Z

Zoster

Keywords

Herpes zoster, zoster, varicella, postherpetic neuralgia, herpes zoster ophthalmicus, Ramsey Hunt syndrome, acyclovir, herpes, chickenpox, varicella zoster

Zoster (herpes zoster, varicella-zoster)

Varicella-zoster virus (VZV) is the infective organism in varicella (chickenpox) and herpes zoster (shingles). Varicella is a typical, benign, neurocutaneous disease of childhood. Complications such as meningoencephalitis, acute cerebellar ataxia, transverse myelitis, and Reye syndrome are rare and may lead to permanent deficits including paresis, seizures, and cognitive changes. In most cases, full recovery is expected.

Herpes zoster (zoster literally, “belt or girdle”) is caused by a latent virus reactivation in the setting of awakened cell-mediated immunity, particularly in the elderly and the immunocompromised. Patients with lymphoma who have had radiation and splenectomy, and patients with AIDS (who usually develop disseminated disease), are at risk.

Typically, zoster presents with pain in a single or several adjacent dermatomes. The pain may precede the vesicular eruption by up to 3 weeks. Pain is described as sharp, lancinating, and associated with itching, dysesthesia, and allodynia (increased skin sensitivity). Associated findings include altered sensation in the involved dermatome; fewer than 5% have segmental weakness. The cerebrospinal fluid (CSF) may show an elevated protein and a mild lymphocytic pleocytosis. Diagnosis is often clinical and is established by typical neurocutaneous rash, Tzanck smear, direct immunofluorescence, viral culture, or comparison of acute and convalescent titers. Demonstration of the presence of VZV DNA (by polymerase chain reaction [PCR] analysis), or of antibodies in CSF to the virus, is strong evidence of infection in the appropriate clinical setting. Serum antibody analysis is of no value. Histologically, zoster is characterized by lymphocytic inflammation and vasculitis, resulting in neuronal loss in ganglia. The process may spread to leptomeninges and adjacent spinal cord.

Complications of the peripheral nervous system

• Herpes Zoster Ophthalmicus: VZV may become latent along the entire neuraxis. The most common sites of reactivation are thoracic and trigeminal dermatomes. When zoster affects the cranium (20% of cases), 90% of sites are in the trigeminal distribution and 60% of these will involve the first division. Complications include corneal involvement, internal or external ophthalmoplegia, iridocyclitis, and uveitis and optic neuritis (rare). The prognosis for improvement of ocular motor disturbance is excellent, whereas return of lost vision is minimal.
• Ramsay Hunt syndrome: Varicella zoster of the geniculate ganglion, presenting with painful vesicles on the tympanic membrane and external auditory canal, a peripheral seventh cranial nerve (CN VII) palsy, and variable CN VIII dysfunction.
• Thoracic zoster: May occasionally produce arm weakness (zoster paresis), whereas lumbar reactivation may be associated with leg weakness and bowel/bladder dysfunction. Rarely, the pain can occur in the absence of any rash (zoster sine herpete), leading to considerations of carcinomatous, lymphomatous, or diabetic radiculopathies.
Analysis of PCR of varicella DNA in CSF and blood mononuclear cells, and antibody titer in CSF, are usually diagnostic.

Treatment:

Acyclovir (800 mg 5 times a day for 7 days), famciclovir (500 mg tid for 7 days), or valacyclovir can be given. Pain management is essential but frequently difficult, and there may be residual pain despite multiple medications.

Postherpetic Neuralgia

Postherpetic neuralgia is characterized by persistent dysesthesias and hyperpathia, persisting beyond healing of the zoster vesicles (usually beyond 2 months).

The pain has three components:

(1) a constant, deep burning pain;
(2) paroxysms of shooting pain;
(3) sharp pains after light stimulation(allodynia).

Pathologically, it is associated with a localized small and large fiber sensory neuropathy and may result from reorganization of inputs to the second-order neurons.

Postherpetic neuralgia is rare in patients younger than 50, but it occurs in up to 50% of patients over 60 and in 75% of those over 70. It resolves within 1 month in 90% of patients and in half of the remainder by 2 months but may last up to 1 year. Only about 2% of patients have persistent pain, which may last for months or years.

Treatment:

Antiviral treatments tend to reduce incidence of the postherpetic neuralgia.
Tricyclic antidepressants: (amitriptyline/nortriptyline 25 to 75 mg PO qd);
Anticonvulsants: carbamazepine (400 to 1200 mg PO qd), phenytoin (300 to 400 mg PO qd), and gabapentin; prednisone (40 to 60 mg qd 3 to 5 days)
Topical aspirin in chloroform or capsaicin 0.75% ointment, 5 times per day for at least 4 weeks, may be used.
Topical lidocaine (ointment or skin patch) may also help.

Complications of the Central Nervous System

Occasionally, reactivation of VZV in either an immunocompetent or immunocompromised patient can cause the virus to spread into the spinal cord and brain. CNS complications of zoster include myelitis, encephalitis, large-vessel granulomatous arteritis, small-vessel encephalitis, meningitis, ventriculitis, and vasculitis. Myelitis usually occurs 1 to 2 weeks after rash development and may be confirmed by CSF PCR of varicella DNA; the illness is mostly severe in immunocompromised patients. Varicella zoster can cause encephalitis as a result of large- or small-vessel vasculopathy. Large-vessel (granulomatous) vasculitis leading to strokes is an important complication that occurs predominantly in immunocompetent patients and presents with focal deficits (strokes can be ischemic or hemorrhagic). Small-vessel encephalitis is the most common complication of CNS varicella zoster and is seen in immunocompromised patients. Deep-seated ischemic or demyelinating lesions may manifest as headache, fever, vomiting, mental status changes, seizures, and focal deficits. A few cases of ventriculitis and meningitis have occurred in immunocompromised patients. The treatment for CNS complications is with IV acyclovir; steroids are used for anti-inflammatory effects.

Treatment: Oral acyclovir accelerates cutaneous healing but has no effect on acute neuritis or postherpetic neuralgia. In the immunocompromised patient, parenteral acyclovir is more effective than vidarabine in preventing dissemination and accelerating cutaneous healing. Corticosteroids may reduce acute pain and the risk of postherpetic neuralgia, but evidence of effectiveness is inconclusive.

Prevention

Live attenuated zoster vaccine: Boosts VZV-specific cellular immunity in older adults. VZV zoster causes substantial morbidity. Treatments may be incompletely effective, especially as symptoms may not be caught within a 72-hour window where treatment would be of maximum benefit. The Shingles Prevention Study, a randomized, double blinded placebo-controlled trial, with 38,546 community dwelling individuals aged 60 and greater, showed that the vaccine reduced incidence of post herpetic neuralgia by 66.5%. Individuals’ pain burden and functional impairment is reduced, and they experience better quality of life outcomes. The Centers of Disease Control and Prevention recommends the vaccine for immunocompetent adults 60 years or older irrespective of prior zoster exposure. The vaccine is contraindicated in patients with prior anaphylactic reactions to gelatin or neomycin, leukemia, lymphomas, other malignancies of bone marrow or lymphatic system, individuals on immunosuppressive therapy, and those on high-dose corticosteroids for more than 2 weeks.