HERPES ZOSTER
Definition
Herpes zoster (also called shingles) is a sporadic disease that results from reactivation of latent VZV from dorsal root ganglia
Varicella-zoster virus (VZV) causes two distinct clinical entities: varicella (chickenpox) and herpes zoster (shingles).
With reactivation of latent VZV (which is most common after the sixth decade of life), herpes zoster presents as a dermatomal vesicular rash, usually associated with severe pain
Epidemiology
Herpes zoster occurs at all ages, but its incidence is highest (5–10 cases per 1000 persons) among individuals in the sixth decade of life and beyond.
Recurrent herpes zoster is exceedingly rare except in immunocompromised hosts, especially those with AIDS
Pathogenesis
Primary Infection
Transmission occurs readily by the respiratory route; the subsequent localized replication of the virus at an undefined site (presumably the nasopharynx) leads to seeding of the reticuloendothelial system and ultimately to the development of viremia.
Vesicles involve the corium and dermis, with degenerative changes characterized by ballooning, the presence of multinucleated giant cells, and eosinophilic intranuclear inclusions.
Infection may involve localized blood vessels of the skin, resulting in necrosis and epidermal hemorrhage.
With the evolution of disease, the vesicular fluid becomes cloudy because of the recruitment of polymorphonuclear leukocytes and the presence of degenerated cells and fibrin.
Ultimately, the vesicles either rupture and release their fluid (which includes infectious virus) or are gradually reabsorbed
Recurrent Infection
The mechanism of reactivation of VZV that results in herpes zoster is unknown
Histopathologic examination of representative dorsal root ganglia during active herpes zoster demonstrates hemorrhage, edema, and lymphocytic infiltration
Active replication of VZV in other organs, such as the lung or the brain, can occur during either chickenpox or herpes zoster but is uncommon in the immunocompetent host
Clinical features
Herpes zoster is characterized by a unilateral vesicular eruption within a dermatome, often associated with severe pain.
The dermatomes from T3 to L3 are most frequently involved.
If the ophthalmic branch of the trigeminal nerve is involved, zoster ophthalmicus results.
The factors responsible for the reactivation of VZV are not known.
In children, reactivation is usually benign; in adults, it can be debilitating.
The continuum of pain from onset to resolution is known as zoster-associated pain.
The onset of disease is heralded by pain within the dermatome, which may precede lesions by 48–72 h; an erythematous maculopapular rash evolves rapidly into vesicular lesions
In the normal host, these lesions may remain few in number and continue to form for only 3–5 days.
The total duration of disease is generally 7–10 days; however, it may take as long as 2–4 weeks for the skin to return to normal.
Patients with herpes zoster can transmit infection to seronegative individuals, with consequent chickenpox.
In a few patients, characteristic localization of pain to a dermatome with serologic evidence of herpes zoster has been reported in the absence of skin lesions.
When branches of the trigeminal nerve are involved, lesions may appear on the face, in the mouth, in the eye, or on the tongue.
Zoster ophthalmicus is usually a debilitating condition that can result in blindness in the absence of antiviral therapy.
In the Ramsay Hunt syndrome, pain and vesicles appear in the external auditory canal, and patients lose their sense of taste in the anterior two-thirds of the tongue while developing ipsilateral facial palsy.
The geniculate ganglion of the sensory branch of the facial nerve is involved.
In both normal and immunocompromised hosts, the most debilitating complication of herpes zoster is pain associated with acute neuritis and postherpetic neuralgia.
Postherpetic neuralgia is uncommon in young individuals; however, at least 50% of zoster patients over age 50 report some degree of pain in the involved dermatome months after the resolution of cutaneous disease.
Changes in sensation in the dermatome, resulting in either hypo- or hyperesthesia, are common.
CNS involvement may follow localized herpes zoster.
Many patients without signs of meningeal irritation have CSF pleocytosis and moderately elevated levels of CSF protein.
Symptomatic meningoencephalitis is characterized by headache, fever, photophobia, meningitis, and vomiting.
A rare manifestation of CNS involvement is granulomatous angiitis with contralateral hemiplegia, which can be diagnosed by cerebral arteriography.
Other neurologic manifestations include transverse myelitis with or without motor paralysis
Like chickenpox, herpes zoster is more severe in immunocompromised than immunocompetent individuals.
Lesions continue to form for >1 week, and scabbing is not complete in most cases until 3 weeks into the illness.
Patients with Hodgkin's disease and non-Hodgkin's lymphoma are at greatest risk for progressive herpes zoster.
Cutaneous dissemination develops in ~40% of these patients.
Among patients with cutaneous dissemination, the risk of pneumonitis, meningoencephalitis, hepatitis, and other serious complications is increased by 5–10%.
However, even in immunocompromised patients, disseminated zoster is rarely fatal
Recipients of hematopoietic stem cell transplants are at particularly high risk of VZV infection.
Of all cases of posttransplantation VZV infection, 30% occur within 1 year (50% of these within 9 months); 45% of the patients involved have cutaneous or visceral dissemination.
The mortality rate in this situation is 10%.
Postherpetic neuralgia, scarring, and bacterial superinfection are especially common in VZV infections occurring within 9 months of transplantation.
Among infected patients, concomitant graft-versus-host disease increases the chance of dissemination and/or death.
Treatment
Aluminum acetate soaks for the management of herpes zoster can be both soothing and cleansing.
Patients with herpes zoster benefit from oral antiviral therapy, as evidenced by accelerated healing of lesions and resolution of zoster-associated pain with acyclovir, valacyclovir, or famciclovir.
Acyclovir, now off patent, is administered at a dosage of 800 mg five times daily for 7–10 days. Famciclovir, the prodrug of penciclovir, is at least as effective as acyclovir and perhaps more so.
One study showed twofold faster resolution of postherpetic neuralgia in famciclovir-treated patients with zoster than in recipients of placebo.
The dose is 500 mg by mouth three times daily for 7 days.
Valacyclovir, the prodrug of acyclovir, accelerates healing and resolution of zoster-associated pain more promptly than acyclovir.
The dose is 1 g by mouth three times daily for 5–7 days.
Compared with acyclovir, both famciclovir and valacyclovir offer the advantage of less frequent administration.
In severely immunocompromised hosts (e.g., transplant recipients, patients with lymphoproliferative malignancies), both chickenpox and herpes zoster (including disseminated disease) should be treated, at least at the outset, with intravenous acyclovir, which reduces the occurrence of visceral complications but has no effect on healing of skin lesions or pain.
The dose is 10–12.5 mg/kg every 8 h for 7 days.
For low-risk immunocompromised hosts, oral therapy with valacyclovir or famciclovir appears beneficial.
Concomitant with the administration of intravenous acyclovir, it is desirable to wean these patients from immunosuppressive treatment.
Patients with varicella pneumonia may require removal of bronchial secretions and ventilatory support.
Persons with zoster ophthalmicus should be referred immediately to an ophthalmologist.
Therapy for this condition consists of the administration of analgesics for severe pain and the use of atropine.
Acyclovir, valacyclovir, and famciclovir all accelerate healing
The management of acute neuritis and/or postherpetic neuralgia can be particularly difficult.
In addition to the judicious use of analgesics, ranging from nonnarcotics to narcotic derivatives, drugs such as gabapentin, pregabalin, amitriptyline hydrochloride, lidocaine patches, and fluphenazine hydrochloride are reportedly beneficial for pain relief
In one study, glucocorticoid therapy administered early in the course of localized herpes zoster significantly accelerated such quality-of-life improvements as a return to usual activity and termination of analgesia.
The dose of prednisone administered orally was 60 mg/d on days 1–7, 30 mg/d on days 8–14, and 15 mg/d on days 15–21.
This regimen is appropriate only for relatively healthy elderly persons with moderate or severe pain at presentation.
Patients with osteoporosis, diabetes mellitus, glycosuria, or hypertension may not be appropriate candidates.
Glucocorticoids should not be used without concomitant antiviral therapy
Prevention
Three methods are used for the prevention of VZV infections.
First, a live attenuated varicella vaccine (Oka) is recommended for all children >1 year of age (up to 12 years of age) who have not had chickenpox and for adults known to be seronegative for VZV.
A single dose of vaccine is administered to children, whereas adults require two doses
A second approach is to administer varicella-zoster immune globulin (VZIG) to individuals who are susceptible, are at high risk for developing complications of varicella, and have had a significant exposure.
This product should be given within 96 h (preferably within 72 h) of the exposure
Lastly, antiviral therapy can be given as prophylaxis to individuals at high risk who are ineligible for vaccine or who are beyond the 96-h window after direct contact.
While the initial studies have used acyclovir, similar benefit can be anticipated with either valacyclovir or famciclovir.
Therapy is instituted 7 days after intense exposure. At this time, the host is midway into the incubation period. This approach significantly decreases disease severity, if not totally preventing disease.