protein (low-fat dairy products, fish, poultry) may decrease the risk of developing polyps and colorectal cancer. Studies on fruits, vegetables, and fiber are mixed. Some evidence suggests that diets very low in fruits and vegetables may increase the risk. In any case, eating a variety of fruits and vegetables should be part of a healthy diet.

A 2007 study in the Journal of the American Medical Association suggested that diet may play a role in colorectal cancer recurrence, as well as prevention. The study evaluated patients with stage III colon cancer who had been treated with surgery and chemotherapy. Patients who ate diets high in red and processed meats, refined grains, and sweets had a higher risk of cancer recurrence and poorer survival than patients whose diets were high in fruits and vegetables, poultry, and fish.

Alcohol and Smoking. Alcohol use and smoking increase the risk for colorectal cancer. Patients who smoke and drink may also be diagnosed with colorectal cancer at a younger age than non-drinkers and non-smokers. Several studies suggest that women who smoke are at especially high risk of developing colorectal cancer.

Obesity. There is a demonstrated link between body mass and colon cancer risk for both men and women. The Centers for Disease Control and Prevention has reported that the risk of colon cancer rises as body mass index increases. Obesity has been associated biologically with higher circulating levels of insulin and a hormone called insulin-like growth factor. Chronically high levels of these substances may increase colorectal cancer risk.

Physical Inactivity. More than 50 studies from around the world suggest that physical activity helps prevent colon cancer. In contrast, exercise does not protect against rectal cancer.

Crohn's disease and ulcerative colitis are chronic afflictions of the large intestine known as inflammatory bowel diseases (IBD). Both have been linked to increased risk for colorectal cancer. (Patients with ulcerative colitis have a higher risk than those with Crohn's disease.) Family histories are helpful in determining risk associated with inflammatory bowel disease. Some studies suggest the following:

Patients with IBD who have a family history of colorectal cancer face up to a five-fold risk of colon cancer themselves.
Individuals without IBD who have relatives who suffered from both IBD and colorectal cancer may face a higher risk for developing colorectal cancer themselves.
Individuals without IBD but with a family history of IBD and no colon cancer most likely face no higher risk for cancer themselves.

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

Polyps. Polyps are tissue growths, usually benign, that develop in the color or rectum, most often in patients over 50 years of age. When pathologists examine polyps removed from the colon, they classify them as either hyperplastic or adenomatous. Both types are benign, but some adenomas will become malignant. As a preventive measure, polyps should be removed (polypectomy).

Ureterosigmoidostomy. People who have had ureterosigmoidostomy, a surgical procedure to correct a birth defect in the bladder or to treat some bladder cancers, may develop tumors near the site of the defect, which is chronically exposed to urine and feces. Such patients have a 5 - 10% chance of developing colon cancer 15 - 30 years after the operation.

Diabetes. Many studies have identified an association between type 2 diabetes and colon cancer. Both diseases share common risk factors of obesity and physical inactivity, but diabetes itself is a risk factor for colorectal cancer. Both men and women who have diabetes are at risk.

Heart Disease. Coronary artery disease (CAD) increases the risk for colorectal cancer. Both CAD and colorectal cancer share important risk factors, including smoking, high fat diet, sedentary lifestyle, and obesity.

Dietary Factors

Some, but not all, studies have suggested that a high intake of fruits and vegetables can lower the risk for colorectal cancer. One study, for example, reported that these foods do not prevent polyps from forming but may help prevent them from becoming cancerous.

Phytochemicals. Many studies have demonstrated the cancer-fighting effects of plant chemicals called phytochemicals. Fruits and vegetables that contain phytochemicals can often be identified by colors:

Dark green (broccoli, spinach, kale, collard greens, mustard greens). These vegetables contain chemicals called isothiocyanates, which have been associated with a lower risk for cancer in general.
Red (red pepper, tomatoes, watermelon, raspberries, pink grapefruit). Lycopene is a chemical found in these foods that may have strong cancer-protective properties. Cooking tomatoes appears to increase their benefits.
Yellow-orange (carrots, pumpkin, sweet potatoes, oranges, tangerines). The colors in these foods are due to carotenoids. Carotenoids have been associated with health protection, although they may not have much effect on colon cancer itself.
Blue-black (many berries). Dark berries appear to have potent antioxidant chemicals that may be protective against cancer.

Organosulfurs are important food chemicals that are part of the allium family. Studies have reported health benefits from foods containing them. These compounds are found in garlic, leeks, onions, chives, scallions, and shallots. A review of 300 studies concluded that people who eat raw or cooked garlic regularly experience about two-thirds the risk of colorectal cancer as people who eat little or none. Another analysis, however, found the available evidence about garlic to be inconclusive. Garlic supplements, in any case, do not appear to be protective.

Fiber. Studies have been mixed on whether fiber (found in fruits, vegetables, and whole grains) protects the colon from cancer. For example, three major studies in 2002 and 2003 reported no difference in the development of colorectal polyps or cancer recurrence with high intake of fiber. On the other hand, results of the 2003 European Prospective Investigation into Cancer and Nutrition (EPIC) -- the largest study ever conducted on the role of diet in the development of cancer -- suggested that fiber is protective regardless of its source. However, in the study, the greatest benefits were observed for the left side of the colon and the least for the rectum. In any case, fiber, which is only found in plant products, may be beneficial for the heart and have other health advantages.

The role of fats in inflammatory bowel disease is complex and not fully known. A 2006 study from the Women’s Health Initiative found that a low-fat diet did not help reduce the risk for colorectal cancer. However, the study did not distinguish between types of fat.

Monounsaturated fats (olive, peanut, canola oils; avocados, nuts) and omega-3 polyunsaturated fats (fish, flaxseed oil, walnuts) are the healthiest types of fats.
Saturated fats (red meat, butter, high-fat dairy products) and trans-fats (hydrogenated fat found in snack foods, fried foods, commercial baked goods) are unhealthy types of fats.

Dietary guidelines recommend that adults limit the total fat in their diet to 25 - 35% of total daily calories. Saturated fat intake should be less than 7%, and trans fats less than 1%, of total daily calories. (Patients with heart disease or diabetes may need to limit unhealthy fat in their diet even further.) Most fats should come from polyunsaturated and monounsaturated fat sources.

[See In-Depth Report #43: Heart healthy diet; and #42: Diabetes diet.]

Evidence strongly suggests that red meat raises the risk for colon cancer development, and perhaps also recurrence. Red meat contains dietary iron, which has been associated with a higher risk for colon cancer.

High-temperature cooking (grilling, broiling, or pan-frying) has been specifically associated with increased risk for colon polyps and colon cancer. Overcooking meat increases the amount of carcinogens called heterocyclic amines, which has been associated with cancerous changes.

Milk, Lactose, and Probiotics. In one study, adults who drank the most milk had the lowest risk for colon cancer. A 2004 study published in the Journal of the National Cancer Institute supported this conclusion. In this review of 10 epidemiologic studies that included more than 500,000 people, those who consumed more milk and calcium had a lower risk of developing colorectal cancer. Milk contains not only calcium but also other compounds, such as lactose, that may help protect against colon cancer.

Yogurt specifically has been associated with a lower risk for colon cancer if it contains live active bacterial cultures, such as Lactobacillus acidophilus, that are called probiotics. These "friendly bacteria" appear to protect the colon from cancerous changes. (Acidophilus and other probiotic capsules are also available in health food stores.)

Calcium. Calcium, which is found in dairy products, is associated with colon cancer protection. Many studies have shown a possible protective effect from either high-calcium diets or calcium supplements. However, a 2006 study from the Women’s Health Initiative found that calcium and vitamin D supplements do not reduce women’s colorectal cancer risk. Many doctors still recommend that postmenopausal women take these supplements for bone health.

Obesity has been associated with colon cancer. In some studies of people under 67 years old, the amounts of fat and protein were less important than the total number of calories consumed: the higher the energy intake, the greater the risk for developing colon cancer. In older adults, high calorie intake did not make any significant difference. Other studies have indicated that eating too much sugar may increase the risk for colon cancer.

Studies conducted in several countries have found that drinking four or more cups of coffee a day is associated with a lower risk for colorectal cancer. Green tea may have also beneficial properties, but more research is needed in both of these areas.

Folate and B Vitamins. For years, many doctors have believed that the B vitamin folate (called folic acid) may help protect against colorectal cancer, particularly for people who are genetically predisposed to this disease. Folate is found in beans, citrus fruits, and green vegetables, but some studies have indicated that the greatest protective benefits come from taking supplements.

However, an important study published in 2007 in the Journal of the American Medical Association challenged this assumption. The study suggested that high-dose folic acid supplements do not prevent colorectal cancer, and may actually increase the risk for developing certain types of colorectal tumors. The study evaluated over 1,000 men and women who had a recent history of non-cancerous colorectal polyps. (Adenomatous polyps, also called colorectal ademomas, are the most common type of polyp found in colorectal cancer screenings.) The results indicated that patients who took 1 mg/day of folic acid supplements were more likely to develop new adenomatous polyps than patients who did not take supplements. Patients in the folic acid supplement group were also more likely to have advanced adenomas and more numerous adenomas.

Adenomatous polyps are benign tumors, but they can potentially develop into cancerous tumors. Researchers are continuing to investigate the role that folic acid plays in colorectal cancer risk and prevention. It is possible that folic acid may help prevent the initial appearance of adenomatous polyps, but increase the risk for additional polyp formation once they have begun to occur.

Antioxidant Supplements. Antioxidants are chemicals that help eliminate harmful particles called oxygen-free radicals that have been associated with cancerous changes. Some studies have associated supplements of the antioxidants selenium and vitamins A, C, D, and E with lower colon cancer risk, but most studies have found no protective effect.

Prevention

Studies indicate that daily exercise is one of the best ways to reduce the risk of colorectal cancer. The more vigorous the activity, the greater the benefit, but even moderate exercise (walking, stair-climbing) can help reduce colorectal cancer risk. The American Cancer Society (ACS) recommends that people engage in at least moderate exercise for 30 minutes or more at least 5 days a week. The ACS also notes that 45 minutes or more of moderate-to-vigorous activity at least 5 days a week may help further reduce cancer risk.

Some studies also suggest that regular exercise may be beneficial for patients who have been diagnosed with colorectal cancer. Two 2006 studies indicated that exercise may reduce the risk of colorectal cancer recurrence and death for patients with stage I - III cancer.

Nonsteroidal anti-inflammatory drugs (NSAIDs) are very common pain relievers that are available over-the-counter and by prescription. They include aspirin, ibuprofen (Motrin), naproxen (Aleve), and the COX-2 inhibitor celecoxib (Celebrex). Several studies have reported that NSAIDs help reduce the risk of colorectal cancer. However, regular use of NSAIDs, even in low doses, can increase the risk of gastrointestinal bleeding and stomach ulcers. Long-term use of NSAIDs can also increase the risk for heart attack and stroke, especially in people who have a history of heart disease. Several 2006 and 2007 studies in the New England Journal of Medicine reported that celecoxib prevented precancerous polyps, but the drug more than doubled patients’ risk for heart attack and other cardiovascular events.

A 2005 Nurse’s Health Study found that aspirin, but not other NSAIDs, does provide protection against colorectal cancer. However, the risk was only reduced for women who took 2 aspirin a day for more than 10 years. In addition, this dose level greatly increases the risk for gastrointestinal bleeding. Furthermore, a 2007 study in the New England Journal of Medicine suggested that aspirin’s protective effects may only apply to some types of colorectal cancer tumors. Another 2007 study, published in the Lancet, indicated that long-term daily use of aspirin can protect against polyps and colorectal cancer, but experts agree that aspirin’s risks do not outweigh its benefits for most people. (Some people who are at high risk for developing colorectal cancer may benefit from aspirin therapy.)

In March 2007, the U.S. Preventive Services Task Force (USPSTF) recommended against the routine use of aspirin and other NSAIDs to prevent colorectal cancer in people at average risk for this disease. (This recommendation does not apply to people who have a family history of colorectal cancer or who are at high risk for developing colorectal cancer due to other risk factors.) Long-term use of NSAIDs can increase the risk for gastrointestinal bleeding, kidney function problems, and heart problems. Aspirin can also increase the risk for hemorrhagic stroke. Due to these risks, the American Cancer Society and other professional associations also recommend against the use of NSAIDs or other types of medications for colorectal cancer prevention.

Medications containing 5-aminosalicylate (5-ASA) are sometimes given to patients with ulcerative colitis to help control inflammation. These drugs, which include sulfasalazine and mesalamine, are chemically related to aspirin. A 2005 review of clinical trials found that patients with ulcerative colitis who used 5-ASA were 49% less likely to develop colorectal cancer than patients who did not use these drugs

Some studies have suggested that cholesterol-lowering statin drugs may help reduce colorectal cancer risk. A 2006 study in the Journal of the National Cancer Institute did not find any protective benefit for statins.

Estrogen has been associated with a lower risk for colon cancer, perhaps because of specific enzymes that prevent cell proliferation. Drugs containing estrogen, then, may help high-risk women:

There is some evidence that hormone replacement therapy (HRT) reduces the risk of colon cancer in postmenopausal women. It carries other risks, however, including a higher risk for breast and uterine cancer and blood clots. A 2004 New England Journal of Medicine study found that while short-term use of estrogen plus progestin reduced the risk of developing colon cancer, combination HRT users who were diagnosed with the disease had more advanced forms of the cancer. Older women who are at higher risk for colon cancer might discuss risks and benefits of HRT with their doctor.
Oral contraceptives may reduce younger women's risk of colon cancer. Duration of use does not seem to be associated with decreased risk, but protection appears stronger for women who have more recently used oral contraceptives.

Diagnosis

Colon and rectal cancers are diagnosed using the screening tests discussed below. These tests can detect precancerous polyps and colorectal cancers at stages early enough for complete removal and cure.

Unfortunately, only 30 - 40% of adults over 50 years old (mostly in the upper socioeconomic group) have regular screening tests that could detect a cancer early enough for curative treatment. A survey reported that many people are not screened because they are too embarrassed. Those who had already had the tests were willing to have them again if they saved one additional day of their lives.

There is some debate about what is the best screening method. Current screening guidelines offer several different options for patients. Doctors agree that not enough people are screened and that these tests, if adopted with the same regularity as such screening tests as Pap smears, would save many lives. It is especially important for anyone at increased risk or with symptoms, such as rectal bleeding or ulcerative colitis, to have testing at an earlier age.

There is also debate about when people should stop being screened. A 2006 study in the Journal of the American Medical Association indicated that screening provides little benefit for elderly people, especially because colorectal cancers grow very slowly. The researchers suggest that doctors should carefully consider the risks versus benefits of screening patients age 80 and older.

Individuals should discuss with their doctors the risks and benefits of all screening procedures. Some controversy exists over how often people without risk factors for cancer should be screened and which detection method should be used for them.

Guidelines for Adults Age 50 and Over with Average Risk. The following are the five screening options recommended for people age 50 and over who have no symptoms and no family history of colon cancer:

Fecal occult blood test (FOBT) or fecal immunochemical test (FIT) every year
Flexible sigmoidoscopy every 5 years
FOBT or FIT every year plus sigmoidoscopy every 5 years
Double-contrast barium enema every 5 years
Colonoscopy every 10 years

Choosing between Colonoscopy and Sigmoidoscopy. The choice between colonoscopy and sigmoidoscopy for routine screening for older adults with average risk is an area of intense debate. The issues are as follows:

Sigmoidoscopy is less costly, less invasive, quicker, and safer than colonoscopy. Although it allows inspection of only the left side of the colon, any abnormal findings from sigmoidoscopy trigger a full colonoscopy. Therefore, experts estimate that sigmoidoscopy can detect 80% of all significant problems.
Colonoscopy is more sensitive than any other current screening method for detecting colon cancer. It can find 75 - 90% of colorectal cancers. If the goal were to reduce the number of cancer cases, regardless of cost, colonoscopy would be the preferred approach. Colonoscopy, however, is more expensive than sigmoidoscopy and has a slightly higher risk for complications (bowel tears or bleeding when a polyp is removed).

There are 3 basic tests for colon cancer: a stool test (to check for blood), sigmoidoscopy (inspection of the lower colon), and colonoscopy (inspection of the entire colon). All 3 are effective in catching cancers in the early stages, when treatment is most beneficial.

Screening, particularly with colonoscopy, in increased- and high-risk populations can save lives. The most important risk factors are a family history of colorectal cancer and personal history of colorectal cancer, polyps, or chronic inflammatory bowel disease. People with these risk factors should be screened before age 50 and may need more frequent screenings.

Guidelines for Increased-Risk Groups. Anyone with first-degree relatives diagnosed with colon cancer younger than 60, or with two relatives who have been diagnosed with colon cancer at any age, should consider beginning the standard screening regimen with a colonoscopy every 5 years, beginning at age 40 or 10 years before the youngest case in the family (whichever is earlier).

Men of African descent are also considered to be at increased risk for colon cancer and should discuss similar screening guidelines with their doctors.

Guidelines for High-Risk Groups. The following guidelines may be useful for specific high-risk groups.

People who have the mutated hereditary nonpolyposis colorectal cancer gene (MSH2 or MLH-). Frequent colonoscopy (for instance, every 1 - 2 years) beginning in their early 20s. (Regular screening for other cancers, such as uterine cancer, is also reasonable.)
People who have the mutated familial adenomatous polyposis (FAP) gene. Frequent screening with endoscopy (flexible sigmoidoscopy or colonoscopy) beginning in early puberty. Genetic testing is now recommended for family members of people with known FAP.
People with predisposing intestinal problems, such as widespread and active ulcerative colitis or Crohn's disease. Annual screening with colonoscopy with biopsies of suspicious areas.

Guidelines for Follow-Up After Detection of Precancerous Polyps. Patients who have had a previous examination in which polyps were detected (and removed) should have a repeat colonoscopy 1 - 3 years later, depending on the size, number, and type of polyps removed.

The digital rectal examination is used to detect tumors in the rectum, lower intestine, and prostate gland. The doctor inserts a lubricated-gloved finger into the patient's rectum and feels for lumps or other abnormalities. The exam is quick and painless but embarrassing for some. Fewer than 10% of colon cancers develop within the region that can be evaluated by a DRE, so it is not useful as a sole screening test.

Blood in bowel movements is not always visible, in which case it is called occult (hidden) blood. Fecal occult blood tests (FOBTs) are used to detect this hidden blood. The most common FOBT method is called the guaiac-based test. The patient is asked to supply up to six stool specimens in a specially prepared package. A small quantity of feces is smeared on specially treated paper, which reacts to hydrogen peroxide. If blood is present, the paper turns blue.

Accuracy. FOBTs can miss more than 75% of advanced cancers. Nevertheless, large studies have indicated that this simple test, performed annually, saves lives and may reduce the risk of dying from colon cancer by 15 - 33%. The following factors may affect its accuracy:

The levels of iron in the blood can affect results. Patients should not take iron supplements or eat red meats several days before the test.
Certain raw fruits and vegetables that contain the chemical peroxidase (cauliflower, horseradish, radishes, melons, and turnips) can cause a positive test reaction even if no blood is present.
Aspirin and NSAIDs are anticoagulants that can cause minor bleeding. They should not be taken for a week before the test. However, a 2005 study suggested that the prescription anticoagulant warfarin does not affect FOBT results.
Vitamin C and foods rich in this vitamin may cause a false negative reaction and should be avoided a few days before the test.
Bleeding from other causes, such as menstruation, hemorrhoids, gingivitis, or urinary infections, can produce blood in the stools and affect results.

Even if none of these conditions is present, a test that shows hidden blood does not necessarily mean that cancer is present. About 20 - 30% of people with occult blood have noncancerous polyps or other conditions, such as gastritis, and only 5 - 10% actually have cancer. Any abnormal result, however, requires further testing, such as colonoscopy.

Lack of Compliance. Compliance is a major problem. Patients are asked to perform the tests at home and send the test cards to the laboratory. Only 35 - 50% of patients actually follow through. Occult-blood tests that give results at home are available but are extremely inaccurate. In one large study, these tests failed to detect advanced cancer in about 62% of cases, although they may detect some early cancers.

If a digital rectal exam (DRE) or fecal occult blood test (FOBT) shows signs of trouble, several methods to visualize the colon are available. They include colonoscopy, sigmoidoscopy, and double-contrast barium enema. They have the following similarities and differences:

Sigmoidoscopy can only view the rectum and the left side of the colon, while colonoscopy and barium enemas allow a view of the entire large intestine.
Both flexible sigmoidoscopy and colonoscopy involve snaking a fiber optic tube through regions of the rectum and colon to view the walls of the intestine. The tube contains a tiny camera that transmits the image to a video screen. The use of an ultrasound (sound wave) scanner is proving to enhance viewing quality. Barium enemas simply use x-rays.
During either sigmoidoscopy or colonoscopy, the doctor is able to remove polyps or other abnormalities revealed by these procedures with surgical instruments inserted through the tube. It is not possible to remove polyps with a barium enema, which is not invasive.

Sigmoidoscopy. Sigmoidoscopy examines the rectum and the lower two feet of the colon. It cannot, however, detect the roughly half of cancers that occur in the right colon. Right-sided cancers are more common in older people.

The procedure uses a flexible fiber optic tube (it is thus referred to as flexible sigmoidoscopy) that contains a tiny camera and surgical instruments.
It lasts about 10 minutes and may be mildly uncomfortable, but it is not painful and is generally very safe. In one study, 70% of patients reported that the procedure was far less unpleasant than they had expected.

This procedure has been found to reduce the risk of fatal cancers in the rectal and sigmoid area by 60%. If polyps are detected, a colonoscopy is then used.

Colonoscopy. Colonoscopy is the most accurate testing method and can reduce cancer incidence by up to 90%. It is clearly indicated for anyone with an increased risk for colorectal cancer, including those with a personal or family history of the disease. As with sigmoidoscopy, a colonoscopy uses a flexible tube, but it is snaked through the entire large intestine.

For about a day before the procedure the patient eats nothing and drinks a laxative solution that cleans out the colon. The taste of the solution is unpleasant, although it has improved in recent years.
The procedure typically uses a sedative that produces a "twilight" sleep and often makes the procedure more comfortable than sigmoidoscopy.
Air may be introduced into the intestine to widen it and allow the tube to navigate curves. A colonoscopy avoids the risk of radiation associated with a barium enema, but it is important to note that even a colonoscopy does not detect all cancers.

Complications are rare, but include the following:

Hyponatremia. Hyponatremia is a low concentration of sodium in the blood. The complication may be caused by the effects of bowel cleaning before the procedure that can result in water retention and reductions in sodium. When severe, it can cause temporary neurological symptoms, such as confusion, lethargy, unsteadiness, and slurred speech. Researchers suggest that sodium concentrations be measured in patients who develop such symptoms after colonoscopy.
Bowel perforation (very low risk, about 2 in 1,000 procedures). The risk for bowel perforation is greater with colonoscopy than flexible sigmoidoscopy.
Bleeding at the site of biopsy or polyp removal.

Overall, colonoscopy is a safe procedure. However, according to a 2006 study in the Annals of Internal Medicine, serious complications occur in about 5 of every 1,000 colonoscopies. Most of these complications occurred when a biopsy or polyp removal was performed. (The risk for complications without biopsy or polyp removal is about 1 in every 1,000 colonoscopies.) This study looked at colonoscopies in general, including those that are done to diagnose the causes of a patient's symptoms. The risk may be lower for colonoscopies performed solely to screen for colorectal cancer.

Barium Enema. The double-contrast barium enema, which uses an x-ray image, is the less expensive alternative for viewing the entire colon. It is not as accurate as colonoscopy, and if any polyps or abnormalities are revealed on x-ray, a colonoscopy is then required to remove suspicious tissue, so it is now recommended much less often than in the past.

The barium enema is a valuable diagnostic tool that helps detect abnormalities in the large intestine (colon). The barium enema, along with colonoscopy, remains the standard in the diagnosis of colon cancer, ulcerative colitis, and other diseases of the colon.

Screening for familial adenomatous polyposis. Genetic screening for familial adenomatous polyposis (FAP) and hereditary nonpolyposis colon cancer (HNPCC) is now available and may be recommended for high-risk patients. The test for FAP detects a mutation in the adenomatous polyposis coli in up to 90% of people who carry it. Testing for HNPCC mutation is somewhat more complex.

Screening for insulin-like growth factor. A gene that regulates insulin-like growth factor (IGF-2) is functional during fetal development and then becomes inactive. Some evidence now suggests that people who have IGF-2 in adulthood have a higher risk for colon cancer. Blood tests for detecting IGF-2, then, may be helpful in identifying patients who should have more intensive screening. Currently, however, this is only used as a research tool.

Stool DNA Testing. A promising technique for colorectal cancer screening is the detection of altered DNA in cancer cells that have shed from the colon and are excreted in the stool. Such tests may prove to detect both inherited and noninherited genetic mutations. This may become a widely used tool in the future. However, larger clinical studies are needed.

Virtual Colonoscopy. A promising experimental technique called virtual colonoscopy allows three-dimensional imaging of the colon without using invasive instruments. As with standard colonoscopy, the patient takes a laxative first to clear out the intestine. The procedure itself involves pumping air into the colon and scanning the intestine using computed tomography (CT). It is very safe and takes about only 10 minutes. The procedure is similar in accuracy to conventional colonoscopy for detection of larger polyps (6 mm or more in diameter) and is also potentially less expensive. Colonoscopy is required, however, if suspicious areas are found, which may occur frequently with the CT procedure, since it erroneously identifies a high number of nonexistent polyps.

A study published in April 2004 in the Journal of the American Medical Association compared results of standard colonoscopy versus virtual colonoscopy in over 600 patients at nine major medical centers. Virtual colonoscopy had much lower rates of successfully finding polyps than standard colonoscopy. Virtual colonoscopy detected polyps of at least 6 mm in 39% of patients and polyps of at least 10 mm in 55% of patients. By contrast, standard colonoscopy detected 99% of polyps of at least 6 mm, and 100% of polyps of at least 10 mm. In addition, accuracy rates varied widely among the different hospitals. The authors advised that until more improvement in training and technique is achieved, virtual colonoscopy "is not yet ready for widespread clinical application."

Magnetic Resonance Colonography. Magnetic resonance colonography (MRC) is another non-invasive technique for visualizing the colon. The patient receives an enema containing a contrast substance, and then magnetic resonance images are taken. MRC is fast, comfortable, and less invasive than colonoscopy. Currently, however, there is a poor detection rate for flat tumors and for polyp tumors less than 10 mm in diameter.

Staging

A diagnosis of cancer will lead to staging and other tests to help determine the outlook and the appropriate treatments.

The large intestine is a long hollow organ lined with mucous membrane (mucosa). Muscle layers wrap around the entire length and help move food material through to the rectum.

Unlike many other cancers, the size of the tumor is not a major factor in determining the outcome of colorectal cancer. Of greater importance is how far the cancer has spread. To determine this, doctors will assign a stage to the tumor. There are several methods for staging. The older system, known as Dukes', categorizes four basic stages: A, B, C, and D. A more recent system refers to these stages as I, II, III, and IV but divides the categories slightly differently. The term "5-year survival" means that patients have lived at least 5 years since diagnosis. Most patients who live 5 years without a recurrence are considered to be cured of their disease.


Stage	Condition	5-Year Survival
A or I	Tumor superficially involves the inner lining of the intestine.	More than 90%
B or II	Tumor has penetrated through the muscle wall of the intestine but has not reached the lymph nodes.	70 - 85%
C or III	Lymph nodes are involved.	65% or below
D or IV	Tumor has spread to other organs (metastasized), usually the liver first.	5 - 9%

Click the icon to see an image of the stages of cancer.

Researchers are continually seeking to identify tumor markers, substances (usually found in blood samples) that will assist in the diagnosis of cancer and in monitoring effects of treatment.

Carcinoembryonic Antigen. High blood levels of a protein called carcinoembryonic antigen (CEA) sometimes indicate the presence of colon cancer. Unfortunately, it is also elevated in other cancers and in some noncancerous conditions. CEA is not effective as a screening tool for healthy people, but might eventually be helpful for patients with cancer.

An advanced diagnostic technique called polymerase chain reaction (PCR) can detect genetic evidence of CEA. One study indicated that when these microscopic footprints of colon cancer are detected in the lymph nodes of patients with Stage II cancer (whose lymph nodes otherwise appear to be not involved with cancer), the outlook is similar to that of patients with Stage III cancer. Patients without this so-called micrometastasis have a very favorable prognosis. Further research is needed, however, before PCR can be used in widespread practice.
In patients with a history of, or active, colon cancer, follow-up measuring of blood CEA levels may be helpful in detecting recurrence of the cancer and effectiveness of treatments.

Defective P53 Gene. The presence of a defective p53 gene is a marker for very poor prognosis in patients with advanced colon cancer. In its normal state, the gene is important for regulation of cell growth. Testing for this abnormality, however, is not widely done because it is not clear how to use this information.

Other Tumor Markers. Other tumor markers under investigation include a protein called GLUT1, cancer antigen 19-9 (CA 19-9), matrix metalloproteinase-9 (MMP-9) RNA, HER-2/neu oncoprotein, transforming growth factor beta-1 (TGF-beta-1), and CD44.

Click the icon to see an image of drawing blood for culture.

A technique known as a sentinel node biopsy is increasingly performed by experienced surgeons in selected patients. This procedure is used to determine if cancer has spread beyond the nodes, possibly reducing the need for complete axillary lymphadenectomies. It involves the following:

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 via the lymphatic system into the so-called 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 remainder of the lymph nodes will be cancer free, and further surgery becomes unnecessary.

It is still not known if the sentinel node biopsy has any survival advantages compared to the standard procedures with lymph nodes removal. However, one study indicated that careful and complete removal of potentially cancerous lymph nodes is still very important for improving survival in patients with Stage II and III colorectal cancer.

Whole-body imaging scans that combine positron emission tomography (PET) and computed tomography (CT) may be helpful in accurately staging colorectal cancer, according to preliminary research published in 2006 in the Journal of the American Medical Association.

Prognosis

Survival rates for colorectal cancer have been rising in recent years. The 5-year survival rate is as high as 90% for cancer that has not spread to the lymph nodes (localized cancer). When cancer has spread to lymph nodes and other parts of the body, survival rates drop to 65% and below. Because many cancers are detected at later stages, the overall survival rate is currently about 60%. African-Americans and other minorities tend to have lower survival rates than Caucasians. Studies suggest, however, these higher mortality rates are largely due to less access to optimal health care, including appropriate surgical care and aggressive treatments.

In most cases, age is not a factor in treatment success. Good survival rates are achieved in the elderly as well as in young people. Chances for survival are less in Stage II cancers if the intestine is obstructed or perforated. If cancer has spread to lymph nodes (Stage III), the outlook is better if three or fewer lymph nodes are involved. Treatment can prolong life even when cancer has spread.

Surgery

Surgical removal of the tumor ("resection") along with any affected surrounding tissue is the standard initial treatment for potentially curable colorectal cancers (cancers that have not spread beyond the colon or lymph nodes). Drug and radiation therapy are often used for advanced cancers and are continuously being tested with surgery in different combinations and sequences.

Although choosing a qualified surgeon is critical, choosing a hospital experienced in procedures is also important. The more often colon cancer surgery is performed at a given hospital, the lower the mortality rate at that hospital is likely to be.

Unless cancer is very advanced, most tumors are removed by an operation known as colectomy:

Colectomy involves removing the cancerous part of the colon and nearby lymph nodes.
The surgeon then reconnects the intestine.
If the surgeon cannot reconnect the intestine, usually because of infection or obstruction, the surgeon will perform a colostomy. The need for colostomies is higher after surgery for rectal cancer. In most cases of colon cancer, colostomies are not needed. [See "Colostomy" below.]

Click the icon to see an illustrated series detailing colon cancer treatment.

The Surgical Approach. The standard technique for a colectomy is open, invasive surgery. Laparoscopy, sometimes called “keyhole surgery,” is a less invasive method. Laparoscopy is still considered an investigational technique for treating colon cancer, but it is gaining more acceptance and showing good results in clinical trials.

Open Surgery:

Open surgery uses a wide incision to open the patient's abdomen. The surgeon then performs the procedures with standard surgical instruments. This is the usual method for performing colectomy.

Laparoscopy:

Laparoscopy uses a few small incisions through which the surgeon passes a fiber optic tube (laparoscope) containing a small camera or tiny instruments. It is generally used for early colon cancer (for tumors less than 2 centimeters or for well-defined tumors less than 3 centimeters).
A 2004 New England Journal of Medicine study found that patients who received laparoscopic colectomy had similar rates of surgical complications, cancer recurrence, and survival as those who received traditional open surgery. However, the patients who had laparoscopy recovered faster and did not need as many narcotic painkillers.
Several 2005 studies indicated that laparoscopy works as well as conventional surgery for treatment of colon cancer. However, laparoscopy does not appear to be as effective for rectal cancer.

Click the icon to see an image detailing pelvic laparoscopy.

Click the icon to see an illustrated series detailing a resection of the large intestine.

Other Investigational Measures. Researchers are testing expandable metal tube-like devices called stents to keep the intestine open. Stents may be used before a procedure to allow bowel cleansing or for long-term use to keep open colons that can't be operated on.

A colostomy is performed in order to bypass or remove the lower colon and rectum. The procedure generally involves creating a passage, called a stoma, through the abdominal wall that is connected to the colon. The feces pass through this passage and are eliminated. Patients must learn how to care for the stoma and keep the area sanitary.

A colostomy usually will have one opening (single-barreled), or there may be two loops opening through the skin (double-barreled).

Usually the colostomy is temporary and can be reversed by a second operation after about 3 - 6 months. It the rectum and sphincter muscles in the rectum need to be removed, the colostomy is permanent. Permanent colostomies are more common when the cancerous regions are within 2 - 3 centimeters of the anus. Fortunately, surgical advances and knowledge of the extent of safe margins are reducing the need for permanent colostomies.

Click the icon to see an illustrated series detailing a colostomy procedure.

Managing Permanent Colostomies. In cases where the colostomy is permanent, the patient must wear a colostomy pouch, which sticks to the skin using a special glue. Pouches are available as one- or two-piece systems. The one-piece system is simpler, but the two piece system allows replacement of the pouch without removing the tape.

For best results, the pouch should be emptied when about one-third full. It should be replaced 1 - 2 times a week, depending on signs of leakage (itching or burning of the skin near the stoma). The pouches are odor proof.

Surgical treatments for cancer in the rectum are complex since they involve muscles and tissue that are critical for urinary and sexual function.

Local Excision or Polypectomy for Early Stages. In order to preserve the function of the anal sphincter and prevent the need for colostomy, Stage I and Stage II tumors may be removed by local excision, sometimes followed by chemotherapy and radiation. In this procedure, the tumor is cut out without removal of a major section of rectum. In some cases cancer recurs, but a second operation may be possible. Another treatment for early-stage rectal cancer, called electrocoagulation, destroys tumors using a high frequency electric current. It is being tested in clinical trials.

Radical Resection. In about a third of cases of rectal cancer, the cancer occurs in the lower part of the rectum, where between 70 - 80% of cancers have spread beyond the rectal wall. These patients need a radical resection, in which surrounding structures, including the sphincter muscles that control bowel movements, must often be removed.

The use of chemotherapy and radiation prior to surgery may prevent the need for permanent colostomy in some patients. This is an active area of clinical research, and trials are under way to address this issue. Another technique, called coloanal anastomosis, reconstructs the area to avoid the need for colostomy, and may be appropriate in some patients.

Total Mesorectal Excision. Total mesorectal excision (TME) involves dissection and removal of the entire cancerous area of the rectum along with surrounding fatty regions where the lymph nodes are located (the mesorectum). When successful, TME preserves the sphincter muscle, reducing the need for a permanent colostomy. Increasing use of this procedure is resulting in lower recurrence rates, lower levels of impotence and incontinence, and better overall survival rates compared to other resection techniques. Some experts now recommend it as a first choice for certain patients with locally advanced rectal cancer.

Combining chemotherapy and radiation either before or after TME is yielding promising long-term results and a low risk for local recurrence. There are many questions, however, and it is not clear which approach is better for specific patients.

Side effects of colon surgery include:

Sexual dysfunction. This is of particular concern. In general, colostomy does not usually affect sexual function. However, wide rectal surgery can cause short- or long-term sexual dysfunction. Sildenafil (Viagra) may help men who experience this after surgery.
Irregular bowel movements.
Gas and flatulence. Pouching filters are available to reduce gas. Certain foods produce more gas than others -- usually within 6 - 8 hours after ingestion for colostomy patients. They include beans, oat bran, most fruit, and certain vegetables (cabbage, cauliflower, Brussels sprouts, broccoli, and asparagus). To prevent swallowing air, patients should avoid sipping through straws, chewing gum, and chewing with their mouths open.
Diarrhea.
Bladder complications.
Sense of urinary urgency.
Fecal incontinence. Patients with rectal surgery have a higher risk for bowel dysfunction than those who had a colostomy.
Complications in or around the stoma. These can occur early after surgery to many years after the procedure. They include skin infection or breakdown, hernias, narrowing of the stoma, bleeding, and collapse.

There are no dietary restrictions, although many patients avoid foods that can produce gas. Everyone should drink plenty of fluids and get sufficient fiber.

The potential side effects of sexual and bowel dysfunction for colorectal surgical patients can be devastating, although many patients do very well and live normal productive lives. Positive emotions play a strong role in recovery. Patients who are depressed should discuss with a doctor all aspects of treatment that affect the quality of life, and consider seeking support groups.

Medications

Chemotherapy uses drugs that kill cancer cells throughout the body. There are two situations in which chemotherapy is used:

The adjuvant setting. Adjuvant refers to the use of chemotherapy after surgery in patients with Stage III tumors and selected patients with high-risk Stage II tumors (disease that is potentially curable). The goal of this therapy is to eliminate any cancer cells that surgery may have missed, thereby preventing recurrence and increasing the chance of cure. Patients of all ages, including the elderly, can benefit.
In metastatic disease. In patients with metastatic disease (where the cancer has spread to other parts of the body) the goal of chemotherapy is to shrink tumors, improve symptoms and quality of life, and lengthen life.

In the adjuvant setting, there are some differences in chemotherapy treatments between colon and rectal cancers:

Chemotherapy for Stage II is considered standard care for Stage II rectal cancer but is under debate for colon cancer.
Chemotherapy is standard for patients with Stage III colon cancer. Chemotherapy is also standard for patients with Stage III rectal cancer but is used in combination with radiation.

Chemotherapy for Stage II Colon Cancer. Adjuvant chemotherapy for Stage II colon cancer is controversial. Such patients tend to have a good outcome after surgery, and the positive effects of chemotherapy have been difficult to demonstrate. To date, the survival advantage of adjuvant chemotherapy in this group has been reported to be only in the range of 2%. However, better trials are still needed to confirm or refute the benefits in specific patient groups.

Although not yet known with certainty, some data suggest that certain patients with Stage II cancer may be at higher risk of recurrence and would theoretically benefit from adjuvant therapy. These include patients with cancers that have:

Obstructed the bowel
Perforated the wall of the colon
Adhered to structures outside the intestine

Advanced diagnostic techniques are under investigation for helping to select appropriate candidates for adjuvant therapy. None of these methods, however, are ready to be used routinely to help make treatment decisions. The decision whether to pursue chemotherapy for Stage II disease should be made after careful discussion between the patient and their oncologist, especially after features, such as bowel perforation or obstruction, are taken into account.

Chemotherapy for Stage III Colon Cancer. Since the early 1990s, adjuvant chemotherapy with 5-FU and leucovorin has been the standard of care for Stage III colon cancer. In recent years, the FOLFOX (5-FU, leucovorin, oxaliplatin) regimen has also been used for chemotherapy following surgery. Numerous trials have shown that adjuvant chemotherapy in this setting reduces the absolute risk of death from colon cancer by about one-third and improves survival by 10%. Clinical trials are also investigating combinations of other drugs.

Chemotherapy for Advanced Colorectal Cancer. Chemotherapy is either given directly into the arteries of the liver or intravenously (through a vein) with 5-FU and leucovorin. Oxaliplatin is sometimes added, but recent evidence suggests that the targeted therapy biologic drug bevacizumab may be a better addition. Other alternative chemotherapy choices are capecitabine, or irinotecan combined with cetuximab. Radiation therapy may be used in place of chemotherapy or in combination with it. Studies indicate that chemotherapy offers only a modest improvement in survival, but may help reduce symptoms.

Seven drugs are currently approved for colorectal cancer chemotherapy:

5-fluorouracil (5-FU, Adrucil), which is often given in combination with leucovorin (Wellcovorin). Leucovorin is a vitamin that helps boost the effectiveness of 5-FU.
Capecitabine (Xeloda)
Oxaliplatin (Eloxatin)
Irinotecan (Camptosar)
Bevacizumab (Avastin)
Cetuximab (Erbitux)
Panitumumab (Vectibix)

Capecitabine is a pill form of 5-FU. The other drugs are administered intravenously. Many of these drugs are given in combination with each other. Common chemotherapy combination regimens include:

5-FU / LV (5-FU and leucovorin)
FOLFOX (5-FU with leucovorin and oxaliplatin)
FOLFORI (5-FU with leucovorin and irinotecan)
IFL (Irinotecan, 5-FU, leucovorin)
XELOX (Capecitabine and oxaliplatin)

Side effects occur with all chemotherapeutic drugs. They are more severe with higher doses and increase over the course of treatment. Because cancer cells grow and divide rapidly, anticancer drugs work by killing fast-growing cells. This means that healthy cells that multiply quickly can also be affected. The fast-growing normal cells most likely to be affected are blood cells forming in the bone marrow, and cells in the digestive tract, reproductive system, and hair follicles. Nausea and vomiting is a very common side effect, but drugs such as ondansetron (Zofran) can help provide relief. In general, side effects are nearly always temporary, and medications can help manage them. Most patients are able to continue with normal activities for all but perhaps 1 - 2 days a month.

5-Fluorouracil (5-FU) with Leucovorin. Adjuvant therapy using 5-fluorouracil, either alone or with leucovorin (5-FU/LV), is the standard treatment for patients with high-risk colon cancer (Stage III or select patients with Stage II tumors). Leucovorin, also called folinic acid, is a form of the B vitamin folic acid, which helps increase 5-FU’s effectiveness. Patients are given a series of cycles that usually continue for at least 6 months.

There are many different ways of giving 5-FU, including intravenously over several hours once a week, intravenously daily for 5 consecutive days every month, or as continuous infusion with a portable pump.

The side effects can be quite different, depending on the way 5-FU is given, and women may be more susceptible than men. In one analysis, 53% of women and 40% of men experienced severe side effects, while response rates and survival were similar for both sexes. Many patients, however, tolerate 5-FU with leucovorin well, with manageable side effects. The most common side effects include nausea and vomiting, diarrhea, loss of appetite, hair loss, swelling of hands and feet, rashes, and mouth sores.

Irinotecan. Irinotecan (Camptosar) blocks an enzyme essential for cell division. Irinotecan can be given alone or in combination with 5-FU and leucovorin. This combination therapy (irinotecan plus 5-FU/LV) is also referred to as the "Salz regimen," or IFL. When it was approved in the mid 1990s, irinotecan was the first new drug developed for colon cancer in over 30 years. Studies have shown that irinotecan combined with 5-fluorouracil and leucovorin (5-FU/LV) significantly delays the time at which tumors progress and improves survival in metastatic cancer compared to 5-FU/LV alone. While the survival advantage is small, the combination has become the standard of care for metastatic cancer. Of concern, however, are studies that have reported an increased risk of death from toxic effects with the use of the three-drug combination. These deaths appeared to be related to blood-clotting complications. Doctors should carefully monitor dosages. Diarrhea is a common side effect of irinotecan.

Capecitabine. Capecitabine (Xeloda), an oral form of 5-FU, was approved in 2001 as a treatment for metastatic colorectal cancer. It is the only pill approved for colorectal cancer. A major 2005 study, published in the New England Journal of Medicine, found that capecitabine works as well as the standard 5-FU/LV regimen and causes significantly fewer side effects. The study involved patients with Stage III colon cancer who had undergone surgical removal of the tumor. In 2005, capecitabine was approved for postsurgical treatment of patients with Dukes’ C colon cancer. Capecitabine is also showing promise in combination with radiation therapy for rectal cancers.

Oxaliplatin. Oxaliplatin (Eloxatin) is related to cisplatin, a widely used platinum-based chemotherapy drug. Oxaliplatin is used in combination with 5-FU and leucovorin. (This triple combination therapy is called the FOLFOX regimen.) Oxaliplatin was first approved in 2002 for use in combination with 5-FU and leucovorin as a second-line treatment for cancer that has progressed after initial therapy.

Since 2002, oxaliplatin has received additional approvals as a first-line treatment for advanced colorectal cancer, and as a post-surgical treatment for patients who have undergone tumor resection.

Oxaliplatin can cause pain and tingling sensations in the hands and feet (neuropathy) that is worsened by exposure to cold. Recent research suggests that adding xaliproden (Xaprila) to the FOLFOX regimen may help reduce the frequency of neuropathy without interfering with the benefits of chemotherapy. Xaliproden is a drug used to treat the neurological disease amyotrophic lateral sclerosis (also known as Lou Gehrig's disease).

Bevacizumab. Bevacizumab (Avastin) was approved in February 2004 as a first-line treatment for patients with metastatic colorectal cancer (advanced cancer that has spread in the body). It is used in combination with IFL (irinotecan, 5-FU, leucovorin). Bevacizumab is a genetically engineered monoclonal antibody that targets and inhibits vascular endothelial growth factor (VEGF), a protein that regulates angiogenesis (the development of new blood vessels that feed a tumor's blood supply). It is the first anti-angiogenic therapy approved for the treatment of colorectal cancer.

In a study of 800 patients with metastatic colorectal cancer, bevacizumab administered intravenously along with IFL extended survival by about 5 months longer than IFL alone. Common side effects of bevacizumab include nosebleeds, fatigue, diarrhea, and high blood pressure. Less common side effects include stroke, heart attacks, angina, and formation of holes in the colon and stomach (gastrointestinal perforation).

Cetuximab. Cetuximab (Erbitux) was approved in February 2004 for the treatment of metastatic colorectal cancer. This monoclonal antibody drug targets epidermal growth factor receptor (EGFR), a protein required by cancer cells in order to proliferate. It can be used either in combination with irinotecan or alone for patients who have not responded to irinotecan. Studies of the cetuximab-irinotecan combination suggest it can help in tumor shrinkage. It has a modest effect on survival, prolonging patients’ lives by about an additional month.

Panitumumab. Panitumumab (Vectibix) was approved in September 2006 for treatment of colorectal cancer that has metastasized following standard chemotherapy. Like cetuximab, panitumumab is a monoclonal antibody drug that targets EGFR. In clinical trials, panitumumab helped delay disease progression and prolong survival by about 3 months. About 8% of patients experienced tumor shrinkage. Common side effects of this drug include skin rash, fatigue, abdominal pain, nausea, and diarrhea or constipation. Serious side effects include pulmonary fibrosis, severe skin rash, and skin reactions at the infusion site.

One of the most promising recent developments in cancer treatment research has been the emergence of so-called "targeted therapies." Traditional chemotherapy drugs can be effective, but because they do not distinguish between healthy and cancerous cells their generalized toxicity can cause severe side effects. Targeted therapies work on a molecular level by blocking specific mechanisms associated with cancer cell growth and division. Because they selectively target cancerous cells, they may induce less severe side effects. In addition, these drugs hold the promise of creating options for more individualized cancer treatment based on a patient's genotype. In the future, diagnostic tests may help doctors identify which patients are more likely to respond successfully to specific drugs.

Biologic therapies use the body's immune system to attack the cancer (immunotherapy). These drugs are derived from biological sources and include vaccines, monoclonal antibodies (MAbs), and gene therapies. Many targeted therapies are classified as biologics. Bevacizumab (Avastin), cetixumab (Erbitux), and panitumumab (Vectibix) are currently the three biologic drugs approved for colorectal cancer treatment, but many other drugs are in development.

Targeted therapies involve many different types of drugs and molecular pathways. These include:

Angiogenesis Inhibitors. Anti-angiogenesis drugs inhibit the formation of new blood vessels that supply tumors with the blood, oxygen, and nutrients vital to tumor growth. Angiogenesis inhibitors, such as the monoclonal antibody bevacizumab (Avastin), target vascular endothelial growth factor (VEGF). Cediranib (Recentin), formerly AZD2171, is a new angiogenesis inhibitor that is in Phase III clinical trials for treatment of colorectal cancer.

Tumor Growth Factor Inhibitors. Tumor growth factors, such as epidermal growth factor, stimulate cell growth. Cetixumab (Erbitux) and panitumumab (Vectibix) are the two currently approved colorectal cancer drugs that target the epidermal growth factor receptor (EGFR). Nimotuzumab (TheraCIM) is currently being studied in combination with irinotecan in Phase III trials.

Tyrosine Kinase Inhibitors. Tyrosine kinase is an enzyme associated with EGFR that is involved with the signaling mechanisms that prompt cell growth. The EGFR/tyrosine kinase inhibitor erlotinib (Tarceva), which is approved for the treatment of pancreatic and lung cancers, is being investigated as an adjuvant treatment for metastatic colorectal cancer. Sunitinib (Sutent), which is approved for renal cell carcinoma, is another tyrosine kinase inhibitor in Phase III trials for colorectal cancer.

Radiation Treatment

Radiation therapy uses x-rays to kill cancer cells that might remain after an operation or to shrink large tumors before an operation so that they can be removed surgically. The object of radiation therapy is to damage the tumor as much as possible without harming surrounding tissues. Radiation may be administered in the following ways:

Externally by an x-ray machine (external beam radiation).
By passing radioactive pellets through thin plastic tubes inserted into the intestine.
By implanting tiny radiation seeds directly into the tumor (brachytherapy).
Computer imaging techniques providing 3-dimensional pictures of the cancerous area are allowing precise targeting of radiation to the tumor.

Postoperative radiation treatment combined with chemotherapy is common practice for patients with rectal cancer in Stages II and III. Such patients are at risk of recurrence both at the site of their original tumor and elsewhere in the body. Although there can be significant long-term side effects, the combination of 5-FU and radiation is still considered standard after surgery.

The standard procedure in the U.S. is to apply radiation after surgery (postoperative). Pre-operative chemotherapy and radiation, however, are sometimes used to preserve sphincter-muscle function and reduce the chance that a patient will need a colostomy. Furthermore, some studies suggest that the use of radiation before surgery reduces the likelihood of recurrences and may slightly prolong survival in some patients with rectal cancer. (It has no additional advantages, however, if the subsequent surgery does not completely remove the cancerous regions.) Studies comparing preoperative and postoperative chemotherapy and radiation are currently under way.

Radiation therapy can also be used during surgery (a procedure called intra-operative radiotherapy). It allows the surgeon to move healthy tissue out of the path of the radiation beam.

Short-term side effects of radiation include:

Diarrhea
Skin irritation around the anus
Incontinence
Fatigue
Bowel movement problems

Longer-term complications may include:

Incontinence
Hip and pelvic fractures
Diarrhea
Increased risk for bowel obstruction

Follow-up Testing

The American Society of Clinical Oncology (ASCO) sets guidelines for follow-up testing to detect recurring cancer after the completion of treatment. The following guidelines are based on ASCO’s 2005 updated recommendations.

Most colorectal cancer recurrences happen within 3 years after surgery. American Society of Clinical Oncology recommends that a colorectal cancer patient sees their doctor for a physical examination every 3 - 6 months for the first 3 years, every 6 months for the fourth and fifth years, and at the doctor's and patient's discretion during subsequent years.

Patients should have a colonoscopy 3 years after surgery. If the results are normal, patients should then receive a colonoscopy every 5 years. Some patients with hereditary types of colorectal cancer may need more frequent screenings.

A flexible sigmoidoscopy is recommended every 6 months for 5 years for patients with Stage II or III rectal cancer who did not receive radiation therapy.

Carcinoembryonic antigen (CEA) levels should be measured every 3 months after surgery for 3 years in patients with Stage II or III cancer. High CEA levels in the blood may indicate that the cancer has spread to other parts of the body.

Patients at high risk for cancer recurrence should receive an annual computerized tomography (CT) scan for the first 3 years after treatment. The CT scan can help determine if cancer has spread to the lungs or liver. Patients who have had rectal cancer, and did not have radiation therapy, should receive a pelvic CT scan. The scan is not recommended for most lower-risk patients with Stage I or II colorectal cancer.

American Society of Clinical Oncology does not recommend other follow-up blood tests such as complete blood count, liver function tests, fecal occult blood tests. There appears to be no additional benefit for these tests.

Treatment for Metastasized Colorectal Cancer

The liver is the most frequent site for colorectal cancers to spread (metastasized). Here, treatments may slow the spread of cancer and even prolong survival. Cure is very rare.

When cancer has spread, surgery to remove or bypass obstructions in the intestine may be performed. In these circumstances, surgery is considered palliative in that it may improve symptoms but will not lead to cure. In rare cases, metastatic colon cancer may be cured with surgical removal of tumors in areas to which the cancer has spread, such as the liver, ovaries, and lung. The liver is the most common site of spread. Only selected patients may be eligible for such surgery, but in these patients, 5-year survival has been 25% or higher.

Chemotherapy may help improve symptoms and possibly prolong survival in metastasized colorectal cancers. Several investigational drugs are being tested. Doctors are also testing chemotherapy administered directly into the liver -- a treatment called hepatic arterial infusion (HAI). A 2006 study found that hepatic arterial infusion improves survival and quality of life for patients whose cancer has spread to the liver. The study indicated that HAI works better for these patients than chemotherapy delivered intravenously.

Other investigative techniques used to destroy liver tumors include:

Cryosurgery. This approach freezes the tumor or surrounding tissue.
Embolization. Embolization employs a catheter to deliver substances into the liver that block blood vessels and therefore starve the tumor. Chemotherapy is often administered during this procedure.
Radiation.

For end-stage cancer, hospice care is a compassionate option.

Resources

www.cancer.org -- American Cancer Society
www.cancer.gov -- National Cancer Institute
www.oncolink.org -- OncoLink cancer information
www.asco.org -- American Society of Clinical Oncology
www.plwc.org -- People Living with Cancer
www.nccn.org -- National Comprehensive Cancer Network
www.cancer.gov/clinicaltrials -- Find clinical trials

References

Chan AT, Ogino S, Fuchs CS. Aspirin and the risk of colorectal cancer in relation to the expression of COX-2. N Engl J Med. 2007 May 24;356(21):2131-42.

Cole BF, Baron JA, Sandler RS, Haile RW, Ahnen DJ, Bresalier RS, et al. Folic acid for the prevention of colorectal adenomas: a randomized clinical trial. JAMA. 2007 Jun 6;297(21):2351-9.

Flossmann E, Rothwell PM; British Doctors Aspirin Trial and the UK-TIA AspirinTrial. Effect of aspirin on long-term risk of colorectal cancer: consistent evidencefrom randomised and observational studies. Lancet. 2007 May 12;369(9573):1603-13.

Kerr DJ, Dunn JA, Langman MJ, Smith JL, Midgley RS, Stanley A, et al. Rofecoxib and cardiovascular adverse events in adjuvant treatment of colorectal cancer. N Engl J Med. 2007 Jul 26;357(4):360-9.

Levin TR, Zhao W, Conell C, Seeff LC, Manninen DL, Shapiro JA, Schulman J. Complications of colonoscopy in an integrated health care delivery system. Ann Intern Med. 2006 Dec 19;145(12):880-6.

Meyerhardt JA, Niedzwiecki D, Hollis D, Saltz LB, Hu FB, Mayer RJ, et al. Association of dietary patterns with cancer recurrence and survival in patients with stage III colon cancer. JAMA. 2007 Aug 15;298(7):754-64.

U.S. Preventive Services Task Force. Routine aspirin or nonsteroidal anti-inflammatory drugs for the primary prevention of colorectal cancer: U.S. Preventive Services Task Force recommendation statement. Ann Intern Med. 2007 Mar 6;146(5):361-4.

Veit-Haibach P, Kuehle CA, Beyer T, Stergar H, Kuehl H, Schmidt J, et al. Diagnostic accuracy of colorectal cancer staging with whole-body PET/CT colonography. JAMA. 2006 Dec 6;296(21):2590-600.

Review Date:
9/8/2007
Reviewed By:
Harvey Simon, MD, Associate Professor of Medicine, Harvard Medical School; Physician, Massachusetts General Hospital.

A.D.A.M. Copyright

adam.com

Diabetes - type 2

FitSugar — Wed, 08 Oct 2008 17:34:58 -0700

In This Report

Highlights
Introduction
Causes
Risk Factors
Symptoms
Screening Tests
Treatment
Lifestyle Changes
Medications
Long-Term Complications
Emergency Complications
Resources
References

HEALTH GUIDE REFERENCE FROM A.D.A.M

Highlights

Drug Approvals

Sitagliptin (Januvia), the first in a new class of diabetes drugs called DPP-4 inhibitors, was approved in 2006.
Janumet, a 2-in-1 pill that contains both sitagliptin and metformin, was approved in 2007.
These drugs are taken by mouth and may be more convenient for patients than exenatide (Byetta), a similar drug. DPP-4 inhibitors do not cause weight gain and may pose a lower risk for hypoglycemia than some other diabetes drugs.

Drug Safety Alert

Rosiglitazone (Avandia) may significantly increase the risk for heart attack, indicates a review published in the Journal of the American Medical Association. In 2007, a panel of experts from the Food and Drug Administration (FDA) agreed the drug increases the risk of heart attacks -- but concluded it should remain on the market. The panel did, however, recommend the FDA require rosiglitazone's maker to add warnings to the drug's label. Rosiglitazone and a similar drug, pioglitazone (Actos), are known to significantly increase the risks for heart failure. There is also evidence that these drugs increase the risk for bone fracture.

Anemia Drugs Warning

Patients with anemia associated with end-stage kidney disease, especially those on dialysis, should be aware of new warnings concerning dosing target levels of erythpoiesis-stimulating drugs. In 2007, the FDA warned that darbepoetin alfa (Aranesp) and epoetin alfa (Epogen and Procrit) can increase the risk for blood clots, stroke, and heart attacks when excessive doses are given. The FDA has defined target hemoglobin levels and recommends that patients who receive these drugs have frequent blood tests. Patients should also report to their doctors any unusual symptoms.

Genetics Research Breakthroughs

Scientists have now identified 10 genes that are associated with increased risk for type 2 diabetes. Six of these genes were discovered in 2006 and 2007.

Diabetes and Pre-Diabetes

About 20 million Americans have type 2 diabetes, and an additional 54 million have pre-diabetes. According to a 2007 study by the U.S. Centers for Disease Control, the prevalence of type 2 diabetes has been increasing by 5% each year since 1990. Rising rates of obesity may be one factor.
For people with pre-diabetes, lifestyle changes, such as losing weight, appear to work as well as drug treatment in delaying the progression to diabetes, according to a 2007 British Medical Journal study.

Introduction

The two major forms of diabetes are type 1 (previously called insulin-dependent diabetes mellitus, IDDM, or juvenile-onset diabetes) and type 2 (previously called noninsulin-dependent diabetes mellitus, NIDDM, or maturity-onset diabetes).

Both type 1 and type 2 diabetes share one central feature: elevated blood sugar (glucose) levels due to insufficiencies of insulin, a hormone produced by the pancreas. Insulin is a key regulator of the body's metabolism. It works in the following way:

During and immediately after a meal the process of digestion breaks down carbohydrates into sugar molecules (including glucose) and proteins into amino acids.
Right after the meal, glucose and amino acids are absorbed directly into the bloodstream, and blood glucose levels rise sharply.
The rise in blood glucose levels signals important cells in the pancreas, called beta cells, to secrete insulin, which pours into the bloodstream. Within 10 minutes after a meal, insulin rises to its peak level.
Insulin enables glucose and amino acids to enter cells in the body, particularly muscle and liver cells. Here, insulin and other hormones direct whether these nutrients will be burned for energy or stored for future use. (The brain and nervous system are not dependent on insulin; they regulate their glucose needs through other mechanisms.)
When insulin levels are high, the liver stops producing glucose and stores it in other forms until the body needs it again.
As blood glucose levels reach their peak, the pancreas reduces the production of insulin.
About 2 - 4 hours after a meal, both blood glucose and insulin are at low levels, with insulin being slightly higher. The blood glucose levels are then referred to as fasting blood glucose concentrations.

The pancreas is located behind the liver and is where the hormone insulin is produced. Insulin is used by the body to store and utilize glucose.

Type 2 diabetes is the most common form of diabetes, accounting for 90 - 95% of cases. The disease mechanisms in type 2 diabetes are not wholly known, but some experts suggest that it may involve the following three stages in most patients:

The first stage in type 2 diabetes is the condition called insulin resistance. Although insulin can attach normally to receptors on liver and muscle cells, certain mechanisms prevent insulin from moving glucose (blood sugar) into these cells where it can be used. Most patients with type 2 diabetes produce variable, even normal or high, amounts of insulin. In the beginning, this amount is usually sufficient to overcome such resistance.
Over time, the pancreas becomes unable to produce enough insulin to overcome resistance. In type 2 diabetes, the initial effect of this stage is usually an abnormal rise in blood sugar right after a meal (called postprandial hyperglycemia). This effect is now believed to be particularly damaging to the body.
Eventually, the cycle of elevated glucose further impairs and possibly destroys beta cells, thereby stopping insulin production completely and causing full-blown diabetes. This is made evident by fasting hyperglycemia, in which elevated glucose levels are present most of the time.

In type 1 diabetes, the disease process is more severe and onset is usually in childhood:

Beta cells in the pancreas that produce insulin are gradually destroyed. Eventually insulin deficiency is absolute.
Without insulin to move glucose into cells, blood glucose levels become excessively high, a condition known as hyperglycemia.
Because the body cannot utilize the sugar, it spills over into the urine and is lost.
Weakness, weight loss, and excessive hunger and thirst are among the consequences of this "starvation in the midst of plenty."
Patients become dependent on administered insulin for survival. [See In-Depth Report #9: Diabetes - type 1.]

Click the icon to see an image of the pancreas.

Conditions that damage or destroy the pancreas, such as pancreatitis, pancreatic surgery, or certain industrial chemicals can cause diabetes. Polycystic ovaries are highly associated with diabetes. Certain drugs can also cause temporary diabetes, including corticosteroids, beta-blockers, and phenytoin. Rare genetic disorders (Klinefelter's syndrome, Huntington's chorea, Wolfram's syndrome, leprechaunism, Rabson-Mendenhall syndrome, lipoatrophic diabetes) and hormonal disorders (acromegaly, Cushing syndrome, pheochromocytoma, hyperthyroidism, somatostatinoma, aldosteronoma) are associated with or increase the risk for diabetes.

Causes

Type 2 diabetes is caused by a complicated interplay of genes, environment, insulin abnormalities, increased glucose production in the liver, increased fat breakdown, and possibly defective hormonal secretions in the intestine. The recent dramatic increase indicates that lifestyle factors (obesity and sedentary lifestyle) may be particularly important in triggering the genetic elements that cause this type of diabetes.

The characteristic features of most patients with type 2 diabetes are:

Insulin resistance in muscle cells
Normal or even excessive levels of insulin (to compensate for this resistance), eventually followed by a drop in insulin production

In addition, researchers are trying to determine the factors that might promote insulin resistance:

Both obesity and insulin resistance at different phases are marked by elevated levels of free fatty acids and the hormones resistin and leptin. It is not known yet if elevated levels are simply a product of obesity or play some causal role in diabetes.
Insulin resistance is associated with a chronic low inflammatory response, which involves a number of immune factors, such as TGH-beta 1 and C-reactive protein. Such factors can cause damage over time and may be responsible for the association between insulin resistance and heart disease.

Type 2 diabetes has a genetic component. In 2006 and 2007, major breakthroughs in genetic research identified six new genes associated with type 2 diabetes. Ten genes have now been positively confirmed as increasing the risk for type 2 diabetes: TCF7L2, SLC30A8, HHEX, PPARG, KCNJ11, IGF2B2, CDKAL1, CDKN2A, CDKN2B, and FTO.

Most of these genes play a role in regulating insulin action, including the processes that occur in the pancreas’ insulin-producing beta cells. The FTO gene increases the risk for obesity, which itself is a risk factor for type 2 diabetes. These genes appear to cluster around three genetic regions that include a number of chromosomes. Scientists hope that future research will help uncover how genes influence the progression from pre-diabetes to diabetes, and how lifestyle and medical intervention may help delay or prevent this process.

Risk Factors

Nearly 21 million Americans have diabetes; up to 95% of these cases are type 2. In addition, 26% of Americans age 20 and older (and 40% of Americans age 65 and older) have impaired fasting glucose, a pre-diabetes condition that increases the risk for diabetes. According to the American Diabetes Association, 54 million people have pre-diabetes, bringing a total of 75 million Americans who either have diabetes or are at risk of developing it.

Historically, type 2 diabetes usually developed after the age of 40, but it is now also increasing in children. The prevalence of diabetes in the U.S. has increased by 5% each year since 1990, and experts believe that obesity is the major factor behind this dramatic growth rate. Given the current epidemic of obesity, experts estimate that over a third of all people born in 2002 will eventually develop diabetes. Furthermore, the dramatic increase in diabetes is occurring worldwide as American lifestyles become global. Evidence strongly suggests that healthy lifestyles can prevent most cases of type 2 diabetes. People with pre-diabetes can substantially lower their risk by losing weight through diet and exercise.

Healthy adults age 45 and older should get tested for diabetes. Patients who are younger than age 45 and who are overweight or have other risk factors should also ask their doctors about testing. According to the National Institutes of Health, the following are major risk factors for diabetes and pre-diabetes:

Age 45 or older
Family history of diabetes
Overweight
Inactive lifestyle (exercise less than 3 times a week)
African-American, Hispanic/Latin American, American Indian and Alaska Native, Asian-American, or Pacific Islander ethnicity
High blood pressure (140/90 mm/Hg or higher)
HDL (“good”) cholesterol less than 35 mg/dL or triglyceride level 250 mg/dL or higher
Have had diabetes during pregnancy (gestational diabetes) or have given birth to a baby that weighed more than 9 pounds
Polycystic ovary syndrome (metabolic disorder that affects female reproductive system
Acanthosis nigricans (dark, thickened skin around neck or armpits)
History of disease of blood vessels to the heart, brain, or legs
Diabetes test history of impaired fasting glucose (IFG) or impaired glucose tolerance (IGT)

Obesity is the number one risk factor for type 2 diabetes. It is estimated that 80 - 95% of the current dramatic increases in type 2 diabetes are due to obesity. Excess body fat appears to play a strong role in insulin resistance, but the way the fat is distributed is also significant. Weight concentrated around the abdomen and in the upper part of the body (apple-shaped) is associated with insulin resistance and diabetes, heart disease, high blood pressure, stroke, and unhealthy cholesterol levels. Waist circumferences greater than 35 inches in women and 40 inches in men have been specifically associated with a greater risk for heart disease and diabetes. (People with a "pear-shape" -- fat that settles around the hips and flank -- appear to have a lower risk for with these conditions.) However, obesity does not explain all cases of type 2 diabetes. It is also common among people in countries where weights tend to be low, such as Asia or India.

Metabolic Syndrome. A set of conditions referred to as metabolic syndrome (also called Syndrome X) is a pre-diabetic condition that is significantly associated with heart disease and higher mortality rates from all causes. The syndrome consists of obesity marked by abdominal fat, unhealthy cholesterol levels, high blood pressure, and insulin resistance. A 2002 study estimated that nearly a quarter of the U.S. population now has this condition. Even worse, according to a 2003 study, nearly a million American teenagers have this syndrome.

Between 25 - 33% of patients with type 2 diabetes have family members with diabetes. Having a first-degree relative with the disease poses a 40% risk of developing diabetes. One study reported that people with diabetic family histories have a higher risk for developing the disease at an earlier stage and with more severe features. Because families share many lifestyle features (eating and exercise habits) it is difficult to determine when genetics or environment play the major role. When clusters of type 1 and type 2 diabetes appear within families, genetic factors should be strongly suspected.

The risk for type 2 diabetes varies among population groups. Diabetes also seems to pose higher or lower risks for specific complications among ethnic groups. Genetic and socioeconomic factors, or both, seem to be involved in some ethnic differences, but in most cases the observed increase in ethnic groups in Americans is due to changes in traditional lifestyles.

African-Americans. African-American men have twice the risk of developing type 2 diabetes as Caucasian men. African-Americans with diabetes are also at higher risk for amputations than Caucasians. This is most likely due to a higher incidence of high blood pressure and smoking as well as poorer health care in African-Americans. Genetic factors may also play a role. For example, there is some evidence that African-Americans process insulin in the liver differently from Caucasians, which may make them more susceptible to diabetes when other risk factors are present.
Native Americans. The Pima tribe in Arizona has an incidence of type 2 diabetes that is 19 times higher than that of the white population. The risk for diabetic complications among young Pima adults is also very high. Other Native American tribes in North America are also at high risk for type 2 diabetes. The association between diet and diabetes among this population remains critical, however, in assessing the reason for their higher risk. For example, Pimas who live in Mexico exercise more and eat less fat (but consume more calories) than Pima tribes in Arizona. Mexican Pimas have a prevalence of diabetes of only 6%, while half of their Arizona Pima neighbors have diabetes.
Hispanic Americans. The rate of type 2 diabetes is also very high among Mexican-Americans, approximately double that for Caucasians. This group may also be at higher risk for heart problems than other ethnic groups with diabetes.
Asian-Americans. Overweight Asian-Americans and Pacific Islanders are at increased risk for developing type 2 diabetes. The risk for some Asian ethnic groups (such as Native Hawaiians and Filipinos) is twice that of Caucasians.

Smoking increases the risk for diabetes. According to a 2006 study, smokers are more than twice as likely to develop diabetes as people who have never smoked. Another 2006 study found that exposure to second-hand cigarette smoke also increases the risk for diabetes in non-smokers.

Low birth weight is now a recognized risk factor for type 2 diabetes and heart disease in adulthood. The reasons are unclear, although studies suggest it may represent a genetic factor. Studies have observed that babies of fathers with type 2 diabetes and of women who later developed type 2 diabetes tend to weigh less than babies of parents without diabetes. Such studies suggest that some parents may have some specific gene that affects insulin factors, putting both themselves and their children at risk for future diabetes. Theoretically, such a gene might also affect insulin factors in the developing fetus, causing low birth weight. (Of note, mothers of very high-weight babies are also at risk for diabetes -- although in these cases it is most often associated with gestational diabetes.)

Obesity-Related Type 2 Diabetes in Children. Until recent years, diabetes in children was almost always type 1 (an autoimmune disease). Between 1982 - 1994, however, the incidence of type 2 diabetes in children increased 10-fold. By 1996, a study reported that a third of all new diabetes cases in children were type 2. This increase parallels the rising epidemic in childhood obesity that has occurred both in the U.S. and worldwide, notably Europe and Japan. In some areas of Japan, type 2 diabetes has now become the dominant form of diabetes in children and adolescents. Obesity in children is also related to abnormalities in cholesterol, blood pressure, and insulin levels in adults. Administering glucose tolerance tests in overweight children may be helpful in identifying those at high risk for diabetes.

Maturity-Onset Diabetes in Caucasian Youth. Maturity-onset diabetes in youth (MODY) is a rare genetic form of type 2 diabetes that develops only in Caucasian teenagers. It accounts for 2 - 5% of type 2 cases. (This form of type 2 diabetes is not associated with obesity.)

An estimated 5% of pregnant women develop a form of type 2 diabetes, usually temporary, in their third trimester called gestational diabetes.

Gestational diabetes is diabetes that first appears during pregnancy. It usually develops during the third trimester of pregnancy. After delivery, blood sugar (glucose) levels generally return to normal, although 25% of these women develop type 2 diabetes within 15 years.

Who Gets Gestational Diabetes? Estimates for the prevalence of gestational diabetes are generally about 4%. Some studies, however, have suggested significantly higher rates. In one German study, 13% of pregnant women were diagnosed with this form of diabetes, including many who did not have any risk factors.

A pregnant woman's risk factors include:

Family history of diabetes
African-American, Hispanic, Asian, or Pacific Islander ethnicity
Overweight
Older than 25 years
Gestational diabetes with past pregnancy
Having given birth to a child weighing over 9 pounds
Diagnosis of pre-diabetes

Who Should Be Tested for Gestational Diabetes? A number of expert groups recommend that all pregnant women be tested for gestational diabetes between their 24th - 28th week. Pregnant women at high risk for diabetes should be tested earlier. The only women who do not need to be tested are those at very low risk. Generally they have the following characteristics:

Under 25 years old
Normal weight
No first-degree relatives with diabetes
Not belonging to high-risk ethnic groups

Effect of Diabetes on the Fetus. Because glucose crosses the placenta, a woman with diabetes can pass high levels of blood glucose to the fetus. In response, the fetus secretes high level of insulin. Studies indicate that such conditions may affect the developing fetus as soon as it is conceived, placing the unborn child at risk for:

Excessive fetal weight gain, which can lead to complications during delivery
Birth defects
Breathing problems and delayed lung development
Low blood sugar
Higher future risk for obesity and diabetes

Effect of Diabetes on the Pregnant Woman. In addition to endangering the fetus, diabetes also presents risks to the pregnant woman.

The most serious potential complications from gestational diabetes are high blood pressure during pregnancy, a condition called preeclampsia that is potentially dangerous. Because gestational diabetes increases the size of the fetus, it is also increases the likelihood that a woman will require a Cesarean delivery. Gestational diabetes also increases the risk that a woman will later develop type 2 diabetes.

How Is Gestational Diabetes Managed? Some suggestions for preventing complications include:

In most cases, increases in glucose levels can be managed with diet and exercise. Aerobic exercise before and during pregnancy may lower glucose levels and help protect women at risk or those who have gestational diabetes. (Any pregnant woman should check with her doctor before embarking on a vigorous exercise regimen.)
If a woman with gestational diabetes cannot control her glucose with lifestyle measures, she is usually given insulin.

The placenta provides the fetus with oxygen and nutrients and takes away waste, such as carbon dioxide, via the umbilical cord.

Polycystic Ovary Syndrome. Polycystic ovary syndrome (PCOS) is a condition that affects about 6% of women and results in the ovarian production of high amounts of androgens (male hormones), particularly testosterone. It appears to be an important cause of many menstrual disorders. Women with PCOS are at higher risk for insulin resistance, and about half of PCOS patients also have diabetes.

Click the icon to see an image of polycystic ovary syndrome.

Schizophrenia. While no definitive association has been established, research has suggested an increased background risk of diabetes among people with schizophrenia. In addition, many of the new generation of antipsychotic medications may elevate blood glucose levels. Patients taking antipsychotic medications (such as clozapine, olanzapine, risperidone, aripiprazole, quetiapine fumarate, ziprasidone) should receive a baseline blood glucose level test and be monitored for any increases during therapy.

Depression. According to a 2007 study, adults who have severe clinical depression may have a greater risk of developing type 2 diabetes than those who have never experienced depressive symptoms.

Hepatitis C. Patients with hepatitis C have a higher incidence of type 2 diabetes. The reasons for this are unclear.

Symptoms

Type 2 diabetes usually begins gradually and progresses slowly. Symptoms in adults include:

Excessive thirst
Increased urination
Fatigue
Blurred vision
Weight loss
In women, vaginal yeast infections or fungal infections under the breasts or in the groin
Severe gum problems
Itching
Erectile dysfunction in men
Unusual sensations, such as tingling or burning, in the extremities

Symptoms in children are often different:

Most children are obese or overweight
Increased urination is mild or even absent
Many children develop a skin problem called acanthosis, which is characterized by velvety, dark colored patches of skin

Screening Tests

There are no clear-cut guidelines for when to screen for diabetes. Some experts recommend that everyone over age 45 be tested regularly for diabetes, although others do not feel this necessary in people without symptoms or risk factors. In fact, early screening may identify some people with impaired glucose levels that would eventually normalize. Such people might be treated unnecessarily with medications that pose a risk for high blood sugar (hypoglycemia).

Still, given the risk for serious complications with diabetes and the potential value of early treatments, most experts recommend that all adults over 45 be screened and that younger adults be screened if they have one or more of the following conditions:

A weight that is 20% more than ideal body weight
Risk factors for heart disease (high blood pressure, unhealthy cholesterol levels -- especially for patients with low HDL cholesterol and high triglyceride levels
A close relative with diabetes
A high-risk ethnic group background
In women, having delivered a baby weighing over 9 pounds or having a history of gestational diabetes

Some experts recommend that children over age 10 should be tested for type 2 diabetes (even if they have no symptoms), if they are overweight and have at least two of the above mentioned risk factors.

Fasting Plasma Glucose. The fasting plasma glucose (FPG) test is the standard test for diabetes. It is a simple blood test taken after 8 hours of fasting. Results indicate:

FPG levels are considered normal up to 100 mg/dL (or 5.5 mmol/L).
Levels between 100 - 125 mg/dL (5.5 - 7.0 mmol/L) are referred to as impaired fasting glucose or pre-diabetes. These levels are considered to be risk factors for type 2 diabetes and its complications.
Diabetes is diagnosed when FPG levels are 126 mg/dL (7.0 mmol/L) or higher.

The FPG test is not always reliable, so a repeat test is recommended if the initial test suggests the presence of diabetes, or if the test is normal in people who have symptoms or risk factors for diabetes. For example, people who take the test in the afternoon and show normal results may actually have abnormal levels that would be revealed if they were tested in the morning.

A 2005 study suggested that even people with FPG levels in the high end of the normal range (high 90s) may be at increased risk for developing type 2 diabetes. Obesity further increases this risk. Patients with FPG levels in the upper 90s should strive to exercise and lose weight to help lower their FPG levels.

Glucose Tolerance Test. The oral glucose tolerance test (OGTT) is more complex than the FPG and may overdiagnose diabetes in people who do not have it. Some experts recommend it as a follow-up after FPG, if the latter test results are normal but the patient has symptoms or risk factors of diabetes. The test uses the following procedures:

It first uses an FPG test.
A blood test is then taken 2 hours later after drinking a special glucose solution.

The following results suggest different conditions:

OGTT levels are considered normal up to 140 mg/dL.
Levels between 140 - 199 mg/dL are referred to as impaired glucose tolerance or pre-diabetes.
Diabetes is diagnosed when OGTT levels are 200 mg/dL or higher.

Both the FPG and OGTT require that the patient not eat for at least 8 hours prior to the test.

Test for Glycated Hemoglobin. Tests for blood levels of glycated hemoglobin, also known as hemoglobin A1c (HbA1c), are not currently used for an initial diagnosis, but they are useful for determining the severity of diabetes. Some experts think this test can help predict complications in people who have FPG levels between 110 - 139, which are above normal but do not indicate full-blown diabetes.

The basis for its use as a diagnostic measurement in diabetes is as follows:

Hemoglobin is a protein molecule found in red blood cells. When glucose binds to it, the hemoglobin becomes modified, a process called glycosylation.
Glycosylation affects a number of proteins, and elevated levels of glycolated hemoglobin are strongly associated with complications of diabetes.
A glycated hemoglobin level of 1% above normal range identifies diabetes in 98% of patients. Normal HbA1c levels do not necessarily rule out diabetes, but if diabetes is present and levels are normal, the risk for complications is low.

The test is not affected by food intake so it can be taken at any time. A home test has been developed that might make it easier to measure HbA1c. In general, measurements suggest the following:

Normal HbA1c levels should be below 7%.
Levels of 11 - 12% glycolated hemoglobin indicate poor control of carbohydrates. High levels are also markers for kidney trouble.

Screening for Heart Disease. All patients with diabetes should be tested for hypertension and unhealthy cholesterol and lipid levels and given an electrocardiogram. For cholesterol, people with diabetes should aim for LDL levels below 100 mg/dL, HDL levels over 50 mg/dL, and triglyceride levels below 150 mg/dL. Blood pressure goals should be 130/80 mmHg or lower. Other tests may be needed in patients with signs of heart disease.

The electrocardiogram (ECG, EKG) is used extensively in the diagnosis of heart disease, from congenital heart disease in infants to myocardial infarction and myocarditis in adults. Several different types of electrocardiogram exist.

Screening for Kidney Damage. The earliest manifestation of kidney damage is microalbuminuria, in which tiny amounts (30 - 300 mg per day) of protein called albumin are found in the urine. About 20% of type 2 patients show evidence of microalbuminuria upon diagnosis of diabetes. (However, not all people with type 2 diabetes eventually develop kidney disease.) Microalbuminuria typically shows up in patients with type 2 diabetes who have high blood pressure.

The American Diabetes Association recommends that people with diabetes receive an annual microalbuminuria urine test. Patients should also have their blood creatinine tested at least once a year. Creatinine is a waste product that is removed from the blood by the kidneys. High levels of creatinine may indicate kidney damage. A doctor uses the results from a creatinine blood test to calculate the glomerular filtration rate (GFR). The GFR is an indicator of kidney function; it estimates how well the kidneys are cleansing the blood.

Screening for Retinopathy. The American Diabetes Association recommends that patients with type 2 diabetes get an initial comprehensive eye exam by an ophthalmologist or optometrist shortly after they are diagnosed with diabetes, and once a year thereafter. (People at low risk may need follow-up exams only every 2 - 3 years.) The eye exam should include dilation to check for signs of retinal disease (retinopathy).

Screening for Neuropathy. All patients should be screened for nerve damage (neuropathy), including a comprehensive foot exam. Patients who have loss of sensation in their feet should be sure to have a foot exam every 3 - 6 months to check for ulcers or infections.

Screening for Thyroid Abnormalities. Thyroid function tests should be administered.

Treatment

Pre-diabetes precedes the onset of type 2 diabetes. People who have pre-diabetes have fasting blood glucose levels that are 100 - 125 mg/dL -- higher than normal, but not yet high enough to be classified as diabetes. (Pre-diabetes used to be referred to as “impaired glucose tolerance.”) Pre-diabetes greatly increases the risk for diabetes.

Treatment of pre-diabetes is very important. Research shows that lifestyle and medical interventions can help prevent, or at least delay, the progression to diabetes. While insulin-regulating drugs such as metformin (Glucophage) and acarbose (Precose) are sometimes prescribed, evidence indicates that lifestyle changes can be at least as effective as drug therapy. The most important lifestyle treatment for people with pre-diabetes is to lose weight through diet and regular exercise. Even a modest weight loss of 10 - 15 pounds can significantly reduce the risk of progressing to diabetes.

Because people with pre-diabetes have a higher risk for heart disease and stroke, diet and exercise are also very important for heart health, as is quitting smoking. It is also important to have your doctor check your cholesterol and blood pressure levels on a regular basis. Your doctor should also check your fasting blood glucose levels every 1 - 2 years.

The major treatment goals for people with type 2 diabetes are:

Treat all conditions that place the patients at risk for heart disease and stroke, which are the major killers of people with type 2 diabetes.
Control blood glucose levels. The goal is to achieve fasting blood glucose levels of less than 110 mg/dL and glycolated hemoglobin (HbA1c) levels of less than 7%. The objective is to reduce complications in small blood vessels and the nerve damage associated with diabetes.

An intensive multi-pronged approach is critical for reducing complications and improving survival rates in patients with diabetes. Intensive therapy includes:

Healthy lifestyle changes: Regular exercise; heart-healthy diet; quitting smoking.
Controlling blood sugar levels. Monitor blood sugar and hemoglobin HbA1C levels. Oral anti-hyperglycemic drugs such as metformin are first-line drug treatments. Insulin may eventually be needed.
Heart-protective drugs. These medications include various drugs to control high blood pressure (ACE inhibitors, diuretics, others) and cholesterol (statins, fibrates). Controlling high blood pressure is a proven factor in reducing mortality rates. Aspirin may help prevent blood clots and heart attack.

Different goals may be required for specific individuals, including pregnant women, very old and very young people, and those with accompanying serious medical conditions. Treating children with type 2 diabetes depends on the severity of the condition at diagnosis. Metformin is approved for children. Formerly, only insulin was approved for treating children with diabetes.

Lifestyle Changes

A simple heart-healthy diet with weight control and exercise is important for people with pre-diabetes and may be sufficient for some people with type 2 diabetes. Some patients may be able to control their blood sugar with lifestyle measures and not need medication. Even for patients who do need to take drugs, lifestyle plays an essential role in controlling diabetes. Lifestyle changes can be difficult to initiate and sustain, however. Patients should surround themselves with a solid network of doctors, dietitians, family, and friends who understand both their condition and their needs.

Although there are many major dietary approaches for protecting health, experts generally agree on the following recommendations for heart protection:

Choose fiber-rich food (whole grains, legumes, nuts) as the main source of carbohydrates, along with a high intake of fresh fruits and vegetables. High fiber foods help improve blood glucose levels. Whole grain cereals, which are rich in both fiber and magnesium, may also help reduce the risk for diabetes.
Limit saturated fats (found mostly in animal products) to less than 7% of total daily calories and avoid trans fatty acids (found in hydrogenated fats and many commercial products and fast foods). Choose unsaturated fats (particularly omega-3 fatty acids found in vegetable and fish oils).
In selecting proteins, choose soy protein, poultry, and fish over meat. A 2006 study found that soy does not help improve cholesterol. However, experts still recommend it as a heart-healthy food choice.
Weight control, quitting smoking, and exercise are essential components of any diet program.

[See In-Depth Report #43: Heart-healthy diet.]

There is no such thing as a single diabetes diet. Patients should meet with a professional dietitian to plan an individualized diet within the general guidelines that takes into consideration their own health needs.

Healthy eating habits along with good control of blood glucose are the basic goals, and several good dietary methods are available to meet them. General dietary guidelines for diabetes recommend:

Carbohydrates should provide 45 - 65% of total daily calories. The type and amount of carbohydrate are both important. Best choices are vegetables, fruits, beans, and whole grains. These foods are also high in fiber. Patients with diabetes should monitor their carbohydrate intake either through carbohydrate counting or meal planning exchange lists.
Fats should provide 25 - 35% of daily calories. Monounsaturated (olive, peanut, canola oils; avocados; nuts) and omega-3 polyunsaturated (fish, flaxseed oil, walnuts) fats are the best types. Limit saturated fat (red meat, butter) to less than 7% of daily calories. Choose nonfat or low-fat dairy instead of whole milk products. Limit trans-fats (hydrogenated fat found in snack foods, fried foods, commercially baked goods) to less than 1% of total calories.
Protein should provide 12 - 20% of daily calories, although this may vary depending on a patient’s individual health requirements. Patients with kidney disease should limit protein intake to less than 10% of calories. Fish, soy, and poultry are better protein choices than red meat.

[For detailed information, including diabetic exchange lists and carbohydrate counting, see In-Depth Report #42: Diabetes diet.]

Being overweight is the number one risk factor for type 2 diabetes. Even modest weight loss can help prevent type 2 diabetes from developing. It can also help control or even stop progression of type 2 diabetes in people with the condition and reduce risk factors for heart disease. Patients should aim to lose weight if their body mass index (BMI) is 25 - 29 (overweight) or higher (obese).

The American Diabetes Association recommends that patients aim for a small but consistent weight loss of ½ - 1 pound per week. Most patients should follow a diet that supplies at least 1,000 - 1,200 kcal/day for women and 1,200 - 1,600 kcal/day for men.

Unfortunately, not only is weight loss difficult to sustain, but many of the oral medications used in type 2 diabetes cause weight gain as a side effect. For obese patients who cannot control weight using dietary measures alone, weight-loss drugs, such as orlistat (Xenical) or sibutramine (Meridia), may be helpful. Orlistat may have specific benefits for people with diabetes. It may not only help achieve weight but also improve glucose, cholesterol, and lipid levels. In 2007, the FDA approved a non-prescription form of orlistat (alli). [See In-Depth Report #53: Obesity.]

Sedentary habits, especially TV watching, are associated with significantly higher risks for obesity and type 2 diabetes. Regular exercise, even of moderate intensity (such as brisk walking), improves insulin sensitivity and may play a significant role in preventing type 2 diabetes -- regardless of weight loss. An important study reported a 58% lower risk for type 2 diabetes in adults who performed moderate exercise for as little as 2.5 hours a week.

Aerobic Exercise. Aerobic exercise has significant and particular benefits for people with diabetes. Regular aerobic exercise, even of moderate intensity, improves insulin sensitivity. People with diabetes are at particular risk for heart disease, so the heart-protective effects of aerobic exercise are especially important. Moderate exercise protects the heart in people with type 2 diabetes, even if they have no risk factors for heart disease other than diabetes itself.

For improving glycemic control, the American Diabetes Association recommends at least 150 minutes per week of moderate-intensity physical activity (50 - 70% of maximum heart rate) or at least 90 minutes per week of vigorous aerobic exercise (more than 70% of maximum heart rate). Exercise at least 3 days a week, and do not go more than 2 consecutive days without physical activity.

Strength Training. Strength training, which increases muscle and reduces fat, is also helpful for people with diabetes who are able to do this type of exercise. The American Diabetes Association recommends performing resistance exercise three times a week. Build up to three sets of 8 - 10 repetitions using weight that you cannot lift more than 8 - 10 times without developing fatigue. Be sure that your strength training targets all of the major muscle groups.

Exercise Precautions. The following are precautions for all people with diabetes, both type 1 and type 2:

Because people with diabetes are at higher than average risk for heart disease, they should always check with their doctors before undertaking vigorous exercise. For fastest results, frequent high-intensity (not high-impact) exercises are best for people who are cleared by their doctors. For people who have been sedentary or have other medical problems, lower-intensity exercises are recommended.
Strenuous strength training or high-impact exercise is not recommended for people with uncontrolled diabetes. Such exercises can strain weakened blood vessels in the eyes of patients with retinopathy. High-impact exercise may also injure blood vessels in the feet.

Patients who are taking medications that lower blood glucose, particularly insulin, should take special precautions before embarking on a workout program:

Monitor glucose levels before, during, and after workouts (glucose levels swing dramatically during exercise).
Avoid exercise if glucose levels are above 300 mg/dL or under 100 mg/dL.
Inject insulin in sites away from the muscles used during exercise; this can help avoid hypoglycemia.
Drink plenty of fluids before and during exercise; avoid alcohol, which increases the risk of hypoglycemia.
Insulin-dependent athletes may need to decrease insulin doses or take in more carbohydrates prior to exercise, but may need to take an extra dose of insulin after exercise (stress hormones released during exercise may increase blood glucose levels).
Wear good, protective footwear to help avoid injuries and wounds to the feet.
Some blood pressure drugs can interfere with exercise capacity. Patients who use blood pressure medication should consult their doctors on how to balance medications and exercise. Patients with high blood pressure should also aim to breathe as normally as possible during exercise. Holding the breath can increase blood pressure.

[See In-Depth Report #29: Exercise.]

According to the American Diabetes Association, people with diabetes should aim for preprandial (before eating) plasma glucose levels of 90 - 130 mg/dL and postprandial (after eating) plasma glucose levels less than 180 mg/dL. Hemoglobin A1C levels should be less than 7%.

Measuring Blood Glucose. In patients being treated with insulin or insulin-producing or sensitizing drugs, it is important to monitor blood glucose levels carefully to avoid hypoglycemia. Different goals may be required for specific individuals, including pregnant women, very old and very young people, and those with accompanying serious medical conditions.

Blood glucose levels are generally more stable in type 2 diabetes than in type 1, so experts usually recommend measuring blood levels only once or twice a day. For patients who have become insulin-dependent, more intensive monitoring is necessary. Usually, a drop of blood obtained by pricking the finger is applied to a chemically treated strip. The glucose level is read on a standard meter or a small, portable digital display device. For patients who have trouble controlling hypoglycemia (low blood sugar) or fluctuating blood sugar levels, continuous glucose sensor monitors are also available. In 2007, the FDA approved the STS-7 System, which continuously measures glucose levels for up to 7 days through a sensor inserted beneath the skin of the abdomen. Continuous glucose sensor monitors do not replace fingerstick glucose meters and test strips, but are used in combination with them. [See In-Depth Report #9: Diabetes - type 1.]

Measuring Hemoglobin A1C. Hemoglobin A1c (also called HbA1c , HA1c, or A1C) is measured periodically every 2 - 3 months to determine the average blood-sugar level over the lifespan of the red blood cell. Normal A1C levels should be below 7%. Home tests are also available for measuring A1C.

To monitor the amount of glucose within the blood a person with diabetes should test their blood regularly. The procedure is quite simple and can often be done at home.

Some research suggests that not getting enough sleep may impair insulin use and increase the risk for obesity. More research is needed, but it is always wise to improve sleep habits.

Medications

The American Heart Association now recommends that patients should aim for the following test results for intensive control of glucose levels:

Fasting plasma glucose concentrations below 110 mg/dL.
Glycolated hemoglobin (HbA1c) levels of less than 7%. Controlling HbA1c is the most important factor for reducing the risk of complications in patients with diabetes. According to one 2000 study, a 1% reduction in people with elevated glycolated hemoglobin levels lowers the risk for complications by 21%.

Evidence clearly supports strict glycemic control for reducing complications in the nervous system and blood vessels that occur in both type 1 and type 2 diabetes. Research shows that tight glucose control can help prevent heart disease and complications.

Managing risk factors for heart disease and stroke, particularly strict control of blood pressure, may be more important for improving survival than strict control of blood glucose levels for some patients. Such goals also seem to be more attainable for many patients with type 2 diabetes.

Oral Anti-Hyperglycemic Drugs. Many oral anti-hyperglycemic drugs are available to help patients with type 2 diabetes control their blood sugar levels. Most of these drugs are aimed at using or increasing sensitivity to the patient's own natural stores of insulin. Metformin is the only drug to date that achieves lower mortality rates. Oral type 2 diabetes drugs include:

Biguanides (metformin). Metformin increases tissue sensitivity to available insulin. Metformin also has beneficial effects on cholesterol, blood pressure, and clotting factors. It does not cause weight gain or hypoglycemia. Diarrhea and digestive problems are the most common side effects. Metformin produces lower mortality rates than other drugs, including insulin, and should be considered as first-line therapy for most patients with type 2 diabetes.
Sulfonylureas (glyburide, glipizide, glimepiride, repaglinide). Stimulate insulin secretion but can cause hypoglycemia more than other drugs.
DPP-4 inhibitors (sitagliptin). Also called gliptins, DPP-4 inhibitors were first approved in 2006 and are the newest class of oral diabetes drugs. Like metformin, they do not cause weight gain and have low risks for hypoglycemia.
Meglitinides (repaglinide, nateglinide). Stimulate insulin secretion. These newer drugs are better than sulfonylureas in controlling glucose spikes after meals.
Thiazolidinediones (pioglitazone and rosiglitazone). Reduce insulin resistance. These drugs improve cholesterol levels and may reduce the risk for blood clots. However, they can cause swelling from fluid build-up, which can worsen heart failure or even precipitate it. They may also injure the liver.
Alpha-glucosidase inhibitors (acarbose and miglitol). Slow intestinal absorption of carbohydrates. Have only modest effects on diabetes and have gastrointestinal side effects. Can slightly raise HDL (“good”) cholesterol levels.
Combinations of these drugs, particularly with metformin, are often used to increase effectiveness.

A 2007 review in the Annals of Internal Medicine compared these various classes of medications. The review found that older drugs -- such as metformin and sulfonylureas -- are less expensive than and work as well as newer diabetes drugs. In particular, the review cited metformin as a safe and effective drug because it does not cause weight gain or too-low blood sugar. Metformin can also help lower LDL (“bad”) cholesterol.

Injectable Anti-Hyperglycemic Drugs. In 2005, the FDA approved two new injectable drugs to help patients improve blood sugar control:

Exenatide (Byetta). Exenatide is the first drug in a new class of drugs called incretin mimetics. It lowers blood glucose levels by increasing insulin secretion. Exenatide is used in combination with oral antihyperglycemics, such as metformin or a sulfonylurea drug.
Pramlintide (Symlin). Pramlintide is a first-in-class drug that is a synthetic form of the hormone amylin. The drug is meant for patients who take insulin but still have difficulty controlling their glucose levels.

Insulin Replacement. Insulin replacement may be required when natural insulin reserves are depleted. It is typically started in combination with an oral drug. Eventually, some patients may need to go on full insulin replacement. In addition to injectable forms of insulin, an inhaled insulin product (Exubera) is now available.

Metformin (Glucophage) is a biguanide, which works by reducing glucose production in the liver and by making tissues more sensitive to insulin. Many experts recommend it as a first choice for most patients with type 2 diabetes who are insulin resistant, particularly if they are overweight. Metformin achieves lower mortality rates from diabetes and all causes than other drugs. In one comparison study, it achieved the lowest mortality rates (8%) compared to insulin (28%), a sulfonylurea (16%), and a thiazolidinedione (14%). Combinations with insulin-secreting drugs, other insulin-sensitizing drugs, or insulin itself are particularly effective.

Metformin does not cause hypoglycemia or add weight, so it is particularly well-suited for obese patients with type 2 diabetes. (In some studies, in fact, patients lost weight.) Metformin also appears to have beneficial effects on cholesterol and lipid levels and may help protect the heart. Some research has suggested that it significantly reduces the risk for heart attack. It is also the first choice for children who need oral drugs and is proving to be very effective for women with polycystic ovary syndrome and insulin resistance.

Side Effects. Side effects include:

A metallic taste
Gastrointestinal problems, including nausea, and diarrhea
Interference with absorption of vitamin B12 and folic acid, (which are important for protection against heart disease)
Rare reports of lactic acidosis, a potentially life-threatening condition, particularly in people with risk factors for it. Major studies, however, found no greater risk with metformin than with any of the other drugs used for type 2 diabetes.

Certain people should not use this drug, including anyone with heart failure or kidney or liver disease. It is rarely suitable for adults over age 80.

Sulfonylureas are oral drugs that stimulate the pancreas to release insulin. They are also first-line oral drugs. For adequate control of blood glucose levels, the drugs should be taken only 20 - 30 minutes before a meal. A number of brands are available, including chlorpropamide (Diabinese), tolazamide (Tolinase), acetohexamide (Dymelor), glipizide (Glucotrol), tolbutamide (Orinase), glyburide (Micronase), glimepiride (Amaryl), and repaglinide (Prandin).

Most patients can take sulfonylureas for 7 - 10 years before they lose effectiveness. Combinations with small amounts of insulin or with other oral anti-hyperglycemic drugs (such as metformin or a thiazolidinedione) may extend their benefits. A combination of glyburide and metformin in one pill (Glucovance) is available. Glucovance may be particularly beneficial for patients with unhealthy cholesterol levels and poor control of their blood sugar levels. Some doctors recommend the combination as first-line treatment.

An encouraging 2000 study of patients with severe type 2 diabetes reporting that combinations of insulin with either chlorpropamide or glipizide achieved better glucose control over the long term than insulin alone.

Side Effects and Complications. In general, sulfonylureas should not be used by women who are pregnant or nursing or by individuals who are allergic to sulfa drugs. Side effects may include:

Weight gain (some sulfonylureas, such as glimepiride, may produce less weight gain than others)
Water retention
Although sulfonylureas pose a lower risk for hypoglycemia than insulin does, the hypoglycemia produced by sulfonylureas may be especially prolonged and dangerous. The newer sulfonylureas, such as glimipiride, have much less risk of hypoglycemia than older sulfonylureas.
Some sulfonylureas may pose a slight risk for cardiac events.

Sulfonylureas interact with many other drugs, and patients should be sure to inform their doctor of any medications they are taking, including alternative or over-the-counter drugs.

Meglitinides stimulate beta cells to produce insulin. They include repaglinide (Prandin), nateglinide (Starlix), and mitiglinide. These drugs are rapidly metabolized and short-acting. If taken before every meal, they actually mimic the normal effects of insulin after eating. Patients, then, can vary their meal times with this drug. (Nateglinide appears to work more quickly and is shorter-acting than repaglinide). These drugs may be particularly helpful in combination with metformin or other drugs. They may also be a good choice for people with potential kidney problems.

Side Effects. Side effects include diarrhea and headache. As with the sulfonylureas, repaglinide poses a slightly increased risk for cardiac events. (Newer drugs, such as nateglinide, may pose less of a risk.) People with heart failure or liver disease should use them with caution and be monitored.

Thiazolidinediones, also known as peroxisome proliferator-activated receptor (PPAR) agonists, include rosiglitazone (Avandia) and pioglitazone (Actos). They improve insulin sensitivity by activating certain genes involved in fat synthesis and carbohydrate metabolism. These drugs are usually taken once or twice per day; however, it may take several days before the patient notices any results from them and several weeks before they take full effect. Thiazolidinediones are usually taken in combination with other oral drugs or insulin.

Side Effects. Thiazolidinediones can have serious side effects. They tend to increase fluid-build up, which can cause or worsen heart failure in some patients. Combinations with insulin increase the risk. They should not be used by patients with existing heart failure and should be used cautiously in those with risk factors for heart failure.

In 2007, a study published in the New England Journal of Medicine (NEJM) raised serious concerns that rosiglitazone may increase the risk of heart attack. The study reviewed 42 clinical trials of rosiglitazone. Results suggested that patients who took rosiglitazone were 43% more likely to have a heart attack, and 64% more likely to die from overall heart causes, than patients with diabetes who did not take the drug. A subsequent interim analysis in the NEJM found that while rosiglitazone was definitely associated with increased risk of heart failure, the data were insufficient to determine if the drug increases heart attack risk. The FDA has concluded that rosiglitazone may increase the risk of heart attack and will likely restrict its use. In 2007, a panel of experts from the Food and Drug Administration (FDA) agreed the drug increases the risk of heart attacks -- but concluded it should remain on the market. The panel did, however, recommend the FDA require rosiglitazone's maker to add warnings to the drug's label. Patients who take rosiglitazone, especially those who have heart disease or who are at high risk for heart attack, should discuss their treatment options with their doctors.

Thiazolidinediones may cause more weight gain than other diabetes medications or insulin. Any patient who experiences sudden weight gain, water retention, or shortness of breath should immediately call their doctor. These drugs have also been linked to increased risks for bone fracture.

There have been rare reports of rosiglitazone causing or worsening diabetic macular edema. This is an eye condition associated with diabetic retinopathy that causes swelling in the macular area of the retina. Symptoms include blurred vision and decreased color sensitivity. Most patients who had this side effect also had swelling in the feet and legs (peripheral edema). The condition resolved or improved when patients stopped taking the drug.

Thiazolidinediones can also cause liver damage. Patients who take these drugs should have their liver enzymes checked regularly.

Alpha-glucosidase inhibitors, including acarbose (Precose, Glucobay) and miglitol (Glyset), reduce glucose levels by interfering with the absorption of starch in the small intestine. Acarbose tends to lower insulin levels after meals, a particular advantage, since higher levels of insulin after meals are associated with an increased risk for heart disease. Some evidence suggests that early use of these drugs may reduce heart risk factors, including high blood pressure. A 2002 study of acarbose suggested that these drugs may possibly delay the development of type 2 diabetes in high-risk individuals. Alpha-glucosidase inhibitors are not as effective alone as other single oral drugs, but combinations, such as with metformin, insulin, or a sulfonylurea, increase their effectiveness.

Side Effects. These medications need to be taken with meals. Unfortunately, about a third of patients stop taking the drug because of flatulence and diarrhea, particularly after high-carbohydrate meals. The drug may also interfere with iron absorption.

Alpha-glucosidase inhibitors do not cause hypoglycemia when used alone, but combinations with other drugs do. In such cases, it is important that the patient receive a solution that contains glucose or lactose, not table sugar. This is because acarbose inhibits the breakdown of complex sugar and starches, which includes table sugar.

Incretin mimetics belong to a new class of drugs that help improve blood sugar control. Incretins include glucagon-like peptide-1 (GLP-1) inhibitors and DDP-4 inhibitors.

In 2005, the FDA approved exenatide (Byetta), the first GLP-1 inhibitor drug. Exenatide is an injectable drug that is a synthetic version of the hormone found in the saliva of the Gila monster, a venomous desert lizard. Exenatide is injected twice a day, 1 hour before morning and evening meals. It is prescribed for patients with type 2 diabetes who have not been able to control their glucose with metformin or a sulfonylurea drug. It can be taken in combination with these drugs or alone.

Side Effects. Exenatide stimulates insulin secretion only when blood sugar levels are high and so has less risk for causing low blood sugar (hypoglycemia) when it is taken alone. However, the risk for hypoglycemia increases when exenatide is taken along with a sulfonylurea drug. There does not appear to be a risk for hypoglycemia when exenatide is used along with metformin. Other side effects may include nausea, vomiting, and diarrhea.

A 2005 study compared exenatide to insulin for improving glucose control in patients taking metformin and a sulfonylurea. Both insulin and exenatide worked well for glucose control. Patients lost weight with exenatide and gained weight with insulin. However, patients who received exenatide had significantly more problems with nausea, vomiting, and diarrhea than those who received insulin.

Dipeptidyl peptidase-4 (DPP-4) inhibitors, also called gliptins, are the second class of incretin drugs. In October 2006, the FDA approved the first DPP-4 inhibitor -- sitagliptin (Januvia). It can be used alone or in combination with metformin or a thiazolidinedione drug. In April 2007, the FDA approved Janumet, which combines sitagliptin with metformin in one pill. Other DPP-4 drugs being studied include vildagliptin (Galvus) and saxagliptin.

DPP-4 inhibitors work in a similar way to GLP-1 inhibitors. However, unlike exenatide, which is given by injection, DPP-4 inhibitor drugs are taken as pills by mouth.

Like exenatide, DPP-4 inhibitors do not cause weight gain, have low risks for hypoglycemia, and have few severe side effects. The most common side effects include upper respiratory tract infection, sore throat, and diarrhea.

Insulin replacement is the best treatment for strict control of blood glucose and is required once natural insulin reserves are depleted. Because type 2 diabetes is progressive, most patients eventually require insulin, typically starting it in combination with an oral anti-hyperglycemic drug. However, when a single oral drug fails to control blood sugar it is not clear whether it is better to add insulin replacement or to add a second or third oral drug.

Some experts advocate using insulin as early as possible for optimal control. However, in patients who still have insulin reserves, there is concern that extra natural insulin will have adverse effects. Low blood sugar (hypoglycemia) and weight gain are the main side effects of insulin therapy. Some research suggests that insulin may also cause heart complications. A 2006 study reported that insulin therapy increases the risk of developing high blood pressure (hypertension). It is still not clear if insulin replacement improves survival rates compared to oral drugs, notably metformin.

One approach is to combine insulin with metformin, which achieves blood glucose control without added weight gain. Newer forms of insulin analogues, such as glargine, may be especially helpful for people with type 2 diabetes and reduce the risk for hypoglycemia.

Fortunately, studies to date have not reported any adverse cardiac effects in patients with type 2 diabetes who take insulin. In fact, insulin has been associated, in some cases, with improvement in heart risk factors. More research is needed to clarify these important issues.

Forms of Insulin. Experts are working toward administering insulin so that it closely mimics the daily pattern of insulin, which responds to blood sugar levels by surging after meals and then falling to a steady base level afterward. To achieve this, doctors may use two insulin types:

Fast-Acting Insulins for Surges. Insulin lispro and aspart are fast-acting insulins. They mimic insulin's response to food intake. They are taken before meals, and their short action reduces the risk for hypoglycemia afterward.
Slower Insulins for Base Levels. Intermediate forms (including NPH and lente) and long-acting forms (glargine, ultralente) were developed to provide a steady level of insulin throughout the day. To date, glargine (Lantus) seems to be the most successful in achieving this goal in type 2 diabetes.

In 2006, the FDA approved the first non-injected form of insulin. Exubera is an inhaled form of insulin. It is approved for adults but should not be used by patients who smoke or have quit smoking within the past 6 months. Patients with asthma, bronchitis, or emphysema should also not use inhaled insulin. Clinical trials indicate that Exubera can provide sustained blood sugar control over a 2-year period. Patients in the trials who took Exubera experienced half as much weight gain as those who took injected insulin. Scientists are also developing other types of non-injected insulin, including spray formulas.

In a 2005 trial, Exubera improved blood sugar control when it was added to or substituted for combination oral drug therapy (sulphonylurea and thiazolidenedione). However, as with other forms of insulin, Exubera caused more hypoglycemia and weight gain than the oral anti-hyperglycemic drugs.

Pramlintide (Symlin) is a new type of injectable drug that may help patients who take insulin but still need better blood sugar control. The FDA approved this drug in 2005. Pramlintide is a synthetic form of amylin, a hormone that is related to insulin. Pramlintide is used in combination with insulin to lower blood sugar levels in the 3 hours after meals.

[See In-Depth Report #9: Diabetes - type 1.]

Sodium Glucose Uptake Transporter 2 (SGLT-2) Inhibitors. SGLT-2 inhibitors are a new class of drug being investigated for treatment of type 2 diabetes. Preliminary trials for two of these drugs, dapagliflozin and serglifozin, have shown promising results in helping improve blood glucose control. The drugs are being tested in combination with metformin.

Various fraudulent products are often sold on the Internet as “cures” or treatments for diabetes. These dietary supplements have not been studied or approved. In 2006, the FDA and Federal Trade Commission (FTC) launched a crackdown on these scams. The FDA and FTC warn patients with diabetes not to be duped by bogus and unproven remedies.

Long-Term Complications

Patients with diabetes have higher mortality rates than people who do not have diabetes regardless of sex, age, or other factors. Heart disease and stroke are the leading causes of death in these patients. All lifestyle and medical efforts should be made to reduce the risk for these conditions.

People with type 2 diabetes are also at risk for nerve damage (neuropathy) and abnormalities in both small and large blood vessels (vascular injuries) that occur as part of the diabetic disease process. Such abnormalities produce complications over time in many organs and structures in the body. Although these complications tend to be more serious in type 1 diabetes, they still are of concern in type 2 diabetes. All people with diabetes should aim for fasting blood glucose levels of less than 110 mg/dL and hemoglobin HbA1C of less than 7%.

There are two important approaches to preventing complications from diabetes:

Intensive control of blood glucose and keeping glycosylated hemoglobin (HbA1c) levels below 7%. Tight blood glucose and HbA1c control can prevent complications due to vascular (blood vessel) abnormalities and nerve damage (neuropathy) that can cause major damage to organs, including the eyes, kidneys, and heart.
Managing risk factors for heart disease. Control of blood glucose also helps the heart, but its benefits occur over time. It is very important that people with diabetes control blood pressure, cholesterol levels, and other factors associated with heart disease.

Heart attacks account for 60% and strokes for 25% of deaths in patients with diabetes. Diabetes affects the heart in many ways:

Both type 1 and 2 diabetes speed the progression of atherosclerosis (hardening of the arteries). Diabetes can adversely affect blood lipid levels by lowering HDL ("good cholesterol") and increasing triglycerides. This can lead to coronary artery disease, heart attack, or stroke. According to a 2007 study, the risk of stroke doubles within 5 years of type 2 diabetes diagnosis.
Impaired nerve function (neuropathy) associated with diabetes also causes heart abnormalities. Some experts estimate that the mortality rates from neuropathy-related heart conditions range between 15 - 53%.
Women with diabetes are at particularly high risk for heart problems. A 2007 study indicated that while progress has been made in reducing mortality rates among men with diabetes, women with diabetes continue to face a high risk of death from heart disease and overall causes.

Tight blood sugar control may help protect blood vessels and reduce the risk for blood clotting. It is still not known whether intensive control will have a major protective effect on the heart, however. People with diabetes must be sure to use other measures as well to protect the heart.

Aspirin for Reducing the Risk for Blood Clots. Taking a daily aspirin (75 - 162 mg/day) reduces the risk for blood clotting and may help protect against heart attacks and heart disease. In a 2000 study, low-dose aspirin was associated with a 30% lower risk for death from heart disease in adults with type 2 diabetes.

Controlling Blood Pressure. Strict control of blood pressure is critical for preventing complications of diabetes and has proven to improve survival rates. Patients should strive for blood pressure levels of less than 130/80 mm Hg (systolic/diastolic). (Controlling systolic pressure may be especially important for reducing the risk for kidney complications.)

Dozens of anti-hypertensive drugs are available. Most fall into the following categories:

Diuretics rid the body of extra sodium (salt) and water. There are three main types of diuretics: Potassium-sparing, thiazide, and loop.
Angiotensin-converting enzyme (ACE) inhibitors reduce the production of angiotensin, a chemical that causes arteries to narrow.
Angiotensin-receptor blockers (ARBs) block angiotensin.
Beta-blockers block the effects of adrenaline and ease the heart’s pumping action.
Calcium-channel blockers (CCBs) decrease the contractions of the heart and widen blood vessels.

The American Diabetes Association (ADA) recommends any of these classes of drugs as first-line treatment for hypertension. New research suggests, however, that beta-blockers are less effective at preventing strokes and heart attacks than other types of blood pressure medications. Many patients require more than one type of drug to control blood pressure. For patients with diabetes who have microalbuminuria, the ADA strongly recommends ACE inhibitors or ARBs. Microalbuminuria is an accumulation of protein in the blood, which can signal the onset of kidney disease (nephropathy).

Anti-hypertensive drugs that block or reduce angiotensin are the first option for many people with diabetes. Angiotensin is a natural chemical that influences all aspects of blood pressure control and also interferes with insulin's normal metabolic signaling. In fact, angiotensin may be the common factor linking diabetes and high blood pressure.

The 2005 landmark Antihypertensive and Lipid Lowering Treatment to Prevent Heart Attack Trial (ALLHAT) indicated that a thiazide-type diuretic works as well as an ACE inhibitor or CCB for patients with diabetes and high blood pressure. Compared with ACE inhibitors or CCBs, diuretics appeared to be better at lowering systolic blood pressure and preventing heart failure. In addition, the trial suggested that diuretics are especially helpful for African-Americans, by offering greater protection than ACE inhibitors or CCBS in preventing strokes.

Several 2006 studies suggested that anti-hypertensive drugs may increase the risk of developing diabetes. One study found more risk for thiazide diuretics and beta-blockers than ACE inhibitors and CCBs. Another study indicated that the ACE inhibitor ramipril had a lower risk of causing diabetes in African-Americans than a CCB or beta-blocker. A 2007 review in the Lancet also found a higher risk for new-onset diabetes with beta-blockers and diuretics, a medium risk with CCBs, and the lowest risk with ARBs and ACE inhibitors.

Research in this subject is important for patients with pre-diabetes who have high blood pressure. Results of future research may help doctors decide which treatment is most appropriate for patients with high blood pressure who are at high risk for diabetes. [See In-Depth Report #14: High blood pressure.]

Improving Cholesterol and Lipid Levels. Abnormal cholesterol and lipid levels are common in diabetes. High LDL (“bad”) cholesterol should always be lowered, but people with diabetes also often have additional harmful imbalances including low HDL (“good”) cholesterol and high triglycerides. Patients should aim for LDL levels below 100 mg/dL, HDL levels over 50 mg/dL and triglyceride levels below 150 mg/dL. Patients with diabetes and existing heart disease should strive for even lower LDL levels; the American Diabetes Association recommends LDL levels below 70 mg/dL for these patients.

Statins are the best cholesterol-lowering drugs. They include atorvastatin (Lipitor), lovastatin (Mevacor, generics), pravastatin (Pravachol), simvastatin (Zocor, generics), fluvastatin (Lescol), and rosuvastatin (Crestor). These drugs are very effective for lowering LDL cholesterol levels. Recent studies indicate that aggressive high-dose statin therapy may be an important treatment approach for high-risk patients who need to substantially lower their LDL levels. A 2006 study found that patients with diabetes and heart disease who were treated with 80 mg daily of atorvastatin had a 25% lower risk of heart attack and stroke than patients who received the standard 10 mg daily dose.

The primary safety concern with statins has involved myopathy, an uncommon condition that can cause muscle damage and, in some cases, muscle and joint pain. A specific myopathy called rhabdomyolysis can lead to kidney failure. People with diabetes and risk factors for myopathy should be monitored for muscle symptoms

Although lowering LDL is beneficial, statins are not as effective as other medications -- such as fibrates, niacin, ezetimbe, or bile acid sequesters -- in addressing HDL and triglyceride imbalances. This is a common problem in type 2 diabetes. Combinations of statins with one of these drugs may be helpful for people with diabetes who have heart disease, low HDL, and near-normal LDL levels. Although combinations of statins and fibrates or niacin increase the risk of myopathy, both combinations are considered safe if used with extra care. Research presented at the 2007 annual meeting of the American Diabetes Association suggested that statins and fibrates may also help reduce the risk of developing peripheral neuropathy, the diabetes-associated nerve damage that can lead to loss of sensation in the feet.

Gemfibrozil (Lopid) and fenofibrate (Tricor) are usually the first choice for fibrate drugs. Niacin has the most favorable effect on raising HDL and lowering triglycerides of all the cholesterol drugs. However, about 30% of patients who take high-dose niacin experience increased blood glucose levels. Moderate doses of niacin can achieve lipid control without causing serious blood glucose problems. [See In-Depth Report #23: Cholesterol.]

Kidney disease (nephropathy) is a very serious complication of diabetes. With this condition, the tiny filters in the kidney (called glomeruli) become damaged and leak protein into the urine. Over time this can lead to kidney failure. Urine tests showing microalbuminuria (small amounts of protein in the urine) are important markers for kidney damage.

Prevention and Treatment of Nephropathy. Tight control of blood sugar and blood pressure is essential for preventing the onset of kidney disease. Long-term studies report that strict control of these two conditions produces a 60% reduction in new cases of nephropathy and a delay in progression of the disease. ACE inhibitors and ARBs, two classes of blood pressure medications, are very helpful for preventing or slowing the progression of diabetic kidney disease.

A doctor may recommend a low-protein diet for patients whose kidney disease is progressing despite tight blood sugar and blood pressure control. Protein-restricted diets can help slow disease progression and delay the onset of end-stage renal disease (kidney failure). However, patients with end-stage renal disease who are on dialysis generally require higher amounts of protein. [See In-Depth Report #42: Diabetes diet.]

Diabetic nephropathy occurs in about 20 - 40% of patients with diabetes and is the leading cause of end-stage renal disease. If the kidneys fail, dialysis is required. Symptoms of kidney failure may include swelling in the feet and ankles, itching, fatigue, and pale skin color.

Anemia is a common complication of end-stage kidney disease. Patients on dialysis usually require injections of erythropoiesis-stimulating drugs to increase red blood cell counts and control anemia. Dosing target levels of erythropoiesis-stimulating drugs are controversial, especially for patients with chronic kidney disease. In 2006, two important New England Journal of Medicine studies indicated that aggressive dosing to completely normalize hemoglobin levels does not work better than standard dosing that only partially corrects anemia.

In 2007, the FDA issued new warnings on darbepoetin alfa (Aranesp) and epoetin alfa (Epogen and Procrit). The warnings describe an increased risk with blood clots, strokes, and heart attacks in patients with end-stage kidney disease when these drugs were given at higher than recommended doses. The FDA has set new dosing and hemoglobin target levels for these drugs.

Another controversy surrounding erythropoiesis-stimulating drugs concerns their overuse at dialysis centers. A 2007 study in the Journal of the American Medical Association suggested that large, for-profit dialysis centers tend to administer higher-than-appropriate doses of these drugs compared to nonprofit facilities. The study suggested that for-profit centers are giving higher doses for financial, not medical, reasons.

The FDA recommends that patients with end-stage kidney disease who receive erythropoiesis-stimulating drugs should:

Maintain hemoglobin levels that do not exceed 12 g/dL
Receive frequent blood tests to monitor hemoglobin levels
Contact their doctors if they experience such symptoms as shortness of breath, pain, swelling in the legs, or increases in blood pressure

[See In-Depth Report #57: Anemia.]

Click the icon to see an image of the pancreas and kidneys.

Diabetes reduces or distorts nerve function, causing a condition called neuropathy. Neuropathy refers to a group of disorders that affect nerves. The two main types of neuropathy are:

Peripheral (affects nerves in the toes, feet, legs, hand, and arms)
Autonomic (affects nerves that help regulate digestive, bowel, bladder, heart, and sexual function)

Peripheral neuropathy particularly affects sensation. It is a common complication that affects nearly half of people with type 1 or type 2 diabetes after 25 years. The most serious consequences of neuropathy occur in the legs and feet and pose a risk for ulcers and, in very severe cases, amputation. Peripheral neuropathy usually starts in the fingers and toes and moves up to the arms and legs (called a stocking-glove distribution). Symptoms include:

Tingling
Weakness
Burning sensations
Loss of the sense of warm or cold
Numbness (if the nerves are severely damaged, the patient may be unaware that a blister or minor wound has become infected)
Deep pain

Autonomic neuropathy can cause digestive problems (constipation, diarrhea, nausea, vomiting), bladder infections, and erectile dysfunction. In some cases, neuropathy may mask angina, the chest pain warning for heart disease and heart attack. Patients with diabetes should be aware of other warning signs of a heart attack, including sudden fatigue, sweating, shortness of breath, nausea, and vomiting.

Blood sugar control is the only treatment for neuropathy. Studies show that tight control of blood glucose levels delays the onset and slows progression of neuropathy. A 2005 study also suggested that heart disease risk factors can increase the likelihood of developing neuropathy. Lowering triglycerides, losing weight, reducing blood pressure, and quitting smoking may help prevent the onset of neuropathy.

Prevention of Neuropathy. Patients with type 2 diabetes should receive regular screenings for loss of sensation in feet and other signs of neuropathy. A 2007 study suggested that statin and fibrate drugs, which are used to control cholesterol, may help protect against diabetic peripheral neuropathy.

Pain Relief for Peripheral Neuropathy. A number of different drugs are used for peripheral neuropathy pain relief. They include:

Nonprescription analgesics such as aspirin, acetaminophen, and non-steroidal anti-inflammatory drugs (NSAIDs). (Patients with stomach or kidney problems should check with their doctors before using these drugs.)
Prescription painkillers, such as tramadol (Ultram). Tramadol is a drug that is similar to opioids. It can help relieve pain but has significant side effects, including nausea, constipation, and headache.
Topical medications, particularly capsaicin (the active ingredient in hot peppers), are applied to the skin to relieve minor local pain. A 5% lidocaine patch has also shown good results in clinical trials.
Tricyclic antidepressants, such as amitriptyline (Elavil) or doxepin (Sinequan), are effective in reducing pain from neuropathy in up to 75% of patients. A combination of doxepin and capsaicin (applied to the skin) may be particularly beneficial. Unfortunately, tricyclics may cause heart rhythm problems.
Duloxetine (Cymbalta) is a serotonin and norepinephrine reuptake inhibitor, a newer type of antidepressant, which was approved in 2004 for treatment of pain associated with diabetic peripheral neuropathy.
The anti-convulsant drug pregabalin (Lyrica) was approved in 2004 for neuropathic pain management. It is classified as a controlled substance (like narcotics), which indicates a potential risk for abuse. Other anti-seizure drugs used for peripheral neuropathy pain relief include gabapentin (Neurontin) and valproate (Depakote).

Treatments under investigation include acetyl-l-carnitine and intravenous alpha-lipoic acid. Patients may also benefit from transcutaneous electrostimulation (TENS), a treatment that involves administering mild electrical pulses to painful areas. Alternative treatments such as hypnosis, biofeedback, relaxation techniques, and acupuncture have helped some patients manage pain. Doctors also recommend lifestyle measures such as walking and wearing elastic stockings.

Treatments for Other Complications of Neuropathy. Neuropathy also impacts other functions, and treatments are needed to reduce their effects. If diabetes affects the nerves in the autonomic nervous system, then abnormalities of blood pressure control and bowel and bladder function may occur. Erythromycin, domperidone (Motilium), or metoclopramide (Reglan) may be used to relieve delayed stomach emptying caused by neuropathy.

Erectile dysfunction is also associated with neuropathy. Evidence shows that phosphodiesterase type 5 (PDE-5) drugs, such as sildenafil (Viagra), vardenafil (Levitra), and tadalafil (Cialis), are safe and effective, at least in the short term, for patients with diabetes. Typical side effects are minimal but may include headache, flushing, and upper respiratory tract and flu-like symptoms.

Perhaps the most serious consequences of diabetic neuropathy occur in the lower limbs. An estimated 15% of patients with diabetes experience serious foot problems. They are the leading cause of hospitalizations for these patients.

Diabetes is responsible for more than half of all lower limb amputations performed in the U.S. Each year there are about 88,000 non-injury amputations, 50 - 75% of them due to diabetes. The number is increasing as the prevalence in diabetes type 2 rises. According to a 2005 study in the Lancet, every 30 seconds someone in the world receives a lower limb amputation due to diabetes. About 85% of amputations start with foot ulcers, which develop in about 12% of people with diabetes.

In general, foot ulcers develop from infections, such as those resulting from blood vessel injury. A 2006 study reported that people with diabetes who develop foot infections are 155 times more likely to have an amputation than people who did not develop infections. Foot infections often develop from injuries. Even minor infections can develop into severe complications. Numbness from nerve damage, which is common in diabetes, compounds the danger since the patient may not be aware of injuries. About one-third of foot ulcers occur on the big toe.

A 2003 government survey found that those at higher risk for foot ulcers tend to be people with diabetes who are overweight, smokers, and those with a long history of diabetes. People who have the disease for more than 20 years and are insulin-dependent are at the highest risk. Related conditions that put people at risk include peripheral neuropathy, peripheral artery disease, foot deformities, and a history of ulcers. [See In-Depth Report #102: Peripheral artery disease and intermittent claudication.]

Charcot Foot. Charcot foot or Charcot joint (medically referred to as neuropathic arthropathy) occurs in about 2.5% of people with diabetes. Early changes appear like an infection, with the foot becoming swollen, red, and warm. A seriously affected foot can become deformed. The bones may crack, splinter, and erode, and the joints may shift, change shape, and become unstable. It typically develops in people who have neuropathy to the extent that they cannot feel sensation in the foot and are not aware of an existing injury. Instead of resting an injured foot or seeking medical help, the patient often continues normal activity, causing further damage.

Charcot foot is initially treated with strict immobilization of the foot and ankle; some centers use a cast that allows the patient to move and still protects the foot. A 2001 study in the U.K. concluded that a single dose of pamidronate, a bisphosphonate, reduces bone turnover, symptoms, and disease activity. When the acute phase has passed, patients usually need lifelong protection of the foot using a brace initially and custom footwear.

Measures to Prevent Foot Ulcers. Preventive foot care can significantly reduce the risk of ulcers and amputation. Some tips for preventing problems include:

Patients should inspect their feet daily and watch for changes in color or texture, odor, and firm or hardened areas, which may indicate infection and potential ulcers.
When washing the feet, the water should be warm (not hot), and the feet and areas between the toes should be thoroughly dried afterward. Check water temperature with the hand or a thermometer before stepping in.
Moisturizers should be applied, but not between the toes.
Corns and calluses should be gently pumiced and toenails trimmed short and the edges filed to avoid cutting adjacent toes.
Patients should not use medicated pads or try to shave the corns or calluses themselves.
Well-fitting footwear is very important. People should be sure the shoe is wide enough; according to a 2001 study, 30% of patients with diabetes wear shoes that are too narrow. Patients should also avoid high heels, sandals, thongs, and going barefoot. Shoes with a rocker sole reduce pressure under the heel and front of the foot by 35 - 65% and may be particularly helpful. Custom-molded boots increase the surface area over which foot pressure is distributed. This reduces stress on the ulcers and allows them to heal.
Shoes should be changed often during the day.
Wear socks, particularly with extra padding (which can be specially purchased).
Patients should avoid tight stockings or any clothing that constricts the legs and feet.
Foot pain, numbness, or tingling is worse at night; diphenhydramine (Benadryl) may help.
A specialist in foot care should be consulted for any problems.

People with diabetes are prone to foot problems because the disease can cause damage to the blood vessels and nerves, which may result in decreased ability to sense trauma to the foot. The immune system is also altered, so that the patient cannot efficiently fight infection.

Treating Foot Ulcers in Diabetes. About one-third of foot ulcers will heal within 20 weeks with good wound care treatments. Treatments include:

Antibiotics are generally given. In some cases, hospitalization and intravenous antibiotics for up to 28 days may be needed for severe foot ulcers.
In virtually all cases, wound care requires debridement, which is the removal of injured tissue until only healthy tissue remains. Debridement may be accomplished using chemical (enzymes), surgical, or mechanical (irrigation) means.
Hydrogels (Nu-Gel, Intrasite Gel, Scherisorb, Clearsite, Duoderm, Geliperm) are helpful in healing ulcers and are noninvasive and soothing.
Felted foam may be helpful in healing ulcers on the sole of the foot. Felted foam uses a multi-layered foam pad over the bottom of the foot with an opening over the ulcer.

Other Treatments for Foot Ulcers. Doctors are also using or investigating other treatments to heal ulcers. These include:

Administering hyperbaric oxygen (oxygen given at high pressure) is showing promise in promoting healing. In one study, patients who had had ulcers that had not responded to treatment for over 3 months received daily treatments that lasted 90 minutes for 2 weeks. About 15 days after completion, patients who received oxygen had significant reduction in ulcers, sometimes with complete healing. Other studies are also demonstrating good results.
Monochromatic near-infrared photo energy (MIRE) uses light therapy to improve sensation in the feet of patients with peripheral neuropathy.
Total-contact casting (TCC) uses a cast that is designed to match the exact contour of the foot and to distribute weight along the entire length of the foot. It is usually changed weekly. It may be helpful for ulcer healing and for Charcot foot. Although it is very effective in healing ulcers, recurrence is common.

Diabetes accounts for 12,000 - 24,000 of new cases of blindness annually and is the leading cause of new cases of blindness in adults age 20 - 74. The most common eye disorder in diabetes is retinopathy. People with diabetes are also at higher risk for developing cataracts and certain types of glaucoma, such as primary-open angle glaucoma (POAG). The risk for POAG is especially high for women with type 2 diabetes. [See In-Depth Report #26: Cataracts and In-Depth Report #25: Glaucoma.]

Description of Retinopathy. Retinopathy is a condition in which the retina in the eye becomes damaged. The two primary abnormalities that occur are a weakening of the blood vessels in the retina and the obstruction in the capillaries -- probably from very tiny blood clots. Retinopathy generally occurs in one or two phases:

Click the icon to see an image of diabetic retinopathy.

The early and more common type of this disorder is called nonproliferative or background retinopathy. The blood vessels in the retina are abnormally weakened. They rupture and leak, and waxy areas may form. If these processes affect the central portion of the retina, swelling may occur, causing reduced or blurred vision.
If the capillaries become blocked and blood flow is cut off, soft, "woolly" areas may develop in the retina's nerve layer. These woolly areas may signal the development of proliferative retinopathy. Often there are no symptoms of progressing retinopathy. In this more severe condition, new abnormal blood vessels form and grow on the surface of the retina. They may spread into the cavity of the eye or bleed into the back of the eye. Major hemorrhage or retinal detachment can result, causing severe visual loss or blindness. The sensation of seeing flashing lights may indicate retinal detachment.

Click the icon to see an animation on diabetic retinopathy.

According to a 2003 study, about 40% of young adults with type 1 diabetes had developed retinopathy within 10 years of diagnosis. (Although this rate is high, it is significantly lower than in previous years when blood glucose control was not as strict.) The risk is lower in patients with type 2 diabetes, although in one study over 20% had signs of retinopathy 6 years after diagnosis. Patients who are newly diagnosed with type 2 diabetes should get a comprehensive eye examination, including dilation. In general, all patients with diabetes should have a yearly eye examination. Patients with no signs of retinal damage or low risk factors for retinopathy may only require screening every 2 - 3 years.

Prevention of Retinopathy. Fortunately, severe and even moderate vision loss is largely preventable with tight control of blood glucose levels. (Intense glucose control can cause early worsening of retinopathy, although this is nearly always counterbalanced by long-term benefits.) Tight control of blood pressure can also help protect against retinopathy. Aspirin therapy does not help prevent retinopathy.

Treatment of Retinopathy. Patients with severe diabetic retinopathy or macular edema (swelling of the retina) should be sure to see an eye specialist who is experienced in the management and treatment of diabetic retinopathy. Once damage to the eye develops, laser eye surgery may be needed. Laser surgery can help reduce vision loss in high-risk patients.

Studies indicate that patients with type 2 diabetes face a higher than average risk of developing dementia caused either by Alzheimer's disease or problems in blood vessels in the brain. Problems in attention and memory can occur even in people under age 55 who have had diabetes for a number of years. In one study of people with type 1 diabetes, high glucose levels (hyperglycemia) were associated with slower brain function, including less verbal fluency and slower ability to do mental arithmetic.

Respiratory Infections. People with diabetes face a higher risk for influenza and its complications, including pneumonia, possibly because the disorder neutralizes the effects of protective proteins on the surface of the lungs. In fact, deaths among people with diabetes increase by 5 - 15% during flu epidemics, and they are six times more likely to be hospitalized with complications from flu than nondiabetic patients who have flu. Everyone with diabetes should have annual influenza vaccinations and a vaccination against pneumococcal pneumonia.

Urinary Tract Infections. Women with diabetes face a significantly higher risk for urinary tract infections, which are likely to be more complicated and difficult to treat than in the general population.

Diabetes doubles the risk for depression. Furthermore, according to one study, depression, in turn, increases the risk for hyperglycemia and complications of diabetes. Restoring mental health, both through medication and psychotherapy, not only improves quality of life but may help patients control their blood sugar levels.

Diabetes changes bone quality and density, but the effects differ, depending on type:

Type 1 diabetes is associated with a slightly reduced bone density, putting patients at risk for osteoporosis and possibly fractures. The best medications for bone loss in patients with diabetes are bisphosphonates, such as alendronate (Fosamax) and risedronate (Actonel). They not only help prevent bone loss but may even reduce daily insulin requirements in patients taking insulin. [See In-Depth Report #18: Osteoporosis.]
Type 2 diabetes, on the other hand, is associated with an increased bone density but is also associated with fractures. In such cases, the bone quality itself may be impaired.

Older patients with either type of diabetes are at risk for falling, which compounds the risk for fracture.

Diabetes increases the risk for other conditions, including:

Hearing loss
Periodontal disease
Carpal tunnel syndrome
Nonalcoholic fatty liver disease, also called nonalcoholic steatohepatitis (NASH), a particular danger for people who are obese
Colorectal cancer
Uterine cancer

Emergency Complications

People with diabetes who need to intensively control glucose levels are at risk for low blood sugar (hypoglycemia). Hypoglycemia, also called insulin shock, develops if blood sugar levels fall below normal. It may also be caused by insufficient intake of food, excess exercise, or alcohol intake. The condition is usually manageable, but occasionally it can be severe or even life threatening, particularly if the patient fails to recognize the symptoms. Mild hypoglycemia is common among people with type 2 diabetes, but severe episodes are rare, even among those who are taking insulin. Still, all patients who intensively control blood sugar (glucose) levels should be aware of warning symptoms.

Risk Factors for Severe Hypoglycemia. People at highest risk for severe hypoglycemia are those who intensively control blood glucose and also have one or more of the following conditions:

Long-term diabetes
Less education on their condition
A previous history of severe hypoglycemia
Hypoglycemia unawareness

Hypoglycemia unawareness is a condition in which people become insensitive to hypoglycemic symptoms. It affects about 25% of patients who use insulin, nearly always people with type 1 diabetes. In such cases, hypoglycemia appears suddenly, without warning, and can escalate to a severe level. Even a single recent episode of hypoglycemia may make it more difficult to detect the next episode. With vigilant monitoring and by rigorously avoiding low blood glucose levels, patients can often regain the ability to sense the symptoms. However, even very careful testing may fail to detect a problem, particularly one that occurs during sleep.

Symptoms. Mild hypoglycemia symptoms usually occur at moderately low and easily correctable levels of blood glucose. They include:

Sweating
Trembling
Hunger
Rapid heartbeat

Severely low blood glucose levels can cause neurologic symptoms, such as:

Confusion
Weakness
Disorientation
Combativeness
In rare and worst cases, coma, seizure, and death

Preventive Measures. The following tips may help avoid hypoglycemia or prepare for attacks:

Patients are at highest risk for hypoglycemia at night. Bedtime snacks may be helpful.
Patients who intensively control their blood sugar should monitor blood levels as often as possible, four times or more per day. This is particularly important for patients with hypoglycemia unawareness.
In adults, it is also particularly critical to monitor blood glucose levels before driving, when hypoglycemia can be very hazardous.
Patients who use medications that put them at risk for hypoglycemia should always carry hard candy, juice, sugar packets, or commercially available glucose substitutes designed for individuals with diabetes.

Family and friends should be aware of the symptoms and be prepared:

If the patient is helpless (but not unconscious), family or friends should administer three to five pieces of hard candy, two to three packets of sugar, half a cup (four ounces) of fruit juice, or a commercially available glucose solution.
If there is inadequate response within 15 minutes, additional oral sugar should be provided or the patient should receive emergency medical treatment, including intravenous administration of glucose.
Family members and friends can learn to inject glucagon, a hormone, which, in contrast to insulin, raises blood glucose.

Click the icon to see a glucagon kit.

Diabetic ketoacidosis (DKA) is a life-threatening complication caused by insulin depletion. Until recently, it was a complication almost exclusively of type 1 diabetes. In such cases, it is nearly always due to noncompliance with insulin treatments. However, DKA is being reported increasingly in type 2 diabetes, especially among Hispanic- and African-Americans. It is not clear what causes total insulin depletion in these patients. Researchers are trying to learn which individuals are at particular risk.

Diabetic ketoacidosis often develop as follows:

The process is usually triggered in insulin-deficient patients by a stressful event, most often pneumonia or urinary tract infections. Other triggers include alcohol abuse, physical injury, pulmonary embolism, heart attacks, or other illnesses.
Severely low insulin levels cause excessive amounts of glucose in the bloodstream (hyperglycemia).
Fat breakdown then accelerates and increases the production of fatty acids.
These fatty acids are converted into chemicals called ketone bodies, which are toxic at high levels.

Symptoms and complications may include:

Nausea and vomiting
Abnormally deep and rapid breathing with frequent sighing
Rapid heartbeat
If the condition persists, coma and, eventually, death, may occur; however, over the past 20 years, death from DKA has decreased to about 2% of all cases.
Other serious complications from DKA include aspiration pneumonia and adult respiratory distress syndrome.

Life-saving treatment uses rapid rehydration with a saline solution followed by low-dose insulin and potassium replacement.

Resources

www.diabetes.org -- American Diabetes Association
www.niddk.nih.gov -- National Institute of Diabetes and Digestive and Kidney Diseases
www.americanheart.org -- American Heart Association
www.kidney.org -- National Kidney Foundation
www.nei.nih.gov -- National Eye Institute
www.medicalert.org -- Medic Alert
www.eatright.org -- American Dietetic Association
http://limaye.ecri.org -- Limaye Center

References

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Review Date:
7/31/2007
Reviewed By:
Harvey Simon, MD, Associate Professor of Medicine, Harvard Medical School; Physician, Massachusetts General Hospital.

A.D.A.M. Copyright

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