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Herpes Simplex

Description

An in-depth report on the causes, diagnosis, treatment, and prevention of herpes simplex.

Alternative Names

Herpes, Oral and Genital

Symptoms

Symptoms vary depending on the stage of the virus: the initial or primary outbreak, latency, and recurrence. Both herpes simplex viruses 1 and 2 produce similar symptoms, but they can differ in severity depending on the site of infection. More than 60% of new HSV-2 infections and about a third of new HSV-1 infections do not produce symptoms.

General Symptoms of a First (Primary) Herpes Simplex Infection

Skin Eruptions and Pain. The first time a person experiences a herpes simplex outbreak, skin eruptions appear two to 12 days after the initial exposure to the virus. They may take the following course:

  • The first sign of infection is fluid accumulation (edema) at the infection site, which is quickly followed by small, grouped blisters-- the characteristic HSV lesions.
  • These form on an inflamed skin base, which is more visible in dry skin areas.
  • The blisters then dry out and heal rapidly without scarring with a week to 10 days. Blisters in moist areas heal more slowly than others. The lesions may sometimes itch, but itching decreases as lesions heal.
  • When the crust falls off, the lesions are no longer contagious. (The virus may still be active in nearby tissue, but such persistence is rare.)
  • Once HSV gains entry to a site in the body, the virus can also spread to nearby mucosal areas through nerve cells. This characteristic spreading can cause fairly large infected areas to erupt at some distance from the initial crop of sores.

The primary skin infection with either HSV-1 or HSV-2 lasts up to two to three weeks, but skin pain can last one to six weeks in a primary (the initial) HSV attack.

Other Symptoms. Some patients experience other symptoms as well, which may occur before the actual outbreak (called a prodrome):

  • Fever rising to about 102F, muscle aches, headache, and flu-like malaise. These general symptoms usually resolve within a week.
  • Lymph glands near the site may be swollen as well.

It may be especially important to identify a primary infection (if possible) and to treat it as soon as possible, since some preliminary research suggests that early treatment may limit the number of viruses that remain latent in the body and reduce the frequency of recurrent outbreaks.

Asymptomless Stages: Latency and Shedding

Latency. After an outbreak, the herpes simplex virus goes into a stage known as latency. During that phase, HSV produces no symptoms at all and the virus is not transmissible.

Asymptomatic Shedding. At certain times, the virus undergoes shedding. During this phase the virus replicates and is capable of being transmitted through fluids and infecting other people. This occurs during an outbreak, but unfortunately, in a third to half of cases shedding occurs without any symptoms at all. One study reported that about 40% of all HSV-infected people experienced asymptomatic shedding of the virus more than 5% of the time. (Other evidence suggests shedding occurs much more often--between 9% and 28% of the time.) About half of asymptomatic shedding episodes occurs within a few days before or after an outbreak and lasts about one and half days. Asymptomatic shedding is much more common with HSV-2 than with HSV-1.

Recurrence Symptoms, Triggers, and Timing

Symptoms of Recurrence. Herpes simplex nearly always recurs. The anatomic site and the type of virus influence the frequency of recurrences. It usually takes the following course:

  • Prodrome. The outbreak of infection is often preceded by a prodrome, an early group of symptoms that may include itching skin, pain, or an abnormal tingling sensation at the site of infection. The patient may also experience headache, enlarged lymph glands, and flu-like symptoms. The prodrome, which may be as brief as two hours or as long as two days, terminates when the blisters develop. In about 25% of cases, recurrence does not develop beyond the prodrome stage.
  • The Outbreak. Recurrent outbreaks of HSV feature most of the same symptoms at the same sites as the primary attack, but they tend to be milder and briefer. After blisters erupt, they heal in approximately six to 10 days. Occasionally, the symptoms may not resemble those of the primary episode but appear as fissures and scrapes in the skin or as general inflammation around the affected area.

Triggers of Recurrence. It is not completely known what triggers renewed infection, but a number of different factors may be involved, such as sunlight, wind, fever, local physical injury, menstruation, suppression of the immune system, or emotional stress. One study linked recurrence in genital herpes to persistent stress (lasting longer than a week) and high levels of anxiety. Temporary mood changes, short-term stress, and life change events were not linked to recurrence. (A study on ocular herpes also found no association between stress and outbreaks of this eye infection and suggested that people may incorrectly recall the stress associated with herpes outbreaks.) Reactivation of oral herpes can be provoked within about three days of intense dental work, particularly root canal or tooth extraction, as well as after laser skin resurfacing, a popular form of cosmetic surgery.

Timing of Recurrences. Recurrent outbreaks may occur at intervals of days, weeks, or years. For most people, outbreaks recur with more frequency during the first year after an initial attack. During that period, the body mounts an immune response to HSV, and in most healthy people recurring infections tend to become progressively less severe and less frequent. The immune system, however, cannot eradicate the virus completely.

Specific Symptoms of Oral Herpes

Oral herpes (herpes labialis) is most often caused by HSV-1 but can also be caused by HSV-2. It usually affects the lips and, in some primary attacks, the mucous membranes in the mouth. A facial herpes infection on the cheeks or in the nose may occur, but this condition is very uncommon.

Primary Oral Herpes Infection. If the primary (or initial) oral infection causes symptoms, they can be very painful, particularly in small children.

  • Blisters form on the lips but may also erupt on the tongue.
  • The blisters eventually rupture as painful open sores, develop a yellowish membrane before healing, and disappear within three to 14 days.
  • Increased salivation and foul breath may be present.
  • Rarely, the infection may be accompanied by difficulty in swallowing, chills, muscle pain, or hearing loss.

In children, the infection usually occurs in the mouth. In adolescents, the primary infection is more apt to occur in the upper part of the throat and cause soreness.

Recurrent Oral Herpes Infection. Most patients experience only a couple of outbreaks a year, although up to 10% of patients experience more frequent recurrences. (HSV-2 oral infections recur less frequently than HSV-1.) Recurrences are usually much milder than primary infections and are known commonly as cold sores or fever blisters (because they may arise during a bout of cold or flu). They usually show up on the outer edge of the lips and rarely affect the gums or throat. (Cold sores are commonly mistaken for the crater-like mouth lesions known as canker sores, which are not associated with HSV.)

Specific Symptoms of Genital Herpes

Genital herpes, which typically affects the penis, vulva, or rectum, is usually caused by HSV-2, although the rate of HSV-1 genital infection is increasing. Studies now report, in fact, that the cases of new symptomatic genital infections are equally split between HSV-1 and HSV-2. Some studies even report a higher incidence of genital HSV-1 cases. (The distinction may not matter, however, since there is no difference in treatments.) Initial genital infections due to HSV-1 may be more severe than those caused by HSV-2. Recurrences tend to be milder and less frequent than with HSV-2, however.

Primary Genital Herpes Infection. The first outbreak usually occurs in or around the genital area between three days and two weeks after exposure to the virus. If there is a long duration between the initial infection and the first outbreak of symptoms, the episode may be quite mild because the immune system has produced antibodies to the virus by that time. Also, such primary infections are less transmissible, heal faster, and produce fewer symptoms.

In about 80% of initial outbreaks of genital herpes, patients develop diffuse symptoms (e.g., flu-like discomfort and fever). The virus sheds for about three weeks. Symptoms in men and women are very different from each other.

In women, the pattern of a first infection is often more complicated and severe than in men with some or all of the following events:

  • In addition to general flu-like discomfort, women may experience nerve pain, itching, lower abdominal pain, urinary difficulties, and yeast infections before or during the eruption of the skin blisters.
  • When the outbreak occurs, blisters form raw sores (ulcers) almost immediately. Later they become crusted and fill with a grayish-white fluid. A new crop often occurs during the second week and is accompanied by swollen lymph glands in the groin. The symptoms may last as long as six weeks.
  • Lesions commonly appear around the vaginal opening, on the buttocks, in the vagina, or on the cervix. If lesions occur inside the vagina, they are not visible and pain may be minimal. Such women, then, may be unaware that they have genital herpes. In such cases, the blisters produce a discharge that is still highly infectious.
  • Lesions develop in places other than the genital region in 10% to 18% of primary HSV-2 infections. In most of these cases, outbreaks occur in the urethra (the channel that carries urine) where they can cause painful burning during urination. Inflammation of the internal reproductive organs, including the uterus lining (endometrium) and the fallopian tubes, is rare.

In men, about six to 10 blisters typically develop on the head or shaft of the penis. They rarely occur at the base. In some cases, they can occur on the buttocks, around the anus, or on the thighs.

Recurrent Genital Herpes Infection. In general, recurrences are much milder than the initial outbreak. The virus sheds for a much shorter period of time (about three days) compared to in an initial outbreak of three weeks. Women may have only minor itching and the symptoms may be even milder in men.

On average, individuals experience four recurrences a year, although this varies widely depending on the severity of the initial outbreak. Men, for example, have 20% more recurrences of genital herpes than women even though their symptoms are milder. There are also some differences in frequency of recurrence depending on whether genital herpes is caused by HSV-2 or HSV-1:

  • HSV-2 Genital Herpes Recurrences. HSV-2 genital infections recur more often than HSV-1, and they tend to be more severe. Up to 90% of HSV-2 genital infections recur within the first year after primary infection. Many patients report five to eight recurrences in the first year, but some experience them as often as every two weeks. Some, though, have only one initial outbreak without any subsequent recurrences, a rate more typical of those with HSV-1.
  • HSV-1 Genital Herpes Recurrences. In one study, 38% of patients with HSV-1 genital infections had no recurrences in the first year after primary infection, 35% had one recurrence, and 27% had two or more recurrences. The average time to recurrence was about seven and a half months. Only 7% of those with genital HSV-1 had two or more recurrences annually for at least two years.

According to one study, patients with genital herpes usually notice a significant reduction in recurrence by the seventh year after infection. Some patients, however, particularly those with genital HSV-2, may actually face an increase in recurrence during the first five years.

Other Forms of HSV-1 and HSV-2

Location and type

Symptoms

Treatments

Eye (ocular herpetic infection). Affects only one eye at a time. Usually caused by HSV-1 but acute cases in the retina are more likely to be due to HSV-2. An estimated 400,000 Americans have recurrent ocular herpes, with 50,000 new cases occurring each year. The incidence has been highest in children, although it is increasing in older individuals.

Primary: Inflammation of the cornea (keratitis), causing sudden and severe pain, blurred vision, or corneal lesions. A cloudy layer can form over the cornea. Swelling may occur around the eyes. Heals within 2 to3 weeks.

Recurrence: About 40% of people have more than one recurrence, usually keratitis in a single eye, but symptoms may be present in the other eye as well. In the experience of some physicians, short, intense exposure to sunlight may trigger a recurrence, but there is no clear evidence concerning sunlight or any other potential triggers.

Branching, ulcerous lesions of the cornea may occur later in the disease. Stromal keratitis, inflammation of inner layers of the cornea, occurs in about 25% of patients. It is a late immune response to the infection and can, in some cases, be very serious. In fact in the US it is the major cause of blindness in the cornea (which is still very uncommon).

Medications of Ocular HSV. Ocular HSV should be treated carefully since certain treatments may aggravate the condition. Artificial tears may be appropriate for mild cases. Treatments include trifluridine (Viroptic) eye drops or acyclovir or vidarabine (Vira A) ointments. Evidence suggests that all are equally effective. Adding interferon, an immune system booster, to trifluridine may speed healing. Interferon in combination with debridement is also helpful. With treatment, most HSV ocular infections resolve within five to nine days. Taking long-term oral acyclovir after an initial episode of ocular HSV reduces recurrences by about 45%.

Medications for Stromal Keratitis. Oral acyclovir also protects against stromal keratitis in patients with a history of it. Trifluridine or cidofovir may also be protective against it. Neither drug, however, has any effect once stromal keratitis develops. Treatment includes artificial tears for mild cases and topical steroids for moderate to severe inflammation.

Procedures. Patients with ocular HSV may also require debridement, in which the surgeon scrapes away the injured tissue with a cotton swab. A patch or soft contact lens may be worn afterward.

Patients with HSV who show scarring in the cornea may require surgery. In rare cases, a corneal transplant may be necessary.

Brain (HSV encephalitis). Usually HSV-1, although HSV-2 is typically the cause in newborns. In about a quarter of HSV-1 encephalitis cases, the infection may be caused by a new strain of the virus. About 2100 cases a year in the US. About a third occur in people under 20 years old, half over 50, and the balance between ages 20 and 50.

Fever, headache, stiff neck, seizures, partial paralysis, stupor, or coma. Other symptoms: smell and taste disturbances, double vision, odd mental states, bizarre or psychotic behavior, loss of the ability to speak or understand, memory loss, confusion, emotional volatility.

Intravenous acyclovir is the treatment of choice for encephalitis and should be started immediately if this complication is suspected. It must be administered for at least 10 days. In rare cases, surgical measures may be needed to relieve the buildup of pressure in the brain.

Finger (herpetic whitlow). One finger, usually thumb or index finger in adults. Any finger in children. HSV-1 the cause in 60% and HSV-2 in 40%. HSV-1 is usually caused by finger-sucking in children or as an occupational condition in adults (usually health care workers not using gloves). HSV-2 is usually acquired by touching infected genital areas.

Primary: Itching or pain, swelling, flushing of the skin, localized tenderness of the infected finger. Clear-yellowish or pus-filled blisters may appear on fingertip lasting 2-3 weeks. Soft tissue around fingernail may become painfully infected. Finger blisters may become secondarily infected with common bacteria, causing fever and swollen glands in the armpit.

Herpetic whitlow on the thumb
A herpetic whitlow is an infection of the herpes virus around the fingernail. In children, this is often caused by thumbsucking or finger sucking while they have a cold sore. It is seen in adult healthcare workers such as dentists because of increased exposure to the herpes virus. The use of rubber gloves prevents herpes whitlow in healthcare workers.

Recurrence: Sometimes intense burning, nerve pain, or excessive sensitivity.

Topical acyclovir for acute attack and oral acyclovir for prevention of recurrences.

Lower back. Usually caused by HSV-2 and typically occurs in bedridden patients or those with AIDS.

Numbness, tingling of the buttocks or the area around the anus, urinary retention, constipation, and impotence. Weakness or extreme skin sensitivity in the lower extremities, possibly persisting for months. Headaches, stiff neck, and, very rarely, paralysis in lower extremities caused by inflammation of the spinal cord.

Acyclovir or foscarnet in patients resistant to acyclovir.

Peripheral nervous system. Affecting nerves other than in the brain and spine. Usually caused by HSV-1.

Portion of the face temporarily paralyzed (Bell's palsy). Other areas of the body may exhibit numbness or loss of feeling to the touch.

Acyclovir or similar drugs in combination with oral prednisone.

Other skin areas (herpetic erythema multiforme). May follow any form of recurrent HSV. Is relatively rare.

Circular or irregular eruptions on backs of arms and hands. Recurrence of erythema multiforme is common in the same areas. This is actually an allergic reaction that lasts two to three weeks.

Usually minor and resolves without complications. Acyclovir and symptom relievers (common pain relievers, cold compresses, topical steroids, saline gargles).

Esophagus. Usually caused by HSV-1. Typically occurs in immunocompromised patients or in those taking long-term steroids or other immunosuppressant drugs, but can occur in infected people with normal immune systems.

Herpetic esophagitis Click the icon to see an image of herpetic esophagitis.

Difficulty swallowing or burning, squeezing throat pain while swallowing, weight loss, pain in or behind the upper chest while swallowing. Herpes lesions difficult to differentiate from other throat sores.

Intravenous acyclovir may be recommended. Recurrences are rare in patients with healthy immune systems, so preventive therapy is usually unnecessary in these patients.

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