Herpes Zoster With Facial Localization ,including Ocular Impairment

State university of medicine and pharmacology

“Nicolae Testemitanu”

Facultate of medicine 2

Infection disease, tropical and medical parasitology department

DIPLOMA THESIS

Herpes zoster with facial localization ,including ocular impairment

Mohamed keiwan
Group:1049, 6th year

Head of department

Tiberio Holban , professor,dr,hab,st.med

thesis leader

assistant professor Dr.Ina Bistritchi

Chisinau 2016

Contents

Introduction

The aim and objectives of the thesis

The theoretical and scientific importance of Herpes Zoster

Bibliographical analysis of theme

The relationship between chickenpox and HZ

1.2 The pathogenesis and viral replication, importance of vaccination

1.3 The latency and reactivation of varicella zoster virus

1.4 The epidemiology of HZ in the world

1.5 The clinical manifestation of HZ with facial localization including ocular modifications

1.6 The relationship between HZ and HIV

1.7 treatment

II. Material and methods of research

2.1 Description of 4 clinical cases with HZ localized on the face

III. Discussion and conclusions

IV. References

Introduction

Herpes zoster (HZ) is an infectious disease and contagious disease caused by the varicella zoster virus that cause chickenpox same. Supposedly varicella-zoster virus persists for a long time (perhaps all life) in the body of people who suffered from chickenpox typical or uniparental form .

Notion of Herpes "was first brought by Hippocrates. Herpes zoster (from the Greek language meaning “to creep”, and zoster meaning “girdle or belt “. Initially these notions encompass both herpes simplex and herpes zosters appoint a vesicular rash. Pliny was the first to differentiate clinically the two diseases. Subsequently Celsus described the injuries the shingles extend "like a snake" looking belt " and expresses the distribution of lesions around the trunk of the midline posterior to the previous one. The relationship between herpes zoster and chickenpox was first mentioned in 1888 by Viennese physician Janos von Bokay. He noted that after contact with a patient with varicella zoster children often do chickenpox..

Hypothesis varicelozosterian virus in the lymph nerve latency was confirmed with detection of viral particles by immunofluorescence or electron microscopy inside these nodes. VZV reactivation Hz occurs following dorsal root ganglia . Active virus migrates along the nervous and produces a vesicular rash strictly local to one or more dermatomes, accompanied by intense pain.

Shingles(herpes zoster ) occurs at all ages, but the highest incidence is 5-10 cases per 1000 persons for group population between the sixth and eighth decade of life. It was found that about 2% of patients with herpes zoster will have a second episode infections.

Hz is less contagious than chickenpox and content produced by skin lesions, causing chickenpox primary infection with VZV.

zoster incidence in Europe is approximately 3 cases per 1,000 inhabitants year and over 10 cases per 1,000 population aged over 80 years. The disease is also registered in Moldova under sporadic forms.

Outside the age VZV reactivation an important role in the length of time it takes from primo infection VZV chickenpox. So in tropical countries, where varicella predominantly affects adults, the incidence of herpes zoster is much lower than in temperate where chickenpox is a disease of children .

It was observed that females have a higher risk of giving developing post herpetic neuralgia incidence of HZ. In the elderly immunosuppression physiological old age explains why this age group is predominantly affected. The risk of Hz is much higher in those with cellular immunosuppression.

Evolution is healing skin lesions within 2 to 4 weeks, but with persistent neuralgia specially in elderly patients with good prognosis in generally , but is reserved to the immunocompromised persons, that area can be generated and may be complicated by neurologic impairment.

The purpose and objectives of the thesis:

aim of the work the clinical and laboratory –Study of patients with Herpes Zoster.

Objectives –Study clinical particularity of shingles in adults depending on age, sex, living environment and other precipitating

factors Making a systematic literature specialists on lasting shingles and complications.

Vaccine influence on the emergence and evolution Hz

Theoretical and scientific importance of the results

Shingles is known since the days of Hippocrates and his diagnosis does not require complicated tools. But so far not been definitively studied catalysts include factors in the appearance and evolution of HZ. This study was tried in the huge addition of new puzzle elements that lead to virus reactivation Hz in some subjects. They were approached various factors that may have any tangent with the appearance and clinical manifestation of reactivation zoster was set forth a hypothesis that there is correlation between the incidence Hz and age, gender, concomitant pathologin

I. BIBLIOGRAPHIC DATA ANALYSIS

1.1 The relationship between chickenpox and shingles

The relationship between shingles and chickenpox is that both of them is caused by a single virus which is called (varicella zoster virus), which is both of them affect human body, which the chickenpox affect children and is transmitted by sneezing or cough but the shingles mostly affect elder people by reactivation due to decreasing immunity.

Shingles occurs when the virus that cause chickenpox starts up again in human body. Then person get better from chickenpox, the virus "sleeps" (is dormant) in nerve roots, this virus can last for lifetime in human body, an when he will be activated is will lead to shingle rash skin which is very painful. There is a small chance that a person with a shingles rash can spread the virus to another person who hasn't had chickenpox and who hasn't gotten the chickenpox vaccine.

The transmission of both of them is caused by virus which is inhaled and replication in your lung and go to the blood stream which is affect the skin but the shingle virus last to so many years and is active when a immune system is fail or is decreased.

The symptom of them is itching, tingling and fever and loos of appetite and lower abdomen pain, headache and dizziness.
The deferent between them is that the chicken pox has one vesicles but the shingle has group of vesicles and its appear in yellow or hemorrhage color fluid, and there is stage for them macula, papule, fluid filled vesicle, crusting in the first week till 3 weeks (incubation period) in chicken pox but in shingles the incubation period is over.

1.2 The pathogenesis and viral replication, importance of vaccination

The pathogeneses of VZV is respiratory transmitted by sneezing or coughing which is inhaled and enter to the respiratory system in a lung which is replicated in regional lymphoid tissue and from there is enter to the blood stream and infected mononuclear cells which take virus to skin where is the lesion form.
But in shingles the pathogenesis is affect the dorsal ganglia and lead to inflammation and also affect the sensory neuron.

(VZV) infection gives rise to 2 distinct syndromes. The primary infection, chickenpox, is a contagious and usually benign febrile illness. After this infection resolves, viral particles remain in the dorsal root or other sensory ganglia, where they may lay dormant for years.

There are two types of varicella vaccines:

A chickenpox vaccine for vaccinating children, adolescents, and adults

A shingles vaccine for vaccinating adults age 50 years and older

Chickenpox vaccine:

The live-virus varicella vaccine produces persistent immunity against chickenpox. The vaccine can prevent chickenpox or reduce the severity of the illness if it is used within 3 days, and possibly up to 5 days, after exposure to the infection.

The childhood chickenpox vaccine can be given as part of combination vaccine that combines measles, mumps, rubella (MMR) and varicella in one product (20). However the combination for both of them will lead to increase the risk for fever, seizure in children age 12-24 months compared to giving separate MMR and varicella injection.
The combination of varicella and MMR vaccine is recommended for the second dose in children age 4-6 years, but children that who are at high risk for seizure cute to family history must be receive separately vaccine (32).
(Www.umm.edu/health/medical/reports/articles/shingles-and-chickenpox-varicellazoster-virus)

Regimens for the Chickenpox Vaccine in Children

The first dose administered when the child is 12 – 15 months years of age

The second dose administered when the child is 4 – 6 years of age Recommendations for the Chickenpox Vaccine in AdultsThe Center of disease control (CDC) recommends that every healthy adult without a known history of chickenpox must be vaccinated. Adults should receive 2 doses of the vaccine, 4 – 8 weeks apart. Adults in the following groups should especially consider vaccination:

Those with high risk of exposure or transmission (hospital or day care workers, parents of young children)

People who may come in contact with those who have compromised immune systems

Non pregnant women of childbearing age

International travelers

Contraindication for vaccination:

Pregnant woman
immune compromised people by drugs or disease.

Patients who cannot be vaccinated but who are exposed to chickenpox receive immune globulin antibodies against varicella virus. This helps prevent complications.

Shingles vaccine
the shingle vaccine is a stronger vaccine, approved in 2006 for adult’s age 60 and older (18). And in 2011 the Food and Drug Administration (FDA) recommended for age 50 because the vaccine contain a live virus. However, the CDC has not yet added the shingles vaccine to its list of recommended vaccines for adults ages 50 – 59(31).

A single shot of the vaccine can reduce the risk of developing shingles by 55 – 70 percent and may also help prevent post herpetic neuralgia and ophthalmic herpes.

The vaccine is recommended only for people who have a healthy immune system, Protection from shingles vaccine lasts about 5 years. And it has a limited insurance and limited availability of the vaccine product.

Contraindication for shingles vaccine:

A person who has ever had a life-threatening or severe allergic reaction to gelatin, the antibiotic neomycin, or any other component of shingles vaccine.

A person who has a weakened immune system (HIV, AIDS, Drugs, cancer of bone marrow or lymphatic system)

Pregnant woman

1.3 The latency and reactivation of varicella zoster virus

In this latent period, it’s happened when the immune system is decrease or influence by some factor, which lead to VZV reactivated again. Such failure may result from a wide spectrum of conditions, ranging from stress to severe immunosuppression, or some medication.

When VZV is activated at the spinal root or cranial nerve neurons, an inflammatory

response occurs that also encompasses the leptomeninges, This inflammation in the dorsal root ganglion can be accompanied by hemorrhagic necrosis of nerve cells. The result is neuronal loss and fibrosis.

The frequency of dermatologic involvement is correlated with the centripetal distribution of the initial varicella lesions. This pattern suggests that the latency may arise from contiguous spread of the virus during varicella from infected skin cells to sensory nerve endings, with subsequent ascent to the ganglia. Alternatively, the ganglia may become infected hematogenously during the viremic phase of varicella, and the frequency of the dermatome involvement in herpes zoster may reflect the ganglia most often exposed to reactivating stimuli.

The appearance of the cutaneous rash due to herpes zoster coincides with a profound VZV-specific T-cell proliferation. Production of interferon alpha appears with the resolution of herpes zoster. In immunocompetent patients, specific antibodies (immunoglobulin G, M, and A [ IgG, IgM, and IgA]) appear more rapidly and reach higher titers during reactivation (herpes zoster) than during the primary infection. The patient has a long-lasting, enhanced, cell-mediated immunity response to VZ.

(16,17,24)

The anatomic location of the involved dermatome often determines the specific manifestations. When cervical and lumbar roots are involved, motor involvement, which is often overlooked, may be evident, depending on the virulence or extent of migration. In at least 1 case of motor neuron involvement, lymphocytic infiltration and myelin breakdown were observed with preservation of axons.

Herpes zoster infections are contagious to persons with no previous immunity to VZV. However, herpes zoster is estimated to be only one third as contagious as primary varicella. It is transmitted either via direct contact with the lesions or via the respiratory route.

(http://emedicine.medscape.com/article/1132465-overview#a3)

1.4 Epidemiology

In Israel During 2006-2010 there were 28,977 newly diagnosed cases of HZ and 1,508 newly diagnosed cases of PHN. Incidence density rate of HZ was 3.46 per 1,000 person-years in the total population and 12.8 per 1,000 person-years in immune-compromised patients. HZ and PHN incidence increased sharply with age. 12.4% and 3.1% of elderly HZ patients (≥65 years) developed PHN or ophthalmic complications, respectively. In multivariable analyses, HZ and PHN were associated with female sex, higher socio-economic status, diabetes mellitus, cancer history, and HIV treatment. (19) (Www.ncbi.nlm.nih.gov/PubMed/23872209)

In the United States, approximately 95% of adults—and 99.5% of adults aged 40 years or older—have antibodies to VZV and thus are vulnerable to reactivation of infection (21). A person of any age with a previous varicella infection may develop zoster, but the incidence increases with advancing age as a consequence of declining immunity.

Approximately 4% of patients with herpes zoster will develop a recurrent episode later in life (42). Recurrent zoster occurs almost exclusively in people who are immunosuppressed. Approximately 25% of patients with HIV and 7-9% of those receiving renal transplantation or cardiac transplantation experience a bout of zoster.

Before the advent of widespread vaccination, an estimated 4 million cases of primary VZV infection occurred annually in the United States alone. Infection was nearly universal by the end of the teenage years, with studies showing only 10% of persons older than age 15 years as remaining susceptible to infection.

Over the period of a lifetime, 10-20% of those with primary infections went on to experience episodes of herpes zoster(13). High-risk groups, such as elderly populations and immunocompromised people, might experience cumulative incidences as high as 50% (29). The estimated annual number of herpes zoster cases in the United States is approximately 1 million.

Since the introduction of widespread vaccination for varicella in 1995, the incidence of primary VZV infection in the United States has been reduced by up to 90%. However, the effect of this vaccination, as well as that of the subsequently approved vaccination for herpes zoster, on the current and future incidence of herpes zoster remains to be determined.

Internationally, the incidence of zoster has not been well studied, but it is probably in the same range as that reported in the United States (6).

 A German study of data on patients in the country’s statutory health system (SHI) for the year 2010 estimated that the mean annual incidence of herpes zoster was 5.79 cases per 1000 person-years, equivalent to 403,625 cases annually in the SHI population (which comprised about 85% of the total German population)(38).

Age-related demographics

Herpes zoster is rare in children and young adults, except in younger patients with AIDS, lymphoma, other malignancies, and other immune deficiencies and in patients who have received bone marrow or kidney transplants. Fewer than 10% of zoster patients are younger than 20 years, and only 5% are younger than 15 years. Even though zoster is primarily a disease of adults, it has been noted as early as the first week of life, occurring in infants born to mothers who had primary VZV infection (chickenpox) during pregnancy.

The incidence of herpes zoster increases with age (23). In the general population, the lifetime incidence rate of herpes zoster is 10-20%, which rises to 50% in those individuals surviving to age 85 years. More than 66% of patients are older than 50 years. The incidence of PHN also rises with advancing age (30).

Sex-related demographics

Herpes zoster generally has not been considered to have a sex predilection. However, one study reported a higher prevalence in women than in men (16). 

the frequency is higher in right-handed patients and that the rash appears more frequently on the left side in female (9).The pathophysiology for these differences is uncertain.

Race-related demographics

Blacks are reported to have a significantly lower risk of developing zoster than whites do; however, zoster has been reported as an early manifestation of HIV infection in young Africans. Research has shown that elderly blacks are up to 75% less likely to develop herpes zoster than elderly. Similar findings have been demonstrated in children (37). In a meta-analysis of controlled herpes zoster clinical trials, a nonwhite racial group was found to be associated with a younger age at zoster onset.

1.5 The clinical manifestation of HZ with facial localization including ocular modifications

Symptom of shingles

Shingles is always occur in adult, usually two or three identifiable symptom stage:

Prodromal: in this phase, cluster-warning symptoms appear 3-4 days before the infection. These symptom lead to (chills, fever, nausea, muscle aches) and abnormal sensation like tingling and itching, which accompanied by deep pain.

Active infection: after prodromal, a rash appear usually in trunk, but it can be in other area, the rash will be in one side of the body and follow the same track of inflamed nerve, usually the rash start small, red. Within 12-24 hours develop small fluid blisters and after become pus filled and painful, within 7-10 days, the blisters form crust and heal.

Post herpetic neuralgia: is a pain that persist for longer than one month after the onset of herpes zoster. Which describe as a deep itching, burning, and extreme sensitive to touch or temperature and persist pain.

Ocular Manifestations of Herpes Zoster Ophthalmicus

Herpes zoster ophthalmic (HZO), a potentially form of acute herpes zoster, results from the reactivation of VZV in the trigeminal (fifth cranial) nerve. Any branch of the nerve may be affected, though the frontal branch within the first division of the trigeminal nerve is most commonly involved. This branch innervates nearly all of the ocular and periocular structures. (25,33)

The eyelids: are commonly involved in (HZO), which is the majority of patient have vascular lesion on the eyelid that resolve with minimal scarring.
Patient may develop blepharitis, which can lead to secondary bacterial infection, eyelid scarring, and loss of eyelashes.

Conjunctiva: is one of the most common complication for HZO, The conjunctiva is often injected and edematous.

Sclera: episcleritis or scleritis associated with HZ maybe nodular or diffuse and can persist for months.

Cornea: Corneal complications occur in approximately 65% of cases with (HZO) (26). This can result in significant visual loss. Symptoms are pain, photosensitivity and poor vision.

The clinical features of corneal disease in (HZO) may be due to:

1- Direct viral infection 2-Antigen – antibody reaction 3-Delayed cell-mediated hypersensitivity reactions 4-Neurotrophic damage.

Retina: The retinitis of herpes zoster ophthalmic is often associated with anterior uveitis. It presents as necrotizing retinitis with hemorrhages and exudates.

Polymerase chain reaction (PCR) nerve studies have detected latent trigeminal VZV in as many as 87% of patients.(27)

http://www.cehjournal.org/wp-content/uploads/download/ceh_16_47_035.pdf)

Auditory system

Herpes zoster oticus (also known as Ramsay Hunt syndrome, geniculate neuralgia, or herpes zoster auricularis) is caused by VZV reactivation involving the facial and auditory nerves. This syndrome may go unnoticed and be difficult to diagnose, especially in elderly patients.

Vesicular eruptions may manifest on the pinna, tragus, or tympanic membrane or in the auditory canal, as well as anywhere in the facial nerve distribution. The patient may experience hearing impairment, nystagmus, vertigo, or a facial nerve palsy mimicking Bell palsy. Patients may lose taste sensation in the anterior two thirds of the tongue (35)(http://emedicine.medscape.com/article/1132465-overview#a3).

1.6 The relationship between HZ and HIV

The relation between HZ and HIV is caused by recurrent VZV infection (zoster or "shingles") occurs with advancing age in immunocompetent hosts, but may occur earlier in immunocompromised hosts as a result of decreased specific VZV immunity.

Zoster usually is self-limited in the immunocompetent host, but immunocompromised persons are at risk of more severe illness with cutaneous or visceral dissemination. (40,34)

Persons with HIV infection are at risk of developing severe illness from zoster. HIV-infected patients with active, symptomatic VZV infection usually require specific antiviral chemotherapy and hospitalization. (3,4)

Administration of the varicella vaccine to prevent primary infection is an important strategy to protect children and adults who have not had prior VZV infection. The vaccine can be given to HIV-infected patients who have CD4 T-lymphocyte counts of >200 cells/µL despite the theoretical risk of live-virus vaccination in this population. (28)

In the immunocompetent host, the period of infection is usually 5-7 days after the lesions first appear. In immunocompromised patients, the healing can be slow and patients may remain infectious for up to several weeks.(11,7)

In the immunocompetent host, the risk of recurrent VZV infection (zoster) increases with advancing age, with the highest incidence occurring between the ages of 50 and 80. A person’s lifetime risk of herpes zoster infection is 15-20%, with the highest incidence occurring in the elderly and in immunocompromised persons. HIV-infected patients are at higher risk of developing zoster than age-matched. (5)

Zoster may occur at any time in the course of HIV-induced immunosuppression,

Recurrent episodes of zoster also may occur in HIV-infected patients, and appear to be more common than in the HIV-uninfected population.

In HIV infected person with a compromised immune system lead to prolong viremia and the duration is extend to a new lesion formation.

by clinical manifestation :

Reactivated VZV infection may occur at any stage of HIV infection,. Zoster typically begins with local pain and discomfort, and then progresses to a localized or segmented erythematous, maculopapular eruption along a single dermatome. Lesions evolve to vesicles, pustules, and crusts. .

Zoster usually remains localized and resolves spontaneously, it can result in significant and persistent pain as well as cutaneous scarring.

In immunocompromised hosts, zoster lesions may be particularly bullous, hemorrhagic, necrotic, and painful. Blisters and crusts usually last 2-3 weeks, and necrotic lesions may last for up to 6 weeks and result in significant scarring. HIV-infected persons are at risk of recurrences, which may be more severe with increasing immunosuppression. (6,12)(http://hivinsite.ucsf.edu/InSite? page=kb-05-03-01#S1X)

Also there is a connection between HIV and ophthalmic zoster with raising the severity of eye when is involvement and can lead to visual loss. Also lead to retinal necrosis and acute retinitis is feared ocular manifestations of VZV disease in patients with HIV infection, and they respond poorly to therapy.

Treatment

Intravenous Acyclovir Is necessary to inhibit the replication of VZV are about 10 times greater than those needed to inhibit HSV, so the dosage of acyclovir must be higher than that used for treatment of HSV. The dose of treatment of VZV is 10 mg/kg every 8 hours. (41)

Oral acyclovir in the dosage used for HSV infection results in steady-state serum levels that are too low to inhibit VZV. High dosages of oral acyclovir (800 mg 5 times daily) are needed to produce serum levels that are adequate to treat VZV infection in adults. . (22,10,14)

Oral acyclovir is effective for the treatment of chickenpox in both immunocompetent children and adults, and it reduces the total number of lesions, duration of fever, and duration of illness as compared with placebo treatment. (39,10,8)

Famciclovir and Val acyclovir are now preferred to treat herpes zoster in most patients because they require fewer daily doses than acyclovir

Over-the-Counter Pain Relievers

Children should take acetaminophen.

Adults may take aspirin or other no steroidal anti-inflammatory drugs, such as ibuprofen (Advil, other brands, generic). 

Treatment with corticosteroids for patients with zoster to prevent post herpetic neuralgia.

Antihistamines. For severe itching, diphenhydramine is useful.

The management of herpes zoster ophthalmic in HIV patient. (3)

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