Herpes zoster


Also known as shingles.

98% of adults have been exposed to the varicella virus and are at risk of getting zoster.

Caused by herpesvirus 3.

Almost one of 5 individuals will develop shingles during their lifetime.

Among people who live until age 85 HZ will develop in approximately half, with an incidence that is increasing.

Annual incidence is approximately 3.4 cases for 1000 persons and rises sharply after the age of 50 years to approximately 11 cases per 1000 by the ninth decade of life.

Incidence has increased over last several decades.

10-20% of individuals that have chickenpox will develop zoster.

Estimated 1,000,000 million cases per year in the U.S.

The incidence has gradually increased since the early 1990s.

The burden of varicella zoster virus disease is substantial: within 90% of the worlds population harbor latent virus and approximately 50% will reactivate and develop herpes zoster by 85 years of age.

25% of cases result in complications.

Following primary infection, which often occurs in childhood, the virus remains dormant in neurosensory ganglia.

The virus may be reactivated, typically years or decades later, and results in cutaneous disease-shingles or herpes zoster.

Typically results in unilateral neurocutaneous reaction in the dermatome served by a particular neurosensory nucleus, causing pain and a pustular rash.

The re-activated virus may migrate centrally, causing arterial inflammation and morphological changes that may result in ischemia and aneurysm.

Herpes zoster associated vasculopathy may be cranial or extra cranial and may result in TIA and stroke.

Incidence of herpes zoster is 1.5- 2 per 1000 person-years in the third and fourth decades of life.

Incidence in general population between 3 and 5 per 1000 person-years.

Incidence rates increase with age and range became four per 1000 patient-years in patients age 50 years and 11 per 1000 patient-years in patients aged 80 years.

Herpes zoster is most frequent in adults over the age of 50 years owing to immunosenescence, but it can occur at any age especially when cell mediated immunity is decreased as a result of disease or drug treatment.

Complications of herpes zoster such as postherpetic neuralgia are more frequent and severe with advanced age.

Can be complicated by stroke described as vasculopathy, granulomatous angiitis,and ophthalmicus

with delayed contralateral hemiparesis when herpes zoster occurs in the ophthalmic distribution of the trigeminal nerve followed by stroke involving the ipsilateral middle cerebral artery.

There is an association between HZ and an increased risk of stroke, TIA, myocardial infarction, amd acute coronary syndrome.

Serious complications can occur such as superinfection, long-term pain, and ophthalmic involvement resulting in significant morbidity.

Up to 4% of patients require hospitalization to help in the management of complications.

Patients over the age of 50 and those immunocompromised are more likely to have complications of HZ ophthalmicus and postherpetic neuralgia.

Incidence rates are highest women.

It is to heredible to some degree.

Is the most common neurological disorder in the U.S.

In the US incidence rate of herpes zoster (HZ) in unvaccinated general population 50 years or older is estimated to be 7 cases per 1000-person years (Insinga RP et al).

Risk of HZ increased by 1.5 to 2 times in patients with rheumatic and immune mediated diseases such as rheumatoid arthritis and Crohn disease.plko’

Recurrence rate is less than 6% among immunocompetent individuals.

Risk increased in immunocompromised conditions, family history, including bone marrow or solid malignancies, and human immunodeficiency virus/AIDS.

Autoimmune diseases, including rheumatoid arthritis, and systemic lupus erythematosus are associated with an almost 2 fold elevated risk of herpes zoster, with a reported of incidence of 8-15 per 1000 person-years.

Inflammatory bowel disease is a risk factor.

The risk ratio of HZ is 1.3 for chronic kidney disease, COPD, diabetes, asthma, and depression.

Depression activates inflammatory response and is associated with reduced herpes zoster virus specific cell mediated immune response.

Statin use is associated with a modest increase in the risk of HZ.

Immunosuppressive medications such as chemotherapy, high-dose corticosteroids, and biological agents increase the risk.

Affects 32% of individuals during their lifetime and as man as 50% of individuals who live to be 85 years of age develop the disease.

Incidence rate approximately 3.6 cases per 1000 person-years, with 1-2 cases per 1000 person-years in patients 20-29 years of age, 10-11 cases per 1000 person-years for individuals older than 80 years.

CDC- approximately 1 million cases of herpes zoster annually in the US and nearly one in three people will develop shingles during their lifetime.

Primarily affects adults who are elderly or immunocompromised.

Increasing age strongly associated with risk.

Most important underlying risk factor is cell mediated immunity impairment by age, disease, or medical therapy.

Immunocompromised hosts with lymphoproliferative disease, organ transplant recipients, and patients with HIV infection are at substantial risk for the process.

Rheumatoid arthritis patients have a risk of HZ elevated by an additional factor of 2-3 fold.

Develops in 10-30% of patients infected with varicella-zoster virus.

Often presents with pain a few days before an eruption of clustered red papulovesicles.

Skin eruption most often in a unilateral and linear pattern in one or a few dermatomes, especially from C2 through L2.

The rash or area on one side of the face or torso, and may last 2-4 weeks.

The major symptom associated with the rash is pain.

HZ may be associated with viral syndrome such as fever, headache, chills, and gastrointestinal upset.

Rarely can lead to pneumonia, hearing problems, blindness, encephalitis or death.

Postherpetic neuralgia occurs in one in five individuals.

Incidence of 0.74 per 1,000 children younger than 9 year of age.

Following the primary infection, the host’s immune system suppresses viral replication, but viral particles can remain dormant for years, most commonly in spinal and cranial nerve ganglia.

The varicella-zoster virus persists in sensory ganglia of cranial nerves and spinal dorsal-root ganglia after the varicella resolves with reactivation after a period of latency.

Viral reactivation results when host immunity fails to suppress the virus, and this can be due to stress, immunosuppression, or direct trauma.

Resurfacing of the varicella-zoster virus requires the movement of the viruses from the neurons to the skin where the virus spreads from cell to cell by evading host immune responses and form lesions that penetrate the epidermis.

Viral reactivation leads to the classical description of a dermatomal rash and neuropathic pain in the distribution of the dermatome of the involves cranial or spinal nerves.

Ganglia neurons and satellite cell are destroyed during the reactivation of the varicella-zoster virus making antiviral therapy of limited value.

Inflammation in the ganglion itself can lead to neuronal necrosis.

When reactivation occurs, the immune system demonstrates a T-cell proliferation with production of interferon-alpha and herpes virus specific antibodies.

Neurological damage begins before the classical rash is evident.

With age there is diminished capacity for peripheral T-cells of patients with previous immunity and latently infected to proliferate and produce interferon-gamma when stimulated with varicella antigens.

In immunocompromised individuals there is loss of varicella T-cell responses.

In adults 50 years of age and older shingles associated with increased risk of stroke and possibly MI in the first 90 days.

Most patients experiencing HZ have only one episode of disease in their lifetime.

Among patients with rheumatoid arthritis or other inflammatory disorders treated with anti-TNF therapies the risk of herpes zoster is not increased (Winthrop KL et al).

Family history consistently found to be a risk factor.

Having a first-degree blood relative with a history of herpes zoster is associated with almost three fold increase risk of herpes zoster(Kawai K).

Recurrences of the process has previously been thought to be limited to immunocompromised individuals.

In a study of 1669 persons documented to have HZ and followed for an average of 7.3 years, the estimate of the recurrence rate at eight years was 6.2%, with the time between episodes in the same person varying from 96 days-10 years (Yawn B et al).

Recurrence rates for immunocompetent people in the above study was 5.7% and 6.2% overall after eight years.

The risk of HZ2 is higher in the summer than other seasons, possibly because of high ultraviolet radiation exposure: ultraviolet radiation from sunlight may suppress cell mediated immune responses.

Herpes zoster recurrences are significantly more likely in persons with zoster associated pain of 30 days or longer at the initial episode and immunocompromised individuals (Yawn B et al).

Ambient UV radiation exposure is associated with a higher risk of HZ in men but not in women.

A history of severe sunburn is associated with a modest increase in risk of HZ in men and women, possibly because of immunosuppression from over exposure to the sun (Kawai K).

Women have more vigorous innate and adaptive immune responses and are less susceptible to UVR induced immunosuppression, explaining the observed sex differences in regard to the risk of herpes zoster with UVR exposure.

While recurrences were more common among immunocompromised individuals at the time of the index HZ episode, most recurrences were in people who were immunocompetent at the time of the initial episode.

Women and individuals aged 50 years or older at the index episode have a greater likelihood of recurrence of herpes zoster than do others.

Black individuals have about half the risk of development of herpes zoster as white individuals.

Having HZ therefore does not ensure protection against a future HZ episode and after adjustment for age and sex, the rate of recurrent episodes is similar to the incidence rate of HZ episodes in the same population, suggesting the risk of having another episode of HZ in people with a history of HZ is about the same as the risk of having the first HZ episode in the general population (Yawn B et al).

In a study of 5040 patiens with rheumatoid arthritis 86 cases of herpes zoster developed in 82 patients: 39 cases were linked to treatment with anti-tumor necrosis factor agents, 23 to fusion protein etanercept, and 24 cases with conventional anti-rheumatic drugs-the incidence of herpes zoster was 11.1 per 1000 patient years in the group treated with the monoclonal antibodies, 8.9 per 1000 patients-years for etanercept, and 5.6 per 1000 patient-years for conventional disease modifying ant rheumatic drugs.

Varicella-zoster virus specific memory T cells probably control stages of reactivation that produce signs of zoster, and when they decline with age an increased risk of zoster occurs.

Anti-varicella-zoster IgG antibodies persist after varicella and continue to protect patients from varicella but are at risk for herpes zoster because of declining T-Cell responses.

Longer-lasting HZ related pain is associated with greater severity of the initial rash and intensity of pain

Involvement of the ophthalmic branch of the trigeminal cranial nerve, associated with the V1 dermatome, can result in blindness in severe cases.

Herpes zoster complications include myelitis, meningoencephalitis, vasculopathy, giant cell arteritis, and multiple eye disorders.

Ophthalmic branch of the trigeminal nerve involved in about 10% of cases.

Lesions on the tip of the nose is ref2242ed to as the Hutchinson’s sign, indicates the involvement of the nasociliary nerve and possible involvement of the eye.

Ocular complications occur in about 50% of patients with zoster ophthalmicus.

Involvement of the eye leads to redness and swelling of the conjunctiva and keratitis is present.

Eye involvement can rarely lead to uveitis and secondary glaucoma.

Eye involvement can lead to loss of vision, neuroparalytic keratopathy, Adie pupil, ophthalmoplegia and optic nerve involvement.

In patients that have received HZ vaccine the incidence of shingles has decreased by 51.3% and there has been a 39% decrease in postherpetic neuralgia(Oxman MN et al).

The use of the chickenpox vaccine during childhood is not related to the rising incidence of herpes zoster (HZ) in individuals older than 65 years of age.

The universal chickenpox vaccine started being used in the United States in 1996.

CDC-recommends HZ vaccine for adults aged 60 years and older.

Goals of treatment include more rapid healing of skin lesions, reduced complication risks, and decreasing the risk of viral dissemination.

Treatment with antiviral therapy should be immediate.

The use of any prescribed ophthalmic steroids should be reduced.

Oral antiviral agents acyclovir, valacyclovir and famciclovir reduce the severity and duration of infection.

Topical antiviral agents are ineffective treatments and not recommended.

Acyclovir is most effective when administered within 48 hours of the onset of a varicella zoster rash.

Acyclovir clinical use is limited by multiple dosing schedule of five times today and less favorable pharmacokinetics profile compared with valacyclovir and famiclovir.

Valacyclovir is the oral prodrug of acyclovir.

Valacyclovir may be have an accelerated resolution of herpes zoster associated pain when compared with acyclovir, but the rash subsides at the same rate.

Famciclovir has a longer half-life than acyclovir allowing three times a day dosing, but the drugs are equivalent in efficacy and speed of resolution of the process.

Foscarnet may be useful in acyclovir resistant viruses.

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