Physical exam: Signs and symptoms associated with herpes viral infections in humans can vary greatly depending upon the specific virus infecting the individual. Healthcare providers diagnose this group of infections by visual inspection and by taking a sample from the sore(s) for testing in a laboratory. Between outbreaks, these herpes infections can be difficult to diagnose. Viral diagnostic tests can also performed to determine what type of herpes virus is infecting the individual.
Herpes viral infections may be confused with other conditions. Varicella-zoster virus (chickenpox), particularly in early stages, may be confused with herpes simplex, impetigo (bacterial skin infection), insect bites, or scabies (skin infection by mites). The early prodromal stage of shingles can cause severe pain on one side of the lower back, chest, or abdomen before the rash appears. It therefore may be mistaken for disorders, such as gallstones, that cause acute pain in internal organs. In the active rash stage, shingles may be confused with herpes simplex virus, particularly in young adults and if the blisters occur on the buttocks or around the mouth. Herpes simplex does not usually generate severe or chronic pain. A diagnosis may be difficult if herpes zoster takes a non-typical course, such as with Bell's palsy (a neurological condition involving facial paralysis) or Ramsay Hunt syndrome (a neurologic disorder caused by a varicella zoster virus that infects certain nerves in the head) or if it affects the eye or causes fever and delirium.
Viral culture: A viral culture uses specimens taken from the blister, fluid in the blister, or sometimes spinal fluid. The samples are sent to a laboratory where they are analyzed. It takes between one and 14 days to detect the virus in the preparation made from the specimen. A viral culture is also sometimes used in vaccinated patients to determine if a varicella-like infection is caused by a natural virus or by the vaccine. This test is useful, but it is sometimes difficult to detect the virus in the samples.
Immunofluorescence assay: Immunofluorescence is a diagnostic technique used to identify antibodies to a specific virus. In the case of herpes zoster, the technique uses ultraviolet rays applied to a preparation composed of cells taken from the patient's zoster blisters. The specific characteristics of the light, as seen through a microscope, will identify the presence of the antibodies. This test is less expensive, more accurate, and faster than a viral culture.
Polymerase chain reaction (PCR): Polymerase chain reaction (PCR) uses a piece of the DNA of the virus, which is then replicated millions of times until the virus is detectable. A sample of the individual's tissue from a sore is prepared and analyzed in a complicated laboratory test. This technique is expensive but is useful for unusual cases, such as identifying infection in the brain and spinal cord. This type of testing would be used to detect the presence of the herpes simplex virus in those who have genital sores, encephalitis (inflammation of the brain), and in newborns suspected of having neonatal herpes (a rare but serious condition where herpes is contracted during birth). A pregnant woman who has been diagnosed with herpes may be monitored regularly prior to delivery to identify a reactivation of her infection (which would indicate the necessity for a caesarean section to avoid infecting the baby). The primary methods of testing for the virus are the herpes culture and HSV DNA testing.
A positive herpes simplex culture or HSV DNA test from a vesicle scraping indicates an active HSV-1 or HSV-2 infection. A negative test result does not definitely rule out the presence of virus; for instance, the test may not be accurate if the herpes simplex virus was not isolated from the vesicle scraping.
signs and symptoms
Herpes simplex virus type 1 (HSV-1, oral herpes): Symptoms of cold sores are blisters on or around the lips and the edge of the mouth. The first symptom that may appear during an outbreak of oral herpes or cold sores may include tingling, burning, or itching in the area around the mouth or nose. This first portion of the outbreak is known as the prodromal stage or period. Within a few hours to days, the area may become reddened and develop small fluid-filled blisters called vesicles. Several of these small blisters may even come together and form one large blister. Cold sore blisters usually break open, weep clear fluid, and then crust over and disappear after a few days. The patient may experience symptoms including a sore mouth that makes eating, drinking, and sleeping uncomfortable. Other symptoms include fever, sore throat, and swollen lymph nodes in the neck. Symptoms usually last seven to ten days.
Herpes simplex virus type 2 (HHV-2, genital herpes): Signs of genital herpes (HSV-2) tend to develop within three to seven days of skin-to-skin contact with an infected person. Genital herpes infections look like small blisters or ulcers (round areas of broken skin) on the genitals. Each blister or ulcer is typically only one to three millimeters in size, and the blisters or ulcers tend to occur in groups. The blisters usually form first then soon open to form ulcers. Herpes infections may be painless or slightly tender. In some individuals, however, the blisters or ulcers can be very tender and painful. In men, genital herpes (sores or lesions) usually appear on or around the penis. In women, the lesions may be visible outside the vagina, but they commonly occur inside the vagina. Lesions inside the vagina may cause discomfort or vaginal discharge, but may be difficult to see, except during a doctor's examination. In any individual, ulcers or blisters may be found anywhere around the genitals (the perineum) and in and around the anus. The first herpes outbreak is usually the most painful, and the initial episode may last longer than later outbreaks. Some individuals develop other signs of herpes infection, particularly with the first episode, including fever, muscle aches, headaches (may be severe), vaginal discharge, painful urination, and swollen and tender lymph glands in the groin (glands swell as the body tries to fight the infection). If the disease returns, later outbreaks generally have much less severe symptoms. Many individuals with recurrent disease develop pain in the area of the infection even before any blisters or ulcers can be seen. This pain is due to irritation and inflammation of the nerves leading to the infected area of skin. These are signs that an outbreak is about to start. An individual is particularly contagious during this period, even though the skin still appears normal.
Varicella-zoster virus (chickenpox):
Individuals with chickenpox may notice several symptoms before the typical chickenpox rash appears. Known as prodromal, or early symptoms, they include fever, a vague feeling of sickness, or decreased appetite. Within a few days, a rash appears as small red pimples or blisters. The rash appears in batches over the next two to four days. It usually starts on the trunk and then spreads to the head, face, arms, and legs. Blisters may also be found in the mouth or the genital areas, because the virus can affect mucous membranes. Although some individuals may have only a few blisters, some have 100-300 blisters present. The pimples will progress to red teardrop blisters about five to ten millimeters (1/4-1/2 inch) wide. The blisters mature, break open, form a sore, and then crust over. Most of the blisters will heal within 10-14 days, and usually do not cause scarring unless the blisters become infected.
Varicella-zoster virus (shingles): Shingles usually begins with an unpleasant itching, burning, tingling, or painful sensation in a band-like area. The period of time when these sensations occur without a skin rash is called the prodromal period. During this time, the individual may have symptoms including fever, muscle aches, fatigue, anxiety (nervousness), and discomfort in the skin (usually on one side of the face, torso, trunk, back, or buttocks). The discomfort may feel like numbness, itching, burning, stinging, tingling, shooting pain, electric shock, sharp pain, and extreme sensitivity to even light touch. Symptoms of active shingles includes a rash that begins as a reddish band or individual bumps running in a line and bumps developing with fluid-filled centers. Over the course of seven to 10 days, the bumps begin to dry and crust over. The individual may continue to have pain and/or itching in the area of the rash. The pain may be severe. If the rash develops on the side of the nose or elsewhere on the face, the individual should contact their healthcare provider immediately. This can signal that the eyes may be infected. Although the rash of active shingles usually subsides within a week to a month, some individuals continue to have pain and discomfort well after the rash has healed. This syndrome of pain in the area of the previously infected nerve is called postherpetic neuralgia (PHN), and it can be quite severe and debilitating.
Epstein Barr virus: Epstein-Barr virus can cause fever, a sore throat, swollen lymph glands- especially in the neck, and extreme fatigue or tiredness. Although typically caused by the Epstein-Barr virus (EBV), mononucleosis can also be caused by other herpes viruses including cytomegalovirus (CMV). Infection with EBV during adolescence or young adulthood results in mononucleosis in 35-50% of the cases. The incubation period for the mononucleosis is usually seven to 14 days in children and adolescents. The incubation period in adults is longer; at times it may be 30-50 days. If symptoms of mononucleosis last more than six months, it is frequently referred to as chronic EBV infection. EBV may be linked to chronic fatigue syndrome, a condition of chronic tiredness and exhaustion.
Symptoms of mononucleosis develop slowly, with such mild symptoms initially that it may be mistaken for a cold or the flu. As the condition progresses the symptoms may include a sore throat that lasts two weeks or more, swollen lymph nodes (in the neck, armpits, and groin), a persistent fever, fatigue (tiredness), and malaise (a vague feeling of discomfort). These symptoms can be mild or so severe that throat pain impedes swallowing and fever reaches 105 degrees Fahrenheit. Some individuals also experience a rash, eye pain, photophobia (discomfort with bright light), and a swollen spleen or liver. In most cases of mononucleosis, no specific treatment is necessary as the illness is usually self-limiting. Although the symptoms of infectious mononucleosis usually resolve in one or two months, the EBV remains dormant in cells in the throat and blood for the rest of the person's life. Periodically, the virus can reactivate and can be found in the saliva of infected persons. This reactivation usually occurs without symptoms of illness, although it may be linked to symptoms of CFS. EBV also establishes a lifelong dormant infection in some cells of the body's immune system.
Cytomegalovirus (CMV): In people with weakened immune systems (such as those with HIV or AIDS), cytomegalovirus (CMV) can cause any number of infections including retinitis (inflammation of the retina), pneumonia, colitis (inflammation of the colon), encephalitis (inflammation of the brain), mononucleosis, pneumonia, hepatitis, and uveitis. CMV syndrome and fever of unknown origin (known as pyrexia) are complications that may occur. CMV is a common a cause of serious disability such as neural tube defects. Neural tube defects (NTDs) are serious birth defects with symptoms that range from mild to severe impairment. They are caused by incomplete development of the brain, spinal cord, and/or their protective coverings.
risk factors and causes
Herpes simplex virus type 1 (HSV-1, herpes labialis): Everyone is at risk for HSV-1 (herpes labialis or oral herpes). It is easily transmitted and is the most common form of the herpes simplex virus. Oral herpes (cold sores or fever blisters) affects between 15-30% of the entire population, and most people are infected when they are with highest incidence first occurring between six months and three years old. HSV-1 can be spread by close contact with someone who has a cold sore or by using items contaminated with the virus. Kissing someone on the mouth will spread the virus and sharing personal items such as razors, towels, or eating utensils with a person who has oral herpes will increase the risk of getting HSV-1. The virus can also be spread to the genital area of another individual by having oral sex. Individuals with oral herpes should not perform oral sex on their partners. They should also avoid kissing. Infants and young children (up to three years old) have an increased risk of being exposed to HSV-1 due to immune systems that are still not fully developed.
Exposure to sunlight or other ultraviolet light is a common trigger for the formation of cold sores. Stress on the body due to illness or excessive exercise can weaken the body's immune system and lead to an outbreak of oral herpes. Common examples of stress or illness include infection, fever, a cold, physical injury, dental surgery, menstruation, medications (including steroids), or illnesses such as human immunodeficiency virus (HIV) that suppress the immune system, eczema, excessive exercise, and emotional stress.
It should be noted that HSV-1 is becoming a major cause of genital herpes as well and in some studies it is now a more important cause.
Herpes simplex virus type 2 (HHV-2, genital herpes): Anyone who is sexually active is at risk for genital herpes and it is on the rise. Some reports estimate 31 million cases of HHV-2 or genital herpes occur in sexually active adults annually in the United States. The risk of HSV-2 infection is higher in women than in men. The largest increases in HSV-2 occur in women after their early twenties. Women have an 80- 90% chance of contracting HSV-2 after unprotected sexual activity with an infected partner and are 1.7 times more likely to be infected than men. Men, however, have twice as many recurrent infections as women. Less than one percent of American children younger than fifteen test positive for HSV-2; sexual abuse should be considered in children with HSV-2. Although African Americans are more likely to test positively for HSV-2, Caucasians have a higher risk for active genital symptoms and over the past few years the greatest increase in HSV-2 has been observed in white adolescents.
Varicella-zoster virus (chickenpox):
Before the introduction of the vaccine, about four million cases of chickenpox were reported in the United States each year. Between 75-90% of chickenpox cases occur in children under 10 years of age. Since a varicella vaccine became available in the United States in 1995, however, the incidence of disease and hospitalizations due to chickenpox are showing a dramatic decrease. Experts expect the disease to become a rarity in the United States.
The risk of chickenpox is high in late winter and early spring months. Primary transmission of chickenpox includes direct contact with the individual carrying the virus or by inhaling the virus from the air. It can also be transmitted from direct contact with the open sores. However, clothing and bedding do not usually spread the disease.
An individual with chickenpox can transmit the disease from about two days before the appearance of the spots to the end of the blister stage. This period lasts about five to seven days. Once dry scabs form, the disease is unlikely to spread.
Most schools allow children with chickenpox back after ten days of onset to avoid the risk of spreading the infection. Some require children to stay home until the skin has completely cleared, although this measure is not necessary to prevent transmission.
Individuals at a higher risk for developing chickenpox include individuals of any age who have neither had chickenpox in the past nor been immunized against chickenpox, newborns, individuals with a weakened immune system, and individuals who are taking immunosuppressant drugs. Also at risk are individuals who are moderately or severely ill and are not yet fully recovered, individuals who have disorders affecting the blood, bone marrow, or lymphatic system, the elderly, and pregnant women. If an individual is not immune to chickenpox, traveling abroad can increase the risk of contracting the condition.
Males (both boys and men) have a higher risk for a severe case of chickenpox than females. The older the child, the higher the risk for a more severe case. But even in such circumstances, chickenpox is rarely serious in children.
Varicella-zoster virus (shingles): About 500,000 cases of shingles occur each year in the United States. Anyone who has had chickenpox has risk for shingles later in life, which means that 90% of U.S. adults are at risk for shingles. Shingles occurs in about 10-20% of adults who have had chickenpox. The risk for herpes zoster increases as people age, so the overall number of cases will undoubtedly increase as the baby boomer generation gets older. One study estimated that an individual who reaches 85 has a 50% chance of having herpes zoster. The risk for postherpetic neuralgia (PHN, or pain that persists after the outbreak healed) is also highest in older people with the infection, increasing dramatically after age 50. Individuals whose immune systems are impaired from diseases such as those with human immunodeficiency virus (HIV), acquired immunodeficiency syndrome (AIDS), or childhood cancer have a risk for herpes zoster that is much higher than those with healthy immune systems. In fact, herpes zoster in people who are HIV positive may be a sign of full-blown AIDS. Current drugs used for HIV, called protease inhibitors, may also increase the risk for herpes zoster. Cancer places people at high risk for herpes zoster. At highest risk are those with Hodgkin's disease (13-15% of these patients develop shingles). About seven to nine percent of patients with lymphomas and between one to three percent of patients with other cancers have herpes zoster. Individuals who take certain drugs that suppress the immune system are at risk for shingles (as well as other infections) including azathioprine (Imuran®), chlorambucil (Leukeran®), cyclophosphamide (Cytoxan®), and cyclosporine (Sandimmune®, Neoral®). These drugs are used in patients who have undergone organ transplantation, but they are also often used for severe autoimmune diseases caused by the inflammatory process. Such disorders include rheumatoid arthritis, systemic lupus erythematosus, diabetes, multiple sclerosis, Crohn's disease, and ulcerative colitis.
Interestingly, one study suggested that previously infected adults who are exposed to children with chickenpox may receive an extra boost in antibody production that can actually help them fight off herpes zoster. This means that as more children are vaccinated against chickenpox, more adults may be at risk for herpes zoster. There is a vaccine now available that may prevent shingles or lessen its effects (Zostavax®). The vaccine is for people 60 or older who have had chickenpox but who have not had shingles.
Although most common in adults, shingles can also develop in children. One study reported that only five percent of shingles cases occur in those under age 15. Children with immune deficiencies are at highest risk. Children with no immune problems and those who had chickenpox before they were one year-old are at higher risk for shingles. It is still uncommon, however.
Herpes simplex virus: Although genital herpes usually causes mild symptoms, some people may experience recurrent painful genital ulcers, which can be especially severe in people with suppressed immune systems. Like other sexually transmitted diseases (STDs), herpes may also increase the risk for transmitting or acquiring the human immunodeficiency virus (HIV).
All herpes viruses can be passed from mother to baby. The chance of giving herpes to the baby is highest if the first infection occurs near the time of delivery. The virus can be transmitted to the fetus while in-utero (inside the womb) or during passage through an infected vagina at birth. First-time infection during pregnancy leads to an increased risk of miscarriage, decreased fetal growth, and preterm labor. About 30-50% of infants who are born vaginally to a mother with first-time infection become infected with the herpes virus. Of babies born to women experiencing recurrent herpes at the time of birth, one to four percent become infected with the herpes-simplex virus.
If a woman is having an active outbreak of genital herpes at the time of delivery, the baby will usually be delivered by cesarean section to prevent transmission of herpes. Of infants infected with herpes at birth, 30-60% die within the first month. Survivors may have long-term complications such as mental retardation and seizures. To prevent transmission of herpes to their babies, pregnant women should discuss any past history of herpes with their healthcare providers and take adequate measures to prevent infection during pregnancy. The risk of herpes can be reduced during pregnancy by avoiding sexual intercourse (vaginal, anal, and oral) during the last three months of pregnancy if the partner is known to have or suspected of having genital herpes and avoiding receptive oral sex during the last three months of pregnancy if the partner is known to have or suspected of having herpes sores on the mouth, tongue, gum, or lips. Infidelity plays an important role in genital herpes transmission.
Herpes simplex viruses (HSV) can also cause several ocular (eye) lesions including HSV blepharitis, HSV conjunctivitis, HSV keratitis, HSV infectious epithelial keratitis, HSV anterior uveitis, and HSV retinitis.
Varicella-zoster virus: Pregnant women and anyone with immune system problems should not be near a person with chickenpox. If a pregnant woman who has not had chickenpox in the past contracts the virus (especially in the first 20 weeks of pregnancy), the fetus is at risk for birth defects. The mother is at risk for more health complications than if she had been infected when she was not pregnant. If the mother develops chickenpox just before or after the child is born, the newborn is at risk for serious health complications. There is no risk to the developing baby if the woman develops shingles during the pregnancy. If a pregnant woman has had chickenpox before the pregnancy, the baby will be protected from infection for the first few months of life, since the mother's immunity gets passed on to the baby through the placenta and breast milk. Those at risk for severe disease or serious complications may be given varicella-zoster immune globulin (VZIG, a vaccine for varicella-zoster virus) after exposure to chickenpox to reduce its severity. This group of people includes newborns whose mothers had chickenpox at the time of delivery, individuals with leukemia or immune deficiencies, and children receiving drugs that suppress the immune system.
Chickenpox rarely causes complications, but it is not always harmless. Five out of every 1,000 children who have the infection require hospitalization, and, in rare cases, chickenpox can be fatal. Chickenpox has caused about 11,000 hospitalizations each year and 100 deaths per year in the United States. Widespread vaccination, however, has produced a dramatic decline in these numbers.
The most common complications of chickenpox include itching, infections (usually from Staphylococcus aureus or Streptococcus pyogenes), scarring (complicated by scratching), ear infections, pneumonia, and encephalitis (inflammation of the brain). Other extremely rare complications of chickenpox include problems in blood clotting and inflammation of the nerves in the hands and feet. Inflammation in other parts of the body, including the heart, testicles, liver, joints, or kidney, may also occur. Such cases of inflammation are almost always temporary in otherwise healthy patients.
Complications of shingles (herpes zoster) include post-herpatic neuropathy (PHN) pain, which can either be continuous burning or aching pain, periodic piercing pain, or spasm similar to electric shock. The pain tends to be more severe at night. Temperature changes can also affect pain. The pain may extend beyond the areas of the initial zoster attack and some areas have no feeling at all. In most cases, it does not affect daily life. Rarely, however, the pain of herpes zoster affects sleep, mood, work, and overall quality of life. This can lead to fatigue, loss of appetite, depression, social withdrawal, and impaired daily functioning. Itching is also common in individuals with shingles. Infections may occur in the blisters associated with shingles.
Shingles may lead to meningitis (inflammation of the membrane around the brain) or encephalitis (inflammation of the brain). The encephalitis is generally mild and resolves in a short period. In rare cases, particularly in patients with impaired immune systems, these inflammations can be severe and even life-threatening. Also, in rare situations herpes zoster can infect the urinary tract and cause difficult urination. The condition is temporary but may require a catheter to eliminate urine in some patients who have prolonged difficulty urinating. If shingles occurs in the face, the eyes are at risk, particularly if the path of the infection follows the side of the nose. Severe infections can occur if the eyes become involved that are difficult to treat and can threaten vision, called herpes zoster ophthalmicus. AIDS patients may be at particular risk for a chronic infection in the cornea of the eye. Herpes zoster can also cause a devastating infection in the retina called imminent acute retinal necrosis syndrome. In such cases, visual changes develop within weeks or months after herpes zoster outbreak has resolved. It should be noted that this complication does not always follow a herpes outbreak in the face but can occur after an outbreak in any part of the body. Prompt treatment with a drug called acyclovir (Zovirax®) can often halt the progress of vision loss, at least in people with healthy immune systems.
In very rare cases, herpes zoster has been associated with Stevens-Johnson syndrome, an extensive and serious condition in which blisters cover most mucous membranes along with large areas of the body.
Ramsay Hunt syndrome:
Ramsay Hunt syndrome is a condition of facial paralysis and rash on the ear or mouth that occurs during a herpes zoster viral infection. Symptoms include severe ear pain and hearing loss, ringing in the ear(s), loss of taste, nausea, vomiting, and dizziness. Ramsay Hunt syndrome may also cause a mild inflammation in the brain. The dizziness may last for a few days or even for weeks, but usually resolves. Severity of hearing loss varies from partial to total. However, this hearing loss almost always goes away. Facial paralysis, on the other hand, may be permanent.
Bell's palsy: Bell's palsy is partial paralysis of the face. In some cases, it is difficult to distinguish between Bell's palsy and Ramsay Hunt syndrome, particularly in the early stages. Ramsay Hunt syndrome tends to be more severe than Bell's palsy. Some healthcare providers recommend oral prednisone (a corticosteroid) along with an antiviral drug (such as acyclovir or Zovirax®) within seven days after symptoms appear.