Friday, February 11, 2011

Alarming New Evidence About Painful Shingles-PHN

Shingles-PHNConventional medical wisdom about shingles, or herpes zoster, has been that it is a one-time occurrence and, thereafter, patients are protected from re-emergence of the varicella zoster virus that causes shingles. However, according to new evidence published in the February edition of Mayo Clinic Proceedings, recurrences of shingles may be more common than previously suspected. At the same time, other research reports that, while herpes zoster vaccine can be effective in reducing first time occurrences of shingles, relatively few persons at risk bother to get vaccinated.

Shingles is estimated to afflict 1 in 3 people during their lifetime, resulting in an estimated 1 million new episodes in the United States each year. It can occur at any age, but the greatest incidence and morbidity is seen in older adults — up to about 70% of cases are in those aged 50 years and older — and in immunocompromised patients. Postherpetic neuralgia (PHN), defined as pain persisting more than 3 months beyond healing of the typical shingles rash, is painful, debilitating, and often difficult to manage [Eastern 2010; Sampathkumar et al. 2009].

A research team from the Olmsted Medical Center, Rochester, MN, examined a medical records database, spanning 1996 to 2001, of nearly 1,700 immunocompetent patients >22 years of age who had a documented episode of shingles [Yawn et al. 2011]. They then searched followup medical records to determine if those patients had been treated for a second occurrence at any point in time. With an average followup of 8 years, the data revealed an estimated recurrence rate of 6.2%, or about the same rate at which persons of the same age would be expected to develop a first case of shingles. Some patients had experienced as many as 3 recurrences during the followup period, and the authors suspected that if all patients could be followed throughout their lifetimes the recurrence rate would be much higher.

The researchers, writing in the February 2011 edition of Mayo Clinic Proceedings, note that women and anyone ≥50 years of age were more likely to experience a recurrence of the disease. Another significant determinant for recurrence was patients' pain during the initial episode; those who had experienced pain lasting more than 30 days after onset of shingles were more likely to have a recurrence, particularly in the first 3 to 4 years after the initial episode. As might be expected, persons who developed compromised immune systems, such as from chemotherapy or medical conditions, were more likely to have shingles recurrences.

In sum, cases of shingles in immunocompetent individuals not only recur, but at rates much higher than might be expected. It also might be suspected that repeat occurrences increase the odds of developing painful PHN. All of this suggests that preventative vaccination against initial outbreaks of shingles could be worthwhile.

Accordingly, a report in the online February 5, 2011 edition of JAMA by researchers from the Kaiser Permanente Department of Research and Evaluation in Pasadena, California, notes that administration of the herpes zoster vaccine was linked to a 55% reduction in risk of developing shingles [Tseng et al. 2011]. Their retrospective cohort study, spanning 2 years and involving 300,000 immunocompetent patients ≥60 years of age, suggests that vaccinating all eligible people could prevent tens of thousands of cases of shingles each year in the U.S.

Using electronic health records, Tseng and colleagues compared the incidence of shingles among a diverse population of 75,761 vaccinated and 227,283 unvaccinated men and women. The participants were community-dwelling, had healthy immune systems, and those who were vaccinated had received their vaccine in a general practice setting. The results showed a significant reduced risk of shingles across all subgroups, including healthy patients and those with chronic conditions such as diabetes, heart, lung, or kidney diseases.

In a third recent report, appearing in the February 2011 edition of American Journal of Preventive Medicine researchers note that, although a herpes zoster vaccine to prevent shingles has been available since 2006, quite small percentages of eligible U.S. seniors ≥60 years of age chose to receive the vaccination as of 2008 [Liu et al. 2011]. The rate of vaccination was much lower among people aged 60-64 years (4.7%) compared with ages 65-67 (7.4%), 75-84 (7.6%), and ≥85 (8.2%).

Those more likely to have been vaccinated were older, female, non-Hispanic white, married, more educated, and also reporting influenza vaccination in the past year. Surprisingly, 95% of younger seniors had missed at least one opportunity to be vaccinated, even though they had seen their physician at least once, been hospitalized, or visited an emergency department that year.

COMMENTARY: Earlier research had concluded that the herpes zoster vaccine reduces the incidence of shingles by 51%, the burden of illness from shingles by 61%, and the risk of developing PHN by 66% [ref. in Sampathkumar et al. 2009]. Therefore, the vaccine is not perfect, but the success rates are substantial with a number-needed-to-treat (NNT) of only 2 or less — that is, for every 2 persons vaccinated at least 1 new case of shingles will be prevented — and those who do develop shingles may have a milder case. Whether or not vaccination reduces the chances of shingles recurrence if given after an initial episode does not appear to have been studied.

The shingles vaccine is relatively expensive and, while most insurance and Medicare plans cover the vaccine cost, other costs might be out-of-pocket. This could be burdensome for some patients, especially for those without adequate insurance. Still, the costs and suffering related to treating shingles and the possibility of developing chronically painful PHN might outweigh the expense and/or any inconvenience associated with vaccination.

ADDENDUM: Zoster (Shingles) Vaccine (Zostavax®) — FDA Lowers Age Approval
In late March 2011, the U.S. Food and Drug Administration and Merck announced an expansion of the approved age of 60 years and older for Zostavax administration in the prevention of herpes zoster — commonly referred to as shingles. The added approval for adults 50 to 59 years of age was based on the results of a large clinical trial that showed a 70% reduction in the risk of vaccinated persons developing shingles when compared with those receiving placebo. For more information, read the FDA Press Release

> Eastern JS. Herpes Zoster. WebMD eMedicine [online]. 2010(Oct) [
article here].
> Liu P-j, Euler GL, Harpaz R. Herpes zoster vaccination among adults aged 60 years and over, in the U.S., 2008. Am J Prev Med. 2011(Feb);40(2):e1-e6 [
abstract here]
> Sampathkumar P, Drage LA, Martin DP. Herpes Zoster (Shingles) and Postherpetic Neuralgia. Mayo Clin Proc. 2009;84(3):274-280 [
article here].
> Tseng HF, Smith N, Harpaz R, et al. Herpes Zoster Vaccine in Older Adults and the Risk of Subsequent Herpes Zoster Disease. JAMA. 2011(Jan);305(2):160-166 [
abstract here].
> Yawn BP, Wollan PC, Kurland MJ, et al. Herpes Zoster Recurrences More Frequent Than Previously Reported. Mayo Clin Proc. 2011(Feb);86(2):88-93 [
abstract here].