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Herpes Simplex Virus Infections

By Craig R. Pringle, BSc, PhD, Professor Emeritus, School of Life Sciences, University of Warwick

Herpes simplex virus infection causes recurring episodes of small, painful, fluid-filled blisters on the skin, mouth, lips (cold sores), eyes, or genitals.

  • This very contagious infection is spread by direct contact with sores or sometimes with the affected area when no sores are present.

  • Herpes causes blisters or sores in the mouth or on the genitals and, often with the first infection, a fever and general feeling of illness.

  • The virus sometimes infects other parts of the body, including the eyes and brain.

  • Usually, doctors easily recognize the sores caused by herpes, but sometimes analysis of material from a sore or blood tests are necessary.

  • No drug can eradicate the infection, but antiviral drugs can help relieve symptoms and help symptoms resolve a little sooner.

Herpes simplex is one of several types of herpesvirus (see Herpesvirus Infection Overview). There are two types of herpes simplex virus (HSV):

  • HSV-1, which is the usual cause of cold sores on the lips (herpes labialis) and sores on the cornea of the eye (herpes simplex keratitis—see Herpes Simplex Keratitis)

  • HSV-2, which is the usual cause of genital herpes

This distinction is not absolute: Genital infections are sometimes caused by HSV-1. Infection can also occur in other parts of the body such as the brain (a serious illness) or gastrointestinal tract. Widespread infection may occur in newborns or in people with a weakened immune system, particularly those who have HIV infection.

HSV is very contagious and can be spread by direct contact with sores and sometimes by contact with the oral and genital areas of people who have chronic HSV infection even when no sores are can be seen.

Primary and recurrent infection

After the first (primary) infection, HSV, like other herpesviruses, remains dormant (latent) in the body and can periodically reactivate and cause symptoms.

The primary HSV infection produces an eruption of tiny blisters. After the eruption of blisters subsides, the virus remains in a dormant state inside the collection of nerve cells (ganglia) near the spinal cord that supply the nerve fibers to the infected area. Periodically, the virus reactivates, begins growing again, and travels through the nerve fibers back to the skin—causing eruptions of blisters in the same area of skin as the earlier infection. Sometimes the virus is present on the skin or mucous membranes even when no blisters can be seen.

The virus may reactivate many times. Reactivation (recurrences) of a latent oral or genital HSV infection may be triggered by a fever, menstruation, emotional stress, or suppression of the immune system (for example, by a drug taken to prevent rejection of an organ transplant). An episode of cold sores can develop after physical trauma, such as a dental procedure or overexposure of the lips to sunlight. Often, the trigger is unknown.

Symptoms and Complications

Tiny blisters appear on the following:

  • Skin: Particularly on a fingertip or the genitals

  • Mucous membranes: Including those lining the eyes, vagina, cervix, or inside of the mouth.

The skin around the blisters is often red.

Oral infection

The first oral infection with HSV usually causes many painful sores inside the mouth (herpetic gingivostomatitis). Before the sores appear, people may feel a tingling discomfort or itching in the area. In addition, people usually feel sick and have a fever, a headache, and body aches.

The mouth sores last 10 to 14 days and are often very severe, making eating and drinking extremely uncomfortable. As a result, people may become dehydrated. In some first oral infections, swollen gums are the only symptom. Occasionally, no symptoms develop. Herpetic gingivostomatitis most commonly develops in children.

Recurrences, unlike the first oral infection, usually produce only a single sore on the rim of the lip. Rarely, a recurrence involves a sore or small cluster of sores on the gums or roof of the mouth.

The lip sore is called a cold sore or fever blister (so named because they are often triggered by colds or fevers). Other triggers include sunburn on the lips, certain foods, anxiety, certain dental procedures, and any condition that reduces the body's resistance to infection. If people have a cold sore, they should postpone dental visits until the sore heals.

Before a cold sore appears, people usually feel a tingling at the site, lasting from minutes to a few hours, followed by redness and swelling. Usually, fluid-filled blisters form and break open, leaving sores. The sores quickly form a scab. After about 8 to 12 days, the scab falls off and the episode ends. Less often, tingling and redness occur without blister formation.

Genital infection

The first genital HSV infection (genital herpes) can be severe and prolonged, with many painful blisters in the genital and/or anal area. In women, internal blisters may develop in the vagina or on the cervix. Internal blisters are less painful and are not visible. Fever and a general feeling of illness (malaise) are common, and some people have burning during urination, difficulty urinating, or constipation. Some people have no symptoms.

Recurrences of genital herpes begin with symptoms (including local tingling, discomfort, itching, or aching in the groin) that precede the blisters by several hours to 2 to 3 days. Painful blisters surrounded by a reddish rim appear on the skin or mucous membranes of the genitals. The blisters quickly break open, leaving sores. Blisters may also appear on the thighs or buttocks or around the anus. In women, blisters may develop on the vulva. These blisters are usually obvious and very painful. A typical episode of recurring genital herpes lasts a week.

Bacteria sometimes infect genital sores due to HSV infection. Such sores may appear more irritated or have a thick or foul-smelling discharge.

Other infections and complications

In people with a weakened immune system, recurrences of oral or genital herpes can result in progressive, gradually enlarging sores that take weeks to heal. The infection may progress inside the body, moving into the esophagus, lungs, brain, tissues that cover the brain and spinal cord (meninges), or colon. Ulcers in the esophagus cause pain during swallowing, and lung infection causes pneumonia with cough and shortness of breath.

Sometimes HSV-1 or HSV-2 enters through a break in the skin of a finger, causing a swollen, painful, red fingertip (herpetic whitlow—see Herpetic Whitlow). Health care workers who are exposed to saliva or other body secretions (such as dentists) when not wearing gloves are most commonly affected.

HSV-1 can infect the cornea of the eye. This infection (called herpes simplex keratitis—see Herpes Simplex Keratitis) causes a painful sore, tearing, sensitivity to light, and blurred vision. Over time, particularly without treatment, the cornea can become cloudy, causing a significant loss of vision.

Infants or adults with a skin disorder called atopic eczema can develop a potentially fatal HSV infection in the area of skin that has the eczema (eczema herpeticum―see Atopic Dermatitis (Eczema)). Therefore, people with atopic eczema should avoid being near anyone with an active herpes infection.

HSV can infect the brain. This infection (called herpes encephalitis) begins with confusion, fever, and seizures and can be fatal.

Infrequently, a pregnant woman can transmit HSV infection to her baby (called neonatal herpes). Transmission usually occurs at birth, when the baby comes into contact with infected secretions in the birth canal. Rarely, HSV is transmitted to the fetus during pregnancy. Transmission during birth is more likely when

  • The mother has recently acquired the herpes infection

  • The mother has visible herpes sores in the vaginal area, although babies may become infected from mothers who have no apparent sores

When acquired at birth, the infection appears between the 1st and 4th week of life. Newborns with HSV infection become very ill. They may have widespread disease, brain infection, or skin infection. Without treatment, about 85% of those with widespread disease and about half of those with a brain infection die. Even with treatment, many have brain damage.

Did You Know...

  • Usually, when cold sores recur, only one develops at a time.


  • Testing of a sample taken from the sore

  • If doctors suspect a brain infection, magnetic resonance imaging and a spinal tap

HSV infection is usually easy for doctors to recognize. If unsure, doctors may use a swab to take a sample of material from the sore and send the swab to a laboratory to grow (culture) and identify the virus.

Sometimes doctors examine material scraped from the blisters under a microscope. Although the virus itself cannot be seen, scrapings sometimes contain enlarged infected cells (giant cells) that are characteristic of infection by a herpes-type virus.

Blood tests to identify antibodies to HSV can also be helpful. Certain blood tests can distinguish between HSV-1 infection and HSV-2 infection.

If a brain infection is suspected, magnetic resonance imaging (MRI) of the brain and a spinal tap (lumbar puncture—see Figure: How a Spinal Tap Is Done) to obtain a sample of cerebrospinal fluid may be done.


People should avoid activities and foods known to trigger recurrences. For example, they people with oral HSV infection should avoid exposure to sunlight as much as possible.

Because HSV infection is contagious, people with infection of the lips should avoid kissing as soon as they feel the first tingling (or, if no tingling is felt, when a blister appears) until the sore has completely healed. They should not share a drinking glass and, if possible, should not touch their lips. They should also avoid oral sex.

People with genital herpes should use condoms at all times. Even when there are no visible blisters and no symptoms, the virus may be present on the genitals and can be spread to sex partners.

Vaccines for the prevention of HSV infections are being developed.


Antiviral drugs

No current antiviral treatments can eradicate HSV infection, and treatment of a first oral or genital infection does not prevent chronic infection of nerves. However, during recurrences, antiviral drugs, such as acyclovir, valacyclovir, or famciclovir, may relieve discomfort slightly and help symptoms resolve a day or two sooner. Treatment is most effective if started early, usually within a few hours after symptoms start—preferably at the first sign of tingling or discomfort, before blisters appear. For people who have frequent, painful attacks, the number of outbreaks can be reduced by taking antiviral drugs every day indefinitely (called suppressive therapy). However, taking antiviral drugs does not prevent infected people from transmitting the infection. Antiviral drugs are available by prescription only.

Penciclovir cream, applied every 2 hours during waking hours, can shorten the healing time and duration of symptoms of a cold sore by about a day. Nonprescription creams containing docosanol (applied 5 times a day) may provide some relief. Acyclovir, valacyclovir, or famciclovir taken by mouth for a few days may be the most effective treatment.

Severe HSV infections, including herpes encephalitis and infections in newborns, are treated with acyclovir given intravenously. If the virus becomes resistant to acyclovir, foscarnet can be given intravenously.

People with herpes simplex keratitis are usually given trifluridine eye drops. An ophthalmologist should supervise treatment.

Other treatments

For people who have minimal discomfort, the only treatment needed for recurring herpes of the lips or genitals is to keep the infected area clean by gentle washing with soap and water. Applying ice may be soothing and reduce swelling.

Applying prescription or nonprescription topical anesthetics, such as tetracaine cream or benzocaine ointment, may help relieve pain. If the mouth contains many sores, the mouth can be rinsed with lidocaine, which should not be swallowed. Topical anesthetics should be used only about once every few hours. If used more often, these drugs can have harmful side effects.

Pain relievers may be taken for pain.

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