Erythema multiforme

Definition

Genital herpes is a sexually transmitted disease caused by a herpes virus. The disease is characterized by the formation of fluid-filled, painful blisters in the genital area.

Description

Genital herpes (herpes genitalis, herpes progenitalis) is characterized by the formation of fluid-filled blisters on the genital organs of men and women. The word "herpes" comes from the Greek adjective herpestes, meaning creeping, which refers to the serpent-like pattern that the blisters may form. Genital herpes is a sexually transmitted disease which means that it is spread from person-to-person only by sexual contact. Herpes may be spread by vaginal, anal, and oral sexual activity. It is not spread by objects (such as a toilet seat or doorknob), swimming pools, hot tubs, or through the air.

Genital herpes is a disease resulting from an infection by a herpes simplex virus. There are eight different kinds of human herpes viruses. Only two of these, herpes simplex types 1 and 2, can cause genital herpes. It has been commonly believed that herpes simplex virus type 1 infects above the waist (causing cold sores) and herpes simplex virus type 2 infects below the waist (causing genital sores). This is not completely true. Both herpes virus type 1 and type 2 can cause herpes lesions on the lips or genitals, but recurrent cold sores are almost always type 1. The two viruses seem to have evolved to infect better at one site or the other, especially with regard to recurrent disease.

To determine the occurrence of herpes type 2 infection in the United States, the Centers for Disease Control and Prevention (CDC) used information from a survey called the National Health and Nutrition Examination Survey III (1988-1994). This survey of 40,000 noninstitutionalized people found that 21.9% of persons age 12 or older had antibodies to herpes type 2. This means that 45 million Americans have been exposed at some point in their lives to herpes simplex virus type 2. More women (25.6%) than men (17.8%) had antibodies. The racial differences for herpes type 2 antibodies were whites, 17.6%; blacks, 45.9%; and Mexican Americans, 22.3%. Interestingly, only 2.6% of adults reported that they have had genital herpes. Over half (50% to 60%) of the white adults in the United States have antibodies to herpes simplex virus type 1. The occurrence of antibodies to herpes type 1 is higher in blacks.

Viruses are different from bacteria. While bacteria are independent and can reproduce on their own, viruses cannot reproduce without the help of a cell. Viruses enter human cells and force them to make more virus. A human cell infected with herpes virus releases thousands of new viruses before it is killed. The cell death and resulting tissue damage causes the actual sores. The highest risk for spreading the virus is the time period beginning with the appearance of blisters and ending with scab formation.

Herpes virus can also infect a cell and instead of making the cell produce new viruses, it hides inside the cell and waits. Herpes virus hides in cells of the nervous system called "neurons." This is called "latency." A latent virus can wait inside neurons for days, months, or even years. At some future time, the virus "awakens" and causes the cell to produce thousands of new viruses which causes an active infection. Sometimes an active infection occurs without visible sores. Therefore, an infected person can spread herpes virus to other people even in the absence of sores.

This process of latency and active infection is best understood by considering the genital sore cycle. An active infection is obvious because sores are present. The first infection is called the "primary" infection. This active infection is then controlled by the body's immune system and the sores heal. In between active infections, the virus is latent. At some point in the future latent viruses become activated and once again cause sores. These are called "recurrent infections" or "outbreaks." Genital sores caused by herpes type 1 recur much less frequently than sores caused by herpes type 2.

Although it is unknown what triggers latent viruses to activate, several conditions seem to bring on infections. These include illness, tiredness, exposure to sunlight, menstruation, skin damage, food allergy and hot or cold temperatures. Although many people believe that stress can bring on their genital herpes outbreaks, there is no scientific evidence that there is a link between stress and recurrences. However, at least one clinical study has shown a connection between how well people cope with stress and their belief that stress and recurrent infections are linked.

Newborn babies who are infected with herpes virus experience a very severe, and possibly fatal disease. This is called "neonatal herpes infection." In the United States, one in 3,000-5,000 babies born will be infected with herpes virus. Babies can become infected during passage through the birth canal, but can become infected during the pregnancy if the membranes rupture early. Doctors will perform a Cesarean section on women who go into labor with active genital herpes.

Causes & symptoms

While anyone can be infected by herpes virus, not everyone will show symptoms. Risk factors for genital herpes include: early age at first sexual activity, multiple sexual partners, and a medical history of other sexually-transmitted diseases.

Most patients with genital herpes experience a prodrome (symptoms of oncoming disease) of pain, burning, itching, or tingling at the site where blisters will form. This prodrome stage may last anywhere from a few hours, to one to two days. The herpes infection prodrome can occur for both the primary infection and recurrent infections. The prodrome for recurrent infections may be severe and cause a severe burning or stabbing pain in the genital area, legs, or buttocks.

Primary genital herpes

The first symptoms of herpes usually occur within two to seven days after contact with an infected person but may take up to two weeks. Symptoms of the primary infection are usually more severe than those of recurrent infections. For up to 70% of the patients, the primary infection causes symptoms which affect the whole body (called "constitutional symptoms") including tiredness, headache, fever, chills, muscle aches, loss of appetite, as well as painful, swollen lymph nodes in the groin. These symptoms are greatest during the first three to four days of the infection and disappear within one week. The primary infection is more severe in women than in men.

Following the prodrome come the herpes blisters, which are similar on men and women. First, small red bumps appear. These bumps quickly become fluid-filled blisters. In dry areas, the blisters become filled with pus and take on a white to gray appearance, become covered with a scab, and heal within two to three weeks. In moist areas, the fluid-filled blisters burst and form painful ulcers which drain before healing. New blisters may appear over a period of one week or longer and may join together to form very large ulcers. The pain is relieved within two weeks and the blisters and ulcers heal without scarring by three to four weeks.

Women can experience a very severe and painful primary infection. Herpes blisters first appear on the labia majora (outer lips), labia minora (inner lips), and entrance to the vagina. Blisters often appear on the clitoris, at the urinary opening, around the anal opening, and on the buttocks and thighs. In addition, women may get herpes blisters on the lips, breasts, fingers, and eyes. The vagina and cervix are almost always involved which causes a watery discharge. Other symptoms that occur in women are: painful or difficult urination (83%), swelling of the urinary tube (85%), meningitis (36%), and throat infection (13%). Most women develop painful, swollen lymph nodes (lymphadenopathy) in the groin and pelvis. About one in ten women get a vaginal yeast infection as a complication of the primary herpes infection.

In men, the herpes blisters usually form on the penis but can also appear on the scrotum, thighs, and buttocks. Fewer than half of the men with primary herpes experience the constitutional symptoms. Thirty percent to 40% of men have a discharge from the urinary tube. Some men develop painful swollen lymph nodes (lymphadenopathy) in the groin and pelvis. Although less frequently than women, men too may experience painful or difficult urination (44%), swelling of the urinary tube (27%), meningitis (13%), and throat infection (7%).

Recurrent genital herpes

One or more outbreaks of genital herpes per year occur in 60-90% of those infected with herpes virus. About 40% of the persons infected with herpes simplex virus type 2 will experience six or more outbreaks each year. Genital herpes recurrences are less severe than the primary infection; however, women still experience more severe symptoms and pain than men. Constitutional symptoms are not usually present. Blisters will appear at the same sites during each outbreak. Usually there are fewer blisters, less pain, and the time period from the beginning of symptoms to healing is shorter than the primary infection. One out of every four women experience painful or difficult urination during recurrent infection. Both men and women may develop lymphadenopathy.

Diagnosis

Because genital herpes is so common, it is diagnosed primarily by symptoms. It can be diagnosed and treated by the family doctor, dermatologists (doctors who specialize in skin diseases), urologists (doctors who specialize in the urinary tract diseases of men and women and the genital organs of men), gynecologists (doctors who specialize in the diseases of women's genital organs) and infectious disease specialists. The diagnosis and treatment of this infectious disease should be covered by most insurance providers.

Laboratory tests may be performed to look for the virus. Because healing sores do not shed much virus, a sample from an open sore would be taken for viral culture. A sterile cotton swab would be wiped over open sores and the sample used to infect human cells in culture. Cells which are killed by herpes virus have a certain appearance under microscopic examination. The results of this test are available within two to ten days. Other areas which may be sampled, depending upon the disease symptoms in a particular patient, include the urinary tract, vagina, cervix, throat, eye tissues, and cerebrospinal fluid.

Direct staining and microscopic examination of the lesion sample may also be used. A blood test may be performed to see if the patient has antibodies to herpes virus. The results of blood testing are available within one day. The disadvantage of this blood test is that it usually does not distinguish between herpes type 1 and 2, and only determines that the patient has had a herpes infection at some point in his or her life. Therefore, the viral culture test must be performed to be absolutely certain that the sores are caused by herpes virus.

Because genital sores can be symptoms of many other diseases, the doctor must determine the exact cause of the sores. The above mentioned tests are performed to determine that herpes virus is causing the genital sores. Other diseases which may cause genital sores are syphilis, chancroid, lymphogranuloma venereum, granuloma inguinale, herpes zoster, erythema multiform, Behçet's syndrome, inflammatory bowel disease, contact dermatitis, candidiasis, and impetigo.

Because most newborns who are infected with herpes virus were born to mothers who had no symptoms of infection it is important to check all newborn babies for symptoms. Any skin sore should be sampled to determine if it is caused by herpes simplex. Babies should be checked for sores in their mouth and for signs of herpes infection in their eyes.

Treatment

There is no cure for herpes virus infections. There are antiviral drugs available which have some effect in lessening the symptoms and decreasing the length of herpes outbreaks. There is evidence that some may also prevent future outbreaks. These antiviral drugs work by interfering with the replication of the viruses and are most effective when taken as early in the infection process as possible. For the best results, drug treatment should begin during the prodrome stage before blisters are visible. Depending on the length of the outbreak, drug treatment could continue for up to 10 days.

Acyclovir (Zovirax) is the drug of choice for herpes infection and can be given intravenously, taken by mouth (orally), or applied directly to sores as an ointment. Acyclovir has been in use for many years and only five out of 100 patients experience side effects. Side effects of acyclovir treatment include nausea, vomiting, itchy rash, and hives. Although acyclovir is the recommended drug for treating herpes infections, other drugs may be used including famciclovir (Famvir), valacyclovir (Valtrex), vidarabine (Vira-A), idoxuridine (Herplex Liquifilm, Stoxil), trifluorothymidine (Viroptic), and penciclovir (Denavir).

Acyclovir is effective in treating both the primary infection and recurrent outbreaks. When taken intravenously or orally, acyclovir reduces the healing time, virus shedding period, and duration of vesicles. The standard oral dose of acyclovir for primary herpes is 200 mg five times daily or 400 mg three times daily for a period of 10 days. Recurrent herpes is treated with the same doses for a period of five days. Intravenous acyclovir is given to patients who require hospitalization because of severe primary infections or herpes complications such as aseptic meningitis or sacral ganglionitis (inflammation of nerve bundles).

Patients with frequent outbreaks (greater than six to eight per year) may benefit from long term use of acyclovir which is called "suppressive therapy." Patients on suppressive therapy have longer periods between herpes outbreaks. The specific dosage used for suppression needs to be determined for each patient and should be reevaluated every few years. Alternatively, patients may use short term suppressive therapy to lessen the chance of developing an active infection during special occasions such as weddings or holidays.

There are several things that a patient may do to lessen the pain of genital sores. Wearing loose fitting clothing and cotton underwear is helpful. Removing clothing or wearing loose pajamas while at home may reduce pain. Soaking in a tub of warm water and using a blow dryer on the "cool" setting to dry the infected area is helpful. Putting an ice pack on the affected area for 10 minutes, followed by 5 minutes off and then repeating this procedure may relieve pain. A zinc sulfate ointment may help to heal the sores. Application of a baking soda compress to sores may be soothing.

Neonatal herpes

Newborn babies with herpes virus infections are treated with intravenous acyclovir or vidarabine for 10 days. These drugs have greatly reduced deaths and increased the number of babies who appear normal at one year of age. However, because neonatal herpes infection is so serious, even with treatment babies may not survive, or may suffer nervous system damage. Infected babies may be treated with long term suppressive therapy.

Alternative treatment

An imbalance in the amino acids lysine and arginine is thought to be one contributing factor in herpes virus outbreaks. A ratio of lysine to arginine that is in balance (that is more lysine than arginine is present) seems to help the immune system work optimally. Thus, a diet that is rich in lysine may help prevent recurrences of genital herpes. Foods that contain high levels of lysine include most vegetables, legumes, fish, turkey, beef, lamb, cheese, and chicken. Patients may take 500 mg of lysine daily and increase to 1,000 mg three times a day during an outbreak. Intake of the amino acid arginine should be reduced. Foods rich in arginine that should be avoided are chocolate, peanuts, almonds, and other nuts and seeds.

Clinical experience indicates a connection between high stress and herpes outbreaks. Some patients respond well to stress reduction and relaxation techniques. Acupressure and massage may relieve tiredness and stress. Meditation, yoga, tai chi, and hypnotherapy can also help relieve stress and promote relaxation.

Some herbs, including echinacea (Echinacea spp.) and garlic (Allium sativum), are believed to strengthen the body's defenses against viral infections. Red marine algae (family Dumontiaceae), both taken internally and applied topically, is thought to be effective in treating herpes type I and type II infections. Other topical treatments may be helpful in inhibiting the growth of the herpes virus, in minimizing the damage it causes, or in helping the sores heal. Zinc sulphate ointment seems to help sores heal and to fight recurrence. Lithium succinate ointment may interfere with viral replication. An ointment made with glycyrrhizinic acid, a component of licorice (Glycyrrhiza glabra), seems to inactivate the virus. Topical applications of vitamin E or tea tree oil (Melaleuca spp.) help dry up herpes sores. Specific combinations of homeopathic remedies may also be helpful treatments for genital herpes.

Prognosis

Although physically and emotionally painful, genital herpes is usually not a serious disease. The primary infection can be severe and may require hospitalization for treatment. Complications of the primary infection may involve the cervix, urinary system, anal opening, and the nervous system. Persons who have a decreased ability to produce an immune response to infection (called "immunocompromised") due to disease or medication are at risk for a very severe, and possibly fatal, herpes infection. Even with antiviral treatment, neonatal herpes infections can be fatal or cause permanent nervous system damage.

Prevention

The only way to prevent genital herpes is to avoid contact with infected persons. This is not an easy solution because many people aren't aware that they are infected and can easily spread the virus to others. Avoid all sexual contact with an infected person during a herpes outbreak. Because herpes virus can be spread at any time, condom use is recommended to prevent the spread of virus to uninfected partners. As of early 1998 there were no herpes vaccines available, although new herpes vaccines are being tested in humans.

Key Terms

Groin

The region of the body that lies between the abdomen and the thighs.

Latent virus

A nonactive virus which is in a dormant state within a cell. Herpes virus is latent in cells of the nervous system.

Prodrome

Symptoms which warn of the beginning of disease. The herpes prodrome consists of pain, burning, tingling, or itching at a site before blisters are visible.

Recurrence

The return of an active herpes infection following a period of latency.

Ulcer

A painful, pus-draining, depression in the skin caused by an infection.

Further Reading

For Your Information

Books

• Ebel, Charles. Managing Herpes: How to Live and Love With a Chronic STD. American Social Health Association, 1998.
• Sacks, Stephen L. The Truth About Herpes. Gordon Soules Book Publisher, 1997.

  Periodicals

• Murray, Michael T. "Natural Help for Herpes and Cold Sores." Let's Live (April 1997): 68+.

  Other

• JAMA Women's Health Information Center. 1997. Http://www.ama-assn.org/special/std/std.htm (8 April 1998).
• Mayo Health Oasis. 1998. http://www.mayohealth.org (3 March 1998).

Gale Encyclopedia of Medicine. Gale Research, 1999.