Genital Herpes

Definition

Genital herpes (herpes genitalis) is a highly contagious sexually transmitted disease (STD) caused by a strain of the herpes simplex virus (HSV). Genital herpes invades the body through mucous membranes, also known as small breaks in the skin.

Description

Genital herpes is characterized by pain, itching, and sores (i.e., blister-like lesions) in the genital areas of the body, including the penis, scrotum, labia, vagina, urethra, anus, upper thighs, groin, or buttocks. Herpes simplex virus (HSV) appears in two recognized forms: HSV type 1 and HSV type 2. Previously, it was believed that HSV type 1 only affected the upper body and the face, especially the mouth, appearing often as cold sores. HSV type 2 was believed to be the infecting organism in genital HSV infections. By 2001, it became known that either HSV type can cause infections in either area of the body (i.e., 15% of all genital herpes infections are caused by HSV type 1, and are believed to be the result of oral-to-genital contact). It is not spread by objects (e.g., toilet seat or doorknob), swimming pools, hot tubs, or through the air.

Herpes viruses are not new to the modern medicine. The name is derived from the Greek adjective, herpestes, which means "creeping," and refers to the serpent-like pattern often formed by the water blisters (vesicles) of genital herpes. Other members of the herpes virus family share similar traits, also infecting human beings. These traits include varicella zoster virus, the source of both chickenpox and shingles. Epstein-Barr virus, another member of the herpes virus family, is the cause of mononucleosis.

As of 2004, in the United States, there are an estimated 60 million adolescents and adults infected with HSV infection with 500,000 new cases diagnosed each year, according to the National Institute of Allergy and Infectious Diseases (NIAID), part of the National Institutes of Health (NIH). A 2002 report in the journal Sexually Transmitted Diseases estimates that by 2025, 50% of all women and 40% of all men in the U.S. could suffer from genital herpes. If those figures become reality, more than 150 million Americans will have genital herpes by 2025. The disease is slightly more common in women, possibly because male-to-female transmission of the virus is more effective; it attacks one out of every four women. In contrast, one out of every five men contract genital herpes, and a greater percentage of black versus white males (i.e., 45.9% vs. 17.6%, respectively) become infected with the virus. According to the web site of the Centers for Disease Control, race and ethnicity in the United States are frequently associated with poverty, access to quality health care, whether health care is sought, illicit drug use, and life in communities with high incidences of STDs. Therefore, it is not surprising that HSV 2 infections are more prevalent among African-Americans (45.9%) than European-Americans (17.6%). Among teenagers, the incidence of genital herpes infections has risen steadily, at 30%, since 1970. That increase, five times higher than it was 20 years ago, is most dramatic among white teenagers in the 12-19. Young adults between the ages of 20 and 29 are now twice as likely to have HSV 2 as they were previously.

Causes and symptoms

While anyone can be infected by the herpes virus, not everyone will have symptoms. Risk factors for genital herpes include early age at first sexual activity, multiple sexual partners, and other STDs.

Most patients with genital herpes experience a prodrome (i.e., symptoms of oncoming disease) that includes pain, burning, itching, or tingling at the site where blisters will form. This prodromal stage may last anywhere from a few hours, to one to two days. The herpes infection prodrome can occur in both the primary infection and recurrent infections. The prodrome for recurrent infections may be intense, and cause 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 patients, the primary infection presents with symptoms that affect the whole body (i.e., "constitutional symptoms"), including tiredness, headache, fever, chills, muscle aches, and loss of appetite. There may also be 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.

Following the prodrome, herpes blisters form; they are similar in 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 scabs, and heal within two to three weeks. In moist areas, the fluid-filled blisters burst, forming painful ulcers that drain before healing. New blisters may appear over a period of one week or more, and may join together to form very large ulcers. The pain is relieved within two weeks; the blisters and ulcers heal, without scarring, by the third to fourth week after the prodrome.

Women may experience a very severe and painful primary infection. Herpes blisters first appear on the vagina's entrance, labia majora (i.e., outer lips), and labia minora (i.e., inner lips). 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, and fingers, and in the eyes (due to spreading from contact with the hands). The vagina and cervix are almost always involved. This causes a watery discharge. Other symptoms that occur in women with primary infections 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 (i.e., 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. Less than half of the men with primary herpes experience the "constitutional symptoms." A significant percentage of men (30-40%) have a discharge from the urinary tube. Some develop lymphadenopathy in the groin and pelvis. Men, although with less frequency than women, 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 the herpes virus. About 40% of 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 appear at the same sites during each outbreak. Usually, there are fewer blisters, less pain, and a shorter time span from symptom onset to healing than in the primary infection. One out of every four women experience painful or difficult urination during recurrent infection. Both men and women may develop lymphadenopathy.

The immune system will naturally create antibodies to fight viruses; herpes viruses are no exception. Herpes viruses, however, share a survival characteristic that makes it very difficult for the immune system to actually eliminate these viruses from the body. Herpes viruses evade antibodies by traveling via nerve pathways and hiding in neurons (i.e., nerve cells). These small colonies of surviving viruses enter what is known as the latent, or dormant phase, and remain that way until reactivated. The mechanisms by which the herpes virus is reactivated are not completely understood. Reactivation, however, can cause further outbreaks of the infection. The latent phase of the herpes virus can last for days, months, or years.

One of the ways that viruses differ from bacteria is in their reproductive ability. While bacteria reproduce independently, viruses require cells from their hosts to do so. When the herpes virus reactivates, it enters cells in its primary site of infection—in this case, the genital region—and causes the cells there to make more virus. Thousands of new herpes virus cells are released into the body's system before each cell dies. This cell death and resulting tissue damage are the actual cause of the lesions that appear during an outbreak of genital herpes. Reactivation of herpes viruses in human beings is specific to each individual, different in both triggers and severity. Evidence, however, supports the prediction that virtually all people infected with HSV type 2 will suffer some form of recurrence; this averages to approximately four times per year. HSV type 1 infections are less likely to suffer further symptomatic outbreaks, with an overall average recurrence rate of once per year. Rates of recurrence tend to diminish over time.

Newborn babies who are infected with herpes virus experience a very severe, potentially fatal disease. This is called "neonatal herpes infection." In the United States, one in every three women of childbearing age are infected with the herpes virus; only one in 2,000 newborns will be born infected. Newborns can be infected during passage through the birth canal or during the pregnancy, should the embryonic sac rupture early. Doctors will normally perform a cesarean section (cs) on women who go into labor with active genital herpes.

All newborn infants should be checked for symptoms of neonatal herpes. Symptoms include skin lesions, listlessness, fever, and lack of appetite. Left untreated, it can cause damage to the infant's brain and central nervous system or death.

The reasons for the reactivation of herpes viruses is not yet completely understood, but research has identified some triggers that are either causative, or suspected of being causative, of recurrent outbreaks.

Among these are:

• prolonged exposure to ultraviolet light (i.e., sunburn), which often reactivates facial herpes infections
• excessive friction or injury to genital areas
• compromise of the strength of the body's immune system, the result of herpes virus' recurrence, and its accompanying symptoms of fatigue and illness
• stress (This has also been considered a prime culprit in bringing about outbreaks. However, clinical research has not proved that there is a causal relationship between stress and reactivation. The investigators of one clinical study have shown a connection between decreased ability to cope with stress and recurrent infections.)
• the presence of HIV (human immunodeficiency virus, which has demonstrated a weakening of the immune system, with a consequent increase in the strength and severity of genital herpes infections)
• the presence of either HSV type 1 or HSV type 2, or both, that are transmitted to others through direct bodily contact (This includes any sexual interaction [i.e., vaginal, anal, or oral], kissing, or skin-to-skin contact. It is passed along with or without the presence of open sores or other prodromal symptoms.)

Notably, HSV infections are symptom free the majority of the time. For this reason, the virus is often transmitted by people infected with HSV who are not even aware that they are infected, or believe that lack of symptoms means that they are not contagious.

Interestingly, an August 2000 report in the New England Journal of Medicine stated that in a University of Washington study, the majority of people who tested positive for HSV 2 infections reported no symptoms whatsoever. Another group of researchers at the University of Washington has assembled a list of ailments about which the subjects complained; they did not know that they had genital herpes. These ailments included:

For women:

• hemorrhoids
• physical irritation from sexual contact
• heat rash
• aching or itching during menses
• allergy to condoms or spermicide
• allergy to elastic in panty hose

For men:

• jock itch
• zipper burn
• hemorrhoids
• acne
• physical irritation from wearing tight jeans

• physical irritation from sexual contact

Genital herpes and HIV

Patients infected with genital herpes simplex virus (HSV) are twice as likely to acquire HIV compared with those who do not have genital herpes. Fifty-two percent of sexually transmitted HIV infections among people who also have herpes simplex virus type 2 can be attributed to infection with the herpes virus. In addition, there is evidence that up to 95% of HIV-positive patients are also infected with HSV-1, HSV-2, or both. According to the Centers for Disease Control and Prevention, HSV-2 infection may play a significant role in the transmission of HIV among heterosexuals because HSV may make patients more susceptible to HIV infection, and HSV may make HIV-infected patients more infectious. Individuals infected with both genital HSV and HIV may experience longer and more severe genital herpes episodes because of their immunocompromised status. HSV may appear in areas of the body other than the skin such as the rectum, the uterus, or the epididymis (a long coiled tube in the testes).

HIV and the herpes virus are a troublesome duo. One can worsen the effects of the other. Research shows that when the herpes virus is active, it may cause HIV to make more copies of itself (the process called replication) than it would otherwise. The more HIV replicates, the more of the body's infection-fighting cells it destroys, eventually leading to AIDS. People infected with both HIV and the herpes virus may have longer-lasting, more frequent, and more severe outbreaks of herpes symptoms, because a weakened immune system can't keep the herpes virus under control as well as a healthy immune system can. It's more difficult to treat genital herpes if the patient also has HIV. Higher doses of antiviral drugs are often needed to treat herpes in people with HIV. Also, many people with HIV have strains of the herpes virus that are resistant to treatment with the standard antiviral drugs. If a patient is taking antiviral drugs for genital herpes and the treatment is not working, their doctor can test the virus for resistance. If the virus is resistant, there are other possible treatment alternatives, including the drugs Foscavir and Vistide. These drugs can be given through an IV, or a Vistide gel can be applied to the herpes sores.

Diagnosis

Because genital herpes is so prevalent, it is diagnosed primarily by the presentation of symptoms. A diagnosis can often be made upon physical examination, and taking of a complete sexual history.

Because a mild case of genital herpes may be overlooked during a routine physical examination, laboratory tests are very important. When possible, it is helpful to know the type of HSV with which a patient is infected. As noted previously, HSV type 2 is potentially life-threatening to newborn infants.

Viral culture is one of the most accurate and specific tests for identifying HSV type 1 or 2. As healing sores do not shed much virus, a sample from an open sore should be taken for viral culture. The doctor must determine the exact cause of the sores. The above-mentioned tests should be performed to confirm that the herpes virus is causing the genital sores.

Other conditions that may produce genital sores are:

• syphilis
• chancroid
• lymphogranuloma venereum
• granuloma inguinale
• herpes zoster
• erythema multiform
• inflammatory bowel disease
• contact dermatitis

• candidiasis
• impetigo

Because of this, a viral culture test should be performed to be absolutely certain that the sores are caused by the HSV.

The results of serological tests (i.e., blood tests [either by finger-stick or blood draw] that reveal antibodies to HSV) are available within one day. They, too, are considered very accurate tests that can be performed whether open lesions are present or not. The disadvantage of this blood test is that it must be taken no earlier than 12 days post-infection; in a first infectious outbreak, antibodies sometimes cannot be detected for three months.

Because most newborns who are infected with herpes virus are born to mothers with no symptoms of infection, it is important to check all newborn babies for symptoms. A culture of any skin sore should be taken to determine if it is caused by HSV. Babies should be checked for sores in their mouths and for signs of herpes infection in their eyes.

Treatment

There is no cure for the herpes virus. There are, however, antiviral drugs available that have some effect in lessening the symptoms and decreasing the length of herpes outbreaks. There is evidence that some of these medications may also prevent future outbreaks.

The 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 a topical ointment. Acyclovir has been in use for many years; only 5 out of 100 patients (5%) 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. They include famciclovir (Famvir), valacyclovir (Valtrex), vidarabine (Vira-A), idoxuridine (Herplex Liquifilm, Stoxil), trifluorothymidine (Viroptic), and penciclovir (Denavir).

Acyclovir is effective in reducing the severity of 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 drug is taken three or five times daily depending on the dose for a period of 10 days. Recurrent herpes is treated with the same doses for a period of five days. Intravenous (IV) acyclovir is given to patients who require hospitalization because of severe primary infections or herpes complications, such as aseptic meningitis or sacral ganglionitis (i.e., inflammation of nerve bundles).

Patients with frequent outbreaks (i.e., greater than six to eight per year) may benefit from longterm use of acyclovir, called "suppressive therapy." Patients on suppressive therapy typically have longer periods between herpes outbreaks. The specific dosage used for suppression would need 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 on special occasions, such as a wedding, or during 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, as may soaking in a tub of warm water and using a blow dryer on the "cool" setting to dry the infected area. Application of an ice pack on the affected area for 10 minutes, followed by five minutes without the ice pack, then repeating this procedure, may relieve pain. A zinc sulfate ointment may also help to heal the sores. Baking soda compresses may be soothing.

Neonatal herpes

Newborn babies with herpes virus infections are treated with acyclovir IV or vidarabine for 10 days. These drugs have greatly reduced neonatal deaths and increased the number of babies who appear normal at one year of age. Infected babies may be treated with long-term suppressive therapy.

Several different vaccines are in various stages of development. These include vaccines made from proteins on the HSV cell surface, peptides or chains of amino acids, and the DNA of the virus itself. NIAID and GlaxoSmithKline are supporting a large clinical trial in women of an experimental vaccine (Herpevac) that may help prevent transmission of genital herpes. The trial is being conducted at more than 35 sites nationwide as of 2005. Topical microbicides, preparations containing microbe-killing compounds, are also in various stages of development and testing. These include gels, creams, or lotions that a woman could insert into the vagina prior to intercourse to prevent infection.

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 (i.e., more lysine than arginine) appears to optimize the function of the immune system work. 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.

Since clinical experience indicates a connection between high stress and herpes outbreaks, some patients may 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 HSV type 1 and 2 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 sulfate 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 life-threatening 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, 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 are not 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 the herpes virus can be spread at any time, condom use is recommended to prevent the spread of virus to uninfected partners. It is also important, however, to realize that condoms cannot stop the transmission of the herpes virus from body areas other than the sexual organs. Though research continues, there is no herpes vaccine proven effective in human beings.

Health care team roles

As genital herpes infections and their consequences may dramatically vary among people, there is diverse and varied involvement of health care team members. These include:

• Primary care physicians, nurse practitioners, and alternative health care providers, all of whom will be involved in physical examinations of people complaining of symptoms. Genital herpes can be diagnosed and treated by the family doctor, dermatologist (i.e., a doctor who specializes in skin diseases), urologists (i.e., doctors who specialize in the urinary tract diseases of men and women and the genital organs of men), gynecologists (i.e., doctors who specialize in the diseases of women's genital organs) and infectious disease specialists. Any of these may also pick up the presence of unknown genital herpes infections on routine examinations.
• Physicians or nurse practitioners routinely do viral cultures. A sterile cotton swab is wiped over open sores and the sample used to infect human cells in culture. Cells killed by the herpes virus have a certain appearance under microscopic examination. The results of this test are available within two to ten days. Though it is considered quite accurate, there are estimates that up to 20% of viral culture tests give a false negative reading. Other areas that 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.
• Finger-stick or blood-drawn laboratory tests are usually done by either nurses or laboratory technicians, but are sometimes carried out by physicians or nurse practitioners.
• Obstetricians (i.e., physicians who deliver newborn babies), nurse midwives (i.e., nurses who deliver newborn babies) and obstetrical nurses (i.e., nurses who assist in the delivery of newborns and the care of mothers and infants after birth) will be involved in assuring that mothers infected with active genital herpes are provided a safe delivery (usually by cesarean section), and that newborns are thoroughly checked for signs and symptoms of the disease. As noted previously, many newborns are born infected with herpes virus to mothers who had no symptoms of infection. Therefore, it is important to check all newborn babies for skin sore or lesions inside the mouth, and for signs of herpes infection in their eyes.
• Physicians, nurse practitioners, and alternative health practitioners will prescribe medications or herbs and diet to alleviate the symptoms of genital herpes.
• Nurses will be involved in the day-to-day care, including the provision of comfort measures, such as the administration of analgesic medications, warm baths, and applying compresses and ointments to those seriously ill enough to require hospitalization or nursing home care. Many of these will be immune system-compromised people, such as those who have AIDS.

Patient education

All health care providers will be involved in providing education about genital herpes. Because STDs are such a sensitive area of health care, it will be important for the health care provider to show understanding and sensitivity for health care consumers infected with HSV. Information and education, given without suggestion of judgment, can be among the most important care provided. It should emphasize that there is currently no cure for genital herpes, that the disease is extremely pervasive, and that precautions must be used during sexual contact in order to avoid infecting others. An important goal of patient education should be to make the patient aware that condoms are an excellent means of protection from HSV and pregnancy. The patients should also learn what laboratory tests will need to be done, and what medications, or treatments, can help alleviate symptoms.

The diagnosis and treatment of this infectious disease should be covered by most insurance providers.

KEY TERMS

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

Latent virus— A non-active virus which is in a dormant state within a cell. Herpes virus is latent in cells of the nervous system.

Lesion— A morbid, or diseased, change in tissue formation at a local site.

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.

Resources

BOOKS

Ebel, Charles, and Anna Wald Managing Herpes: How To Live and Love with a Chronic STD. Research Triangle Park, NC: American Social Health Association, 2002.

Handsfield, Hunter H., et al. Genital Herpes. New York: McGraw-Hill Professional Publishing, 2001.

Icon Health Publications. The Official Patient's Sourcebook on Genital Herpes: A Revised and Updated Directory for the Internet Age. San Diego: Icon Health Publications, 2002.

Westheimer, Ruth, and Pierre A. Lehu. Dr. Ruth's Guide to Talking About Herpes. New York: Grove Press, 2004.

PERIODICALS

Beauman, John G. "Genital Herpes: A Review." American Family Physician (Oct. 15, 2005): 1527.

Celum, Connie, et al. "Genital Herpes and Human Immunodeficiency Virus: Double Trouble." Bulletin of the World Health Organization (June 2004): 447-453.

Gorgos, Diana. "Survey Reveals New Insights into Genital Herpes." Dermatology Nursing (October 2004): 460.

Remington, Michael. "Minimizing Recurrences of Genital Herpes—A Role for Supportive Antiviral Therapy: Stress May Contribute to Recurrent Episodes of Genital Herpes, Which Themselves Cause More Stress. Minimizing the Frequency of Recurrences—Or Eliminating Them Altogether—May Help to Break the Cycle." JAAPA-Journal of the American Academy of Physician Assistants (August 2004): 19-24.

Wenner, Christopher, and Joan Nashelsky. "Antiviral Agents for Pregnant Women with Genital Herpes." American Family Physician (Nov. 1, 2005): 1807.

ORGANIZATIONS

National Herpes Resource Center and Hotline, American Social Health Association. P.O. Box 13827, Research Triangle Park, NC 27709-9940. (919) 361-8488. 〈www.ashastd.org〉.

National Institute of Allergy and Infectious Diseases, Office of Communications and Public Liaison. 6610 Rockledge Drive, MSC 6612, Bethesda, MD 20892-6612. (301) 496-5717. 〈www.niad.nih.gov〉.