Prevention of herpes zoster and postherpetic in older adults

Kevin Joseph Overbeck, DO Joshua S. Coren, DO, MBA, FACOFP

cientific advancements in Sthe 21st century continue to provide new options for primary care providers to promote health through prevention. remains a key strategy for prevention and is a benchmark for quality of care.1 The zoster has proven to be effective at reducing the incidence and severity of herpes zoster (HZ) and the scourge of postherpetic neuralgia (PHN). Older adults are particularly vulnerable to missing this important intervention, but primary care providers are positioned to champion its use.

16 AOA Health Watch Prevention of herpes zoster and postherpetic neuralgia in older adults December 2013 aricella, or , long thought Vof as a benign, often pruritic rash that lasts about a week, is better characterized as a viremia caused by the varicella-zoster virus (VZV) that results in seeding of multiple sensory ganglia. HZ, known commonly as , is a painful rash with distribution along a which occurs as a result of reactivation of latent VZV in the cranial nerve or dorsal root ganglia. It has been estimated that 50% of unvaccinated individuals who live to 85 years will develop or will have had HZ.2 Because T-cell immunity decreases with age, age is the major risk factor for developing HZ.3 Some experts have theorized that older adults may be at an even greater risk because of the success of pediatric varicella immunization programs. Older adults now experience less natural exposure to VZV during their lifetime because their grandchildren are contracting chickenpox less often due to programs. Natural exposure to the virus is believed to bolster older adults’ dwindling immunity.3,4,5 Immunologists have confirmed that Physicians and the The incidence and severity of PHN HZ is a reactivation of an individual’s increase with age. The childhood virus; nevertheless, the overall public are now was approved by the FDA on the basis of effect of childhood immunization for results from a randomized, double-blind chickenpox on the adult incidence equipped -controlled trial. In this study, of HZ remains to be seen. 6.8% of individuals aged 60 to 69 years Prompt initiation of antiviral therapy with an in the placebo group with confirmed with acyclovir, , or valacyclovir HZ went on to develop PHN, whereas has been approved by the US Food effective 18.5% of individuals aged 70 years and Drug Administration (FDA) and and older in the placebo group with demonstrates a decrease in the severity approach— confirmed HZ went on to develop PHN.7 of acute , halting of the propagation a vaccine—to prevent PHN further threatens the of the rash as well as hastening its independence of older patients in many resolution. To further complicate matters herpes zoster. ways. It has been associated with severe in older adults (and in any individual pain requiring prescription medications, with chronic kidney disease), prescribers which may further promote the cycle of of these antiviral medications should concerning in older adults because depression, weight loss, and fatigue.8 A make adjustments to the dose and/or anorexia and pain are often debilitating meta-analysis published in 2009 failed its scheduling based on renal function. and result in impairment of function, to show a significant reduction in the HZ has been associated with thereby threatening an individual’s incidence of PHN through the use simultaneous or subsequent independence. Older adults who are of antivirals9 and serves to reinforce development of Bell palsy, Ramsay Hunt treated appropriately with or prevention as the key strategy. syndrome, transverse myelitis, and even are at increased risk for Physicians and the public are now stroke6 and necessitates ophthalmologic the development of delirium and falls, equipped with an effective approach—a evaluation when it occurs in the which further threatens independence. vaccine—to prevent HZ and the trigeminal nerve V1 distribution PHN is a particularly devastating potential catastrophe brought about (Figure 1). In addition to potential potential consequence of HZ, in which by PHN. In 2006, the zoster vaccine severe neurologic complications, the pain persists beyond 90 days (and even was approved by the FDA for use in development of HZ is particularly years) after the HZ rash has resolved. adults aged 60 years and older. The

December 2013 Prevention of herpes zoster and postherpetic neuralgia in older adults AOA Health Watch 17 Figure 1. Selected complications position regarding administration of the be avoided in patients receiving (a) of herpes zoster in nonimmuno­ vaccine in those aged 60 years and older. >20mg/d of prednisone, (b) >0.4mg/ compromised persons. kg/wk of methotrexate, (c) azathioprine >3mg/kg/d, or (d) anti-tumor necrosis Contraindications factor therapy.8,14 The American College Aseptic meningitis The zoster vaccine contains a live, of Rheumatology has recommended and should be administering zoster vaccination Bacterial superinfection avoided in individuals with primary or prior to initiating DMARDs (disease- Bell palsy secondary causes of ; modifying antirheumatic drugs).15 Eye involvement (herpes this includes individuals with a Older individuals with multiple zoster ophthalmicus) hematologic cancer (ie, leukemia, chronic medical conditions, and Hearing impairment lymphoma), and HIV when CD4 cell particularly those with multiple Motor neuropathy count is <200.14 The immunosenescence prescribers, are at particularly high Postherpetic neuralgia associated with normal aging is not risk for adverse drug events. Prior Ramsay Hunt syndrome considered an immunodeficiency, to zoster vaccine administration, Transverse myelitis and therefore advanced age should it is worthwhile to take a focused Vasculopathy (encephalitis) not be a barrier to vaccination. history regarding medication use, High-dose immunosuppressive especially those prescribed or therapy remains a contraindication administered intravenously or injected Adapted from Cohen JI. Clinical practice: Herpes zoster. N Engl J Med. 2013;369(3):255-263. for zoster vaccine administration. Any by subspecialists (ie, infliximab individual who is actively undergoing [Remicade]). For example, an older chemotherapy or radiation for any individual may continue to follow up major efficacy trial published within condition should not receive this with routine care from her gynecologist the same year demonstrated that the vaccination. Experts have recommended who prescribes and administers vaccine reduced not only the incidence delaying vaccination in such instances denosumab (Prolia) for osteoporosis. by 51.3%, but also the severity of until at least 3 months following the last Denosumab is a monoclonal HZ-associated pain by more than administration of these therapies.8 The that is FDA approved for the treatment 60%.7 This trial further established a immunization against HZ also should of osteoporosis and that has been reduction in the incidence of PHN by 66%. Although vaccination efficacy is Figure 2. Considerations when administering live reduced in adults aged 70 years and attenuated herpes zoster vaccine. older (compared to that in individuals 60-69 years old) as primary prevention, data demonstrate that PHN prevention is unchanged with age.10 Experts have Recommendation indicated that because of both the ACIP: Healthy adults aged 60+years, regardless of prior history of zoster severity and duration of illness caused FDA: Healthy adults aged 50+ years by PHN, the routine vaccination of ACR: Administer before initiating biologic DMARDs older adults is justified.11 The benefits Contraindications of immunization are noted to persist for Pregnancy at least 5 years and perhaps longer.12 Anaphylactic hypersensitivity to neomycin or gelatin There is no indication that re-vaccination Known severe immunodeficiency is needed and the safety and efficacy of Other Considerations re-vaccination has not been established. No need to defer for “at-risk contacts”—transmission risk low The Advisory Committee on No need to defer if recent transfusion, Ab-containing products Immunization Practices (ACIP) of the Centers for Disease Control and Administration Prevention has recommended that the Must be administered within 60 minutes of reconstitution zoster vaccine be administered once to 0.65 mL delivered subcutaneously individuals aged older than 60 years.13 Adverse Effects In March 2011, the vaccine was FDA Occasional mild varicella-like rash at vaccine site approved for use in individuals aged 50 Duration of Protection years and older10; the ACIP declined, At least 5 years however, to recommend routine No booster recommended immunization in individuals aged 50 Abbreviations: ACR, American College of Rheumatology; DMARD, disease-modifying anti-rheumatic drug. to 59 years and recently confirmed its Source: http://www.cdc.gov/mmwr/preview/mmwrhml/rr5705a.htm.

18 AOA Health Watch Prevention of herpes zoster and postherpetic neuralgia in older adults December 2013 Figure 3. Herpes zoster vaccination rates by state, percent of older adult population.

WA

MT ND ME

MN OR VT NH ID SD WI MA MI NY WY CT RI

IA PA NE NV NJ IN OH MD IL DE UT CO CA WV KS VA MO KY

NC TN AZ OK AR NM SC

GA MS AL

TX LA 0.05-2.77 2.89-2.52 3.54-4.08 (includes Alaska) FL 4.16-5.76 5.80-11.02 (includes Hawaii)

Source: Langan SM, Smeeth L, Margolis DJ, Thomas SL. (2013) Herpes zoster vaccine effectiveness against incident herpes zoster and post-herpetic neuralgia in an older US population: a cohort study. PLoS Med. 2013;10(4): e1001420. doi:10.1371/journal.pmed.1001420 © 2013 Langan et al.

associated with an increased risk of offers the primary care provider an incidence of HZ has been consistently ; prescribers should avoid opportunity to update vaccination history increasing in both men and women, zoster vaccination of those individuals and to educate older patients about the with age.18,19 The increased incidence who take denosumab until the safety advantages of this vaccine. Any concerns of HZ is likely not fully explained by of concomitant use with the zoster about side effects or contraindications the varicella immunization pediatric vaccine is identified. Primary care also could be addressed during the visit. program as discussed earlier. People are providers should seek opportunities to Although it is well established that living longer and at times are carrying collaborate with local pharmacists, who there is no role for the zoster vaccine a significant burden of chronic medical have access to records enumerating during acute HZ illness, the timing conditions, which also increases the medications prescribed by subspecialists. of vaccination following resolution is probability that the latent VZV will It should further be noted that zoster unclear. Recurrence following a recent resurface. For example, it was noted vaccination should not be given to episode is relatively rare and it has been in previous studies that treatment any individuals who have anaphylactic demonstrated that cellular immunity for rheumatoid arthritis with TNF reaction to gelatin, neomycin, or any following HZ is similar to that generated inhibitors, steroids, or disease-modifying other component of the vaccine. by the vaccination.16,17 Although there antirheumatic medications is associated is no known harm to do so earlier, with an increased incidence of HZ.20,21 some experts believe it is sensible to Timing of the vaccination delay immunization for approximately The zoster vaccine can be administered 3 years following an HZ episode.7 Provider, practice, and simultaneously with other , Despite strong recommendations patient barriers including the from an authority such as the ACIP, Despite the evidence supporting the and the .13-15 The as well as evidence to support the routine use of the zoster vaccine, its new Medicare Annual Wellness Visit effectiveness of the vaccine, the use has been poor—less than 16% of

December 2013 Prevention of herpes zoster and postherpetic neuralgia in older adults AOA Health Watch 19 The cost of the zoster vaccine itself also is a major perceived barrier.6 When the zoster vaccine was introduced, many of the major insurance carriers did not immediately initiate coverage and reimbursement. Today Medicare and most insurance plans reimburse the cost of the zoster vaccine for eligible individuals. Of course, a patient who is within the “donut hole” of Medicare and those not yet meeting their insurance deductible coverage may incur full financial responsibility for the vaccine’s cost. For uninsured and underinsured patients who do not have vaccine coverage, expense of the vaccine could certainly be a barrier to immunization.5

Overcoming barriers Although the financial concerns remain a barrier to routine administration, several studies have suggested that routine immunization with the zoster vaccine would result in substantial cost savings.29-31 Inter-professional and inter- disciplinary partnerships are helping to develop strategies to improve patient care and outcomes, and it would be advantageous for physicians the target population in 2011.22 The to partner with local pharmacies and lack of knowledge of HZ immunization to assist in vaccination. Pharmacists guidelines, schedules, contraindications, have access to prescription records for and vaccine side effects is a major individuals with multiple subspecialists barrier for providers and patients.23,24 The benefits of and prescribers and thereby will be In 1 study, only 13.7% of patients had herpes zoster better able to avoid administration of any communication with their medical the vaccine to persons who are not providers regarding the zoster vaccine, immunization candidates because of concurrent with 70% of the patients never having immunosuppressive therapies. heard about the vaccine before.25 persist for at least Because pharmacists often have better Providers who care for populations of storage capability, one strategy employed HIV-infected patients scored poorly 5 years—and by primary care providers is to have on a knowledge-based assessment perhaps longer. the patient fill the prescription at the regarding potency of the zoster pharmacy on the day of the appointment vaccine (47.5% correctly answered) and then present to the office/clinic for and mechanism of reactivation of VZV barriers within a practice setting—cost vaccination administration. Also, similar (66% correctly answered), noting lack of a necessary additional freezer and lack to the influenza and pneumococcal of guidance from the CDC on use of adequate spacing for the equipment. vaccines, the zoster vaccine can be of this vaccine in HIV patients.26 The diluent necessary to mix in the administered by pharmacists who The vaccine must be stored in vaccine would be stored in a separate obtain permission to administer the a freezer at temperatures between refrigerator. Recommendations from vaccine in the pharmacy itself. A novel -58°F and +5°F until it is prepared the National Institute of Standards approach utilized by some includes and administered to a patient.27 Proper and Technology further advise that having those pharmacists themselves storage is essential for both the safety all providers use stand-alone freezers collaborate with the health care team to and the efficacy of the zoster vaccine, and not combination freezers to participate in mass vaccination clinics but may present additional financial store all their frozen vaccines.28 at senior housing or assisted living

20 AOA Health Watch Prevention of herpes zoster and postherpetic neuralgia in older adults December 2013 facilities. Clearly such a strategy is most 8. Cohen JI. Clinical practice: Herpes zos- 22. Harpaz R, Kempe A. Update: Herpes zoster helpful for individuals with functional ter. N Engl J Med. 2013;369(3):255-263. (shingles) vaccine. Paper presented at: Meet- ing of the Advisory Committee on Immunization impairments who likely have limitations 9. Gilden D, Cohrs RJ, Mahalingam R, Nagel Practices; February 25-26, 2009; Atlanta, GA. with using public transportation and/ MA. vasculopathies: diverse clinical manifestations, laborato- or driving their own vehicles. 23. Hurley LP, Harpaz R, Daley MF, et al. National ry features, pathogenesis, and treatment. survey of primary care physicians regarding Lancet Neurol. 2009;8(8):731-740. herpes zoster and the herpes zoster vaccine. J Infect Dis. 2008;197 [suppl 2]:S216 -S223. Final notes 10. Schmader KE, Levin MJ, Gnann JW Jr, et al. Efficacy, safety, and tolerability of 24. Prislin R, Sawyer MH, Nader PR, Goerlitz M, There exists an increased risk for HZ herpes zoster vaccine in persons age 50-59 De Guire M, Ho S. Provider-staff discrepan- and PHN among the aged; therefore years. Clin Infect Dis. 2012;54(7):922-928. cies in reported immunization knowledge and older adults should be the primary 11. Arvin A. Aging, immunity, and the varicella-zos- practices. Prev Med. 2002;34(5):554-561. care provider’s clear target of HZ ter virus. N Engl J Med. 2005;352(22):2266-2267. 25. Joon Lee T, Hayes S, Cummings DM, et al. immunization practices. Primary care 12. Schmader KE, Oxman MN, Levin MJ, Herpes zoster knowledge, prevalence, and providers are in the position to bridge et al; Shingles Prevention Study Group. vaccination rate by race. J Am Board Fam Med. chronic disease management with health Persistence of the efficacy of zoster vac- 2013;26(1):45-51. promotion through prevention. Diligence cine in the shingles prevention study and 26. Aziz M, Kessler H, Huhn G. Providers’ lack of the short-term persistence substudy. in keeping well-informed of advancing knowledge about herpes zoster in HIV-infected Clin Infect Dis. 2012;55(10):1320-1328. medical knowledge, persistence with patients is among barriers to herpes zoster 13. Harpaz R, Ortega-Sanchez IR, Seward JF; vaccination. Int J STD AIDS. 2013;24(6):433-439. patient education, and participation Advisory Committee on Immunization 27. Centers for Disease Control and Prevention. in novel approaches to promote HZ Practices (ACIP) Centers for Disease Control & Handling Toolkit. immunization will help primary care and Prevention (CDC). Prevention of herpes November 2012. http://www.cdc.gov/vaccines zoster: recommendations of the Advisory physicians overcome barriers and yield /recs/storage/toolkit/storage-handling-toolkit. Committee on Immunization Practices (ACIP). fruitful patient-oriented outcomes. pdf#page=54. Accessed September 12, 2013. MMWR Recomm Rep. 2008;57(RR-5):1-30. 28. Hurley LP, Lindley MC, Harpaz R, et al. References 14. Zostavax [package insert]. Whitehouse Station, NJ: Merck & Co, Inc; 2013. Barriers to the use of herpes zoster vac- 1. Immunization Work Group of the National cine. Ann Intern Med. 2010;152(9):555-560. and Global Public Health Committee of the 15. Tseng HF, Smith N, Sy LS, Jacobson SJ. 29. Hornberger J, Robertus K. Cost-effective- Infectious Diseases Society of America. Evaluation of the incidence of herpes zoster ness of a vaccine to prevent herpes zoster Executive summary—actions to strengthen after concomitant administration of zoster and postherpetic neuralgia in older adults. adult and adolescent immunization cover- vaccine and polysaccharide pneumococcal Ann Intern Med. 2006;145(5):317-325. age in the United States: policy principles of vaccine. Vaccine. 2011;29(20):3632-3638. the Infectious Diseases Society of America. 16. Tseng HF, Chi M, Smith N, Marcy SM, Sy LS, 30. Rothberg MB, Virapongse A, Smith KJ. Cost- Clin Infect Dis. 2007;44(12):1529-1531. Jacobsen SJ. Herpes zoster vaccine and effectiveness of a vaccine to prevent herpes zoster and postherpetic neuralgia in older 2. Brisson M, Edmunds WJ, Gay NJ. Var- the incidence of recurrent herpes zoster adults. Clin Infect Dis. 2007;44(10):1280-1288. icella vaccination: impact of vaccine in an immunocompetent elderly popula- efficacy on the of VZV. tion. J Infect Dis. 2012;206(2):190-196. 31. Brisson M, Pellissier JM, Camden S, J Med Virol. 2003;70 [suppl 1]:S31-S37. 17. Weinberg A, Zhang JH, Oxman MN, et al; US Quach C, De Wals P. The potential cost- Department of Veterans Affairs (VA) Coopera- effective­ness of vaccination against herpes 3. Hayward AR, Herberger M. Lymphocyte tive Studies Program Shingles Prevention Study zoster and post-herpetic neuralgia. responses to varicella zoster virus in the Investigators. Varicella-zoster virus-specific im- Hum Vaccin. 2008;4(3):238-245. HW elderly. J Clin Immunol. 1987;7(2):174-178. mune responses to herpes zoster in elderly par- 4. Thomas SL, Wheeler JG, Hall AJ. Contacts ticipants in a trial of a clinically effective zoster with varicella or with children and protection vaccine. J Infect Dis. 2009;200(7):1068-1077. against herpes zoster in adults: a case-con- 18. Rimland D, Moanna A. Increasing incidence of trol study. Lancet. 2002;360(9334):678-682. Kevin Joseph Overbeck, DO, is an assistant herpes zoster among veterans. Clin Infect Dis. professor at Rowan School of Osteopathic 5. Brisson M, Gay NJ, Edmunds WJ, 2010;50(7):1000-1005. Medicine in New Jersey (formerly UMDNJ- Andrews NJ. Exposure to varicella boosts 19. Yih WK, Brooks DR, Lett SM, et al. The inci- SOM) where he also serves as the geriatrics immunity to herpes-zoster: implications dence of varicella and herpes zoster in Massa- fellowship director at the New Jersey for mass vaccination against chicken- chusetts as measured by the Behavioral Risk pox. Vaccine. 2002;20(19-20):2500-2507. Factor Surveillance System (BRFSS) during a Institute for Successful Aging. Dr Overbeck can be reached at [email protected]. 6. The Harvard Medical School Family Health period of increasing cover- Guide. The shingles vaccine: why hasn’t it age, 1998-2003. BMC Public Health. 2005;5:68. Joshua S. Coren, DO, MBA, FACOFP, is vice caught on? www.health.harvard.edu/fhg/ 20. Smitten AL, Choi HK, Hochberg MC, et al. The updates/The-shingles-vaccine.shtml. Updated risk of herpes zoster in patients with rheuma- chair and associate professor of family September 2007. Accessed October 20, 2013. toid arthritis in the United States and the United medicine and the director of continuing medical education at Rowan University 7. Oxman MN, Levin MJ, Johnson GR, et Kingdom. Arthritis Rheum. 2007;57(8):1431-1438. School of Osteopathic Medicine in New al; Shingles Prevention Study Group. A 21. Strangfeld A, Listing J, Herzer P, et al. Risk vaccine to prevent herpes zoster and of herpes zoster in patients with rheuma- Jersey (formerly UMDNJ-SOM). Dr Coren postherpetic neuralgia in older adults. toid arthritis treated with anti-TNF-alpha can be reached at [email protected]. N Engl J Med. 2005;352(22):2271-2284. agents. JAMA. 2009;301(7):737-744.

December 2013 Prevention of herpes zoster and postherpetic neuralgia in older adults AOA Health Watch 21