Related Terms

• Acquired immunodeficiency syndrome, AIDS, antiviral, B-cell lymphotrophic virus, Bell's palsy, CFS, chicken pox, chickenpox, chronic fatigue syndrome, CMV syndrome, cold sore, colitis, contagious, corticosteroid, cutaneous, cytomegalovirus, down syndrome, EBV, encephalitis, epidural, Epstein-Barr virus, exanthema subitum, fetal alcohol syndrome, fever blister, fibromyalgia, genital herpes, gingivostomatitis, glomerulonephritis, Guillain-Barré syndrome, hepatitis, herpes labialis, herpes zoster ophthalmicus, herpetic, HHV-1, HHV-2, HHV-3, HHV-4, HHV-5, HHV-6, HHV-7, HHV-8, HIV, Hodgkin's disease, HSV anterior uveitis, HSV blepharitis, HSV conjunctivitis, HSV infectious epithelial keratitis, HSV keratitis, HSV neonatal infection, HSV retinitis, human herpesvirus type 4, human herpesvirus type 5, human herpesvirus type 6, human herpesvirus type 7, human herpesvirus type 8, human immunodeficiency virus, immunocompromised, immunofluorescence, Kaposi's sarcoma, Kaposi's sarcoma-associated virus, KS, latency, lesion, lymphocryptovirus, lymphocytes, lymphoma, lymphoproliferative disorders, lyphotrophic virus, MCD, meningitis, mono, monocytes, mononucleosis, multicentric Castleman's disease, myocarditis, neuropathy, ocular lesions, oropharyngeal, PCR, PEL, PHN, pneumonia, polymerase chain reaction, postherpetic neuralgia, primary effusion lymphoma, prodromal, pyrexia, Ramsay Hunt syndrome, retinitis, rhadinovirus, roseola, roseola infantum, roseolovirus, sexually transmitted disease, shedding, shingles, STD, steroid, topical, uveitis, vaccine, varicella-zoster virus, vesicle, VZV.

Background

• Herpes is a group of viruses that infect humans. Types of herpes viruses include herpes simplex virus types 1 and 2 (HSV-1 and HSV-2, respectively), human herpesvirus type 3 (HHV-3, or the varicella-zoster virus), human herpesvirus type 4 (HHV-4, including Epstein-Barr virus and lymphocryptovirus), human herpesvirus type 5 (HHV-5, or cytomegalovirus), human herpesvirus type 6 (HHV-6, including human B-cell lymphotrophic virus and roseolovirus), human herpesvirus type 7 (HHV-7), and human herpesvirus type 8 (HHV-8, including rhadinovirus and Kaposi's sarcoma-associated virus).

• The viruses fall into three categories: alpha-herpes viruses (HSV-1, HSV-2, and varicella-zoster virus), beta-herpes viruses (cytomegalovirus, HHV-6, and HHV-7), and gamma-herpes viruses (Epstein-Barr virus, lymphocryptovirus, and HHV-8). The viruses are different and cause various conditions with many unique signs and symptoms. However, all herpes viruses share some common properties, including a pattern of active symptoms followed by latent (inactive) periods with no symptoms that can last for months, years, or even for a lifetime. Herpes symptoms may even never reappear. The severity of herpes symptoms depends on the type of virus with which the individual is infected.

• Herpes simplex virus type 1 (HSV-1) is also known as a cold sore or fever blister. Herpes simplex virus type 2 (HSV-2) is also known as genital herpes. Human herpesvirus type 3 is also referred to as varicella-zoster virus or VZV. Herpes varicella is the primary infection that causes chicken pox, and herpes zoster is the reactivation of the varicella virus that causes shingles.

• Herpes simplex type 1 and type 2 infections are generally marked by painful, watery blisters in the skin or mucous membranes (such as the mouth or lips) or on the genitals. Lesions heal with a crust-forming scab, the hallmark of herpes. This is particularly likely during an outbreak, although individuals may shed virus between outbreaks. Although no cure is yet available, antiviral treatments exist that reduce the likelihood of viral shedding. An HSV infection on the lips, commonly known as a "cold sore" or "fever blister," should not to be confused with a canker sore; canker sores (painful sores on the tongue or oral membranes in the mouth) are not caused by HSV.

• Herpes is a contagious infection that spreads when the carrier is producing and releasing (or "shedding") the virus. Herpes viruses are transmitted from human to human in different ways. With HSV-1, contact and infection can occur directly from another human (such as mouth-to-mouth or hand-to-mouth contact) or through the use of everyday objects that have come in contact with the virus, including razors, towels, dishes, and glasses. Genital herpes, or HSV-2, can only be contracted through direct sexual contact with an infected partner (genital-to-genital, mouth-to-genital, or hand-to-genital contact, not through kissing). Occasionally, oral-genital contact can spread oral herpes to the genitals (and vice versa). Individuals with active herpes lesions on or around their mouths or their genitals should avoid oral sex. The varicella-zoster (chicken pox) virus spreads through the humidity in the air when inhaled and mainly spreads during the incubation period, which is just before an outbreak of symptoms.

• After an initial or primary infection, herpes viruses establish a period called latency, during which the virus is present in the cell bodies of nerves that innervate (attach) to the area of the original viral outbreak (such as the genitals, mouth, and lips). At some point, this latency ends, and the virus becomes active again. While active, the virus begins to multiply (this is called shedding) and becomes transmittable again. This shedding may or may not be accompanied by symptoms. During reactivation, virus is produced in nerve cells and transported outwardly via the nerve to the skin. The ability of herpes viruses to become latent and reactive explains the chronic (long-term), recurring (returning) nature of a herpes infection.

• Recurrence of the viral symptoms is usually milder than the original infection. Recurrence may be triggered by menstruation, sun exposure, fever-related illness, stress, immune system imbalances, and other unknown causes.

Type of Herpes

• Herpes simplex virus (HSV-1 and HSV-2):

• Herpes simplex virus (HSV): There are two types of HSV, including herpes simplex virus type 1 (HSV-1) and herpes simplex virus type 2 (HSV-2). Although some symptoms of HSV-1 and HSV-2 are similar (such as lesions), they are usually transmitted differently and involve different areas of the body.

• Herpes simplex virus type 1 (HSV-1): Herpes simplex virus type 1 is the cause of herpes labialis (fever blisters, cold sores) and involves the lips and inflammation of the gums and mouth. Other conditions caused by HSV-1 include oropharyngeal, cutaneous, and ocular lesions, including HSV blepharitis, HSV conjunctivitis, HSV keratitis, HSV infectious epithelial keratitis, HSV anterior uveitis, HSV retinitis, and HSV neonatal infection.

• HSV-1 is a very common virus, affecting more than 50% of the adult population in the United States by the age of 20. However, it is thought that up to 90% of adults have been exposed to the virus during their lifetime. After the first episode, the virus lies dormant in the nerves or skin around the original area until something sets the virus off into another eruption. Colds, flu, and even stress can cause an outbreak of cold sores. It is not well understood why an individual has an outbreak at one time of life and not another. Most people contract oral herpes when they are children by receiving a kiss from a friend or relative.

• The first symptoms usually appear within one, two, or as late as three weeks after contact with an infected person. The lesions of herpes labialis usually last for 7-10 days, then begin to resolve. Typically, the first episode of HSV-1 infections involves the formation of a single blister or cluster of blisters; during this first episode, the symptoms are usually the most pronounced. Following the active infection, the virus becomes latent (dormant), residing in the nerve cells, and may reactivate later, causing a new outbreak at or near the original site. Approximately 25% of people infected by HSV-1 experience recurrent episodes or outbreaks.

• It should be noted that HSV-1 is becoming a major cause of genital herpes as well, due to unprotected sex. In some studies, it is now a more important cause of genital herpes than HSV-2.

• Herpes simplex virus type 2 (HSV-2): HSV-2 is considered the primary cause of genital herpes. According to the Centers for Disease Control and Prevention (CDC), in the United States, at least 45 million people aged 12 years and older have had herpes simplex virus type 2 (HSV-2, or genital herpes) infection. According to researchers at the CDC, HSV-2 is present in as many as one in six people aged 14-49 years in the United States.

• HSV-2 is a sexually transmitted disease (STD), meaning that an individual must engage in sexual activity (oral or manual sex or intercourse) in order to transmit or be infected with this virus. In men and women aged 14-49 years, HSV-2 infection is more common in women (approximately one out of five women) than in men (almost one out of nine). This may be because male-to-female transmissions are more likely than female-to-male transmission. Anyone who is sexually active may contract genital herpes. There are no documented cases of a person getting genital herpes from an inanimate object such as a toilet seat, bathtub, or towel. Herpes is a very fragile virus and does not live long on surfaces outside the body. Signs and symptoms that occur during the first outbreak, which usually takes place within two weeks of virus transmission, can be quite severe. Lesion formation is the most common HSV-2 symptom; these lesions are commonly blisterlike but may also resemble a red spot, a pimple, an ingrown hair, razor burn, hemorrhoids, or an insect bite. The sores associated with HSV-2 infections typically heal within 2-4 weeks. In addition to the first outbreak of sores, other signs and symptoms that often occur during the primary episode may include a second crop of sores and flulike symptoms such as fever and swollen glands.

• However, an estimated 90% of individuals infected with HSV-2 are not aware of their infection. Many people infected with HSV-2 may never have sores, or they may have very mild sores that go unrecognized or are mistaken for insect bites, abrasions, yeast infections, "jock itch," or other skin conditions. In fact, approximately one-third of individuals with active lesions in their genital area are still unaware that they are showing this symptom.

• Most people diagnosed with a first episode of genital herpes can expect to have 4-5 outbreaks (called symptomatic recurrences) within a year. Symptoms of these outbreaks can include warning symptoms, or "prodromes," that include itching, tingling, or painful feelings at the site of the outbreak approximately two days before the recurrent lesion forms. Often these outbreaks decrease in frequency over time, although the virus is still present in the body. There is no cure for this recurrent (returning) infection, which may cause embarrassment and emotional distress. Having genital herpes does not preclude an individual from having a normal relationship. If the individual or partner is infected with HSV-2, steps can be taken to manage the transmission of the virus (see Precautions).

• With HSV-2 (genital herpes), transmission of the virus can occur when the infected sexual partner does not have an active outbreak. Although some individuals may not know they are infected with HSV-2 or do not show symptoms of the infection, they can still transmit the virus to others.

• Although HSV-2 is widely recognized as a cause of genital herpes, it can cause oral herpes as well. Moreover, HSV-1 can cause genital herpes, resulting in similar symptoms as infections caused by HSV-2.

• With genital infections, HSV-2 is more likely to shed than HSV-1, especially in women. It is possible that over half of the people infected with HSV-2 shed the virus at some time without having any symptoms or rash. It is also estimated that one-third of all HSV-2 infections are caused when a noninfected person comes in contact with someone who is shedding virus without symptoms.

• HSV-2 can be passed in the urine or genital discharge of an infected person. The viruses become reactivated secondary to certain stimuli, including fever, physical, or emotional stress, ultraviolet light exposure (sunlight or tanning beds), and nerve injury.

• Human herpesvirus type 3 (varicella-zoster, or HHV-3):

• Human herpesvirus type 3 (varicella-zoster):Both shingles and chicken pox are caused by human herpesvirus type 3 (HHV-3), or the varicella-zoster virus. HHV-3 is still referred as either herpes varicella (the primary infection that causes chicken pox) or herpes zoster (the reactivation of the virus that causes shingles). Humans are the only known carriers of HHV-3.

• Chicken pox: Chicken pox is usually a childhood disease. Over 90% of cases occur in children aged 14 years and younger. Before widespread vaccination, the incidence of chicken pox in the United States approached the annual birth rate, averaging between 3.1-3.8 million cases per year. Chicken pox can occur at any time of year.

• Chicken pox is acquired by direct contact with infected blister fluid or by inhalation of respiratory droplets from an infected individual. When individuals with chicken pox cough or sneeze, they expel tiny droplets that carry the varicella virus. A person who has never been exposed to chicken pox then inhales these droplets, and the virus enters the lungs. It then is carried through the bloodstream to the skin, where it causes a rash.

• While the virus is in the bloodstream (before the rash begins), it causes typical viral symptoms such as fever, fatigue, joint pains, headache, and swollen glands. These symptoms usually resolve by the time the rash develops. The incubation period (the time before the full-blown symptoms of the virus appear) of chicken pox averages 14 days, with a range of 10-21 days.

• The chicken pox rash usually begins on the trunk of the body and spreads to the face and extremities. The chicken pox lesion starts as a 2-4-millimeter red papule that develops an irregular outline (similar to a rose petal). A thin-walled, clear vesicle (a blister that looks like a dew drop) develops on top of the area of redness. This lesion is unique to chicken pox. After about 8-12 hours, the fluid in the vesicle gets cloudy and the vesicle breaks, leaving a crust. The fluid is highly contagious, but once the lesion crusts over, it is not considered contagious. The crust usually falls off after seven days, sometimes leaving a craterlike scar. Although one lesion goes through this complete cycle in about seven days, another hallmark of chicken pox is the fact that new lesions can crop up every day for several days. Therefore, it may take about a week until new lesions stop appearing and existing lesions crust over. Children should not be sent back to school until all lesions have crusted over.

• The number of chicken pox lesions a person gets varies considerably. The usual range is 100-300 lesions. Usually, older children and adults develop more lesions than young children. Individuals who have previously traumatized skin, such as sunburn or eczema, may also develop more severe lesions.

• In addition to affecting the skin, chicken pox can also cause lesions on the mucous membranes in the eyes, mouth, throat, and vagina.

• There is a varicella-zoster vaccine for use in individuals aged 12 months through 12 years. The chicken pox vaccine is a live attenuated vaccine, meaning the live, disease-producing virus was modified or weakened in the laboratory to produce an organism that can grow and produce immunity in the body without causing illness.

• Shingles: Shingles (also called herpes zoster) is a disease caused by a reactivation of the varicella-zoster virus (VZV), the same virus that causes chicken pox. After an individual develops the VZV, it remains dormant within the nerve roots (nerve tissue). Outbreaks are then termed shingles. Shingles affects an estimated one out of every three people in the United States. More than one million people in the Unites States develop shingles annually. It is most common in individuals over the age of 60 and those who have previously had chicken pox. Shingles is also more common in individuals with weakened immune systems, which can result from HIV infection, radiation treatment, certain medications (including steroids and chemotherapy), and high levels of or chronic (long-term) stress.

• The first sign of shingles is often burning or tingling pain, or sometimes numbness or itch, in a particular location on only one side of the face or body. After 1-5 days, a rash of fluid-filled blisters (similar to chicken pox) appears in the affected location. Shingles pain can be mild or severe. Some individuals experience only itching, while others feel pain from a gentle touch or breeze. The most common location for shingles is a band, called a dermatome, spanning one side of the trunk around the waistline. Other possible symptoms of shingles may include fever, headache, chills, or upset stomach. In rare cases, shingles may lead to eye complications (including blindness), pneumonia, hearing problems, encephalitis (brain inflammation), or death. Anyone who has had chicken pox is at risk for developing shingles at some point in their lives.

• There is no cure for shingles. Early treatment with drugs that fight the virus may help. These medicines may also help prevent lingering pain. There is a vaccine now available (Zostavax®) that may prevent shingles or lessen its effects. The vaccine is for people aged 60 or over who have had chicken pox but who have not had shingles.

• Postherpetic neuralgia: Some individuals continue to feel pain long after the shingles rash and blisters heal. This condition is termed postherpetic neuralgia (PHN). Not everyone who has had a recurrence of the virus develops PHN. Postherpetic neuralgia is a common complication of shingles in older adults but rarely occurs in people under the age of 40. The primary symptom of PHN is pain that can be debilitating. The pain associated with PHN may be aching, throbbing, stabbing, sharp, or piercing. Stress may intensify the severity of the pain. The intensity of the pain can vary, but pain-free intervals are rare. Some individuals who have had PHN describe the pain as the worst pain they have ever felt. The greater the age when the virus reactivates, the greater the chance the individual will develop PHN. In most individuals, the pain of PHN lessens over time, resolving itself in a few weeks or months. Treatments for PHN that may ease nerve-related pain include antidepressants (such as amitriptyline or Elavil®), anticonvulsants (such as gabapentin or Neurontin®), steroids (such as prednisone or Deltasone®), painkillers (such as opiates, including oxycodone or Percocet®), and topical anesthetic patches (such as lidocaine or Lidoderm®).

• Human herpesvirus type 4 (HHV-4):

• Epstein-Barr virus (EBV): Epstein-Barr virus is a herpes virus (human herpesvirus type 4) that causes a viral syndrome referred to as mononucleosis. EBV has also been found to play a role in the development of Burkitt's lymphoma (a rare cancer of the lymph system) and nasopharyngeal carcinoma (cancer of the nose and throat) in humans. Mononucleosis (also known as mono, kissing disease, and Epstein-Barr viral syndrome) causes fever, a sore throat, swollen lymph glands (especially in the neck), and extreme fatigue (tiredness). Although typically caused by the Epstein-Barr virus (EBV), mononucleosis can also be caused by other herpes viruses, including cytomegalovirus (CMV). As many as 95% of adults 35-40 years of age have been infected with EBV in the United States. Infants become susceptible to EBV once antibodies against EBV, which are provided by the mother before birth, disappear. Infection with EBV during adolescence or young adulthood results in mononucleosis in 35-50% of cases. The incubation period for mononucleosis is usually 7-14 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 (CFS), a condition of chronic tiredness and exhaustion.

• Mononucleosis spreads by contact with moisture from the mouth and throat of a person who is infected with the virus. Kissing, touching anything that has been near the mouth of an infected person, or sharing drinking glasses, eating utensils, or toothbrushes may result in transmission of the disease. The infection develops 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, 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 people 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. While the symptoms of infectious mononucleosis usually resolve in one or two months, an individual infected by the EBV carries dormant cells in the throat and blood for the rest of his or her 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.

• Human herpesvirus type 5 (HHV-5):

• Cytomegalovirus (CMV): The cytomegalovirus is a herpes virus (human herpesvirus type 5) found in body fluids, including urine, saliva (spit), breast milk, blood, tears, semen, and vaginal fluids. CMV is one of the most common congenital (present at birth) infections in newborns in the United States. Congenital CMV infections affect approximately 35,000 infants each year in the United States, and approximately 5,500 of these infants later experience CMV-related disabilities. The virus is commonly transmitted from an infected pregnant woman to her unborn child. It is an opportunistic virus that does not usually cause disease in those with healthy immune systems. In people with weakened immune systems (such as those with HIV or AIDS), 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. Spina bifida is the most common neural tube defect. Spina bifida occurs when the spine fails to close properly during the first few weeks of pregnancy, causing damage to the nerves and spinal cord. It is estimated that more than 70,000 people in the United States are living with spina bifida.

• Other herpes viruses:

• Human herpesvirus type 6 (HHV-6): Human herpesvirus type 6 has been linked to two conditions, roseola and lymphotrophic virus. HHV-6 has also been considered as a possible cause of chronic fatigue syndrome (CFS), along with HHV-3 (varicella-zoster). CFS patients can have extremely high levels of antibodies to HHV-6, meaning that an infection is present. HHV-6 infection is a major cause of opportunistic viral infections in patients with compromised immune systems, especially due to AIDS or organ transplants. HHV-6 may cause rejection of transplanted organs and death. HHV-6 may also be a cause of multiple sclerosis (MS), a chronic (long-term) inflammatory condition of the central nervous system (CNS) resulting in changes in sensation, visual problems, muscle weakness, depression, difficulties with coordination and speech, severe fatigue, cognitive impairment, problems with balance, overheating, and pain. MS causes impaired mobility and disability in more severe cases.

• Roseola (also known as sixth disease, exanthem subitum, and roseola infantum) is a viral illness in young children, most commonly affecting those between the ages of six months and two years. It is typically marked by several days of high fever (over 102 degrees Fahrenheit), followed by a distinctive rash that occurs when the fever breaks.

• There are two different types of HHV-6, the first type being responsible for roseola and the second responsible for infections in adults with weakened immune systems due to HIV/AIDS or cancer. This is the type that is thought to be associated with chronic fatigue syndrome (CFS).

• Human herpesvirus type 7 (HHV-7): Human herpesvirus type 7 is closely related to both HHV-6 and cytomegalovirus (CMV). Of the three viruses, HHV-7 is the least pathogenic (disease-causing). Like HHV-6, HHV-7 primarily causes roseola in infants and young children, which is a febrile (fever) illness that typically lasts for six days.

• Human herpesvirus type 8 (HHV-8): Human herpesvirus type 8 is a type of herpes virus responsible for diseases such as Kaposi's sarcoma (KS), lymphoproliferative disorders (when too many white blood cells are produced), primary effusion lymphoma (PEL), and multicentric Castleman's disease (MCD). This virus only attacks individuals with weakened immune systems, such as those with HIV and AIDS. The virus has been identified in all types of KS, including classic, endemic, post-transplant, and AIDS-related KS, all of which have identical features under the microscope. Research suggests that HHV-8 infection is spread by mouth-to-mouth contact (kissing) or genital contact. Previous studies on Kaposi's sarcoma have indicated that HHV-8 was more commonly found in saliva than in genital secretions.

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 15-30% of the entire population, and the highest incidence first occurs between six months and three years of age. 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. 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.

• 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 such stresses and illnesses include infection, fever, a cold, physical injury, dental surgery, menstruation, eczema, excessive exercise, emotional stress, HIV, or medications (including steroids) that suppress the immune system.

• 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 of genital herpes than HHV-2.

• Herpes simplex virus type 2 (HHV-2, genital herpes): Anyone who is sexually active is at risk for genital herpes, which is on the rise. Some reports estimate 31 million cases 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 15 test positive for HSV-2; sexual abuse should be considered in those children with HSV-2. Although African-Americans are more likely to test positive 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 (chicken pox): Before the introduction of the vaccine, about four million cases of chicken pox were reported in the United States each year. Between 75% and 90% of chicken pox 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 chicken pox has shown a dramatic decrease. Experts expect the disease to become a rarity in the United States.

• The risk of chicken pox is high in late winter and early spring months. Primary transmission of chicken pox includes direct contact with the individual carrying the virus or inhaling the virus from the air. It can also be transmitted from direct contact with open sores. However, clothing and bedding do not usually spread the disease.

• An individual with chicken pox 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 5-7 days. Once dry scabs form, the disease is unlikely to spread.

• Most schools allow children with chicken pox back 10 days after 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 chicken pox include those of any age who have neither had chicken pox in the past nor been immunized against chicken pox, newborns, those with a weakened immune system, and those who take 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 chicken pox, traveling abroad can increase the risk of contracting the condition.

• Males (both boys and men) have a higher risk of a severe case of chicken pox than females. The older the child, the higher the risk of a more severe case. But even in such circumstances, chicken pox is rarely serious in children.

• An individual experiencing the blister phase of the shingles virus may be able to spread chicken pox, although the chance is low if the blister is covered. A person with shingles is no longer at risk for spreading chicken pox once the blisters develop crusts.

• Varicella-zoster virus (shingles): About one million cases of shingles occur each year in the United States. Anyone who has had chicken pox is at risk for shingles later in life, which means that 90% of U.S. adults are at risk for shingles. Shingles occurs in approximately one-fifth to one-third of adults who have had chicken pox. 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 60.

• 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 7-9% of patients with lymphomas and 1-3% 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); these include 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 chicken pox 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 chicken pox, more adults may be at risk for herpes zoster. There is a vaccine now available (Zostavax®) that may prevent shingles or lessen its effects. The vaccine is for people 60 or older who have had chicken pox 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 chicken pox before they were one year old are at higher risk for shingles. It is still uncommon, however.

• Epstein-Barr virus (EBV): Mononucleosis spreads by contact with moisture from the mouth and throat of a person who is infected with the virus. Kissing, sharing drinking glasses, eating utensils, and toothbrushes, or touching anything that has been near the mouth of an infected person may result in transmission of the disease.

• While the symptoms of infectious mononucleosis usually resolve in one or two months, an individual infected by the EBV carries dormant cells in the throat and blood for the rest of his or her 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 chronic fatigue syndrome (CFS). EBV also establishes a lifelong dormant infection in some cells of the body's immune system.

• Cytomegalovirus (CMV): Pregnant women may become infected by CMV if saliva or urine from a young child infected with the virus passes into her eyes, nose, or mouth. In addition, a pregnant woman can become infected with the virus after having sexual contact with an infected adult who is shedding the virus.

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 7-10 days.

• Herpes simplex virus type 2 (HHV-2, genital herpes): Signs of genital herpes (HSV-2) tend to develop within 3-7 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 1-3 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 they may be difficult to see, except during a doctor's examination. In any individual, ulcers or blisters may be found anywhere around the genitals (for example, 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 (which may be severe), vaginal discharge, painful urination, and swollen and tender lymph glands in the groin (the 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 (chicken pox): Individuals with chicken pox may notice several symptoms before the typical chicken pox 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 2-4 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 may have 250-500 blisters. The pimples will progress to red teardrop blisters about 5-10 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. From 48 to 72 hours before blister appearance until all of the blisters have crusted, an individual may be contagious for chicken pox.

• Varicella-zoster virus (shingles): Shingles usually begins with an unpleasant itching, burning, tingling, or painful sensation in a bandlike 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 (tiredness), 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, sharp or shooting pain, electric shock, and extreme sensitivity to even light touch. Symptoms of active shingles include 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 7-10 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 a healthcare provider immediately, as 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 (EBV): Epstein-Barr virus can cause fever, a sore throat, swollen lymph glands (especially in the neck), and extreme fatigue (tiredness). Although typically caused by the 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 cases. The incubation period for the mononucleosis is usually 7-14 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 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.

Diagnosis

• 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 be performed to determine which type of herpes virus is infecting the individual.

• Herpes viral infections may be confused with other conditions. Varicella-zoster virus (chicken pox), particularly in early stages, may be confused with herpes simplex, impetigo (bacterial skin infection), insect bites, or scabies (skin infection by mites). The prodromal (early) 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, which 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 nontypical 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 1-14 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 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 or 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 Cesarean 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.

• Serological laboratory evaluations: Individuals suspected of being infected by the Epstein-Barr virus and presenting with symptoms of mononucleosis (fever, pharyngitis, and lymphadenopathy for 1-4 weeks) may be tested using serological assays. EBV infection is confirmed by a high white blood cell count, an elevated percentage of atypical white blood cells, and a positive reaction to a "mono spot" test. Direct detecting of EBV in blood or tissue is not available for routine diagnosis. However, EBV infections can be confirmed by testing for antibodies to several EBV-associated antigens, including viral capsid antigen, the early antigen, and the EBV nuclear antigen (EBNA).

• Serological tests are also used to diagnose cytomegalovirus (CMV) infections. However, the results from these tests cannot predict if a pregnant woman infected with the virus will give birth to a child with congenital (present at birth) CMV.

Complications

• 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 inutero (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, 1-4% 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 chicken pox. If a pregnant woman who has not had chicken pox in the past contracts the virus (especially in the first 20 weeks of pregnancy), the fetus is at risk for birth defects, particularly congenital varicella syndrome (CVS). The mother is more at risk for health complications, including varicella-zoster virus pneumonia, than if she had been infected when she was not pregnant. If the mother develops chicken pox just before or after the child is born, the newborn is at risk for serious health complications. It is recommended that pregnant women who show signs of chicken pox begin treatment with oral acyclovir or valacyclovir. There is no risk to the developing baby if the woman develops shingles during the pregnancy. If a pregnant woman has had chicken pox 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 chicken pox to reduce its severity. This group of people includes newborns whose mothers had chicken pox at the time of delivery, individuals with leukemia or immune deficiencies, and children receiving drugs that suppress the immune system.

• Chicken pox 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, chicken pox can be fatal. Chicken pox 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 chicken pox 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 chicken pox include problems in blood clotting, uncoordinated muscle movement, 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 postherpetic neuropathy (PHN) pain, which can either be continuous burning or aching pain, periodic piercing pain, or spasms 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 may 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. If the eyes become involved, severe infections, called herpes zoster ophthalmicus, that are difficult to treat can occur and can threaten vision. 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 a 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, 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 it usually resolves. The severity of the hearing loss varies from partial to total. However, this hearing loss almost always goes away. The 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.

• Epstein-Barr virus (EBV): Chronic EBV infection may occur in a very small portion of patients infected by the virus. However, most patients presenting with symptoms of EBV infection for longer than four months do not show positive test results for chronic EBV infection. Therefore, if the symptoms last for more than six months, the infected individual should be evaluated for other chronic illnesses, such as chronic fatigue syndrome (CFS).

• In individuals with weakened immune systems, EBV may cause hairy leukoplakia (white patches on the tongue) and B-lymphoproliferative neoplasms, in addition to mononucleosis. In addition, the virus has been linked as a contributory factor or cofactor in Burkitt's lymphoma, a fast-growing form of non-Hodgkin's lymphoma, and nasopharyngeal carcinoma. However, the association between Burkitt's lymphoma and EBV infections is found mainly for the African and only rarely for the North American virus types.

• Cytomegalovirus (CMV): Some infants (approximately 20%) with congenital (present at birth) CMV infections may develop health problems during their first few years. These problems may include hearing loss, vision loss, intellectual disability, lack of coordination, seizures, and death.

Treatment

• Herpes simplex virus:

• Genital herpes: There are three antiviral medications that the U.S. Food and Drug Administration (FDA) has approved for the treatment of genital herpes. Approved antiviral drugs include acyclovir (Zovirax®), valacyclovir (Valtrex®), and famciclovir (Famvir®). Antiviral medication is commonly prescribed for patients having a first episode of genital herpes, but it can be used for recurrent episodes as well. There are two kinds of treatment regimens: episodic therapy and suppressive therapy.

• With episodic therapy, the patient begins taking the medication at the first sign of recurrence. The medication is then taken for several days to hasten the recovery or healing or to prevent a full outbreak from fully occurring. All three of the antiviral treatments mentioned above have been proven to help shorten the amount of time that a person may experience symptoms of herpes. However, results may vary from person to person. Side effects of antiviral medicines include stomach upset, loss of appetite, nausea, vomiting, diarrhea, headache, dizziness, and weakness.

• Suppressive therapy is used in individuals with genital herpes who want to suppress (eliminate) outbreaks altogether. Suppressive therapy is usually given to patients who have six or more recurrences per year. For these individuals, studies have reported that suppressive therapy may reduce the number of outbreaks by at least 75% while the medication is being taken. Also, for some, taking an antiviral on a daily basis can prevent outbreaks altogether. Suppressive therapy may completely prevent outbreaks in some patients. Side effects include nausea and vomiting. Suppressive therapy may need to be taken life-long.

• Over-the-counter (OTC) creams and ointments are usually not recommended for the treatment of genital herpes, as they may cause the outbreaks to last longer by inhibiting the healing process.

• Oral herpes: Medications that are swallowed to treat oral herpes include the antiviral medications acyclovir (Zovirax®), valacyclovir (Valtrex®), and famciclovir (Famvir®). There are two topical antiviral medications prescribed for the treatment of oral herpes simplex virus type 1 (HSV-1): topical acyclovir ointment (Zovirax®) and topical penciclovir cream (Denavir®). Both of these drugs work to speed up the healing process and reduce the viral activity. These drugs are put directly on the lesions themselves but can also be used at the onset of prodrome (early symptoms of itching and burning lasting 1-2 days).

• Other over-the-counter (OTC) topical treatments for oral herpes are available, but they are not antiviral compounds like acyclovir and penciclovir. Some also contain anesthetic ingredients (such as lidocaine or benzocaine) that numb the area and induce temporary relief from the discomfort of an outbreak. Unfortunately, some OTC treatments may actually delay symptom healing time due to further irritation at the infected area with repeated applications. Docosanol (Abreva®) is the only OTC cream to be approved by the U.S. Food and Drug Administration (FDA) to help speed the healing process.

• Infected individuals can also prevent recurring outbreaks by avoiding some of the known causes. During an outbreak, symptomatic relief may be obtained by keeping the area clean and dry, or by taking pain relievers (such as aspirin, acetaminophen, or ibuprofen). Some patients with genital herpes find relief by taking a bath (simply sitting in a tub with warm water up to the hips).

• Varicella-zoster virus (chicken pox):

• Pain medications: Treatment for chicken pox includes pain medicines such as acetaminophen (Tylenol®) or ibuprofen (Motrin®, Advil®). Do not give children less than 18 years of age aspirin, as a dangerous condition called Reye's syndrome can develop.

• Soothing baths: Frequent baths are particularly helpful in relieving itching, especially when used with preparations of colloidal (finely ground) oatmeal. Commercial preparations of oatmeal, such as Aveeno®, are available in drugstores, or one can be made at home by grinding or blending dry oatmeal into a fine powder. Use about two cups per bath. The oatmeal will not dissolve, and the water will have a scum. One-half to one cup of baking soda in a bath may also be helpful.

• Lotions: Calamine® lotion and similar over-the-counter preparations can be applied to soothe the skin and help dry out blisters and soothe the skin.

• Antihistamines: For severe itching, a type of over-the-counter medication called antihistamine diphenhydramine (Benadryl®) is useful; it also helps children sleep.

• Antiviral drugs: Acyclovir is an antiviral drug that may be used in adult varicella-zoster patients or those of any age with a high risk for complications and severe forms of chicken pox. The drug may also benefit smokers with chicken pox, who are at higher-than-normal risk for pneumonia. Some experts recommend its use for children who catch chicken pox from other family members, because such patients are at risk for more serious cases. To be effective, oral acyclovir must be taken within 24 hours of the first signs of the rash. Early intravenous (IV; into the veins) administration of acyclovir is also a treatment for chicken pox pneumonia. Foscavir (Foscarnet®) is an injectable antiviral agent commonly used in treating cytomegalovirus (an infection caused by herpesvirus type 5). It is used in cases of varicella-zoster strains that have become resistant to acyclovir (Zovirax®) and similar drugs. Administered intravenously, the drug can have toxic effects, such as kidney damage (which is reversible) and seizures. Fever, nausea, and vomiting are common side effects. It can also cause ulcers on the genital organs. As with other drugs, it does not cure shingles. Antiviral drugs require a prescription.

• Varicella-zoster virus (shingles):

• The treatment goals for an acute (immediate) attack of shingles (herpes zoster) include reducing pain, reducing discomfort, hastening the healing of blisters, and preventing the disease from spreading. Over-the-counter remedies are often effective in reducing the pain of an attack.

• Antiviral drugs: Antiviral agents (acyclovir, valacyclovir, and famciclovir) are sometimes given to patients with severe symptoms, particularly if they are older and at risk for postherpes neuralgia.

• Antihistamines: In general, to prevent or reduce itching, home treatments are similar to those used for chicken pox. Patients can try antihistamines, particularly diphenhydramine (Benadryl®, either orally or topically), oatmeal baths, and calamine lotion.

• Oral corticosteroids: Drugs called oral corticosteroids, including methylprednisolone (Medrol®) or prednisone (Deltasone®), are used for inflammation associated with shingles. They have some benefit for reducing pain and accelerating healing in acute attacks of shingles when used with acyclovir (Zovirax®). However, they are not recommended without acyclovir. They also may be helpful for improving symptoms of Bell's palsy and Ramsay Hunt syndrome. Corticosteroids do not appear to prevent a further attack or reduce the risk for postherpetic neuralgia (PHN). Side effects of corticosteroids, including weight gain and lowered immunity, can be severe, and oral steroids should be taken at as low a dose and for as short a time as possible.

• Epidural blocks: Epidural blocks are injections of local anesthetics, pain medications, or steroids outside the tough membrane surrounding the spinal cord (the dura matter). The injected substances block the nerves and offer relief from acute herpes zoster pain for some people. Some studies, but not all, have indicated that if they are given early enough (within two months), they may prevent nerve damage that leads to postherpetic neuralgia. Combinations of anesthetics with steroids in the epidural blockade may be particularly beneficial. This procedure is invasive, however, and not widely used.

• Over-the-counter (OTC) pain relievers: For an acute (immediate) shingles attack, individuals may take over-the-counter (OTC) pain relievers, including acetaminophen (Tylenol®) or ibuprofen (Motrin®, Advil®). Children should take acetaminophen, not aspirin. Adults may take aspirin. Such remedies, however, are not very effective for postherpetic neuralgia.

• Postherpetic neuralgia (PHN):

• Postherpetic neuralgia (PHN) is difficult to treat. Once PHN develops, a multidisciplinary approach that involves a pain specialist, psychiatrist, primary care physician, and other healthcare professionals may provide the best means to relieve the pain and distress associated with this condition.

• Anesthetic patches: Topical (on the skin) preparations, including a skin patch containing the anesthetic drug lidocaine (Lidoderm®), are generally used. They are effective in many people without producing any known severe side effects. The patch appears to reduce pain and improve quality of life for many patients. One to four patches can be applied over the course of 24 hours. Another patch, EMLA®, contains both the anesthetic drugs lidocaine and prilocaine. These patches are expensive and require a prescription. The most common side effects are skin redness or rash.

• Topical creams: Capsaicin (Zostrix®) is prepared from the active ingredient in hot chili peppers. An over-the-counter (OTC) ointment form has been approved for postherpetic neuralgia and is available. Its benefits are limited, however, and it is uncertain whether they are meaningful for most patients. A new patch form that uses a higher-than-standard dose may be more effective than current options. In one study, it reduced pain by 33% in nearly half of patients. Capsaicin should not be used until the blisters have completely dried out and are falling off the skin. Capsaicin ointment should be handled using a glove and applied to affected areas three or four times daily. The patient will usually experience a burning sensation when the drug is first applied, but this sensation diminishes with use. It may take up to six weeks for the patient to experience its full effect, however, and about a third cannot tolerate the burning sensation. Many find no benefit.

• Topical aspirin, known chemically as triethanolamine salicylate (Aspercreme®), may bring relief. Also, menthol-containing creams such as Ben Gay® and Flexall 454® may be helpful.

• Oral medicines: Low-dose tricyclic antidepressants (TCAs), preferably nortriptyline (Pamelor®, Aventyl®), are also used. Side effects include drowsiness, fatigue (tiredness), dry mouth, and constipation. If that does not work, gabapentin (Neurontin®), an antiseizure drug, can be used. Doctors usually start with a low dose and slowly increase the amount given until relief or severe side effects occur. Side effects include drowsiness and nausea or vomiting. Also, a type of painkilling drugs known as opiates, including oxycodone (OxyContin®) or hydrocodone (Vicodin®, Lortab®), may be used. These drugs cause drowsiness and may cause physical dependence, even in short-term use (two weeks or less).

• Investigative agents: Cannabinoids are compounds in cannabis (marijuana) that may have properties that protect nerve cells. They are being studied for a number of nerve disorders, including chronic nerve-related pain. In one study, they were effective in reducing pain and had no major side effects.

• Mexiletine (Mexitil®) is a calcium channel-blocking agent that alters nerve impulse transmission. It is normally used for heart rhythm disorders but is being used in some cases for PHN in patients who do not respond to standard agents. The agent can have adverse effects, including serious allergic reactions, nausea, vomiting, flushing, and arrhythmias (irregular heartbeat).

• Psychological approaches: A number of relaxation and stress-reduction techniques are helpful in managing chronic pain. They include meditation, deep breathing exercises, biofeedback, and muscle relaxation. Such techniques may apply to those with severe pain from acute infection and from persistent long-term postherpetic neuralgia. Cognitive behavioral therapy is showing benefit in enhancing patients' beliefs in their own abilities to deal with pain. Using specific tasks and self-observation, patients gradually shift their fixed ideas that they are helpless against the pain that dominates their lives to the perception that it is only one negative and, to a degree, a manageable experience among many positive ones.

• Epstein-Barr virus:

• While antiviral drugs or vaccines are lacking for the treatment of EBV-induced mononucleosis, some doctors may prescribe a five-day course of steroids to treat the swelling of the throat and tonsils that often coincides with the infection.

• Cytomegalovirus (CMV):

• Ganciclovir (Cytovene®) is an antiviral medication that is prescribed to individuals with weakened immune systems experiencing CMV retinitis (infection of the eye that can lead to blindness). In addition, ganciclovir may be prescribed to individuals with acquired immunodeficiency syndrome (AIDS) or to those who have received an organ transplant to prevent CMV infection.

Integrative Therapies

• Good scientific evidence:

• Aloe: Limited evidence suggests that aloe in a cream preparation is an effective treatment for genital herpes in men. Additional research is warranted in this area.

• Caution is advised when taking aloe supplements, as adverse effects, including diarrhea and drug interactions, are possible. Aloe supplements should not be used if pregnant or breastfeeding, unless otherwise directed by a doctor. Do not use for more than three days without consulting a doctor.

• Green tea: Polyphenon E® ointment, containing an extract of green tea, has been approved in the United States for treatment of genital warts caused by human papillomavirus. Although this shows promise, further research is needed before a stronger conclusion can be made.

• Take care when using green tea with alcohol, antifungals, birth control pills, decongestants, and diuretics, and in patients with blood disorders, cardiovascular disorders, breast disease, an empty stomach, eye disorders, gastrointestinal disorders, impaired iron metabolism, iron deficiency, liver disorders, or psychiatric disorders. Use with caution in postmenopausal women, patients prone to headaches, and those at risk for prostate cancer or osteoporosis. Use with caution in patients using agents to treat eye disorders, agents that affect the gastrointestinal system, agents that affect hormone levels, agents that may damage the liver, or agents that affect the nervous system, as well as when using iron, painkillers, or other agents containing caffeine. Use of the green tea extract Polyphenon E® ointment may result in skin irritation or sun sensitivity. Avoid taking in excessively high amounts by mouth; during pregnancy and breastfeeding; or with known allergy or sensitivity to green tea, its constituents, caffeine, tannins, or members of the Theaceae family.

• Lemon balm: Several clinical studies have reported that a topical preparation of lemon balm (Melissa officinalis) heals sores associated with oral herpes simplex virus infections (herpes simplex type 1). However, rigorous clinical data are lacking, even though preliminary clinical studies demonstrate promising effects. According to available research, lemon balm taken by mouth has been reported to be relatively well tolerated when taken for up to eight weeks. Evidence for topical administration of cream suggested minimal side effects from up to 10 days of application. Avoid if allergic or hypersensitive to lemon balm. Avoid with Graves' disease or thyroid hormone replacement therapy. Use cautiously in glaucoma, because lemon balm may increase eye pressure. Use caution when operating heavy machinery. Lemon balm preparations may contain trace amounts of lead. Avoid if pregnant or breastfeeding.

• Para-aminobenzoic acid: Actipol® is a 0.007% para-aminobenzoic acid (PABA) solution for eye use that has been studied for the treatment of inflamed corneas caused by the herpes virus. The solution has been found to be effective in curing most patients. Further studies may provide additional useful information on the use of PABA for this condition.

• Sun exposure has been shown to stimulate the reactivation of a herpes simplex virus infection on the lips, as well as in the mouth or gums. Limited research suggests that PABA in sunscreen may be effective in preventing recurrent herpes labialis. Further studies will provide additional useful information on the use of PABA for this condition.

• PABA taken by mouth is generally well tolerated. Doses taken by mouth may need to be adjusted in patients with impaired kidney function. Pharmaceutical doses of PABA and its derivatives should only be taken under the supervision of a qualified healthcare provider. PABA given intravenously may increase the risk of bleeding. Caution is advised in patients with bleeding disorders or those taking drugs, herbs, or supplements that may increase the risk of bleeding. PABA may lower blood sugar levels. Caution is advised in patients with diabetes or hypoglycemia, and in those taking drugs, herbs, or supplements that affect blood sugar. Use with caution in patients with kidney disease and when taking by mouth in doses greater than eight grams daily. Discontinue if rash, nausea, or anorexia occur. Avoid taking at the same time as sulfonamide antibiotics, as it may reduce their effectiveness. Avoid giving by mouth to children, due to an increased risk of serious side effects. Avoid in pregnant or breastfeeding women, due to a lack of available scientific evidence. Avoid with known allergy or hypersensitivity to para-aminobenzoic acid (PABA) and its derivatives para-aminomethylbenzoic acid (PAMBA), butyl aminobenzoate (BAB), padimate O (octyl dimethyl PABA), potassium para-aminobenzoate (KPAB or POTABA®), N-benzoyl-L-tyrosyl PABA, Actipol®, or ursodeoxycholic acid-PABA.

• Zinc: Low-quality studies have been conducted to assess the effects of zinc (topically or taken by mouth) on herpes simplex virus type 1 or type 2. Several of these studies used combination treatments or permitted the continued use of other medications, so the exact role of zinc in those studies is unclear. However, the positive results obtained in most trials suggest that zinc may represent a safe and effective alternative treatment for herpes simplex virus type 1 and type 2 and should encourage further research into the topic using well-designed studies.

• Zinc is generally considered safe when taken at the recommended dosages. Use cautiously in patients with bleeding disorders, diabetes, or low blood sugar levels, or in patients taking agents for these conditions. Use cautiously in patients with high cholesterol or blood fats, a high risk of developing heart disease, various skin disorders, gastrointestinal disorders, liver disease, genitourinary conditions, blood disorders, neurological disorders, pulmonary or respiratory disorders, immune disorders, or kidney disease, or in patients taking antidepressants, potassium-sparing diuretics, antibiotics (particularly tetracyclines and quinolones), iron, penicillamine, thyroid hormones, or copper. Avoid in patients who are homozygous for hemochromatosis (a metabolic disorder involving the deposition of iron-containing pigments in the tissues and characterized by bronzing of the skin, diabetes, and weakness) or with a known allergy or hypersensitivity to zinc compounds. Avoid use of intranasal Zicam®.

• Unclear or conflicting scientific evidence:

• Acupuncture: According to early research, acupuncture therapy may help treat herpes zoster and improve symptoms of pain associated with postherpetic neuralgia (PHN). However, more high-quality studies are needed before a conclusion can be made.

• Needles must be sterile in order to avoid disease transmission. Avoid with valvular heart disease, infections, bleeding disorders or anticoagulants (drugs that increase the risk of bleeding), medical conditions of unknown origin, or neurological disorders. Avoid on areas that have received radiation therapy and during pregnancy. Use cautiously in those with pulmonary disease (like asthma or emphysema). Use cautiously in elderly or medically compromised patients, diabetics, or those with history of seizures. Avoid electroacupuncture with arrhythmia (irregular heartbeat) or in patients with pacemakers.

• Astragalus: Some studies suggest that astragalus may inhibit herpes viruses. Additional research is needed in this area.

• Use cautiously in patients using immunosuppressant agents or those who have autoimmune disease. Use cautiously in patients with bleeding disorders or those taking agents that may increase the risk of bleeding. Use cautiously in patients with diabetes or low blood sugar, and in those taking agents that affect blood sugar. Use cautiously in patients with high blood pressure or those taking agents that affect blood pressure. Use cautiously with agents that increase urination, anesthetics, beta-blockers, colchicines, dopamine agonists, growth hormones, neuromuscular blockers, and stimulants. Astragalus is not suggested during pregnancy or breastfeeding. Avoid with known allergy or hypersensitivity to Astragalus membranaceus, its constituents, or other members of the Fabaceae family. In theory, patients with allergies to members of the Leguminosae (pea) family may react to astragalus. Cross-reactivity with quillaja bark (soapbark) has been reported. A positive skin reaction to Huangqi powder injection has been reported.

• Chlorophyll: Oral consumption of chlorophyll liquid was reported in clinical research to be effective in both herpes simplex and varicella-zoster infections. More clinical research is needed.

• Avoid if allergic or hypersensitive to chlorophyll or any of its metabolites. Use cautiously in those with photosensitivity, compromised liver function, diabetes, or gastrointestinal conditions or obstructions. Use cautiously in those taking immunosuppressant agents or antidiabetic agents. Avoid if pregnant or breastfeeding.

• Dimethylsulfoxide (DMSO): DMSO may help treat herpes zoster. This treatment may work even better when used with the drug idoxuridine. Further research is necessary before a conclusion can be made.

• Avoid if allergic or hypersensitive to DMSO. Use caution with urinary tract cancer or liver or kidney dysfunction. Avoid if pregnant or breastfeeding.

• Echinacea: A small clinical trial assessing the potential benefit of oral echinacea for recurrent genital herpes found no effect. However, because research on the effect of echinacea for recurrent genital herpes is limited, conclusions cannot be made without further trials.

• Use injectable preparations of echinacea cautiously. Its safety has not been established. Use tinctures cautiously with alcoholic patients or in patients taking agents processed by the liver or those that affect or damage the liver (including anabolic steroids, amiodarone, methotrexate, or ketoconazole), agents that affect the immune system, amoxicillin, anticancer agents, disulfiram or metronidazole, or kava. Use cautiously in patients with HIV/AIDS, collagen vascular diseases, multiple sclerosis, tuberculosis, some types of cancer, rheumatologic diseases (such as rheumatoid arthritis or lupus), hemochromatosis (an iron storage disease), or asthma; those at risk for allergic skin reactions; or those taking agents to treat any of these conditions. During pregnancy or breastfeeding, injection or infusion of echinacea is not recommended. Tinctures are not recommended due to their high alcohol content. Avoid in patients undergoing anesthesia (those put to sleep for surgery). Avoid with known allergy or sensitivity to echinacea, its constituents, or any members of the Asteraceae (Compositae) family (including ragweed, chrysanthemum, marigold, and daisy).

• Honey: Preliminary research found honey effective in treating labial but not genital herpes. More research is needed in this area to draw a firm conclusion.

• Avoid if allergic or hypersensitive to honey, pollen, celery or bees. Honey is generally considered safe in recommended doses. Avoid honey from the genus Rhododendron because it may cause a toxic reaction. Avoid in infants younger than 12 months of age. Use cautiously with antibiotics. Potentially harmful contaminants (like C. botulinum or grayanotoxins) can be found in some types of honey and should be used cautiously in pregnant or breastfeeding women.

• Hypnotherapy, hypnosis: A small study showed potential benefit of a hypnotherapeutic treatment program for patients suffering from recurrent herpes infections on the mouth or face. Further research is needed to confirm these results.

• Use cautiously in those with mental illnesses like psychosis, schizophrenia, manic depression, multiple personality disorder, or dissociative disorders. Use cautiously in those with seizure disorders.

• Licorice: Laboratory studies have found that deglycyrrhizinated licorice (DGL) may hinder the spread and infection of herpes simplex virus. Studies in humans have been small, but they suggest that topical application of carbenoxolone cream may improve healing and prevent recurrence.

• Avoid licorice in those with a known allergy to licorice, any component of licorice, or any member of the Fabaceae (Leguminosae) plant family. Avoid licorice in those with congestive heart failure, coronary heart disease, kidney or liver disease, fluid retention, high blood pressure, or hormonal abnormalities, and in those taking diuretics. Licorice can cause abnormally low testosterone levels in men or high prolactin or estrogen levels in women. This may make it difficult to become pregnant and may cause menstrual abnormalities.

• Lysine: Lysine has been claimed to be effective in the treatment and prevention of episodes of recurrent herpes simplex infection. Research results are conflicting at this time. Additional high-quality clinical research is needed to make a conclusion. High-quality studies examining the effect of high doses (>1,000 milligrams) compared to lower doses (<1,000mg) are needed. Also, the effect of reducing arginine in the diet also needs to be determined, as the ratio of lysine to arginine is thought to play a role in the outcome of lysine therapy.

• Use cautiously in patients with blood disorders or those using blood thinners, as lysine may increase the risk of bleeding. Use cautiously in patients with diabetes or those who are using agents that lower their blood sugar levels, as lysine may decrease blood sugar levels. Use cautiously in patients taking protein-based drugs, such as aprotinin, as lysine may block the reabsorption of some proteins. Use cautiously in patients with compromised pancreatic function. Use high doses cautiously in patients prone to gallstones. Use cautiously in immunocompromised or immunosuppressed patients, patients with thymus disorders, patients with disorders that alter the metabolism of lysine or other amino acids, patients with high cholesterol, and patients using agents that interact with 5-hydroxytryptamine (5-HT4) receptors (e.g., cisapride, tegaserod). Avoid in patients with liver impairment or kidney disorders.

• Ozone therapy: In preliminary research, OzonyTron®, a device used to generate ozone, was used on patients with lip herpes. However, there is not enough evidence to show that ozone therapy can prevent oral herpes infections (cold sores).

• The safety of various types of ozone therapy has not been systematically studied. Because ozone is a toxic gas, the safety of ozone therapy has been questioned. A case of death has been reported due to gas embolism. Caution is advised. Serious side effects may occur from the introduction of ozone into the body, including shortness of breath, blood vessel swelling, poor circulation, heart problems, or stroke. Autohemotherapy has been associated with transmission of viral hepatitis and with a possible case of dangerously lowered blood cell counts. Patients are advised to make sure that fresh or sterile needles are used for any medical procedure. Insufflating (blowing into) the ear carries a risk of tympanic membrane (eardrum) damage, and colon insufflation may increase the risk of bowel rupture. There is one case of a patient with HIV becoming psychotic with hallucinations while receiving ozone therapy, but it is not clear that ozone was the cause. It is not recommended to rely on ozone therapies alone to treat potentially dangerous medical conditions. Ozone therapy may lower blood sugar levels. Caution is advised when using medications, herbs, or supplements that may lower blood sugar. Use cautiously in patients with respiratory disorders such as asthma. Ozone therapy is not recommended in pregnant or breastfeeding women, due to a lack of available scientific evidence.

• Peppermint: A case study found that topical peppermint oil was effecting in reducing the pain of postherpetic neuralgia. There is currently insufficient research available to determine if there are benefits of peppermint oil in the treatment of postherpetic neuralgia. More high-quality studies are needed in this area.

• Use cautiously in patients with gastrointestinal disorders, kidney disorders, liver problems, heart conditions, iron deficiency, sexual dysfunction, hormonal imbalances (for men), glucose-6-phosphate dehydrogenase (G6PD) deficiency, or gallbladder disease, or in patients taking agents for any of these conditions. Use cautiously in patients taking cyclosporine, salicylates, cytochrome P450-metabolized agents, aminophylline, or agents used on the skin, or when used on the skin in combination with a heating pad. Avoid in patients with known allergy to peppermint, its constituents, or other members of the Lamiaceae (Labiatae) family. Avoid excessive consumption of peppermint. Avoid use of peppermint oil around the facial or chest areas of infants and young children, especially around the nose.

• Propolis: Laboratory studies report that propolis may have anti-inflammatory effects as well as action against viruses, including herpes simplex virus type 1 and type 2. Early results from poorly designed human studies suggest that propolis used on the skin may improve lesions from genital herpes virus infections. However, without better human research, including comparisons to prescription drugs, firm conclusions cannot be drawn.

• There is limited research on propolis for the treatment of eye complications of varicella-zoster, the virus that causes chicken pox or shingles. Some evidence suggests that propolis may speed up healing and improve sight. However, human research is needed before a conclusion can be made.

• Avoid if allergic or hypersensitive to propolis, black poplar (Populus nigra), poplar bud, bee stings, bee products, honey, and balsam of Peru. Severe allergic reactions have been reported. Use cautiously in those with asthma or gastrointestinal disorders. Avoid if pregnant or breastfeeding, because of the high alcohol content in some products.

• Reishi mushroom: Reishi extract was effective in decreasing postherpetic pain (pain after herpes lesions heal) in one case series. Further research is needed to confirm these results.

• Avoid if allergic or hypersensitive to any constituents of Ganoderma lucidum or any member of the Ganodermataceae family. Use cautiously in those with diabetes, blood disorders (including hemophilia), low blood pressure, or ulcers. Avoid if pregnant or breastfeeding.

• Rhubarb: One double-blind, controlled trial indicates that topically applied rhubarb-sage extract cream may reduce the symptoms of herpes. More high-quality studies using rhubarb as a monotherapy are needed to discern rhubarb's effect on herpes symptoms.

• Avoid if allergic or hypersensitive to rhubarb, its constituents, or related plants from the Polygonaceae family. Avoid using rhubarb for more than two weeks, because it may induce tolerance in the colon, melanosis coli, laxative dependence, pathological alterations to the colonic smooth muscles, and substantial loss of electrolytes. Avoid with atony, colitis, Crohn's disease, dehydration with electrolyte depletion, diarrhea, hemorrhoids, insufficient liver function, intestinal obstruction or ileus, irritable bowel syndrome, menstruation, renal disorders, ulcerative colitis, and urinary problems. Avoid handling rhubarb leaves, as they may cause contact dermatitis. Avoid rhubarb in children under age 12 due to water depletion. Use cautiously in those with bleeding disorders, cardiac conditions, coagulation therapy, constipation, history of kidney stones, or thin or brittle bones. Use cautiously if taking antipsychotic drugs or oral drugs, herbs, or supplements (including calcium, iron, and zinc).

• Sage: Early research has shown that sage extracts may prevent the ability of the herpes virus to affect cells. In human research, a product containing sage leaf and other ingredients helped reduce side effects on the skin normally associated with herpes. Additional research is needed in this area.

• Use cautiously in patients with hypertension (high blood pressure) or hypotension (low blood pressure), or in patients taking agents that affect blood pressure. Use cautiously in patients with bleeding disorders or in those taking agents that may increase the risk of bleeding. Use cautiously in patients with diabetes or hypoglycemia or in those taking drugs, herbs, or supplements that affect blood sugar. Use cautiously if driving or operating heavy machinery or if taking certain sedatives or antidepressants. Use the essential oil or tincture of sage cautiously in patients with epilepsy. Only sterile preparations of sage should be used in the eye. Avoid use above dietary levels if pregnant or breastfeeding. Avoid if allergic or hypersensitive to sage species, their constituents, or to members of the Lamiaceae family.

• Sangre de grado: Sangre de grado has been studied as a treatment for herpes virus infection in patients with AIDS, with positive results. Additional studies are needed before a conclusion can be made.

• Avoid with known allergy or sensitivity to sangre de grado or any of its parts.

• Shiitake: According to preliminary research, lentinan, a derivative of shiitake, may influence the immune system and reduce the recurrence rate of genital warts. Further well-designed studies are needed to confirm these results. Currently, more proven therapies are recommended.

• Avoid if allergic or hypersensitive to shiitake mushrooms.

• Siberian ginseng: Limited research suggests that Siberian ginseng may reduce the severity, duration, and frequency of outbreaks of genital herpes after three months of use. Further research is required before conclusions can be made.

• Use caution when taking for longer than two months without a 2-3-week break. Caution is advised in patients with bleeding disorders, diabetes, hypoglycemia, blood pressure disorders, autoimmune disorders, psychiatric disorders, or impaired gastrointestinal function, or in those taking agents for any of these conditions. Caution is advised in patients taking central nervous system (CNS) depressants (such as hexobarbital), digoxin, alcohol, ACE inhibitors, antiallergy agents, morphine, estrogens, antidepressants, sedatives, stimulants, or agents processed by the liver's cytochrome P450 enzyme system, p-glycoprotein, or SULT1A3; and in patients undergoing steroid treatment or radiotherapy. Avoid in children and pregnant or breastfeeding women, or with known allergy or sensitivity to Siberian ginseng (Eleutherococcus senticosus, also known as Acanthopanax senticosus), its constituents, related products, or members of the Araliaceae family.

• Tai chi: A small trial showed that treatment with tai chi might increase immunity to the virus that causes chicken pox. This may suggest the use of tai chi in the prevention of chicken pox and shingles, but further well-designed large studies must be done before a conclusion can be made.

• Avoid with severe osteoporosis or joint problems, acute back pain, sprains, or fractures. Avoid during active infections, right after a meal, or when very tired. Some believe that visualization of energy flow below the waist during menstruation may increase menstrual bleeding. Straining downwards or holding low postures should be avoided during pregnancy, and by people with inguinal hernias. Some tai chi practitioners believe that practicing for too long or using too much intention may direct the flow of chi (qi) inappropriately, possibly resulting in physical or emotional illness. Tai chi should not be used as a substitute for more proven therapies for potentially serious conditions. Advancing too quickly while studying tai chi may increase the risk of injury.

• Tea tree oil: Laboratory studies show that tea tree oil has activity against some viruses, and it has been suggested that a tea tree gel may be useful as a treatment on the skin for recurrent herpes labialis. However, there is currently not enough information to make a conclusion on this use of tea tree oil.

• Avoid if allergic or hypersensitive to tea tree oil, any of its constituents, balsam of Peru, benzoin, colophony (rosin) tinctures, eucalyptol, or other members of the Myrtle (Myrtaceae) family. Avoid taking tea tree oil by mouth. Avoid if taking antineoplastic agents. Use tea tree oil applied to the skin cautiously in patients with previous tea tree oil use. Avoid if pregnant or breastfeeding.

• TENS: Transcutaneous electrical nerve stimulation (TENS) has been used in postherpetic neuralgia. However, there is insufficient evidence from controlled clinical trials upon which to base conclusions.

• Avoid with implantable devices, like defibrillators, pacemakers, intravenous infusion pumps, or hepatic artery infusion pumps. Use cautiously in those with decreased sensation, like neuropathy, or seizure disorders. Avoid if pregnant or breastfeeding.

• Transfer factor: Some studies have reported improvements, such as shorter duration of pain, in patients with herpes after treatment with transfer factor. Additional high-quality studies are needed in this area.

• Use caution in patients with neurological conditions, Wiskott-Aldrich syndrome, diabetes, or hypoglycemia; in pregnant or breastfeeding women; or in those taking agents that affect blood sugar. Avoid with known allergy or sensitivity to transfer factor or any of its constituents. Transfer factor therapy should be provided by a trusted source and supervised by a qualified healthcare provider. Theoretically, transfer factor prepared from cattle that have "mad cow disease" may cause brain and nerve damage. Some preparations of transfer factor may be contaminated with other substances.

• Historical or theoretical uses lacking sufficient evidence:

• Alizarin: Limited evidence suggests that alizarin may improve various herpes infections, including herpes simplex, herpes zoster, induced herpes zoster, and chicken pox. Additional research is needed in this area.

• Avoid if allergic or hypersensitive to alizarin or any plants in the Rubiaceae family. Alizarin may be toxic and should not be handled for long periods of time, rubbed in the eyes or eaten. Avoid if pregnant or breastfeeding.

• Arabinoxylan: Arabinoxylan is produced from Hyphomycetes mycelia mushroom extract. Arabinoxylan has been used traditionally for herpes zoster infection and postherpetic neuralgia. Arabinoxylan increases immune function and may help the body fight off infection. Clinical studies are needed to support these uses.

• Use cautiously in the elderly or those with kidney dysfunction, due to potentially high calcium and phosphorus content. Use cautiously in those with diabetes. Avoid if pregnant or breastfeeding.

• Black currant: The black currant shrub is indigenous to Europe and parts of Asia and is particularly popular in Eastern Europe and Russia. Theoretically, black currant may help treat symptoms associated with herpes simplex virus type 1 and type 2, as well as herpes zoster virus. However, further research is necessary.

• Use cautiously with venous disorders or gastrointestinal disorders. Avoid if allergic or hypersensitive to black currant, its constituents, or plants in the Saxifragaceae family. Avoid with hemophilia or those on blood thinners unless otherwise recommended by a qualified healthcare provider. Avoid if pregnant or breastfeeding.

• Bromelain: Bromelain is a sulfur-containing proteolytic digestive enzyme that is extracted from the stem and the fruit of the pineapple plant (Ananas comosus, family Bromeliaceae). Theoretically, bromelain may be used to treat symptoms associated with herpes, including pain associated with shingles or postherpetic neuralgia. However, clinical research is needed.

• Avoid if allergic to bromelain, pineapple, honeybee, venom, latex, birch pollen, carrots, celery, fennel, cypress pollen, grass pollen, papain, rye flour, wheat flour, or other members of the Bromeliaceae family. Use cautiously in those with history of bleeding disorder, stomach ulcers, heart disease, liver or kidney disease. Use caution before dental or surgical procedures or while driving or operating machinery. Avoid if pregnant or breastfeeding.

• Bulbous buttercup: Bulbous buttercup (Ranunculus bulbosus) is named for the uniquely bulbous, white protrusion that is found at the base of its stem. Traditionally bulbous buttercup has been used to treat symptoms associated with herpes zoster and shingles, but clinical research is needed to confirm the effectiveness of this treatment. There is currently a lack of high-quality studies on the medicinal applications of bulbous buttercup, and the following safety information is based on traditional use and expert opinion.

• Avoid if allergic or hypersensitive to bulbous buttercup. Avoid in patients with compromised liver function, heart conditions, respiratory conditions, diarrhea, vomiting, skin conditions, and gastrointestinal disorders or obstructions. Avoid if pregnant or breastfeeding.

• Calendula: Calendula (Calendula officinalis), also known as marigold, has been widely used topically to treat a variety of conditions. Traditionally, calendula has been used topically to treat minor wounds, burns, and other skin problems. According to limited research, calendula may improve symptoms associated with herpetic keratitis and herpes simplex virus infections.

• Avoid if allergic to plants in the Aster or Compositae family, such as ragweed, chrysanthemums, marigolds, and daisies. Use cautiously in patients taking sedatives, blood pressure medications, cholesterol medications, blood sugar-altering agents, and immunomodulators. Use cautiously in those with diabetes and in children. Avoid if pregnant or breastfeeding.

• Chaparral: Chaparral (Larrea tridentata) is one name for a particular herbaceous woody shrub that grows in the southwestern region of the United States and the northern region of Mexico. Topical preparations of chaparral have been made as lotions in oils to be used to treat chicken pox and genital herpes simplex. Theoretically, chaparral may treat symptoms associated with other herpes simplex viruses, herpes zoster virus, and Epstein-Barr virus. Further research is necessary.

• Avoid if allergic to chaparral or any of its components, including nordihydroguaiaretic acid. Use cautiously if taking anticoagulants (blood thinners), blood sugar medications, or drugs that are broken down by the liver (like amiodarone, phenobarbital, valproic acid). Stop use two weeks before surgery or dental or diagnostic procedures with a bleeding risk, and do not use immediately after these procedures. Use cautiously if driving or operating heavy machinery. Avoid if pregnant or breastfeeding.

• Eucalyptus oil: Eucalyptus is plant that is native to Australia. In cell cultures, eucalyptus has exhibited antiviral activity against herpes simplex virus type 1. In animal research, eucalyptus oil has been shown to prevent herpes simplex virus type 2 infections. Theoretically, eucalyptus oil may be useful for treating symptoms associated with shingles or herpes virus infections.

• Avoid in those allergic to eucalyptus oil or with a history of seizure, diabetes, asthma, heart disease, abnormal heart rhythms, intestinal disorders, liver disease, kidney disease, or lung disease. Use caution if driving or operating machinery. Avoid in those with a history of acute intermittent porphyria. Avoid if pregnant or breastfeeding. A strain of bacteria found on eucalyptus may cause infection. Toxicity has been reported with oral and inhaled use.

• Goldenseal: Goldenseal is one of the five top-selling herbal products in the United States and can be found in dietary supplements, eardrops, feminine cleansing products, cold and flu remedies, allergy remedies, laxatives, and digestive aids. According to limited research, goldenseal may used to treat symptoms associated with chicken pox, herpes labialis, cold sores, or herpetic uveitis.

• Avoid if allergic or hypersensitive to goldenseal or any of its constituents, like berberine and hydrastine. Use cautiously in those with bleeding disorders, diabetes, or low blood sugar. Avoid if pregnant or breastfeeding.

• Physical therapy: Physical therapy is tailored to the patient's condition and health issues. A common goal of physical therapy is to increase how the patient functions at home and at work. According to limited evidence, physical therapy may help treat pain associated with herpes zoster infections and postherpetic neuralgia. However, clinical research is needed to support the use of physical therapy for these indications.

• Not all physical therapy programs are suited for everyone, and patients should discuss their medical history with a qualified healthcare professional before beginning any treatments. Physical therapy may aggravate preexisting conditions. Persistent pain and fractures of unknown origin have been reported. Physical therapy may increase the duration of pain or cause limitation of motion. Pain and anxiety may occur during the rehabilitation of patients with burns. Both morning stiffness and bone erosion have been reported in the physical therapy literature, although causality is unclear. Erectile dysfunction has also been reported. Physical therapy has been used in pregnancy and although reports of major adverse effects are lacking the available literature, caution is advised nonetheless. All therapies during pregnancy and breastfeeding should be discussed with a licensed obstetrician or gynecologist before initiation.

• St. John's wort: Extracts of Hypericum perforatum L. (St. John's wort) have been recommended traditionally for a wide range of medical conditions. According to limited information, St. John's wort may help treat herpes virus infections.

• Rare skin reactions, including rash and itching, have been reported in human studies. Avoid taking if pregnant or breastfeeding.

• Stinging nettle: According to limited information, stinging nettle may help reduce symptoms associated with chicken pox and herpes virus infections.

• Avoid if allergic or hypersensitive to nettle, the Urticaceae family, or any ingredient of nettle products. Use cautiously in those with diabetes, bleeding disorders, or low sodium levels in the blood. Use cautiously in those using diuretics and anti-inflammatory drugs. The elderly should also use nettle cautiously. Avoid if pregnant or breastfeeding.

• Thymus extract: According to limited studies in humans, thymus extract may be used to treat symptoms related to chicken pox, cold sores, cold sore recurrence, and shingles.

• Avoid if allergic or hypersensitive to thymus extracts. Use bovine thymus extract supplements cautiously, due to the potential for exposure to the virus that causes "mad cow disease." Avoid use in those with an organ transplant or other forms of allografts or xenografts. Avoid in those receiving immunosuppressive therapy; taking hormonal therapy; or with thymic tumors, myasthenia gravis (a neuromuscular disorder), or untreated hypothyroidism. Avoid if pregnant or breastfeeding; thymic extract increases human sperm motility and progression.

Prevention

• Herpes simplex virus type 1 (HSV-1, herpes labialis, oral herpes):

• Taking steps to guard against the development of cold sores, to prevent spreading them to other parts of the body, or to avoid passing them along to another person is important when dealing with oral herpes.

• Contact with infected individuals: The virus can spread easily as long as there are moist secretions from blisters. In individuals with depressed immune systems, the virus can be spread even after the skin appears to be healed. Also, it is important to avoid kissing others on the mouth if a herpes viral infection is present.

• Sharing common items: Utensils, towels, water glasses, and other commonly used items can spread the virus when blisters are present.

• Clean hands: Washing the hands carefully before touching another person when a cold sore is present is very important. The eyes and genital area may be particularly susceptible to spread of the virus.

• Triggers: Avoiding or preventing conditions that stress the body, such as poor diet, not getting enough sleep, or staying in the sun for long periods of time without applying sunblock is very important in preventing oral herpes outbreaks.

• Herpes simplex virus type 2 (HSV-2, genital herpes):

• Measures for preventing genital herpes are the same as those for preventing other sexually transmitted diseases (STDs). HSV-2 is highly contagious while lesions are present. The best way to prevent infection is to abstain from sexual activity or to limit sexual contact to only one person who is infection free. Individuals should use, or have their partner use, a latex condom during each sexual contact; limit the number of sex partners; avoid any contact with a partner who has sores until the sores are completely healed; use a male or female condom during anal, oral, or vaginal sex (however, transmission can still occur if the condom does not cover the sores); avoid having sex just before or during an outbreak since the risk for transmission is highest at that time; and ask the sexual partner if they have ever had a herpes outbreak or been exposed to the herpes virus. Also, getting tested for herpes simplex viruses is important if the individual is sexually active outside of a monogamous relationship.

• If an individual is pregnant, it is important to tell the doctor that HSV is present. If the individual has had unprotected sex and is unsure, testing for HSV is recommended by healthcare professionals. Watch for signs and symptoms of HSV during pregnancy. A doctor may recommend that the individual start taking herpes antiviral medications when about 36 weeks pregnant to try to prevent an outbreak from occurring around the time of delivery. If the individual is having an outbreak when going into labor, the doctor will probably suggest a Cesarean section to reduce the risk of passing the virus to the baby.

• In 2002, two clinical trials that tested the efficacy of an HSV-2 vaccine found that the vaccine may reduce the occurrence of HSV-2 disease by approximately 70% in women who were negative for previous HSV-1 or HSV-2 infections. Evidence of efficacy in women who had previously been infected with HSV-1 or in men (HSV-1 positive or negative) was lacking. Based on these results, a larger study (the Herpevac Trial for Women) was conducted more recently to further evaluate the efficacy of this same vaccine in women who were negative for antibodies to HSV-1 and HSV-2. However, according to results from this larger study, the efficacy of the vaccine in preventing genital herpes disease was only 20%. While the vaccine showed a moderate reduction in the rate of HSV-1 infection (35%), a reduction in the rate of HSV-2 infection was lacking.

• Human herpesvirus type 3 (varicella-zoster virus, chicken pox):

• Varivax®: A vaccine for varicella-zoster infections is now used to prevent chicken pox. Varivax®, a live virus vaccine, produces persistent immunity against chicken pox. Data show that the vaccine can prevent chicken pox or reduce the severity of the illness even if it is used within three days, and possibly up to five days, after exposure to the infection. The vaccine against chicken pox is now recommended in the United States for all children between the ages of 18 months and adolescence who have not yet had chicken pox. Children are given one dose of the vaccine. Two doses 1-2 months apart are given to people over 13 years of age. To date, more than 75% of children have been vaccinated.

• Some experts suggest that every healthy adult without a known history of chicken pox be vaccinated. Adults without such a history of infection by varicella-zoster should strongly consider vaccination if they are adults who are at high risk of exposure or transmission (hospital or daycare workers, parents of young children), individuals who live or work in environments in which viral transmission is likely, individuals who are in contact with people who have compromised immune systems, nonpregnant women of childbearing age, adolescents and adults living in households with children, and international travelers.

• Women who are trying to become pregnant should postpone conception until three months after the vaccine.

• Side effects of Varivax® include discomfort at the injection site. About 20% of vaccine recipients have pain, swelling, or redness at the injection site. Only about five percent of adverse reactions are serious. Adverse events may include seizures, pneumonia, anaphylactic reaction (a life-threatening allergic reaction), encephalitis (inflammation of the brain), Stevens-Johnson syndrome, neuropathy (nerve damage), herpes zoster, and blood abnormalities. The vaccine may also produce a mild rash within about a month of the vaccination that has been known to transmit chicken pox to others. Individuals who have recently been vaccinated should avoid close contact with anyone who might be susceptible to severe complications from chicken pox until the risk for a rash has passed. Months or even years after the vaccination, some people develop a mild infection termed modified varicella-like syndrome (MVLS). The condition appears to be less contagious and have fewer complications than naturally acquired chicken pox.

• There is currently intense debate over the long-term protection of the vaccine. Studies have reported that more than 15% of vaccinated children still develop chicken pox (called breakthrough infections). The long-term protective effect for adults is even less clear. Between 1979 and 1999, it was reported that although nine percent developed chicken pox months to years after their last vaccination, in all cases, infection was mild, with none of the serious complications of adult chicken pox. A 2003 study on booster shots in older adults suggests that revaccination with the live virus is safe and effective.

• Varicella-zoster immune globulin (VZIG): Varicella-zoster immune globulin (VZIG) is a substance that triggers an immune response against the varicella-zoster virus (VZV). It is used to protect high-risk patients who are exposed to chicken pox or those who cannot receive a vaccination of the live virus. Such groups include pregnant women with no history of chicken pox, newborns under four weeks who are exposed to chicken pox or shingles, premature infants, children with weakened immune systems, adults with no immunity to VZV, and recipients of bone marrow transplants (even if they have had chicken pox). VZIG should be given within 96 hours and no later than 10 days after exposure to someone with chicken pox.

• Human herpesvirus type 3 (varicella-zoster virus, shingles):

• Zostavax®: Zostavax® is a live vaccine made from the herpes zoster virus that causes shingles. Zostavax® has been reported to reduce the incidence of herpes zoster by 51.3% in adults aged 60 and older. The vaccine reduced the number of cases of postherpetic neuralgia by 66.5% and reduced the severity and duration of pain and discomfort associated with shingles by 61.1%. In May 2006, the U. S. Food and Drug Administration (FDA) approved the use of Zostavax®. Although Zostavax® has been FDA approved for people 50 years and older, the Advisory Committee on Immunization Practices (ACIP) of the Centers for Disease Control and Prevention (CDC) recommends it only for adults aged 60 and older, primarily due to supply concerns. Clinical trials have actually shown that the vaccination is more effective in younger populations (50-59 years, 70% efficacy) compared to older age groups (≥80 years, 20% efficacy).

• However, the use of Zostavax® is contraindicated in certain individuals. For instance, Zostavax® should be avoided in individual who have life-threatening allergies to gelatin, the antibiotic neomycin, or other components of the herpes zoster vaccine. In addition, Zostavax® is contraindicated (inadvisable) in individuals with a weakened immune system due to human immunodeficiency virus (HIV), acquired immunodeficiency syndrome (AIDS), or any other disease. Patients receiving Zostavax® should not be on other disease medications, such as steroids, radiation, or chemotherapy, that affect the immune system. There should be no history of cancer of the bone marrow or lymphatic system, such as leukemia or lymphoma, and also no active or untreated tuberculosis. Side effects include headache, itching, and tenderness or redness at site of injection.

• Zostavax® is not a substitute for Varivax® in children and is not indicated for use in individuals who have previously received Varivax® vaccinations.

• Varivax®: Although Varivax® is actually a chicken pox vaccination, its use may reduce the prevalence of shingles in the future. Because shingles is a re-emergence of the same virus that causes chicken pox, people who do not get chicken pox can never get shingles.

• Cytomegalovirus (CMV):

• Ganciclovir (Cytovene®) is an antiviral medication that is prescribed to individuals with weakened immune systems experiencing CMV retinitis (an infection of the eye that can lead to blindness). In addition, ganciclovir may be prescribed to individuals with acquired immunodeficiency disorders (AIDS) or to those who have received an organ transplant to prevent CMV infection.

• Clinical trials have evaluated the use of CMV glycoprotein-B vaccinations to prevent CMV infection. Initially, the vaccine efficacy was evaluated in CMV-negative women within one year of giving birth. According to the results from this study, the women who received the vaccination were less likely to become infected within 42 months of treatment compared to placebo (50% vaccine efficacy). Later, the same vaccine was given with MF59 adjuvant, an immune response stimulator, to patients expecting to receive either a kidney or liver transplant. Results from the study indicated that, for those patients who developed a CMV infection after receiving the transplant, the vaccination reduced the duration of infection and the number of days needed to treat with ganciclovir compared to the control group.

Author Information

• This information has been edited and peer-reviewed by contributors to the Natural Standard Research Collaboration (www.naturalstandard.com).

Bibliography

Natural Standard developed the above evidence-based information based on a thorough systematic review of the available scientific articles. For comprehensive information about alternative and complementary therapies on the professional level, go to www.naturalstandard.com. Selected references are listed below.

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