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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

Complications

The severity of symptoms depends on where and how the virus gains entry into the body. Except in very rare instances and in special circumstances, the disease is not life threatening, although it can be very debilitating and cause great emotional distress.

Effects of Herpes Virus on Pregnancy

Depending on specific factors, HSV can have serious effects on both a pregnant woman and her child. It should be noted, however, that about one million pregnancies occur each year in women who have been infected with HSV-2, but complications occur in less than four out of a 1000 infected pregnant women.

Congenital herpes
Infants may acquire congenital herpes from a mother with an active, possibly inapparent herpes infection at the time of birth. Aggressive treatment with antiviral medication is required, but may not be effective in the case of systemic herpes.

Effects on the Brain and Central Nervous System

Herpes Encephalitis. Each year accounts for 2100 cases of encephalitis in the US, a rare but extremely serious brain disease. HSV-1 is almost always the culprit, except in newborns. In about 70% of infant herpes encephalitis, the disease occurs when a latent HSV-2 virus is activated. Untreated, herpes encephalitis is fatal in over 70% of cases. Respiratory arrest can occur within the first 24 to 72 hours. Fortunately, rapid diagnostic tests and treatment with acyclovir have significantly improved both survival rates (up to about 80%) and reduced complication rates (to nearly 40%). For those who recover, nearly all suffer some impairment, ranging from very mild neurological changes to paralysis. Recovery from HSV encephalitis is dependent on the patient's age, the level of consciousness, duration of the disease, and the promptness of treatment. The best chances for a favorable outcome occur in patients who are treated with acyclovir within two days of becoming ill.

Herpes Meningitis. Herpes meningitis, an inflammation of the membranes that line the brain and spinal cord, occurs in up to 10% of cases of primary genital HSV-2. Women are at higher risk for it than men are. Symptoms include headache, fever, stiff neck, vomiting, and sensitivity to light. Fortunately, herpes meningitis usually resolves without complications, lasting for only two to seven days, although recurrences have been reported.

Meninges of the brain Click the icon to see an image of the meninges of the brain.

Alzheimer's Disease. Some studies indicate a higher risk for Alzheimer's in people who have both HSV-1 and a gene called ApoE4, a known risk factor for Alzheimer's. Furthermore, a protein found in HSV-1 has been shown to mimic beta amyloid, a protein now strongly believed to be a critical player in the Alzheimer's disease process.

Other Neurologic Diseases. Other neurologic syndromes that have been linked to HSV infection include epilepsy, multiple sclerosis, atypical pain syndromes, ascending or transverse myelitis (inflammation of the spinal column), and neuralgia (severe stabbing pain along a nerve or group of nerves).

Eczema Herpeticum

A form of herpes infection called eczema herpeticum, also known as Kaposi's varicellum eruption, can afflict patients with preexisting skin disorders and immunocompromised patients. The disease tends to develop into widespread skin infection and resemble impetigo. Symptoms appear abruptly and can include fever, chills, and malaise. Clusters of dimpled blisters emerge over seven to 10 days and spread widely. They can become secondarily infected with staphylococcal or streptococcal organisms. When treated, lesions heal in two to six weeks. Untreated, this condition can be extremely serious and possibly fatal.

Ocular Herpes and Vision Loss

Herpetic infections of the eye (ocular herpes) occur in about 50,000 Americans each year. In most cases it causes inflammation and sores on the lids or outside of the cornea that resolves in a few days.

Eye Click the icon to see an image of the eye.

Stromal Keratitis. Stromal keratitis occurs in up to 25% of ocular herpes. In this condition, deeper layers of the cornea are involved, possibly as an abnormal immune response to the original infection. In these rare cases, scarring and corneal thinning develop, which may cause the eye's globe to rupture and result in blindness. Although rare, it is the major cause of corneal blindness in the US.

Iridocyclitis. Iridocyclitis is another serious complication of ocular herpes, in which the iris and the area around it become inflamed.

Gingivostomatitis

HSV can cause multiple painful ulcers on the gums and mucous membranes of the mouth, a condition called gingivostomatitis. This condition usually affects children between the ages of one and five. It nearly always subsides within two weeks. In rare cases, it can progress to a systemic viral infection. Children with gingivostomatitis commonly develop herpetic whitlow, or herpes of the fingers.

Other Disorders Linked to Herpes Simplex

A number of other conditions have been linked to HSV infections, although the association has not been substantiated in most cases.

  • Arthritis, usually in a single joint, has been sporadically reported as a result of HSV infection.
  • People with HSV-2 may have an increased susceptibility for sexually transmitted hepatitis C.
  • Some evidence suggests that HSV-1 may slightly increase the risk for certain cancers of the mouth or throat in people who are already at higher risk because of cigarette smoking or infection with another microorganism called human papillomavirus.
  • Some studies have reported associations between herpes simplex and other infectious agents with heart disease, including lower survival rates. Such infections may produce persistent inflammation in the arteries leading to heart trouble. Research is ongoing.
  • Other rare complications of herpes simplex include erosion or ulcers in the lining of the esophagus and stomach. Certain kidney and blood diseases have also been reported in conjunction with HSV infection. These are very uncommon, however, particularly in people with healthy immune systems.

Emotional and Social Effects of Genital Herpes

Not least among the damaging effects of genital herpes is its impact on the social and emotional life of patients. In one survey of herpes patients, 82% felt depressed and 75% were worried about rejection. Over a quarter had suicidal thoughts. In nearly 80% of the respondents, the disease had a profound effect on their sexual lives. The patient must notify sexual partners, past and present, about their condition, a deeply humiliating experience. Guilt and anger are common emotions, and relationships may be shattered. It is important to note that the condition is often dormant for many years and may not have been transmitted by a current sexual partner. Support groups or couple therapy can be very helpful.

Herpes in Patients with Compromised Immune Systems from HIV or Other Causes

Herpes simplex is particularly devastating when it occurs in immunocompromised patients, and, unfortunately, coinfection is common. People infected with HSV have a fourfold increased risk for contracting HIV, the virus that causes AIDS. Furthermore, studies report between 68% and 81% of patients with HIV are also infected with the HSV-2. Other immunocompromised patients include cancer or burn patients and people who are using immunosuppressant drugs (e.g., agents used after organ transplantation, long-term or high-dose steroids).

Patients with HIV are particularly vulnerable to complications. When both viruses are present, there appears to be a synergy between them, with each increasing the severity of the other. However, herpes simplex in any patient with a seriously compromised immune system can cause serious and even life-threatening complications, including the following:

  • Pneumonia.
  • Liver damage, including hepatitis. Hepatitis caused by primary or recurrent HSV can sometimes develop into a life-threatening condition called fulminant liver failure. This condition is treatable with medications or even a liver transplant when diagnosed promptly. Early symptoms may include nausea, vomiting, and abdominal pain. (This is an uncommon complication in HSV-infected people with healthy immune systems, but cases have been reported, such as after surgical procedures.)
  • Inflammation of the esophagus.
  • Encephalitis (inflammation of the brain).
  • Destruction of the adrenal glands.
  • Disseminated herpes (spread of infection throughout the body).

Less serious conditions include stomach and anal ulcers, inflammation in the colon, and eczema herpeticum.

Herpes in the Pregnant Woman and the Newborn

HSV can cause serious complications in both the mother and the child. It should be noted, however, that each year about one million women infected with HSV-2 become pregnant, but complications occur in less than one in a thousand of them.

Effect of HSV on the Pregnant Woman

Pregnant women who are infected with either HSV-2 or HSV-1 genital herpes have a higher risk for miscarriage, premature labor, retarded fetal growth, or transmission of the HSV infection to the infant while in the uterus or at the time of delivery. One study also suggested a link between HSV-2 infection in mothers and the subsequent development of schizophrenia and other forms of psychoses in their adult offspring, although further study is needed. Recurrence in women previously infected with HSV is also common during pregnancy.

Approach to the Pregnant HSV Patient. The approach to a pregnant woman who has been infected by either HSV-1 or 2 in the genital area is usually determined by when the infection was acquired and the mother's condition around the time of delivery:

  • If lesions are present at the time of birth, Cesarean section is usually recommended. An important 13-year study confirmed that this approach helps prevent transmission. In the study the baby became infected in only 1.1% of Cesarean sections compared to 7.7% of vaginal deliveries. (Even a Cesarean section is no guarantee that the child will be HSV-free and the newborn must still be tested.)
  • If lesions erupt shortly before the baby is due then samples must be taken and sent to the laboratory. Samples are cultured to detect the virus at three- to five-day intervals prior to delivery to ascertain whether viral shedding is occurring. If no lesions are present and cultures indicate no viral shedding, the delivery is normal and the newborn is examined and cultured after delivery.

The safety of acyclovir and other agents used to treat herpes in nonpregnant patients is unproven. These drugs, then, are generally not used during pregnancy for either primary infection or to prevent recurrences unless the HSV infection is life threatening. Some physicians, however, recommend suppression therapy during late pregnancy for patients with a known history of genital herpes. Small studies to date indicate that acyclovir does not harm the fetus under these circumstances, although it is also not completely protective against recurrence. (Evidence has also not found any higher risk for birth defects in the unborn child if the mother has been taking acyclovir in early pregnancy.) In general, however, evidence supporting anti-viral suppression treatment during pregnancy is not strong and the risks are still unknown.

How HSV is Transmitted to Newborns

Although 25% to 30% of pregnant women in the US and Europe have a history of HSV-2 infection, the risk of transmission to the newborn is low, occurring in between one in 3,500 to 20,000 births depending on the population group.

The greatest danger to the baby is from an asymptomatic infection during a vaginal delivery in women who acquired the virus for the first time late in the pregnancy. In such cases, between 30% and 50% of the newborns become infected. Recurring herpes or a first infection that is acquired early in the pregnancy poses a much lower risk (less than 1%) to the infant.

The reasons for the higher risk with a late primary infection are the following:

  • During a first infection the virus is shed for longer periods and more viral particles are excreted.
  • An infection that first occurs in the late term does not allow the mother to develop antibodies that would help her baby fight off the infection at the time of delivery.

The risk for transmission also increases if infants with infected mothers are born prematurely, if there is invasive monitoring, or if instruments are required during vaginal delivery. Transmission can occur if the amniotic membrane of an infected woman ruptures prematurely, or as the infant passes through an infected birth canal. Very rarely, the virus is transmitted across the placenta, a form of the infection known as congenital herpes.

Unfortunately, only 5% of infected pregnant women have a history of symptoms, so in many cases HSV infection is not suspected or symptoms are missed at the time of delivery. Occasionally, lesions on the mother's buttocks may help indicate the presence of the virus.

Effects of HSV in the Newborn

HSV infection in a newborn is a very serious and even-life threatening condition if it goes undiagnosed and untreated. Fortunately, since the introduction of acyclovir the outlook for these children has significantly improved. In general, there are three categories of HSV in the newborn:

  • Localized infection affects the skin, eyes, and mucous membranes. This condition is usually caused by HSV-1 and is temporary. However, in some cases, most often HSV-2 infections, later complications develop in between 5% and 10% of infants. If untreated, it may progress to very severe complications, notably disseminated or central nervous system infection.
  • Disseminated disease can affect internal organs, such as the liver, the lungs, and the adrenal glands. It is fatal in up to 80% of newborns if left untreated and those who survive are at high risk for complications, particularly in the eyes. If infants are treated, however, survival rates are close to 90%.
  • Central nervous system infection can cause meningitis or encephalitis. This form is also highly fatal and complications that affect learning and mental functions are common in surviving children.

Factors that Indicate a Higher Risk for Severe Complications:

  • Acute infection in the mother at delivery.
  • Prematurity.
  • Seizures in the infant.
  • Disseminated intravascular coagulopathy, a blood clotting disorder that can occur in response to infection.

Factors that Indicate a Lower Risk for Severe Complications:

  • Newborn infection caused by a recurring HSV-2 infection in the mother. (Mothers with such infections appear to pass along protective antibodies to the newborn. It should be noted that antibodies to HSV-1 do not appear to offer similar protection to the newborn.)
  • Newborn infections that are confined to the skin and do not cause frequent outbreaks within the first six months.

Tests for the Newborn at Risk for HSV. Any newborn with an infected or high-risk mother should be tested and checked carefully for symptoms. (Experts are divided, however, over whether the high cost of testing mothers specifically for HSV before delivery, even in high-risk groups, is worth the benefit for such a small group of mothers and infants.)

  • In the asymptomatic newborn delivered from an infected mother, cultures should be taken between 24 and 48 hours after birth. A culture taken right at the time of delivery may give a false indication of infection in the baby, simply because it can carry some of the mother's virus from the birth canal.
  • Testing specimens for viral DNA using a test called polymerase chain reaction (PCR) is proving to be very important in newborns, particularly when central nervous system infection is suspected, since it eliminates the need for brain biopsies.
  • While results are pending, the baby should be checked regularly for rashes and blisters, particularly in areas where the skin is broken, along with any signs of illness including fever, lethargy, respiratory distress, and poor feeding.

Symptoms of HSV in the Newborn. Although treatments have improved the outlook of infected newborns, there has been little change over the past 20 years in the time between the onset of symptoms and the initiation of treatments. Physicians and parents should be suspicious of any signs if there is any risk of infection to the newborn.

When symptoms occur in newborns, they usually become apparent within five to 17 days of life, but they may develop as early as 24 hours or as late as 34 days.

  • An unstable temperature can be the first indication of the infection.
  • About half of infected infants develop a rash. Lesions may range from raised spots to large isolated blisters. They can be anywhere on the skin or eyes or in the mouth.
  • The other half of infected infants does not develop lesions until later in the course of the infection. The absence of lesions, therefore, in high-risk infants should not be considered a guarantee that HSV has not been transmitted.
  • Other symptoms to watch for include irritability, blotchy skin, discharge in the eyes, sensitivity to light, tearing, lethargy, jaundice, pallor, coughing, rapid breathing, a swollen abdomen (enlarged spleen), seizures, or tremors. Infection should be suspected in any infant with fever, irritability, lethargy, or poor feeding at one week of age.

Treatment of HSV in the Newborn. If HSV infection in a newborn infant is suspected, intravenous acyclovir treatment should begin immediately, since the potential dangers of the condition far outweigh any risks associated with the drug. (The newer agents valacyclovir and famciclovir offer no additional advantage.) Vidarabine (Vira-A) is sometimes used as an alternative to acyclovir, but it is much less effective and should be used only if the baby is resistant to acyclovir.

The following are recommendations for treating infants who have been infected or are at risk for infection:

  • If disseminated or central nervous system infection has developed or is suspected, intravenous acyclovir treatment should continue for 21 days.
  • If the infection is limited to the skin, eyes, or mouth and the infant is at low risk for more serious complications, treatment may be given for 10 to 14 days.

The American Academy of Pediatrics Committee on Infectious Diseases now recommends higher-than-standard doses to improve outcome in infants who have any of these infections. Investigators are studying whether giving long-term oral acyclovir to newborns following the initial infection will improve the outcome.

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