Diagnosing and Classifying Genital Herpes

If you have herpes and become pregnant or if you are diagnosed with herpes for the first time during your pregnancy, your doctor classifies the type of infection you have to determine appropriate treatment.

Symptoms during initial (primary) herpes episodes are usually more severe than during recurrent episodes. If you have a primary infection during pregnancy, the risk of infecting your baby increases. If this is your first episode, your doctor will probably recommend antiviral medication, which helps protect your baby and hasten the healing of your sores.

How Is Genital Herpes Diagnosed?

Your doctor can identify your infection through a physical examination if you have the classic vesicles (small blisters)-multiple, grouped, and painful. But, if you are like many patients, you may not visit your doctor until the vesicles have evolved into ulcers (inflamed lesions) or crusted over.

There are several major concerns raised by a diagnosis of genital herpes. Even if you do have easily identifiable sores, the diagnosis should be confirmed by laboratory methods. Blood tests are available, which detect antibodies produced in response to HSV-1 or HSV-2. (Your body produces antibodies specific to organisms that invade the body; their job is to combat or kill these pathogens. If a blood test shows them present in your blood, it is evidence of current or past infection.) These tests can now differentiate between the two types of HSV: HSV-1, which is the more common cause of herpes labialis manifested by sores around the mouth and lips (commonly called ?cold sores?) and HSV-2, the more common cause of genital herpes. IgM antibodies to either of these two viruses indicate recent infection, but if you have IgG antibodies to either or both of the two viruses, it is impossible to tell when you acquired the infection or if the current outbreak is related to an active herpes infection. Therefore, more specific methods can be used to determine if the lesions are from herpes.

Is Acyclovir Safe to Use During Pregnancy?

This is an extremely important question because of possible harm to the baby-and especially because a woman may be prescribed this drug during her first trimester, before she knows that she is pregnant.

Acyclovir does pass through the placenta and can concentrate in amniotic fluid. This raises a valid concern about possible toxicity to the baby's kidneys, which must filter the drug. However, increasing evidence has shown that acyclovir is safe for the mother and baby during pregnancy. Acyclovir is now a class B drug, meaning that it is considered safe during pregnancy. In addition, available information indicates that acyclovir is not harmful to the baby if the mother takes it near delivery. An Acyclovir in Pregnancy Registry has been established to define the risks of its use. So far, no adverse outcomes in the fetus or newborn have been reported.

Usual Dosage

The original recommended oral dose of acyclovir was 200 milligrams (mg), five times daily for seven to 10 days. However, 400 mg, three times daily is now considered just as effective and costs less. Remember, however, that drug doses vary. Your doctor will determine the correct dosage for you.

Treatment for First-Episode Genital Herpes*
DRUGDOSAGE
Acyclovir200 mg, five times daily
Acyclovir400 mg, three times daily
Valacyclovir1,000 mg, twice daily

What Is the Usual Treatment for First-episode Genital Herpes?

Acyclovir (Zovirax) is the antiviral agent prescribed most often to patients (both pregnant and non-pregnant) with first-episode genital herpes. While acyclovir is typically administered orally, some patients should be treated intravenously (those who are hospitalized due to severe complications). Significant clinical improvement has been reported in pregnant women who have had complications caused by herpes, such as pneumonitis, hepatitis, meningitis, or encephalitis when they are given intravenous therapy. As a general rule, topical acyclovir is considered ineffective for either primary or recurrent infection.

A related drug, valacyclovir (Valtrex), is increasingly prescribed instead of acyclovir since it is closely related to acyclovir, but has to be taken fewer times during the day.

Should I Take Medication to Prevent Recurrence?

Once you complete treatment for the primary infection, discuss with your doctor whether you should take suppressive medication for the remainder of your pregnancy in order to decrease the likelihood of recurrences and to lower the risk of transmitting the infection to your baby.

Cell Culture

A reliable diagnostic method involves taking a sample of the fluid from the base of a vesicle or ulcer and having it cultured (grown) in a laboratory. Usually, a culture result can be obtained within four days. If the virus is present, you have the infection. The older the active lesions are, the more difficult it may be to obtain a positive culture. This test is 100% specific for the actual virus being cultured (whether HSV-1 or HSV-2) and has fairly high yield on fresh specimens.

*Adapted from Edwards RK, Duff P. Herpes simplex virus infections in women. In: Stovall TG, Ling FW (eds.). Gynecology for the Primary Care Physician, 1999. Used with permission from Current Medicine, Inc. Prices given are wholesale (AWP) from the 1998 Drug Topics Red Book.

Acyclovir is very well tolerated, although it may rarely cause a headache or a rash. Most experts suggest continuing treatment until all lesions have healed, rather than for some arbitrary length of time. Higher doses of acyclovir, such as those used to treat herpes zoster or ?shingles? (800 mg five times daily), may cause nausea and indigestion.

Oral acyclovir is incompletely absorbed. A related drug, valacyclovir (Valtrex), is more completely absorbed and is rapidly converted to acyclovir in the wall of the intestine and in the liver. Valacyclovir is as effective as acyclovir at treating first-episode or recurrent genital herpes. It also has a dosing advantage over acyclovir (fewer daily doses), and the side effects are similar for both.

There are additional concerns about use of acyclovir and valacyclovir:

  • patients who take cimetidine (Tagamet) or probenecid (Benemid) should be sure their doctor knows because either one decreases the clearance of acyclovir and valacyclovir through the kidneys; and
  • patients who have AIDS or another condition that affects the immune system should be sure their doctor knows. Valacyclovir (but not acyclovir) has been reported to cause a thrombocytopenic purpura/hemolytic-uremic syndrome in some severely immunocompromised patients, usually people with advanced AIDS or bone marrow transplants. This syndrome is associated with a low platelet count, bleeding, anemia, and liver dysfunction, and can be fatal. However, the studies reporting this rare complication were done with extremely high doses of valacyclovir (8 grams per day) not used in current recommendations. Hence, this complication is exceedingly rare.

Smears

A test known as a Tzanck smear is a rapid method for identifying herpes infections. To perform this test, your doctor scrapes cells from a fresh ulcer or blister. These cells are spread on a glass slide, stained, and analyzed under a microscope. (A Papanicolaou smear (Pap smear) may also show evidence of herpes infection.)

Still, these smears have limitations: they cannot differentiate between HSV-1, HSV-2, and VZV (varicella-zoster, the chickenpox virus) infections. In addition, the smear test has a sensitivity of only 60 percent. So, in addition to a Tzanck smear, your doctor may also perform another diagnostic test, such as a viral culture or a polymerase chain reaction (PCR).

DNA Testing

PCR, a rapid test to detect HSV DNA, is one of the most accurate tests available. It involves taking a cell sample, isolating the cell's genetic material, and replicating it to make identification of the virus easier. This method has several advantages:

  • results are available in a matter of hours and are at least as accurate as a cell culture;
  • PCR is a more sensitive test. It can recognize infection for as long as the lesion is present. With a viral culture there are a larger number of false-negative results (people who have been infected but test negative when the lesion is old); and
  • PCR can identify asymptomatic viral shedding of HSV.

Although PCR may be the future standard for diagnosing HSV infection, it is currently expensive and cumbersome and not used routinely in the diagnosis of oral and genital herpetic lesions. Its use at present is restricted to the diagnosis of HSV in the cerebrospinal fluid.

A Word about Patients with HIV.

In patients with HIV, cultures techniques are often used to make a definitive diagnosis of herpes simplex. The signs and symptoms of HSV infection may be altered in these patients, and it can be difficult to tell the difference between HSV infection and other causes of genital ulcers. Many infections can cause genital ulcers, and may be confused with HSV infection (including syphilis, chancroid, lymphogranuloma venereum, granuloma inguinale, Crohn's disease of the vulva, Behçet's disease, and trauma).

How Are Genital Herpes Infections Classified?

Genital HSV infections are designated as primary or recurrent infections.

  • A primary infection occurs when IgG antibodies to both HSV-1 and HSV-2 are absent at the time a patient acquires genital HSV. (There may be a time lapse between when the infection develops and when IgG antibodies can be detected through a blood test.) However, IgM antibodies to the herpes simplex virus causing the infection most likely will be present at that point. Symptoms tend to be most severe in primary infections.
  • Recurrent infections result from reactivation of genital HSV from a latent infection. (For example, the infection was ?dormant? within nerve cells but has come out of latency and is currently causing symptoms.) The IgG antibodies against the offending virus are present at this point. This class of infection tends to be the least severe.

Many people infected with HSV have no symptoms during their initial infection. As a result, the first time you are diagnosed with HSV, it may represent either a primary or a recurrent infection.

What Are the Signs and Symptoms of a First-episode Infection?

In primary genital herpes, three to seven days after exposure, multiple vesicles (small blisters) appear on the skin in the genital region. In women, these lesions may occur on the vulva, urethra, vagina, cervix, or perineal area. The vesicles then open and form ulcers, which can be painful. It takes four to six weeks for these ulcers to heal. If the ulcers appear on the skin, they crust over before healing; if they appear on mucous membranes, they heal without crusting over. Ulcers do not leave scars.

Primary infections are often accompanied in the first few days by fever, headache, muscle aches, and malaise (not feeling well). Lymphadenopathy, a condition in which the lymph nodes in the groin become swollen and tender, may occur for the first three weeks of infection.

What Are the Signs and Symptoms of a Recurrent Infection?

Recurrent genital herpes occurs in patients already infected with HSV-2 (or, less commonly, HSV-1). In recurrent episodes, lesions are less likely to be accompanied by other ?systemic? (body) symptoms. In addition, the lesions are fewer and tend to clear up in two weeks or less.

Type of InfectionNumber of Lesions

(average)
Days of Pain (average)
Primary Infection15-1612
Recurrent Infection9-108-9

Recurrent infections often occur only on one side of the body, as compared to primary infections where lesions occur on both sides. But, despite the decreased severity compared with primary infections, the lesions of recurrent infections may be quite painful, especially in women. Before a recurrent infection, about one-half of patients report what is known as prodromal (warning) symptoms, which consists of hyperesthesia (an increased sensitivity to touch) or tingling at the site where blisters will develop. The prodrome usually lasts from several hours to several days.

Added Risks for Immunocompromised Patients.

Patients who have weakened immune functioning (due to HIV infection) are more likely to develop serious infections, such as meningitis (infection of the protective coverings of the brain and spinal cord) or encephalitis (infection of the brain). The risk of severe infection is especially high during primary HSV infections.