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Fever blisters and canker sores are two of the most common disorders of the mouth, causing discomfort and annoyance to millions of Americans. Both cause small sores to develop in or around the mouth, and often are confused with each other. Canker sores, however, occur only inside the mouth- on the tongue and the inside linings of the cheeks, lips and throat. Fever blisters, also called cold sores, usually occur outside the mouth-on the lips, chin, cheeks or in the nostrils. When fever blisters do occur inside the mouth, it is usually on the gums or the roof of the mouth. Inside the mouth, fever blisters are smaller than canker sores, heal more quickly, and often begin as blisters. Both canker sores and fever blisters have plagued man- kind for thousands of years. Scientists at the National Institute of Dental Research, one of the federal government's National Institutes of Health, are seeking ways to better control and ultimately prevent these and other oral disorders.

Fever Blisters

In ancient Rome, an epidemic of fever blisters prompted Emperor Tiberius to ban kissing in public ceremonies. Today fever blisters still occur in epidemic proportions. About 100 million episodes of recurrent fever blisters occur yearly in the United States alone. An estimated 45 to 80 percent of adults and children in this country have had at least one bout with the blisters.


What causes fever blisters?

Fever blisters are caused by a contagious virus called herpes simplex. There are two types of herpes simplex virus. Type 1 usually causes oral herpes, or fever blisters. Type ' usually causes genital herpes. Although both type I and typ4 2 viruses can infect oral tissues, more than 95 percent of recurrent fever blister outbreaks are caused by the type 1 virus.

Herpes simplex virus is highly contagious when fever blisters are present, and the virus frequently is spread by kissing. Children often become infected by contact with parents, siblings or other close relatives who have fever blisters. A child can spread the virus by rubbing his or her cold sore and then touching other children. About 10 percent of oral herpes infections in adults result from oral-genital sex with a person who has active genital herpes (type 2). These infections, however, usually do not result in repeat bouts of fever blisters.

Most people infected with the type I herpes simplex virus became infected before they were 10 years old. The virus usually invades the moist membrane cells of the lips, throat or mouth. In most people, the initial infection causes no symptoms. About 15 percent of patients, however, develop many fluid-filled blisters inside and outside the mouth 3 to 5 days after they are infected with the virus. These may be accompanied by fever, swollen neck glands and general aches. The blisters tend to merge and then collapse. Often a yellowish crust forms over the sores, which usually heal without scarring within 2 weeks.

The herpes virus, however, stays in the body. Once a person is infected with oral herpes, the virus remains in a nerve located near the cheekbone. It may stay permanently inactive in this site, or it may occasionally travel down the nerve to the skin surface, causing a recurrence of fever blisters. Recurring blisters usually erupt at the outside edge of the lip or the edge of the nostril, but can also occur on the chin, cheeks, or inside the mouth. The symptoms of recurrent fever blister attacks usually are less severe than those experienced by some people after an initial infection. Recurrences appear to be less frequent after age 35. Many people who have recurring fever blisters feel itching, tingling or burning in the lip I to 3 days before the blister appears.


What causes a recurrence of Fever Blisters?

Several factors weaken the body's defenses and trigger an outbreak of herpes. These include emotional stress, fever illness, injury and exposure to sunlight. Many women have recurrences only during menstruation. One study indicates, that susceptibility to herpes recurrences is inherited. Re search is under way to discover exactly how the triggering factors interact with the immune system and the virus to prompt a recurrence of fever blisters.


What are the treatments for fever blisters?

Currently there is no cure for fever blisters. Some medications can relieve some of the pain and discomfort associated with the, sores, however. These include ointments that numb the blisters, antibiotics that control secondary bacterial infections, and ointments that soften the crusts of the sores.

Is there a vaccine for fever blisters?

Currently there is no vaccine for herpes simplex virus available to the public. Many research laboratories, however, are working on this approach to preventing fever blisters. For example, scientists at the National Institute of Dental Research and the National Institute of Allergy and Infectious Diseases have developed a promising experimental herpes vaccine. In tests on laboratory mice, the vaccine has prevented the herpes simplex virus from infecting the animals and establishing itself in the nerves.

Although these findings are encouraging, the scientists must complete more animal studies on the safety and effectiveness of the vaccine before a decision can be made whether to test it in humans. The vaccine would be useful only for those not already infected with herpes simplex virus.

What can the patient do?

If fever blisters erupt, keep them clean and dry to prevent bacterial infections. Eat a soft, bland diet to avoid irritating the sores and surrounding sensitive areas. Be careful not to touch the sores and spread the virus to new sites, such as the eyes or genitals. To make sure you do not infect others, avoid kissing them or touching the sores and then touching another person. There is good news for people whose fever blister out- breaks are triggered by sunlight. Scientists at the National Institute of Dental Research have confirmed that sunscreen on the lips can prevent sun-induced recurrences of herpes. They recommend applying the sunscreen before going out- side and reapplying it frequently during sun exposure. The researchers used a sun block with a protection factor of 15 in their studies. Little is known about how to prevent recurrences of fever blisters triggered by factors other than sunlight. People whose cold sores appear in response to stress should try to avoid stressful situations. Some investigators have suggested adding lysine to the diet or eliminating foods such as nuts, chocolate, seeds or gelatin. These measures have not, how- ever, been proven effective in controlled studies.

What research is being done?

Researchers are working on several approaches to pre- venting or treating fever blisters. As mentioned earlier, they are trying to develop a vaccine against herpes simplex virus. Several laboratories are developing and testing antiviral drugs designed to hamper or prevent fever blister outbreaks. Researchers also are trying to develop ointments that make it easier for antiviral drugs to penetrate the skin.

Acyclovir is an antiviral drug that prevents the herpes simplex virus from multiplying. The U.S. Food and Drug Administration has approved the drug for use in treating genital herpes, and is considering its approval for use in treating oral herpes. Researchers have found that acyclovir taken in pill form reduces the symptoms and frequency of fever blister recurrences in some patients. In one study, 50 percent of patients who took four acyclovir pills daily for 4 months had no fever blister outbreaks. Before taking the drug, they had an average of one recurrence every 2 months. In separate studies, pills taken at the onset of symptoms or acyclovir cream applied to the blisters or to areas of the lip that tingled or itched were found to be only minimally effective. The long-term effects of daily oral doses of acyclovir are not known, nor are the effects the drug might have on an unborn child.

Basic research on how the immune system interacts with herpes simplex viruses may lead to new therapies for fever blisters. The immune system uses a wide array of cells and chemicals to defend the body against infections. Scientists are trying to identify the immune components that prevent recur- rent attacks of oral herpes. Scientists are also trying to determine the precise form and location of the inactive herpes virus in nerve cells. This information might allow them to design antiviral drugs that can attack the herpes virus while it lies dormant in nerves. In addition, researchers are trying to understand how sunlight, skin injury and stress can trigger recurrences of fever blisters. They hope to develop methods for blocking reactivation of the virus.