how to cure herpes

Herpes simplex (Ancient Greek: ἕρπης - herpes, lit. "creeping") is a viral disease caused by both herpes simplex virus 1 (HSV-1) and herpes simplex virus 2 (HSV-2). Infection with the herpes virus is categorized into one of several distinct disorders based on the site of infection. Oral herpes, the visible symptoms of which are colloquially called cold sores, infects the face and mouth. Oral herpes is the most common form of infection. Genital herpes, commonly known simply as herpes, is the second most common form of herpes. Other disorders such as herpetic whitlow, herpes gladiatorum, ocular herpes (keratitis), cerebral herpes infection encephalitis, Mollaret's meningitis, neonatal herpes, and possibly Bell's palsy are all caused by herpes simplex viruses.

Herpes viruses cycle between periods of active disease—presenting as blisters containing infectious virus particles—that last 2–21 days, followed by a remission period, during which the sores disappear. Genital herpes, however, is often asymptomatic, though viral shedding may still occur. After initial infection, the viruses move to sensory nerves, where they reside as life-long, latent viruses. Causes of recurrence are uncertain, though some potential triggers have been identified. Over time, episodes of active disease reduce in frequency and severity.

Herpes simplex is most easily transmitted by direct contact with a lesion or the body fluid of an infected individual. Transmission may also occur through skin-to-skin contact during periods of asymptomatic shedding. Barrier protection methods are the most reliable method of preventing transmission of herpes, but they merely reduce rather than eliminate risk. Oral herpes is easily diagnosed if the patient presents with visible sores or ulcers. Early stages of orofacial herpes and genital herpes are harder to diagnose; laboratory testing is usually required. Twenty percent of the U.S. population has antibodies to HSV-2, although not all of them have a history of genital lesions.^[1]

There is no cure for herpes. Once infected, the virus remains in the body for life. However, after several years, some people will become perpetually asymptomatic and will no longer experience outbreaks, though they may still be contagious to others. Vaccines are in clinical trials but have not demonstrated effectiveness. Treatments can reduce viral reproduction and shedding, prevent the virus from entering the skin, and alleviate the severity of symptomatic episodes.

Herpes simplex should not be confused with conditions caused by other viruses in the herpesviridae family such as herpes zoster, which is a viral disease caused by varicella zoster virus. There is also a possibility of confusion with "hand, foot and mouth disease" due to apparition of lesions on the skin.

The infection can be classified via the type of herpes virus causes the infection: either HSV1 or HSV2.

Signs and symptoms

HSV infection causes several distinct medical disorders. Common infection of the skin or mucosa may affect the face and mouth (orofacial herpes), genitalia (genital herpes), or hands (herpes whitlow). More serious disorders occur when the virus infects and damages the eye (herpes keratitis), or invades the central nervous system, damaging the brain (herpes encephalitis). Patients with immature or suppressed immune systems, such as newborns, transplant recipients, or AIDS patients are prone to severe complications from HSV infections. HSV infection has also been associated with cognitive deficits of bipolar disorder,^[2] and Alzheimer's disease,^[3] although this is often dependent on the genetics of the infected person.

There is a single report of a systemic infection with HSV-2, where a healthy 28-year old woman with a healthy immune system died 12 days after contracting the virus.^[4]

In all cases HSV is never removed from the body by the immune system. Following a primary infection, the virus enters the nerves at the site of primary infection, migrates to the cell body of the neuron, and becomes latent in the ganglion.^[5] As a result of primary infection, the body produces antibodies to the particular type of HSV involved, preventing a subsequent infection of that type at a different site. In HSV-1 infected individuals, seroconversion after an oral infection will prevent additional HSV-1 infections such as whitlow, genital herpes, and keratitis. Prior HSV-1 seroconversion seems to reduce the symptoms of a later HSV-2 infection, although HSV-2 can still be contracted. Most indications are that an HSV-2 infection contracted prior to HSV-1 seroconversion will also immunize that person against HSV-1 infection.^[6]

Herpes labialis Infection occurs when the virus comes into contact with oral mucosa or abraded skin.

Herpes genitalis When symptomatic, the typical manifestation of a primary HSV-1 or HSV-2 genital infection is clusters of inflamed papules and vesicles on the outer surface of the genitals resembling cold sores.

Herpetic whitlow Herpes whitlow is a painful infection that typically affects the fingers or thumbs. Occasionally infection occurs on the toes or on the nail cuticle.

Herpes gladiatorum Individuals that participate in contact sports such as wrestling, rugby, and soccer sometimes acquire a condition caused by HSV-1 known as herpes gladiatorum, scrumpox, wrestler’s herpes, or mat herpes, which presents as skin ulceration on the face, ears, and neck. Symptoms include fever, headache, sore throat and swollen glands. It occasionally affects the eyes or eyelids.

Herpetic keratoconjunctivitis Primary infection typically presents as swelling of the conjunctiva and eye-lids (blepharoconjunctivitis), accompanied by small white itchy lesions on the surface of the cornea.

Herpesviral encephalitis A herpetic infection of the brain that is thought to be caused by the retrograde transmission of virus from a peripheral site on the face following HSV-1 reactivation, along the trigeminal nerve axon, to the brain. HSV is the most common cause of viral encephalitis. When infecting the brain, the virus shows a preference for the temporal lobe.^[7].

Herpesviral meningitis HSV-2 is the most common cause of Mollaret's meningitis, a type of recurrent viral meningitis.

Neonatal herpes simplex Neonatal HSV infection is a rare but serious condition, usually caused by vertical transmission of HSV (type 1 or 2) from mother to newborn.

During immunodeficiency In patients with a weakened immune system, herpes simplex can cause unusual lesions in the skin. One of the most striking is the appearance of clean linear erosions in skin creases, with the appearance of a knife cut.^[8]

Herpetic sycosis Herpetic sycosis is a recurrent or initial herpes simplex infection affecting primarily the hair follicle.^[9]:369

Eczema herpeticum Infection with herpesvirus in patients with chronic atopic dermatitis may result in spread of herpes simples throughout the eczematous areas.^[9]:373

Bell's palsy

In a mouse model, a type of facial paralysis called Bell's palsy has been linked to the presence and reactivation of latent HSV-1 inside the sensory nerves of the face (geniculate ganglia).^[10][11] This is supported by findings that show the presence of HSV-1 DNA in saliva at a higher frequency in patients with Bell's palsy relative to those without the condition.^[12]

However, since HSV can also be detected in these ganglia in large numbers of individuals that have never experienced facial paralysis, and high titers of antibodies for HSV are not found in HSV-infected individuals with Bell's palsy relative to those without, this theory has been contested.^[13] In other studies, HSV-1 DNA was not detected in the cerebrospinal fluid of Bell's palsy sufferers, raising questions whether HSV-1 is the causative agent in this type of facial paralysis.^[14][15] The potential effect of HSV-1 in the etiology of Bell's palsy has prompted the use of antiviral medication to treat the condition. The benefits of acyclovir and valacyclovir have been studied.^[16] But the effect appears small, if at all detectable.

[edit] Alzheimer's disease

Scientists discovered a link between HSV-1 and Alzheimer's disease in 1979.^[17] In the presence of a certain gene variation (APOE-epsilon4 allele carriers), HSV-1 appears to be particularly damaging to the nervous system and increases one’s risk of developing Alzheimer’s disease. The virus interacts with the components and receptors of lipoproteins, which may lead to the development of Alzheimer's disease.^{[18] [19]} Without the presence of the gene allele, HSV type 1 does not appear to cause any neurological damage and thus increase the risk of Alzheimer’s.^[20]

A study published in The Journal of Pathology,^[21] has shown a striking localization of herpes simplex virus type 1 DNA within the beta-amyloid plaques that characterize Alzheimer's disease, and suggests that this virus is a major cause of the plaques and hence probably a significant aetiological factor in Alzheimer's disease.

Herpes is contracted through direct contact with an active lesion or body fluid of an infected person.^[22] Herpes transmission occurs between discordant partners; a person with a history of infection (HSV seropositive) can pass the virus to an HSV seronegative person. The only way to contract Herpes simplex virus 2 is through direct skin-to-skin contact with an infected individual. To infect a new individual, HSV travels through tiny breaks in the skin or mucous membranes in the mouth or genital areas. Even microscopic abrasions on mucous membranes are sufficient to allow viral entry.

HSV asymptomatic shedding occurs at some time in most individuals infected with herpes. It can occur more than a week before or after a symptomatic recurrence in 50% of cases.^[23] Infected people that show no visible symptoms may still shed and transmit virus through their skin; asymptomatic shedding may represent the most common form of HSV-2 transmission.^[23] Asymptomatic shedding is more frequent within the first 12 months of acquiring HSV. Concurrent infection with HIV increases the frequency and duration of asymptomatic shedding.^[24] There are indications that some individuals may have much lower patterns of shedding, but evidence supporting this is not fully verified; no significant differences are seen in the frequency of asymptomatic shedding when comparing persons with 1 to 12 annual recurrences to those that have no recurrences.^[23]

Antibodies that develop following an initial infection with a type of HSV prevents reinfection with the same virus type—a person with a history of orofacial infection caused by HSV-1 cannot contract herpes whitlow or a genital infection caused by HSV-1. In a monogamous couple, a seronegative female runs a greater than 30% per year risk of contracting an HSV infection from a seropositive male partner.^[25] If an oral HSV-1 infection is contracted first, seroconversion will have occurred after 6 weeks to provide protective antibodies against a future genital HSV-1 infection.

Autoinoculation (Self infection) The virus requires physical contact to spread, and accordingly it is possible for the virus to spread to other points on the infected individual's body prior to seroconversion. This can occur after the virus presents itself on the hands or fingers ("herpes whitlow") - which can occur via masturbation or simply prodding an infected site. Grooming can also spread the virus, for example via shaving ("herpes barbae"), or simply by rubbing the infected areas vigorously with a towel. A classic case would be a toddler with a primary oral infection sucking his thumb and giving himself a herpetic whitlow.

Primary orofacial herpes is readily identified by clinical examination of persons with no previous history of lesions and contact with an individual with known HSV-1 infection. The appearance and distribution of sores in these individuals typically presents as multiple, round, superficial oral ulcers, accompanied by acute gingivitis.^[26] Adults with non-typical presentation are more difficult to diagnose. Prodromal symptoms that occur before the appearance of herpetic lesions help differentiate HSV symptoms from the similar symptoms of other disorders, such as allergic stomatitis. When lesions do not appear inside the mouth primary orofacial herpes is sometimes mistaken for impetigo, a bacterial infection. Common mouth ulcers (aphthous ulcer) also resemble intraoral herpes, but do not present a vesicular stage.^[26]

Genital herpes can be more difficult to diagnose than oral herpes since most HSV-2-infected persons have no classical symptoms.^[26] Further confusing diagnosis, several other conditions resemble genital herpes, including lichen planus, atopic dermatitis, and urethritis.^[26] Laboratory testing is often used to confirm a diagnosis of genital herpes. Laboratory tests include: culture of the virus, direct fluorescent antibody (DFA) studies to detect virus, skin biopsy, and polymerase chain reaction (PCR) to test for presence of viral DNA. Although these procedures produce highly sensitive and specific diagnoses, their high costs and time constraints discourage their regular use in clinical practice.^[26]

Serological tests for antibodies to HSV are rarely useful to diagnosis and not routinely used in clinical practice^[26], but are important in epidemiological studies. Serologic assays cannot differentiate between antibodies generated in response to a genital versus or an oral HSV infection, and as such cannot confirm the site of infection. Absence of antibody to HSV-2 does not exclude genital infection because of the increasing incidence of genital infections caused by HSV-1.

For genital herpes, condoms are highly effective in limiting transmission of herpes simplex infection.^[27][28] The virus cannot pass through latex, but a condom's effectiveness is somewhat limited on a public health scale by their limited use in the community,^[29] and on an individual scale because the condom may not completely cover blisters on the penis of an infected male, or the base of the penis or testicles not covered by the condom may come into contact with free virus in vaginal fluid of an infected female. In such cases, abstinence from sexual activity or washing of the genitals after sex is recommended. The use of condoms or dental dams also limits the transmission of herpes from the genitals of one partner to the mouth of the other (or vice versa) during oral sex. When one partner has a herpes simplex infection and the other does not, the use of antiviral medication, such as valaciclovir, in conjunction with a condom, further decreases the chances of transmission to the uninfected partner.^[5] Topical microbicides which contain chemicals that directly inactivate the virus and block viral entry are currently being investigated.^[5] Vaccines for HSV are currently undergoing trials. Once developed, they may be used to help with prevention or minimize initial infections as well as treatment for existing infections.^[30]

As with almost all sexually transmitted infections, women are more susceptible to acquiring genital HSV-2 than men.^[31] On an annual basis, without the use of antivirals or condoms, the transmission risk of HSV-2 from infected male to female is approximately 8-10%.^[25][32] This is believed to be due to the increased exposure of mucosal tissue to potential infection sites. Transmission risk from infected female to male is approximately 4-5% annually.^[32] Suppressive antiviral therapy reduces these risks by 50%.^[33] Antivirals also help prevent the development of symptomatic HSV in infection scenarios—meaning the infected partner will be seropositive but symptom free—by about 50%. Condom use also reduces the transmission risk by 50%.^[27][28][34] Condom use is much more effective at preventing male to female transmission than vice-versa.^[27] The effects of combining antiviral and condom use is roughly additive, thus resulting in approximately a 75% combined reduction in annual transmission risk.^{[citation needed]} These figures reflect experiences with subjects having frequently-recurring genital herpes (>6 recurrences per year). Subjects with low recurrence rates and those with no clinical manifestations were excluded from these studies.^{[citation needed]}

The risk of transmission from mother to baby is highest if the mother becomes infected at around the time of delivery (transmission risk 30 to 60%),^[35][36] but the risk falls to 3% if it is a recurrent infection, and is less than 1% if there are no visible lesions.^[37] To prevent neonatal infections, seronegative women are recommended to avoid unprotected oral-genital contact with an HSV-1 seropositive partner and conventional sex with a partner having a genital infection during the last trimester of pregnancy. A seronegative mother that contracts HSV at this time has up to a 57% chance of conveying the infection to her baby during childbirth, since insufficient time will have occurred for the generation and transfer of protective maternal antibodies before the birth of the child, whereas a woman seropositive for both HSV-1 and HSV-2 has around a 1-3% chance of transmitting infection to her infant. HSV-1 being transmitted by oral sex as HSV-2 is not very common but there is always the risk ^[38][39] Women that are seropositive for only one type of HSV are only half as likely to transmit HSV as infected seronegative mothers. Mothers infected with HSV are advised to avoid procedures that would cause trauma to the infant during birth (e.g., fetal scalp electrodes, forceps, and vacuum extractors) and, should lesions be present, to elect caesarean section to reduce exposure of the child to infected secretions in the birth canal.^[5] The use of antiviral treatments, such as aciclovir, given from the 36th week of pregnancy limits HSV recurrence and shedding during childbirth, thereby reducing the need for caesarean section.^[5]

HSV-2 infected individuals are at higher risk for acquiring HIV when practicing unprotected sex with HIV positive persons,^[40] particularly during an outbreak with active lesions.^[41]

There is currently no cure that can eradicate herpes virus from the body, but antiviral medications can reduce the frequency, duration, and severity of outbreaks. Antiviral drugs also reduce asymptomatic shedding; it is believed asymptomatic Genital HSV-2 viral shedding occurs on 20% of days per year in patients not undergoing antiviral treatment, versus 10% of days while on antiviral therapy.^[23] Non-prescription analgesics can reduce pain and fever during initial outbreaks. Topical anesthetic treatments such as prilocaine, lidocaine or tetracaine can also relieve itching and pain.^[42][43

Antiviral medications used against herpes viruses work by interfering with viral replication, effectively slowing the replication rate of the virus and providing a greater opportunity for the immune response to intervene. All drugs in this class depend on the activity of the viral enzyme thymidine kinase to convert the drug sequentially from its prodrug form to monophosphate (with one phosphate group), diphosphate (with two phosphate groups), and finally to the triphosphate (with three phosphate groups) form which interferes with viral DNA replication.^[44]

There are several prescription antiviral medications for controlling herpes simplex outbreaks, including aciclovir (Zovirax), valaciclovir (Valtrex), famciclovir (Famvir), and penciclovir. Acyclovir was the original, and prototypical, member of this drug class; it is now available in generic brands at a greatly reduced cost. Valaciclovir and famciclovir—prodrugs of aciclovir and penciclovir, respectively—have improved solubility in water and better bioavailability when taken orally.^[44] Aciclovir is the recommended antiviral for suppressive therapy for use during the last months of pregnancy to prevent transmission of herpes simplex to the neonate in cases of maternal recurrent herpes.^[45] The use of valaciclovir and famciclovir, while potentially improving treatment compliance and efficacy, are still undergoing safety evaluation in this context.

Several studies in humans and mice provide evidence that early treatment with famciclovir soon after the first infection with herpes can significantly lower the chance of future outbreaks of herpes. Early use of famciclovir has been shown to reduce the amount of latent virus in the neural ganglia.^[46][47][48] A review of human subjects treated for five days with famciclovir 250 mg three times daily during their first herpes episode found that only 4.2 percent experienced a recurrence within six months after the first outbreak, a fivefold decrease compared to the 19 percent recurrence in acyclovir-treated patients.^[49] Despite these promising results, early famciclovir treatment for herpes in this or similar dosage regimes has yet to find mainstream adoption. As a result, some doctors and patients have opted for off-label use. One suggested regime is famciclovir at 10–20 mg/kg per day for 5–10 days, with treatment to commence as soon as possible after the first herpes infection(not the first symptoms or outbreak), and the most effective time for initiating treatment to be five days or less after the first herpes infection. However, the window of opportunity for this treatment is only a few months after first infection with the virus, following this the potential effect on latency drops to zero.^[50]

Antiviral medications are also available as topical creams for treating recurrent outbreaks on the lips, although their effectiveness is disputed.^[51] Penciclovir cream has a 7-17 hour longer cellular half-life than aciclovir cream, increasing its effectiveness relative to aciclovir when topically applied.^[52]

Docosanol is available as a cream for direct application to the affected area of skin. It prevents HSV from fusing to cell membranes, thus barring the entry of the virus into the skin. Docosanol was approved for use after clinical trials by the FDA in July 2000.^[53] Docosanol is marketed by Avanir Pharmaceuticals under the name Abreva. It was the first over-the-counter antiviral drug approved for sale in the United States and Canada. Avanir Pharmaceuticals and GlaxoSmithKline Consumer Healthcare were the subject of a U.S. nationwide class-action suit in March, 2007 due to the misleading claim that it cut recovery times in half.^[54]

Tromantadine is available as a gel that inhibits the entry and spread of the virus by altering the surface composition of skin cells and inhibiting release of viral genetic material. Zilactin is a topical analgesic barrier treatment, which forms a "shield" at the area of application to prevent a sore from increasing in size, and decrease viral spreading during the healing process.

Lipactin by Novartis is another over-the-counter topical gel which has been clinically shown to reduce symptoms and healing duration of a Herpes Simplex infection.

There is some limited research that has shown that tea tree oil may have topical anti-viral activity, especially with the Herpes virus^[55] Upon first feeling tingling or soreness in the area (i.e when one bites their lip), prior to any physical manifestation, apply tea tree oil constantly for several hours. If caught early enough a cold sore will not form.

Cimetidine, a common component of heartburn medication, and probenecid have been shown to reduce the renal clearance of aciclovir.^[56] These compounds also reduce the rate, but not the extent, at which valaciclovir is converted into aciclovir.

Limited evidence suggests that low dose aspirin (125 mg daily) might be beneficial in patients with recurrent HSV infections. Aspirin (acetylsalicylic acid) is an non-steroidal anti-inflammatory drug which reduces the level of prostaglandins—naturally occurring lipid compounds—that are essential in creating inflammation.^[57] A recent study in animals showed inhibition of thermal (heat) stress induced viral shedding of HSV-1 in the eye by aspirin, and a possible benefit in reducing the frequency of recurrences.^[58]

Another treatment is the use of petroleum jelly. Healing of cold sores is sped by barring water or saliva from reaching the sore.

The National Institutes of Health (NIH) in the United States is currently conducting phase III trials of Herpevac, a vaccine against HSV-2.^[59] The vaccine has only been shown to be effective for women who have never been exposed to HSV-1. Overall, the vaccine is approximately 48% effective in preventing HSV-2 seropositivity and about 78% effective in preventing symptomatic HSV-2.^[59] During initial trials, the vaccine did not exhibit any evidence of preventing HSV-2 in males.^[59] Additionally, the vaccine only reduced the acquisition of HSV-2 and symptoms due to newly acquired HSV-2 among women who did not have HSV-2 infection at the time they got the vaccine.^[59] Because about 20% of persons in the United States have HSV-2 infection, this further reduces the population for whom this vaccine might be appropriate.^[59]

Researchers at the University of Florida have made a hammerhead ribozyme that targets and cleaves the mRNA of essential genes in HSV-1. The hammerhead which targets the mRNA of the UL20 gene greatly reduced the level of HSV-1 ocular infection in rabbits and reduced the viral yield in vivo.^[60]

Certain dietary adjustments, dietary supplements, and alternative remedies are believed to be beneficial in the treatment of herpes, either alone, or in conjunction with prescribed antiviral therapy. There is currently insufficient scientific and clinical evidence to support the effective use of many of these compounds to treat herpes in humans.^[61]

Lysine supplementation has been used for the prophylaxis and treatment of herpes simplex. Lysine shows greater effect against HSV-1 but may not be active against all virus variants. Dosage is critical with less than 1 gram (1000 mg) per day ineffective and more than 8 grams (8000 mg) gaining no additional benefit. Lysine is most effective if corn based products (which contain high amounts of Arginine) such as popcorn are avoided during an outbreak. Lysine treatment is somewhat body mass sensitive with higher dosage required for effective treatment as body mass increases. It should be taken as 3 or more doses in a 24 hour period and should be started when first outbreak symptoms, such as skin numbness or itching, are detected.^[62][63][64]

Aloe vera, available as a cream or gel, makes an affected area heal faster and may prevent recurrences.^[65]

Lemon balm (Melissa officinalis) has antiviral activity against HSV-2 in cell culture and may reduce HSV symptoms in herpes infected people.^[66][67][67]

Carrageenans—linear sulphated polysaccharides extracted from red seaweeds—have been shown to have antiviral effects in HSV-infected cells and in mice.^[68][69]

There is conflicting evidence on a possible benefit from extracts from the plant echinacea in treating oral^[70], but not genital, herpes.^[71]

Resveratrol, a compound naturally produced by plants and a component of red wine, prevents HSV replication in cultured cells and reduces cutaneous HSV lesion formation in mice. It is not considered potent enough to be an effective treatment on its own.^[72][73]

Extracts from garlic have shown antiviral activity against HSV in cell culture experiments, although the extremely high concentrations of the extracts required to produce an antiviral effect was also toxic to the cells.^[74]

The plant Prunella vulgaris, commonly known as selfheal, also prevents expression of both type 1 and type 2 herpes in cultured cells.^[75]

Lactoferrin, a component of whey protein, has been shown to have a synergistic effect with aciclovir against HSV in vitro.^[76]

Some dietary supplements have been suggested to positively treat herpes. These include vitamin C, vitamin A, vitamin E, and zinc.^[77][78]

Butylated hydroxytoluene (BHT), commonly available as a food preservative, has been shown in cell culture and animal studies to inactivate herpes virus.^[79][80] However, BHT has not been clinically tested and approved to treat herpes infections in humans.

Following active infection herpes viruses establish a latent infection in sensory and autonomic ganglia of the nervous system. The double-stranded DNA of the virus is incorporated into the cell physiology by infection of the nucleus of a nerve's cell body. HSV latency is static—no virus is produced—and is controlled by a number of viral genes, including Latency Associated Transcript (LAT).^[81]

Many HSV infected people experience recurrence within the first year of infection.^[5] Prodrome precedes development of lesions. Prodromal symptoms include tingling (paresthesia), itching, and pain where lumbosacral nerves innervate the skin. Prodrome may occur as long as several days or as short as a few hours before lesions develop. Beginning antiviral treatment when prodrome is experienced can reduce the appearance and duration of lesions in some individuals. During recurrence fewer lesions are likely to develop, lesions are less painful and heal faster (within 5–10 days without antiviral treatment) than those occurring during the primary infection.^[5] Subsequent outbreaks tend to be periodic or episodic, occurring on average four to five times a year when not using antiviral therapy.

The causes of reactivation are uncertain, but several potential triggers have been documented. A recent study (2009) showed that a protein VP16 plays a key role in reactivation of the dormant virus.^[82] Changes in the immune system during menstruation may play a role in HSV-1 reactivation.^[83][84] Concurrent infections, such as viral upper respiratory tract infection or other febrile diseases, can cause outbreaks. Reactivation due to infection is the likely source of the historic terms cold sore and fever blister.

Other identified triggers include: local injury to the face, lips, eyes, or mouth, trauma, surgery, radiotherapy, and exposure to wind, ultraviolet light, or sunlight.^{[85][86][87][88][89]}

The frequency and severity of recurrent outbreaks vary greatly between patients. Some individuals' outbreaks can be quite debilitating with large, painful lesions persisting for several weeks, while others will experience only minor itching or burning for a few days. An immunity to the virus is built over time. Most infected individuals will experience fewer outbreaks and outbreak symptoms will often become less severe. After several years, some people will become perpetually asymptomatic and will no longer experience outbreaks, though they may still be contagious to others. Immunocompromised individuals may experience episodes that are longer, more frequent, and more severe. Antiviral medication has been proven to shorten the frequency and duration of outbreaks.^[90] Outbreaks may occur at the original site of the infection or in proximity to nerve endings that reach out from the infected ganglia. In the case of a genital infection, sores can appear at the original site of infection or near the base of the spine, the buttocks, or the back of the thighs.

Herpes antiviral therapy began in the early 1960s with the experimental use of medication that interfered with viral replication called deoxyribonucleic acid (DNA) inhibitors. The original use was against normally fatal or disabilitating illness such as adult encephalitis,^[91] keratitis,^[92] in immunocompromised (transplant) patients,^[93] or disseminated herpes zoster.^[94] The original compounds used were 5-iodo-2'-deoxyuridine, AKA idoxuridine, IUdR, or(IDU) and 1-β-D-arabinofuranosylcytosine or ara-C,^[95] later marketed under the name cytosar or cytorabine. The usage expanded to include topical treatment of herpes simplex,^[96] zoster, and varicella.^[97] Some trials combined different antivirals with differing results.^[91] The introduction of 9-β-D-arabinofuranosyladenine, AKA ara-A or vidarabine, considerably less toxic than Ara-C, in the mid 1970s, heralded the way for the beginning of regular neonatal antiviral treatment. Vidarabine was the first systemically administered antiviral medication with activity against HSV for which therapeutic efficacy outweighed toxicity for the management of life-threatening HSV disease. Intravenous vidarabine was licensed for use by the U.S. Food and Drug Administration (FDA) in 1977. Other experimental antivirals of that period included: Heparin ^[98], trifluorothymidine (TFT)^[99], Ribivarin,^[100] interferon,^[101] Virazole,^[102] and 5-methoxymethyl-2'-deoxyuridine (MMUdR).^[103] The introduction of 9-(2-hydroxyethoxymethyl)guanine, AKA acyclovir, in the late 1970s^[104] raised antiviral treatment another notch and led to vidarabine vs. acyclovir trials in the late 1980s.^[105] The lower toxicity and ease of administration over vidarabine has led to acyclovir becoming the drug of choice for herpes treatment after it was licensed by the FDA in 1998.^[106] Another advantage in the treatment of neonatal herpes included greater reductions in mortality and morbidity with increased dosages, something that did not occur when compared with increased dosages of vidarabine.^[106] On the other side of the equation, acyclovir seems to inhibit antibody response and newborns on acyclovir antiviral treatment experienced a slower rise in antibody titer than those on vidarabine.^[106]