Shingles can be confused with herpes simplex, dermatitis herpetiformis and impetigo, and skin reactions caused by contact dermatitis, candidiasis, certain drugs and insect bites.

If the rash has appeared, identifying this disease (making a differential diagnosis) requires only a visual examination, since very few diseases produce a rash in a dermatomal pattern (see map). However, herpes simplex virus (HSV) can occasionally produce a rash in such a pattern (zosteriform herpes simplex). The Tzanck smear is helpful for diagnosing acute infection with a herpes virus, but does not distinguish between HSV and VZV.

When the rash is absent (early or late in the disease, or in the case of zoster sine herpete), shingles can be difficult to diagnose. Apart from the rash, most symptoms can occur also in other conditions.

Laboratory tests are available to diagnose shingles. The most popular test detects VZV-specific IgM antibody in blood; this appears only during chickenpox or shingles and not while the virus is dormant. In larger laboratories, lymph collected from a blister is tested by polymerase chain reaction for VZV DNA, or examined with an electron microscope for virus particles. Molecular biology tests based on in vitro nucleic acid amplification (PCR tests) are currently considered the most reliable. Nested PCR test has high sensitivity, but is susceptible to contamination leading to false positive results. The latest real-time PCR tests are rapid, easy to perform, and as sensitive as nested PCR, and have a lower risk of contamination. They also have more sensitivity than viral cultures.

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. Adults with atypical 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.

Genital herpes can be more difficult to diagnose than oral herpes, since most HSV-2-infected persons have no classical symptoms. Further confusing diagnosis, several other conditions resemble genital herpes, including fungal infection, lichen planus, atopic dermatitis, and urethritis. 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 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.

Until the 1980s serological tests for antibodies to HSV were rarely useful to diagnosis and not routinely used in clinical practice. The older IgM serologic assay could not differentiate between antibodies generated in response to HSV-1 or HSV-2 infection. However, a glycoprotein G-specific (IgG) HSV test introduced in the 1980s is more than 98% specific at discriminating HSV-1 from HSV-2.

It should not be confused with conditions caused by other viruses in the "herpesviridae" family such as herpes zoster, which is caused by varicella zoster virus. The differential diagnosis includes hand, foot and mouth disease due to similar lesions on the skin.

As with almost all sexually transmitted infections, women are more susceptible to acquiring genital HSV-2 than men. On an annual basis, without the use of antivirals or condoms, the transmission risk of HSV-2 from infected male to female is about 8–11%.

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 around 4–5% annually. Suppressive antiviral therapy reduces these risks by 50%. 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 significantly. Condom use is much more effective at preventing male-to-female transmission than "vice versa". Previous HSV-1 infection may reduce the risk for acquisition of HSV-2 infection among women by a factor of three, although the one study that states this has a small sample size of 14 transmissions out of 214 couples.

However, asymptomatic carriers of the HSV-2 virus are still contagious. In many infections, the first symptom people will have of their own infections is the horizontal transmission to a sexual partner or the vertical transmission of neonatal herpes to a newborn at term. Since most asymptomatic individuals are unaware of their infection, they are considered at high risk for spreading HSV.

In October 2011, the anti-HIV drug tenofovir, when used topically in a microbicidal vaginal gel, was reported to reduce herpes virus sexual transmission by 51%.

The diagnosis of chickenpox is primarily based on the signs and symptoms, with typical early symptoms followed by a characteristic rash. Confirmation of the diagnosis is by examination of the fluid within the vesicles of the rash, or by testing blood for evidence of an acute immunologic response.

Vesicular fluid can be examined with a Tzanck smear, or by testing for direct fluorescent antibody. The fluid can also be "cultured", whereby attempts are made to grow the virus from a fluid sample. Blood tests can be used to identify a response to acute infection (IgM) or previous infection and subsequent immunity (IgG).

Prenatal diagnosis of fetal varicella infection can be performed using ultrasound, though a delay of 5 weeks following primary maternal infection is advised. A PCR (DNA) test of the mother's amniotic fluid can also be performed, though the risk of spontaneous abortion due to the amniocentesis procedure is higher than the risk of the baby's developing fetal varicella syndrome.

Herpesviral Encephalitis can be treated with high-dose intravenous acyclovir. Without treatment, HSE results in rapid death in approximately 70% of cases; survivors suffer severe neurological damage. When treated, HSE is still fatal in one-third of cases, and causes serious long-term neurological damage in over half of survivors. Twenty percent of treated patients recover with minor damage. Only a small population of survivors (2.5%) regain completely normal brain function. Indeed, many amnesic cases in the scientific literature have etiologies involving HSE. Earlier treatment (within 48 hours of symptom onset) improves the chances of a good recovery. Rarely, treated individuals can have relapse of infection weeks to months later. There is evidence that aberrant inflammation triggered by herpes simplex can result in granulomatous inflammation in the brain, which responds to steroids. While the herpes virus can be spread, encephalitis itself is not infectious. Other viruses can cause similar symptoms of encephalitis, though usually milder (Herpesvirus 6, varicella zoster virus, Epstein-Barr, cytomegalovirus, coxsackievirus, etc.).

Diagnosis starts by examining the patient's symptoms. Symptoms can vary. Symptoms can include headache, sensitivity to light, neck stiffness, nausea, and vomiting. In some patients, fever is absent. Neurological examination and MRI can be normal.

Mollaret's meningitis is suspected based on symptoms, and can be confirmed by HSV 1 or HSV 2 on PCR of Cerebrospinal fluid (CSF), although not all cases test positive on PCR. PCR is performed on spinal fluid or blood, however, the viruses do not need to enter the spinal fluid or blood to spread within the body: they can spread by moving through the axons and dendrites of the nerves.

During the first 24 h of the disease the spinal fluid will show predominant polymorphonuclear neutrophils and large cells that have been called endothelial (Mollaret’s) cells.

A study performed on patients who had diffuse symptoms, such as persistent or intermittent headaches, concluded that although PCR is a highly sensitive method for detection, it may not always be sensitive enough for identification of viral DNA in CSF, due to the fact that viral shedding from latent infection may be very low. The concentration of viruses in CSF during subclinical infection might be very low.

Investigations include blood tests (electrolytes, liver and kidney function, inflammatory markers and a complete blood count) and usually X-ray examination of the chest. The most important test in identifying or ruling out meningitis is analysis of the cerebrospinal fluid (fluid that envelops the brain and the spinal cord) through lumbar puncture (LP). However, if the patient is at risk for a cerebral mass lesion or elevated intracranial pressure (recent head injury, a known immune system problem, localizing neurological signs, or evidence on examination of a raised ICP), a lumbar puncture may be contraindicated because of the possibility of fatal brain herniation. In such cases, a CT or MRI scan is generally performed prior to the lumbar puncture to exclude this possibility. Otherwise, the CT or MRI should be performed after the LP, with MRI preferred over CT due to its superiority in demonstrating areas of cerebral edema, ischemia, and meningeal inflammation.

During the lumbar puncture procedure, the opening pressure is measured. A pressure of over 180 mm HO is suggestive of bacterial meningitis.

It is likely that Mollaret meningitis is underrecognized by physicians, and improved recognition may limit unwarranted antibiotic use and shorten or eliminate unnecessary hospital admission.

PCR testing has advanced the state of the art in research, but PCR can be negative in individuals with Mollaret's, even during episodes with severe symptoms. For example, Kojima et al. published a case study for an individual who was hospitalized repeatedly, and who had clinical symptoms including genital herpes lesions. However, the patient was sometimes negative for HSV-2 by PCR, even though his meningitis symptoms were severe. Treatment with acyclovir was successful, indicating that a herpes virus was the cause of his symptoms.

The spread of chickenpox can be prevented by isolating affected individuals. Contagion is by exposure to respiratory droplets, or direct contact with lesions, within a period lasting from three days before the onset of the rash, to four days after the onset of the rash. The chickenpox virus is susceptible to disinfectants, notably chlorine bleach (i.e., sodium hypochlorite). Like all enveloped viruses, it is sensitive to desiccation, heat and detergents.

Most individuals with HSE show a decrease in their level of consciousness and an altered mental state presenting as confusion, and changes in personality. Increased numbers of white blood cells can be found in patient's cerebrospinal fluid, without the presence of pathogenic bacteria and fungi. Patients typically have a fever and may have seizures. The electrical activity of the brain changes as the disease progresses, first showing abnormalities in one temporal lobe of the brain, which spread to the other temporal lobe 7–10 days later. Imaging by CT or MRI shows characteristic changes in the temporal lobes (see Figure). Definite diagnosis requires testing of the cerebrospinal fluid (CSF) by a lumbar puncture (spinal tap) for presence of the virus. The testing takes several days to perform, and patients with suspected Herpes encephalitis should be treated with acyclovir immediately while waiting for test results.

Vaccination is available against tick-borne and Japanese encephalitis and should be considered for at-risk individuals. Post-infectious encephalomyelitis complicating smallpox vaccination is avoidable, for all intents and purposes, as smallpox is nearly eradicated. Contraindication to Pertussis immunization should be observed in patients with encephalitis.

People should only be diagnosed with encephalitis if they have a decreased or altered level of consciousness, lethargy, or personality change for at least twenty-four hours without any other explainable cause. Diagnosing encephalitis is done via a variety of tests:

- Brain scan, done by MRI, can determine inflammation and differentiate from other possible causes.

- EEG, in monitoring brain activity, encephalitis will produce abnormal signal.

- Lumbar puncture (spinal tap), this helps determine via a test using the cerebral-spinal fluid, obtained from the lumbar region.

- Blood test

- Urine analysis

- Polymerase chain reaction (PCR) testing of the cerebrospinal fluid, to detect the presence of viral DNA which is a sign of viral encephalitis.

Testing peoples blood, including those who are pregnant, who do not have symptoms for HSV is not recommended. This is due to concerns of greater harm than benefit such as relationship problems in the setting of a high rate of tests that may be falsely positive.

The diagnosis of viral meningitis is made by clinical history, physical exam, and several diagnostic tests. Most importantly, cerebrospinal fluid (CSF) is collected via lumbar puncture (also known as spinal tap). This fluid, which normally surrounds the brain and spinal cord, is then analyzed for signs of infection. CSF findings that suggest a viral cause of meningitis include an elevated white blood cell count (usually 10-100 cells/µL) with a lymphocytic predominance in combination with a normal glucose level. Increasingly, cerebrospinal fluid PCR tests have become especially useful for diagnosing viral meningitis, with an estimated sensitivity of 95-100%. Additionally, samples from the stool, urine, blood and throat can also help to identify viral meningitis.

In certain cases, a CT scan of the head should be done before a lumbar puncture such as in those with poor immune function or those with increased intracranial pressure.

Herpes simplex virus is commonly found in humans, yet uncommonly results in systemic manifestations. Suppression of HIV with antiretroviral medications, careful monitoring of immunosuppressive medications are important means of prevention. Antiviral prophylaxis such as daily acyclovir in immunocompromised individuals may be considered.

Key measures to prevent outbreaks of the disease are maintaining hygiene standards and using screening to exclude persons with suspicious infections from engaging in contact sports. A skin check performed before practice or competition takes place can identify individuals who should be evaluated, and if necessary treated by a healthcare professional. In certain situations, i.e. participating in wrestling camps, consider placing participants on valacyclovir 1GM daily for the duration of camp. 10-year study has shown 89.5% reduction in outbreaks and probable prevention of contracting the virus. Medication must be started 5 days before participation to ensure proper concentrations exist.

The majority of cases (85%) occur during birth when the baby comes in contact with infected genital secretions in the birth canal, most common with mothers that have newly been exposed to the virus (mothers that had the virus before pregnancy have a lower risk of transmission), an estimated 5% are infected in utero, and approximately 10% of cases are acquired postnatally. Detection and prevention is difficult because transmission is asymptomatic in 60% - 98% of cases.

Although DNA analysis techniques such as Polymerase chain reaction can be used to look for DNA of herpesviruses in spinal fluid or blood, the results may be negative, even in cases where other definitive symptoms exist.

About 16 percent of Americans between the ages of 14 and 49 are infected with genital herpes, making it one of the most common sexually transmitted diseases. More than 80% of those infected are unaware of their infection. Annually, 776,000 people in the United States get new herpes infections.

Tests for herpes are not routinely included among STD screenings. Performers in the pornography industry are screened for HIV, chlamydia, and gonorrhea with an optional panel of tests for hepatitis B, hepatitis C and syphilis, but not herpes. Testing for herpes is controversial since the results are not always accurate or helpful. Most sex workers and performers will contract herpes at some point in their careers whether they use protection or not.

CMV, VZV as well as HIV infections of the esophagus can have a similar presentation. Tissue culture is the most accurate means of distinguishing between the different viral causes. Caustic esophagitis, pill-induced esophagitis as well as yeast esophagitis can have a similar clinical presentation.

Reductions in morbidity and mortality are due to the use of antiviral treatments such as vidarabine and acyclovir. However, morbidity and mortality still remain high due to diagnosis of DIS and CNS herpes coming too late for effective antiviral administration; early diagnosis is difficult in the 20-40% of infected neonates that have no visible lesions. A recent large scale retrospective study found disseminated NHSV patients least likely to get timely treatment, contributing to the high morbidity/mortality in that group.

Harrison's Principles of Internal Medicine, recommends that pregnant women with active genital herpes lesions at the time of labor be delivered by caesarean section. Women whose herpes is not active can be managed with acyclovir. The current practice is to deliver women with primary or first episode non primary infection via caesarean section, and those with recurrent infection vaginally, even in the presence of lesions because of the low risk (1-3%) of vertical transmission associated with recurrent herpes.

Development of new therapies has been hindered by the lack of appropriate animal model systems for some important viruses and also because of the difficulty in conducting human clinical trials for diseases that are rare. Nonetheless, numerous innovative approaches to antiviral therapy are available including candidate thiazolide and purazinecarboxamide derivatives with potential broad-spectrum antiviral efficacy. New herpes virus drugs include viral helicase-primase and terminase inhibitors. A promising new area of research involves therapies based on enhanced understanding of host antiviral immune responses.

The likelihood of the infection being spread can be reduced through behaviors such as avoiding touching an active outbreak site, washing hands frequently while the outbreak is occurring, not sharing items that come in contact with the mouth, and not coming into close contact with others (by avoiding kissing, oral sex, or contact sports).

Because the onset of an infection is difficult to predict, lasts a short period of time and heals rapidly, it is difficult to conduct research on cold sores. Though famciclovir improves lesion healing time, it is not effective in preventing lesions; valaciclovir and a mixture of acyclovir and hydrocortisone are similarly useful in treating outbreaks but may also help prevent them.

Acyclovir and valacyclovir by mouth are effective in preventing recurrent herpes labialis if taken prior to the onset of any symptoms or exposure to any triggers. Evidence does not support L-lysine.

Treatments of proven efficacy are currently limited mostly to herpes viruses and human immunodeficiency virus. The herpes virus is of two types: herpes type 1 (HSV-1, or oral herpes) and herpes type 2 (HSV-2, or genital herpes). Although there is no particular cure; there are treatments that can relieve the symptoms. Drugs like Famvir, Zovirax, and Valtrex are among the drugs used, but these medications can only decrease pain and shorten the healing time. They can also decrease the total number of outbreaks in the surrounding. Warm baths also may relive the pain of genital herpes.

Human Immunodeficiency Virus Infection (HIV) is treated by using a combination of medications to fight against the HIV infection in the body. This is called antiretroviral therapy (ART). ART is not a cure, but it can control the virus so that a person can live a longer, healthier life and reduce the risk of transmitting HIV to others around him. ART involves taking a combination of HIV medicines (called an HIV regimen) every day, exactly as prescribed by the doctor. These HIV medicines prevent HIV Virus from multiplying (making copies of itself in the body), which reduces the amount of HIV in the body. Having less HIV in the body gives the immune system a chance to recover and fight off infections and cancers. Even though there is still some HIV in the body, the immune system is strong enough to fight off infections and cancers. By reducing the amount of HIV in the body, HIV medicines also reduce the risk of transmitting the virus to others. ART is recommended for all people with HIV, regardless of how long they’ve had the virus or how healthy they are. If left untreated, HIV will attack the immune system and eventually progress to AIDS.

Herpesviral meningitis is meningitis associated with herpes simplex virus (HSV).

HSV-2 is the most common cause of Mollaret's meningitis, a type of recurrent viral meningitis. This condition was first described in 1944 by French neurologist Pierre Mollaret. Recurrences usually last a few days or a few weeks, and resolve without treatment. They may recur weekly or monthly for approximately 5 years following primary infection.

Herpes outbreaks should be treated with antiviral medications like Acyclovir, Valacyclovir, or Famcyclovir, each of which is available in tablet form.

Oral antiviral medication is often used as a prophylactic to suppress or prevent outbreaks from occurring. The recommended dosage for suppression therapy for recurrent outbreaks is 1,000 mg of valacyclovir once a day or 400 mg Acyclovir taken twice a day. In addition to preventing outbreaks, these medications greatly reduce the chance of infecting someone while the patient is not having an outbreak.

Often, people have regular outbreaks of anywhere from 1 to 10 times per year, but stress (because the virus lies next to the nerve cells), or a weakened immune system due to a temporary or permanent illness can also spark outbreaks. Some people become infected but fail to ever have a single outbreak, although they remain carriers of the virus and can pass the disease on to an uninfected person through asymptomatic shedding (when the virus is active on the skin but rashes or blisters do not appear).

The use of antiviral medications has been shown to be effective in preventing acquisition of the herpes virus. Specific usage of these agents focus on wrestling camps where intense contact between individuals occur on a daily basis over several weeks. They have also been used for large outbreaks during seasonal competition, but further research needs to be performed to verify efficacy.