Herpes Virus Infections 51 Varicella Zoster

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Varicella-zoster virus (VZV) is a DNA virus and a member of the herpes virus family. It causes two distinct clinical syndromes: primary disseminated infection, which is manifested as chickenpox, and reactivation of latent virus in the dorsal root ganglia, leading to herpes zoster or "shingles." Herpes zoster is a painful, vesicular exanthem which erupts in one to two dermatomes after a prodrome of days to weeks and may take up to a month to heal (86). Most patients report a deep aching or burning sensation, altered sensation to touch with paresthesias, dysesthesia, or hyperesthesia. Herpes zoster is a common condition with a cumulative lifetime incidence of 10-20% with most of the risk concentrated in older age (87). The overall incidence is 215 per 100,000 person-years, but rates rise sharply with increasing age to 1425/100,000 for persons older than 75 yr.

Postherpetic neuralgia (PHN) is the presence of pain more than 1 mo after onset of the eruption (86). PHN afflicts the elderly much more frequently than the young, occurring in 27-68% of persons age 60 and older, compared with 3-10% of persons under age 50 (88). In addition to age, severity of acute pain, rash severity, prodromal symptoms, and the degree of sensory impairment are predictors of PHN (89). Approx 20% of persons with PHN who are over age 60 will have pain for more than 1 yr. The pathological changes seen in PHN include fibrosis and loss of neurons in the dorsal ganglion and axon and myelin loss in the affected side (86). Once PHN develops, treatment of pain is often ineffectual. The great variety of treatments that are available for PHN is an indication that none are very effective. Topical formulations of aspirin and anesthetics, such as lidocaine and prilocaine, may provide some short-term benefit (86). Capsaicin cream, which depletes the neurotransmitter, substance P, is the only drug approved for the treatment of PHN by the Food and Drug Administration. Neuropathic pain is generally not very responsive to narcotics, although some patients derive benefit. The most beneficial systemic agents available for PHN are the tricyclic antide-

Table 3

Therapy for Acute Herpes Zoster Within 72 Hours of Rash

Antiviral Dose Duration

Valacyclovir 1 g, three times a day 7 d

Famciclovir 750 mg, three times a day 7 d

Acyclovir 800 mg, five times a day 7-10 d

Consider in persons with no contraindications" to corticosteroids: antiviral + prednisone 60 mg/d, tapered over 21 d.

"Contraindications include: diabetes, hypertension, and glaucoma.

pressant drugs. Randomized clinical trials of amitriptyline and desipramine showed that 45-65% of elderly PHN patients achieved some pain relief (88). Anticonvulsants, such as phenytoin, carbamazepine, and gabapentin, may be helpful to reduce the lacinating component of neuropathic pain (86). Other treatments, such as transcutaneous electrical nerve stimulation (TENS), biofeedback, relaxation therapy, and regional neuron blockade have all been used with variable success.

Because PHN is often refractory to treatment, efforts have been directed toward prevention using antivirals and corticosteroids. Five controlled trials have evaluated the use of corticosteroids to prevent PHN. Two studies showed a benefit, but the other two did not (86). The fifth study was done in 208 persons over age 50 with localized zoster of less than 72 h duration. Treatments included acyclovir, 800 mg, five times a day for 21 d, and prednisone, starting at 60 mg/d, with a taper over 21 d. Four treatment arms include acyclovir and prednisone, acyclovir alone, prednisone alone, and placebo. The acyclovir-plus-prednisone group showed accelerated time to cessation of acute pain, time to uninterrupted sleep and time to return to daily activities (90). Of note, no effect on chronic pain at 6 mo was observed. The new antivirals, famciclovir and valacyclovir, also show significant reduction in the duration of zoster pain in placebo-controlled trials (88,91). However, 20% of patients in both studies developed chronic pain despite early treatment with antiviral drugs.

In summary, if begun within 72 h of the rash, acyclovir, famciclovir, and valacyclovir all reduce acute pain in immunocompetent adults with zoster and, thus, are worthwhile, regardless of their effect on PHN. Corticosteroids also do not alter the course of PHN but may improve the quality of life after zoster, and their use, in combination with an antiviral, is reasonable in persons over 50 yr of age with no contraindication to corti-costeroids (see Table 3) (86).

The optimal way to prevent PHN may be to prevent zoster itself. Trials to evaluate the live OKA-strain varicella vaccine in older adults to prevent herpes zoster are ongoing. Immunization of adults who are immune to varicella-zoster results in increases in humoral and cellular immune responses. However, it will take many years to know if these encouraging results translate into decreased rates of herpes zoster (86).

5.2. Epstein-Barr Virus

The Epstein-Barr Virus (EBV) is a double-stranded DNA virus in the herpes virus family. Infection with EBV establishes lifelong infection. Primary infection may occur in childhood when infection is asymptomatic or during adolescence when the symptoms of classic mononucleosis are most often observed (92). Although primary infection is uncommon in old age, the manifestations may be different than in youth, making diagnosis challenging.

Seroepidemiologic studies indicate that 3-10% of older adults are at risk for primary infection as indicated by the absence of EBV antibodies (92). Because primary EBV infection is uncommon in older age, the diagnosis is often not considered. Diagnosis is also often delayed because symptoms may be misleading. Lymphadenopathy, pharyngitis, and splenomegaly are significantly less common and jaundice is more common in older persons as compared with the young (93). The neurologic manifestations of EBV infection are protean, and acute EBV encephalitis has been documented in an elderly woman (94). To add to the difficulty in making a correct diagnosis, development of atypical lymphocytosis may be absent or delayed in the elderly. Diagnosis of primary EBV is made by the presence of heterophile antibodies or EBV-specific IgM. Although acyclovir has in vitro activity against EBV, no benefit has been demonstrated in the treatment of acute EBV infection. Therefore treatment is supportive.

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