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National Institute of Dental and
Craniofacial Research
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 a blister.
Both canker sores and fever blisters have plagued mankind for thousands of years. Scientists at the National Institute of Dental and Craniofacial 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.
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.
Fever blisters are caused by a contagious virus called herpes simplex. Them are two types of herpes simplex virus. Type 1 usually causes oral herpes, or fever blisters. Type 2 usually causes genital herpes. Although both type 1 and type 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 1 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 1 to 3 days before the blister appears.
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. Research 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.
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.
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 and Craniofacial 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.
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 much 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 outbreaks are triggered by sunlight. Scientists at the National Institute of Dental and Craniofacial Research have confirmed that sunscreen on the lips can prevent sun-induced recurrences of herpes. They recommend applying the sunscreen before going outside and reapplying it frequently during sun exposure. The researchers used a sunblock 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, however, been proven effective in controlled studies.
Researchers are working on several approaches to preventing 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 recurrent 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.
Recurrent canker sores afflict about 20 percent of the general population. The medical term for the sores is aphthous stomatitis.
Canker sores are usually found on the movable parts of the mouth such as the tongue or the inside linings of the lips and cheeks. They begin as small oval or round reddish swellings, which usually burst within a day. The ruptured sores are covered by a thin white or yellow membrane and edged by a red halo. Generally, they heal within 2 weeks. Canker sores range in size from an eighth of an inch wide in mild cases to more than an inch wide in severe cases. Severe canker sores may leave scars. Fever is rare, and the sores are rarely associated with other diseases. Usually a person will have only one or a few canker sores at a time.
Most people have their first bout with canker sores between the ages of 10 and 20. Children as young as 2, however, may develop the condition. The frequency of canker sore recurrences varies considerably. Some people have only one or two episodes a year, while others may have a continuous series of canker sores.
The cause of canker sores is not well understood. More than one cause is likely, even for individual patients. Canker sores do not appear to be caused by viruses or bacteria, although an allergy to a type of bacterium commonly found in the mouth may trigger them in some people. The sores may be an allergic reaction to certain foods. In addition, there is research suggesting that canker sores may be caused by a faulty immune system that uses the body's defenses against disease to attack and destroy the normal cells of the mouth or tongue.
British studies show that, in about 20 percent of patients, canker sores are due partly to nutritional deficiencies, especially lack of vitamin B12, folic acid and iron. Similar studies performed in the United States, however, have not confirmed this finding. In a small percentage of patients, canker sores occur with gastrointestinal problems, such as an inability to digest certain cereals. In these patients, canker sores appear to be part of a generalized disorder of the digestive tract.
Female sex hormones apparently play a role in causing canker sores. Many women have bouts of the sores only during certain phases of their menstrual cycles. Most women experience improvement or remission of their canker sores during pregnancy. Researchers have used hormone therapy successfully in clinical studies to treat some women.
Both emotional stress and injury to the mouth can trigger outbreaks of canker sores, but these factors probably do not cause the disorder.
Women are more likely than men to have recurrent canker sores. Genetic studies show that susceptibility to recurrent outbreaks of the sores is inherited in some patients. This partially explains why the disorder is often shared by family members.
Most doctors recommend that patients who have frequent bouts of canker sores undergo blood and allergy tests to determine if their sores are caused by a nutritional deficiency, an allergy or some other preventable cause. Vitamins and other nutritional supplements often prevent recurrences or reduce the severity of canker sores in patients with a nutritional deficiency. Patients with food allergies can reduce the frequency of canker sores by avoiding those foods.
There are several treatments for reducing the pain and duration of canker sores for patients whose outbreaks cannot be prevented. These include numbing ointments such as benzocaine, which are available in drug stores without a prescription. Anti-inflammatory steroid mouthrinses or gels can be prescribed for patients with severe sores.
Mouthrinses containing the antibiotic tetracycline may reduce the unpleasant symptoms of canker sores and speed healing by preventing bacterial infections in the sores. Clinical studies at the National Institute of Dental and Craniofacial Research have shown that rinsing the mouth with tetracycline several times a day usually relieves pain in 24 hours and allows complete healing in 5 to 7 days. The U.S. Food and Drug Administration warns, however, that tetracycline given to pregnant women and young children can permanently stain youngsters' teeth. Both steroid and tetracycline treatments require a prescription and care of a dentist or physician.
Patients with severe recurrent canker sores may need to take steroid or other immuno-suppressant drugs orally. These potent drugs can cause many undesirable side effects, and should be used only under the close supervision of a dentist or physician.
If you have canker sores, avoid abrasive foods such as potato chips that can stick in the cheek or gum and aggravate the sores. Take care when brushing your teeth not to stab the gums or cheek with a toothbrush bristle. Avoid acidic and spicy foods. Canker sores are not contagious, so patients do not have a worry about spreading them to other people.
Researchers are trying to identify the malfunctions in patients' immune systems that make them susceptible to recurrent bouts of canker sores. By analyzing the blood of people with and without canker sores, scientists have found several differences in immune function between the two groups. Whether these differences cause canker sores is not yet known.
Researchers also are developing and testing new drugs designed to treat canker sores. Most of these drugs alter the patients' immune function. Although some of the drugs appear to be effective in treating canker sores in some patients, the data are still inconclusive. Until these drugs are proven to be absolutely safe and effective, they will not be available for general use.
Public Information and Reports Section
Office of Planning, Evaluation and Communications
National Institute of
Dental Research
Bethesda, Maryland 20892
U.S. DEPARTMENT OF HEALTH AND HUMAN
SERVICES
Public Health Service
National Institutes of Health
NIH
Publication No. 92-247
Revised July 1992
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