Elderly patients are at greatest risk for debilitating postherpetic neuralgia, but antiviral therapies ease the pain and shorten its duration, and a new vaccine offers hope of prevention.

With the aging of the U.S. population, the number of herpes zoster (HZ), or shingles, cases is increasing dramatically. Lifetime incidence of HZ, a reactivation of varicella-zoster virus (VZV) lying dormant in the sensory ganglia, is estimated at 10%-20%; the incidence in people aged 85 and older is as high as 50%.1

The pain of postherpetic neuralgia (PHN), often described as burning, throbbing, or aching, is frequently the most debilitating aspect of HZ. Pain syndromes may result in chronic fatigue, sleep disorder, and psychiatric disorders, such as depression or anorexia. In the elderly, pain from PHN disrupts basic activities of living, such as dressing, bathing, and walking.1 A substantial subset of elderly patients with HZ is refractory to treatment and has a poor prognosis for PHN relief. The incidence and severity of HZ are also higher among immunocompromised individuals and patients with hematologic malignancies.

Clinical presentation and treatment

HZ has a characteristic prodrome stage marked by pain, tingling, itching, and burning. Patients may also have a mild, viral-like syndrome with fever and malaise. Depending on its location, the pain can be so severe that HZ may be mistaken for other serious conditions, including MI, cholecystitis, muscle pain, and migraine. The eruption of HZ is a unilateral rash in one or two dermatomes. The rash, which is maculopapular at first and then becomes vesicular, most often has an erythematous base. Lesions evolve over 7-10 days and heal over two to three weeks.

Antiviral therapy should ideally begin within 72 hours after the initial outbreak. Studies show that antiviral therapy shortens the duration of the initial outbreak by one to three days compared with placebo and that acute pain resolves more rapidly with these medications.2,3

Three antiviral agents are available for HZ: acyclovir, famciclovir, and valacyclovir. Because of their greater bioavailability and ease of use compared with acyclovir, famciclovir and valacyclovir have become the standard treatment for HZ.

Antiviral treatment cannot prevent PHN. However, a randomized, double-blind, controlled trial showed that famciclovir accelerated lesion healing while shortening the period of viral shedding by one to two days and the median duration of PHN by approximately two months.3

In the acute phase of HZ, minor pain may be treated with analgesics, nonsteroidal anti-inflammatory drugs, or antihistamines. For many patients, these medications do not suffice. Other options include anticonvulsants, tricyclic antidepressants, and anesthetics.

Development of the zoster vaccine

A new live attenuated Oka/Merck zoster vaccine (Zostavax) intended for the prevention of HZ has recently been approved by the FDA and recommended by the CDC’s Advisory Committee for Immunization Practices.


To evaluate the vaccine’s efficacy, Oxman et al enrolled 38,546 adults aged 60 and older in a randomized, double-blind, placebo-controlled study.4 Because a preliminary study had demonstrated that increased potencies were necessary to elicit a significant increase in cell-mediated immunity to VZV, the minimum potency of the vaccine used in the study was at least 14 times greater than the currently licensed varicella vaccine. Subjects in the vaccine group received 0.5 mL subcutaneously of the trial agent.

Burden of illness (BOI): Each subject who had an episode of zoster rated his or her worst pain on a pain inventory. The rating was used to calculate a severity-of-illness score. The BOI score was the mean severity-of-illness score for each treatment group. Vaccine efficacy with respect to the BOI of HZ (VEBOI) was defined as the relative reduction in the BOI score in the vaccine group as compared with that in the placebo group. Overall, VEBOI was 61.1% (P <.001) for the total study population, a result that met the prespecified criteria for success.

Incidence of PHN: Vaccine efficacy with respect to the incidence of PHN (VEPHN) was defined as the relative reduction in the incidence of PHN in the vaccine group as compared with that in the placebo group. There were 107 cases of PHN, 27 in the vaccine group and 80 in the placebo group (0.46 case vs. 1.38 cases per 1,000 person-years, respectively; P <.001). Overall, the VEPHN was 66.5%. In a time-to-event analysis, the cumulative incidence of PHN was significantly lower in the vaccine group than in the placebo group (P <.001).

Incidence of HZ: Overall HZ incidence per 1,000 person-years was significantly reduced by the vaccine, from 11.12 in the placebo group to 5.42 in the vaccine group (P <.001). Vaccine efficacy with respect to HZ (VEHZ) incidence was 51.3%. In a time-to-event analysis, the cumulative incidence of HZ was significantly lower in the vaccine group than in the placebo group (P <.001). The VEHZ was 37.6% among subjects 70 years of age or older and 63.9% among younger subjects (P <.001). There was no difference in VEHZ by sex.

Adverse events: Over the entire study period, the numbers and percentages of deaths were similar in both the vaccine and placebo groups. During the first 42 days, varicellalike rashes at the injection site occurred more frequently among those in the vaccine group than among those in the placebo group, but varicellalike rashes at other sites occurred at similar rates in the two groups. There were seven confirmed cases of HZ in the vaccine group and 24 in the placebo group during the first 42 days after vaccination.4

In an adverse-events substudy, a significantly greater number of subjects in the vaccine group had one or more adverse events than in the placebo group, reflecting a greater frequency of adverse events at the injection site among subjects in the vaccine group (erythema 35.8%), pain or tenderness (34.5%), swelling (26.2%), and pruritus (7.1%).

Throughout the clinical trials, there was a significant difference in total serious adverse events between the two groups (1.9% in the vaccine group and 1.3% in the placebo group), but on post hoc review, no clinically meaningful differences were identified by the writing committee.

Zostavax is recommended prophylactically for adults aged 60 years and older. The dose is 0.65 mL administered once by subcutaneous injection in the upper arm. The vaccine has been shown to be effective in preventing HZ but is not indicated for treatment of HZ or PHN. Patients who had HZ a decade or more ago can receive the vaccine to prevent recurrence, but it is not indicated in those who have recently recovered.

Dr. Weinberg is director of clinical research in the Department of Dermatology, St. Luke’s-Roosevelt Hospital Center and Beth Israel Medical Center, and clinical assistant professor of dermatology at Columbia University, all in New York City. Dr. Weinberg is a member of the Cortlandt Forum advisory board and is on the speakers’ bureau for Merck.

References

1. Schmader K. Herpes zoster in older adults. Clin Infect Dis. 2001;32:1481-1486.

2. Oster G, Harding G, Dukes E, et al. Pain, medication use, and health-related quality of life in older persons with postherpetic neuralgia: results from a population-based survey. J Pain. 2005;6:356-363.

3. Tyring S, Barbarash RA, Nahlik JE, et al. Famciclovir for the treatment of acute herpes zoster: effects on acute disease and postherpetic neuralgia. A randomized, double-blind, placebo-controlled trial. Ann Intern Med. 1995;123:89-96.

4. Oxman MN, Levin MJ, Johnson GR, et al. A vaccine to prevent herpes zoster and postherpetic neuralgia in older adults. N Engl J Med. 2005;352:2271-2284.