Protect Patients from Painful Shingles

Vaccinations are very important for preventing numerous viral infections such as influenza, hepatitis A and B, and varicella zoster virus.¹

The varicella zoster virus has 2 distinct yet similar diseases: the chickenpox and shingles.¹

Prior to getting infected with shingles, a person becomes infected with chickenpox, typically at an early age. After the chickenpox viral infection resolves, the virus becomes dormant in the dorsal sensory and cranial ganglion for many years, or even decades.

After an unknown period of time, the virus may become reactivated later in life and cause a very painful maculopapular rash that is known as herpes zoster, or shingles. As people age, the risk of developing herpes zoster increases significantly, as well as the duration and severity of the virus.

For many years, scientists have known that there is a common link between chickenpox and shingles that stays in a latent stage. To control or keep the varicella zoster virus in its latent stage, it is important to have a sufficient amount of specific cell-mediated immunity.

Receiving the herpes zoster vaccination later in life has been shown to help decrease the ability of the virus to become reactivated.

In 1995, the varicella vaccine became licensed in the United States, and in 2006, the herpes zoster vaccine did the same. The development of the varicella vaccine was a remarkable milestone in helping to prevent future shingles cases.

Prior to the introduction of the varicella vaccine, there were an estimated 4 million cases of chickenpox annually in the United States. Five years after the release of the varicella vaccine, the incidence of chickenpox was reduced by 76% to 87%.

With a greater than 75% decrease in incidence of chickenpox, it stands to reason that there would be a corresponding decrease in incidence of shingles once those vaccinated individuals reached an older age. With the addition of the varicella vaccine, however, these patients are at a higher risk of getting shingles later in life if the virus reactivates.

Because patients are getting varicella vaccines, it is necessary for them to receive the zoster vaccine once they reach the appropriate age.

Shingles onset can be divided into 3 phases: acute herpetic neuralgia, subacute herpetic neuralgia, and postherpetic neuralgia (PHN)—the most common complication, which is often very painful. Postherpetic neuralgia is a persistent pain where the rash was previously located. Unfortunately, PHN can persist for anywhere from 180 days to many years after the onset of shingles rash, and it is less likely to subside than the previous phases.²

One double-blind, placebo-controlled trial of live attenuated herpes zoster vaccine in approximately 38,000 adults aged 60 years or older sought to determine the vaccine’s efficacy for each year through year 7 after patients received the zoster vaccine or placebo. The results showed the vaccine to be most efficacious in the first year after immunization.³

“Overall, the vaccine compared to placebo decreased the zoster burden of illness by 50%, the incidence of postherpetic neuralgia by 60%, and the incidence of herpes zoster by 40%,” the researchers wrote.³

Although their data suggested continued vaccine efficacy in years 6 and 7, it was not statistically significant, so the efficacy beyond 5 years remains unknown.³

Currently, the US Centers for Disease Control and Prevention (CDC) recommends that all individuals aged 60 years and older get vaccinated with one dose of the zoster vaccine.⁴ Cell-mediated immunity is crucial in order to keep the varicella zoster virus in the dormant stage.

Evidently, as people age, there is a corresponding decrease in varicella zoster virus specific cell-mediated immunity. Therefore, additional trials have investigated the age at which the zoster vaccine should be given.

One trial examined healthy subjects aged 50 to 59 years with a history of varicella or residence in a varicella zoster virus endemic area for at least 30 years. All of the subjects were given a 0.65-mL subcutaneous injection of either zoster virus or placebo. The individuals were followed for an average of 1.3 years for the development of suspected herpes zoster.⁵

Of the total study group, 277 patients were evaluated for the development of suspected shingles. Of those patients, 148 (53%) did not have shingles, though the remaining 129 (47%) had confirmed herpes zoster.⁵

Of the 129 confirmed cases, 30 were in the zoster treatment group, and 99 were in the placebo group. Of the 129 confirmed zoster cases, none of the patients developed a second episode of shingles.⁵

Overall, compared with placebo, the zoster vaccine significantly reduced the incidence of shingles in the study population.⁵

This study also evaluated the durability of vaccine efficacy and found that it remained stable throughout specified consecutive periods, which were broken down into 0 to 0.5 years, 0.5 to 1 years, 1 to 1.5 years, and greater than 1.5 years. It also evaluated the “severity by duration” pain score and found that it was lower in the zoster treatment group than the placebo population.⁵

Both groups reported that the majority of their pain occurred within the first 8 days following shingles onset; however, this decreased over the remaining 21-day follow-up period.⁵

In addition, the zoster vaccine was well tolerated with few adverse effects. The most common reported systemic adverse effect was headache, which occurred in 9.4% of zoster group versus 8.2% in the placebo group. Of these percentages, approximately 3% were related to the vaccine in the zoster group, compared with approximately 2% in the placebo group.

Of the total study population, only one individual had an anaphylactic reaction, which was appropriately treated with epinephrine and methylprednisolone.

Overall, the study proved that the zoster vaccine is effective in decreasing the incidence of herpes zoster by 70% in patients aged 50 to 59 years. Of note, approximately 20% of zoster cases occur in this age group.⁵

This study is beneficial in supporting the use of the zoster vaccine in younger patients to help decrease their overall risk of developing shingles. When the vaccine was given to patients aged 50 to 59 years, the estimated vaccine efficacy was similar to a person aged 60 to 69 years (63.9%) and significantly greater than a person aged 70 years or older (37.6%).

This is most likely due to stronger varicella zoster vaccine specific cell-mediated immunity boost in younger patients. It is also thought younger patients have stronger immune systems, which in turn produce stronger immunity to many different viruses, including zoster.

It is also important to acknowledge that the acute pain experienced by this younger patient population is similar to the acute pain experienced by the older population. However, since this group of younger individuals primarily continues to work, the acute pain associated with the zoster virus could be a burden on the workforce. This could translate to missed workdays, decreased pay, and less productivity.

If patients aged 50 to 59 years can be vaccinated, mount a proper immune response, and continue to work and be productive, then such a vaccination program should be employed throughout the United States. It would be advantageous to vaccinate patients as early as possible against herpes zoster to help decrease health care costs. Vaccinating patients at a younger age could lead to a decrease in hospitalizations, as well.

Current European guidelines recommend Zostavax for the prevention of herpes zoster and PHN in adults aged 50 years and older. The Committee for Medicinal Products for Human Use has determined that the use of Zostavax in patients aged 50 years and older provides more benefits than risks. These recommendations from Europe are based on the findings that patients receiving Zostavax had a lower incidence of shingles and a decrease in PHN.⁶

It is important to understand that the zoster vaccine has very few side effects. Although the injection itself may be painful, and patients may experience an injection site reaction or sore arm for a few days, it is worthwhile to endure minor vaccine pain versus potentially experiencing PHN or other adverse effects associated with shingles.

However, it is just as important not to use this vaccine in immunosuppressed patients, anyone with a history of anaphylactic reactions to gelatin or neomycin, or pregnant women.⁷

Since the zoster vaccine was only approved by the FDA in 2006, it is difficult to determine whether patients need to be given a booster dose, which would potentially be similar to the pneumonia booster. It would stand to reason that when the titer levels decrease below a specified value, it would put the patient at an increased risk for the virus reactivating.

At this point, it is unclear whether patients need to be revaccinated with a booster because not enough trials have been completed. Currently, there are a few trials reviewing this very topic to help determine whether a booster is needed.

At this time, the FDA and CDC are not recommending a booster dose. When updated results do become available, however, the CDC may update its guidelines to reflect any relevant changes.

It is currently recommended that patients aged 60 years or older get a single dose of the Zostavax vaccine. With the evidence presented above, however, it would be beneficial for clinicians to begin administering the vaccine when patients turn 50.

Of note, the FDA changed the indication for the Zostavax vaccine in 2011 to include patients 50 years and older, though neither the FDA nor the CDC is recommending routine vaccination at age 50.⁸ Instead, the agencies are advising clinicians to use their best judgment to determine which patients should receive the vaccine at an earlier age.

It is clear that the use of the zoster vaccine is beneficial in decreasing the incidence of shingles as well as PHN associated with shingles. This can be a debilitating disease that could potentially cause an increase in health care costs and hospitalizations if the population is not properly vaccinated.

It is imperative for health care professionals to realize the potential benefits and harms related to the herpes zoster disease itself, as well as the vaccine. Currently, the zoster vaccine is underused in the United States.⁹ Hopefully, with an increase in provider awareness, Zostavax use will increase to help protect the general public from experiencing the burden of the shingles disease.

References

1. Centers for Disease Control and Prevention. Shingles (herpes zoster). http://www.cdc.gov/shingles/hcp/clinical-overview.html. Accessed October 18, 2013.

2. Kim, KH. Herpes zoster vaccination. Korean J Pain. 2013 July;26(3): 2242-248.

3. Schmader KE, Oxman MN, Levin MJ. Persistence of the efficacy of zoster vaccine in the Shingles Prevention Study and the Short-Term Persistence Substudy. CID. 2012;55(10):1320-8.

4. Centers for Disease Control and Prevention. Adult immunization schedule. 2013. http://www.cdc.gov/vaccines/schedules/downloads/adult/adult-schedule.pdf. Accessed October 18, 2013.

5. Schmader KE, Levin MJ, Gnann JW, et al. Efficacy, safety, and tolerability of herpes zoster vaccine in persons aged 50-59 years. CID. 2012:54(1):922-8.

6. European Medicines Agency. Zostavax. 2013. http://www.ema.europa.eu/ema/index.jsp?curl=pages/medicines/human/medicines/000674/human_med_001185.jsp&mid=WC0b01ac058001d125. Accessed October 24, 2013.

7. Zostavax Package insert. http://www.merck.com/product/usa/pi_circulars/z/zostavax/zostavax_pi2.pdf. Accessed October 24, 2013.

8. Centers for Disease Control and Prevention. Herpes zoster vaccination information for health care professionals. 2013. http://www.cdc.gov/vaccines/vpd-vac/shingles/hcp-vaccination.htm. Accessed October 24, 2013.

9. Langan SM, Smeeth L, Margolis DJ. Herpes zoster vaccine effectiveness against incident herpes zoster and post-herpetic neuralgia in an older US population: a cohort study. PLOS Medicine. 2013;10(4):1-10.