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Herpes Zoster

Disease Details

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Description: Herpes zoster, also known as shingles, is a viral infection causing a painful rash, typically appearing as a stripe of blisters on one side of the body.
Type: Herpes zoster, also known as shingles, is caused by the reactivation of the varicella-zoster virus (VZV), which is the same virus responsible for chickenpox. Herpes zoster is not transmitted genetically; rather, it is the result of the reactivation of a previous VZV infection that has remained dormant in the body's nerve cells.
Signs And Symptoms: The earliest symptoms of shingles, which include headache, fever, and malaise, are nonspecific, and may result in an incorrect diagnosis. These symptoms are commonly followed by sensations of burning pain, itching, hyperesthesia (oversensitivity), or paresthesia ("pins and needles": tingling, pricking, or numbness). Pain can be mild to severe in the affected dermatome, with sensations that are often described as stinging, tingling, aching, numbing or throbbing, and can be interspersed with quick stabs of agonizing pain.Shingles in children is often painless, but people are more likely to get shingles as they age, and the disease tends to be more severe.In most cases, after one to two days—but sometimes as long as three weeks—the initial phase is followed by the appearance of the characteristic skin rash. The pain and rash most commonly occur on the torso but can appear on the face, eyes, or other parts of the body. At first, the rash appears similar to the first appearance of hives; however, unlike hives, shingles causes skin changes limited to a dermatome, normally resulting in a stripe or belt-like pattern that is limited to one side of the body and does not cross the midline. Zoster sine herpete ("zoster without herpes") describes a person who has all of the symptoms of shingles except this characteristic rash.Later the rash becomes vesicular, forming small blisters filled with a serous exudate, as the fever and general malaise continue. The painful vesicles eventually become cloudy or darkened as they fill with blood, and crust over within seven to ten days; usually the crusts fall off and the skin heals, but sometimes, after severe blistering, scarring and discolored skin remain. The blister fluid contains varicella zoster virus, which can be transmitted through contact or inhalation of fluid droplets until the lesions crust over, which may take up to four weeks.
Prognosis: The rash and pain usually subside within three to five weeks, but about one in five people develop a painful condition called postherpetic neuralgia, which is often difficult to manage. In some people, shingles can reactivate presenting as zoster sine herpete: pain radiating along the path of a single spinal nerve (a dermatomal distribution), but without an accompanying rash. This condition may involve complications that affect several levels of the nervous system and cause many cranial neuropathies, polyneuritis, myelitis, or aseptic meningitis. Other serious effects that may occur in some cases include partial facial paralysis (usually temporary), ear damage, or encephalitis. Although initial infections with VZV during pregnancy, causing chickenpox, may lead to infection of the fetus and complications in the newborn, chronic infection or reactivation in shingles are not associated with fetal infection.There is a slightly increased risk of developing cancer after a shingles episode. However, the mechanism is unclear and mortality from cancer did not appear to increase as a direct result of the presence of the virus. Instead, the increased risk may result from the immune suppression that allows the reactivation of the virus.Although shingles typically resolves within 3–5 weeks, certain complications may arise:

Secondary bacterial infection.
Motor involvement, including weakness especially in "motor herpes zoster".
Eye involvement: trigeminal nerve involvement (as seen in herpes ophthalmicus) should be treated early and aggressively as it may lead to blindness. Involvement of the tip of the nose in the zoster rash is a strong predictor of herpes ophthalmicus.
Postherpetic neuralgia, a condition of chronic pain following shingles.
Onset: Herpes zoster, commonly known as shingles, typically has an onset characterized by the following:

1. **Prodromal Phase**: Often begins with symptoms such as headache, fever, malaise, and sensations of tingling, burning, itching, or pain in a localized area on one side of the body.

2. **Rash Development**: Within a few days to a week, a painful, blistering rash appears. Initially, the rash consists of red patches that develop into fluid-filled blisters.

3. **Location**: The rash typically follows a dermatomal pattern, meaning it is localized to the area of the skin innervated by a single sensory nerve.

The term "nan" does not appear relevant to the onset description of herpes zoster.
Prevalence: The prevalence of herpes zoster (shingles) varies by age, but it is estimated that about 1 in 3 people in the United States will develop the condition in their lifetime. The incidence rates increase with age, with about half of cases occurring in people aged 60 and older.
Epidemiology: Varicella zoster virus (VZV) has a high level of infectivity and has a worldwide prevalence. Shingles is a re-activation of latent VZV infection: zoster can only occur in someone who has previously had chickenpox (varicella).
Shingles has no relationship to season and does not occur in epidemics. There is, however, a strong relationship with increasing age. The incidence rate of shingles ranges from 1.2 to 3.4 per 1,000 person‐years among younger healthy individuals, increasing to 3.9–11.8 per 1,000 person‐years among those older than 65 years, and incidence rates worldwide are similar.
This relationship with age has been demonstrated in many countries, and is attributed to the fact that cellular immunity declines as people grow older.
Another important risk factor is immunosuppression. Other risk factors include psychological stress. According to a study in North Carolina, "black subjects were significantly less likely to develop zoster than were white subjects." It is unclear whether the risk is different by sex. Other potential risk factors include mechanical trauma and exposure to immunotoxins.There is no strong evidence for a genetic link or a link to family history. A 2008 study showed that people with close relatives who had shingles were twice as likely to develop it themselves, but a 2010 study found no such link.Adults with latent VZV infection who are exposed intermittently to children with chickenpox receive an immune boost. This periodic boost to the immune system helps to prevent shingles in older adults. When routine chickenpox vaccination was introduced in the United States, there was concern that, because older adults would no longer receive this natural periodic boost, there would be an increase in the incidence of shingles.
Multiple studies and surveillance data, at least when viewed superficially, demonstrate no consistent trends in incidence in the U.S. since the chickenpox vaccination program began in 1995. However, upon closer inspection, the two studies that showed no increase in shingles incidence were conducted among populations where varicella vaccination was not as yet widespread in the community. A later study by Patel et al. concluded that since the introduction of the chickenpox vaccine, hospitalization costs for complications of shingles increased by more than $700 million annually for those over age 60. Another study by Yih et al. reported that as varicella vaccine coverage in children increased, the incidence of varicella decreased, and the occurrence of shingles among adults increased by 90%. The results of a further study by Yawn et al. showed a 28% increase in shingles incidence from 1996 to 2001. It is likely that incidence rate will change in the future, due to the aging of the population, changes in therapy for malignant and autoimmune diseases, and changes in chickenpox vaccination rates; a wide adoption of zoster vaccination could dramatically reduce the incidence rate.In one study, it was estimated that 26% of those who contract shingles eventually present complications. Postherpetic neuralgia arises in approximately 20% of people with shingles. A study of 1994 California data found hospitalization rates of 2.1 per 100,000 person-years, rising to 9.3 per 100,000 person-years for ages 60 and up. An earlier Connecticut study found a higher hospitalization rate; the difference may be due to the prevalence of HIV in the earlier study, or to the introduction of antivirals in California before 1994.
Intractability: Herpes zoster, also known as shingles, is not inherently intractable. It is usually treatable with antiviral medications, which can help reduce the severity and duration of the outbreak if administered early. Pain associated with herpes zoster can often be managed with analgesics, corticosteroids, or other medications. However, some complications, such as postherpetic neuralgia, can be more persistent and challenging to manage.
Disease Severity: Herpes zoster, also known as shingles, can vary in severity. In most cases, it causes a painful rash with blisters that scab over in 7 to 10 days and usually clears up within 2 to 4 weeks. Some individuals may experience complications such as postherpetic neuralgia, which is severe pain in the areas where the rash occurred, lasting for months or even years. In rare instances, shingles can cause more severe complications, such as vision loss if the rash occurs near the eyes, neurological problems, and skin infections.
Healthcare Professionals: Disease Ontology ID - DOID:8536
Pathophysiology: The causative agent for shingles is the varicella zoster virus (VZV)—a double-stranded DNA virus related to the herpes simplex virus. Most individuals are infected with this virus as children which causes an episode of chickenpox. The immune system eventually eliminates the virus from most locations, but it remains dormant (or latent) in the ganglia adjacent to the spinal cord (called the dorsal root ganglion) or the trigeminal ganglion in the base of the skull.Shingles occurs only in people who have been previously infected with VZV; although it can occur at any age, approximately half of the cases in the United States occur in those aged 50 years or older. Shingles can recur. In contrast to the frequent recurrence of herpes simplex symptoms, repeated attacks of shingles are unusual. It is extremely rare for a person to have more than three recurrences.The disease results from virus particles in a single sensory ganglion switching from their latent phase to their active phase. Due to difficulties in studying VZV reactivation directly in humans (leading to reliance on small-animal models), its latency is less well understood than that of the herpes simplex virus. Virus-specific proteins continue to be made by the infected cells during the latent period, so true latency, as opposed to chronic, low-level, active infection, has not been proven to occur in VZV infections. Although VZV has been detected in autopsies of nervous tissue, there are no methods to find dormant virus in the ganglia of living people.
Unless the immune system is compromised, it suppresses reactivation of the virus and prevents shingles outbreaks. Why this suppression sometimes fails is poorly understood, but shingles is more likely to occur in people whose immune systems are impaired due to aging, immunosuppressive therapy, psychological stress, or other factors. Upon reactivation, the virus replicates in neuronal cell bodies, and virions are shed from the cells and carried down the axons to the area of skin innervated by that ganglion. In the skin, the virus causes local inflammation and blistering. The short- and long-term pain caused by shingles outbreaks originates from inflammation of affected nerves due to the widespread growth of the virus in those areas.As with chickenpox and other forms of alpha-herpesvirus infection, direct contact with an active rash can spread the virus to a person who lacks immunity to it. This newly infected individual may then develop chickenpox, but will not immediately develop shingles.The complete sequence of the viral genome was published in 1986.
Carrier Status: Herpes zoster, also known as shingles, is caused by the reactivation of the varicella-zoster virus (VZV), the same virus responsible for chickenpox. There is no carrier status for herpes zoster in the traditional sense. Instead, individuals who have had chickenpox carry the dormant virus in their nerve tissues and may develop herpes zoster later in life if the virus reactivates.
Mechanism: Herpes zoster, commonly known as shingles, is caused by the reactivation of Varicella-Zoster Virus (VZV), the same virus responsible for chickenpox.

**Mechanism:**
1. **Primary Infection:** VZV causes chickenpox, after which the virus remains dormant in the dorsal root ganglia or cranial nerve ganglia.
2. **Reactivation:** The virus can reactivate later in life due to factors like aging, immunosuppression, or stress, leading to herpes zoster.
3. **Pathophysiology:** Upon reactivation, VZV travels down the nerve fibers to the skin, causing painful, unilateral vesicular eruptions.

**Molecular Mechanisms:**
1. **Latency:** During latency, VZV expresses limited viral proteins, which helps it evade immune detection. Key factors include:
- Latency-associated transcript (LAT) genes which help maintain the latent state.
2. **Immune Evasion:** VZV can modulate and evade the immune response by:
- Downregulating Major Histocompatibility Complex (MHC) molecules.
- Modulating cytokine production.
3. **Reactivation Triggers:** Immunosenescence, stress, and immunosuppressive therapies can disrupt the balance between the host immune system and latent virus, prompting reactivation.
4. **Neuropathic Pain:** VZV-induced inflammation and direct nerve damage contribute to postherpetic neuralgia, a common complication of herpes zoster.

Understanding these mechanisms highlights the balance between viral persistence and host immune surveillance, essential for managing and potentially preventing herpes zoster.
Treatment: The aims of treatment are to limit the severity and duration of pain, shorten the duration of a shingles episode, and reduce complications. Symptomatic treatment is often needed for the complication of postherpetic neuralgia.
However, a study on untreated shingles shows that, once the rash has cleared, postherpetic neuralgia is very rare in people under 50 and wears off in time; in older people, the pain wore off more slowly, but even in people over 70, 85% were free from pain a year after their shingles outbreak.
Compassionate Use Treatment: For herpes zoster, commonly known as shingles, there are some off-label and experimental treatments being explored.

1. **Brivudin**: Though not commonly used in many countries, it has shown effectiveness in specific regions for the treatment of herpes zoster.

2. **Famciclovir**: Another antiviral similar to acyclovir and valacyclovir, sometimes used off-label depending on the availability and patient-specific factors.

Experimental treatments include several investigational drugs and therapies:

1. **Pritelivir**: An investigational antiviral agent that inhibits the helicase-primase enzyme complex of herpesviruses, offering a different mechanism of action than traditional nucleoside analogs.

2. **FV-100**: An investigational nucleoside analogue with the potential to reduce neuropathic pain and the duration of shingles-associated pain.

3. **Gene therapy**: Research is ongoing in this area to potentially provide long-term solutions to viral infections like herpes zoster by targeting the virus’s DNA directly.

Using these treatments may involve a compassionate use request, typically when standard treatments are insufficient or unsuitable, and must be approved by regulatory bodies depending on the location.
Lifestyle Recommendations: Lifestyle recommendations for managing herpes zoster (shingles) include:

1. **Healthy Diet**: Maintain a balanced diet rich in fruits, vegetables, and whole grains to support overall immune health.

2. **Adequate Hydration**: Drink plenty of water to stay hydrated.

3. **Stress Management**: Practice stress-reducing techniques like yoga, meditation, or regular exercise to keep the immune system strong.

4. **Rest**: Ensure sufficient rest and sleep to help the body heal and recover.

5. **Gentle Skin Care**: Keep the affected area clean and dry. Use cool, moist compresses to reduce pain and itching.

6. **Avoid Scratching**: Refrain from scratching the rash to prevent infection.

7. **Loose Clothing**: Wear loose-fitting, natural-fiber clothing to minimize irritation of the affected area.

8. **Avoid Contact**: Stay away from pregnant women, infants, and immunocompromised individuals until the rash has crusted over to prevent spreading the virus.
Medication: The primary medication for treating herpes zoster, also known as shingles, is antiviral drugs. Common antiviral medications include:

1. Acyclovir
2. Valacyclovir
3. Famciclovir

These medications are most effective when started within 72 hours of the appearance of the rash. They help to shorten the duration of the outbreak, reduce the severity of symptoms, and decrease the risk of complications such as postherpetic neuralgia. Pain management may also involve analgesics, anticonvulsants, or corticosteroids depending on the case.
Repurposable Drugs: For herpes zoster, also known as shingles, there are several drugs considered for repurposing. These include:

1. **Famciclovir** – Originally used for herpes simplex virus infections, it can be repurposed for treating shingles.
2. **Valacyclovir** – Another antiviral used primarily for herpes simplex, but effective for herpes zoster as well.
3. **Gabapentin** – Typically used for neuropathic pain, it can alleviate postherpetic neuralgia, a common complication of shingles.
4. **Pregabalin** – Similar to gabapentin, it is repurposed for managing postherpetic neuralgia.

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Metabolites: For herpes zoster (shingles), the term "metabolites" typically refers to substances produced during the metabolism of antiviral medications used to treat the condition. Key antiviral drugs include acyclovir, valacyclovir, and famciclovir. These drugs are metabolized in the body to active forms that help inhibit viral replication. For example, valacyclovir is converted into acyclovir, and further into acyclovir triphosphate, which is the active form that inhibits the replication of the herpes zoster virus.
Nutraceuticals: Nutraceuticals, which are food-derived products with potential health benefits, have been explored for their role in managing herpes zoster, commonly known as shingles. Key nutraceuticals that might be beneficial include:

1. **Vitamin C**: Known for its immune-boosting properties, high doses of vitamin C may help reduce the severity and duration of shingles.
2. **Lysine**: This amino acid is thought to inhibit the replication of the herpes virus, potentially reducing the frequency and severity of outbreaks.
3. **Vitamin E**: Helps in skin healing and might alleviate pain associated with postherpetic neuralgia, a common complication of shingles.
4. **Zinc**: Plays a critical role in immune function and might help control viral replication.
5. **Probiotics**: These can improve gut health and overall immune function, potentially helping the body resist viral infections.

Always consult a healthcare provider before starting any new supplementation, especially when dealing with viral infections like herpes zoster.
Peptides: Herpes zoster, commonly known as shingles, involves the reactivation of the varicella-zoster virus. In the context of peptides, research is being conducted to develop peptide-based vaccines and therapeutic agents to prevent or treat the disease. These peptides can target specific viral components to elicit an immune response or inhibit viral replication.

Regarding nanoparticles (nan), nanotechnology is being explored for the delivery of antiviral drugs and vaccines. Nanoparticles can enhance the stability and delivery efficiency of therapeutic agents, potentially improving the treatment and prevention outcomes for herpes zoster.

Both areas are promising fields of investigation, aiming to enhance the management of herpes zoster through innovative biomedical approaches.