May/June 2013

Treating Shingles

By Shengping Zou, MD, and Steven Ropers, MD
Today’s Geriatric Medicine
Vol. 6 No. 3 P. 28

The incidence of shingles (herpes zoster) in the United States among people aged 60 and older is about 10 per 1,000 people, according to the Centers for Disease Control and Prevention (CDC). With an estimated 1 million cases each year, nearly one in three Americans will develop shingles, and between 1% and 4% of people suffering from shingles are hospitalized for complications, the CDC notes.

Shingles is a painful skin condition caused by the reactivation of a dormant varicella zoster virus (VZV). VZV often is contracted early in life and causes chicken pox, but it is not fully cleared by the immune system. Instead, the virus stays in the nerve cell bodies and less frequently in the non-neuronal satellite cells of the dorsal root ganglia, cranial nerve, or autonomic ganglia, where it remains in a dormant state until it becomes reactivated later in life.

Reactivation of VZV often happens in individuals over the age of 60 or when the immune system is weakened by medications or disease. It typically presents with pain, a rash, and blistering in a dermatomal distribution. Shingles usually lasts from two to three weeks, and early treatment with antiviral agents can reduce complications. The most common complication is the development of postherpetic neuralgia (PHN), which is nerve pain lasting for more than three months after the acute rash has healed.1 PHN can be debilitating and last for years. Other rare complications may occur, including aseptic meningitis, facial paralysis, and encephalitis.

Epidemiology
The incidence of shingles in healthy individuals is about 0.2% in patients under the age of 50 and increases to 1% in those over the age of 80.2 The increase in herpes zoster in the elderly is thought to be a consequence of decreasing cellular immune function. Other risk factors include being female and reduced immune function for various reasons, such as HIV infection, cancer, prolonged steroid therapy, chemotherapy, and psychological stress.3

Although difficult to estimate, PHN occurs in 10% to 20% of shingles patients.4 Individuals over the age of 60 are at increased risk of developing PHN and suffering a prolonged course.5 Risk factors are thought to include more severe acute pain, the presence of a prodrome (preeruptive pain), and a more severe rash.6

Signs and Symptoms
The earliest symptoms of shingles are nonspecific and include headache, fever, and malaise. A painful vesicular rash in a unilateral dermatomal distribution, often involving the T3-L3 dermatomes or the ophthalmic division of the trigeminal nerve, usually follows the initial symptoms. The pain often is described as having two components: an ongoing burning or raw, severe aching and superimposed paroxysmal pains of stabbing or electric quality.7 Preeruptive pain (prodrome) before the development of the typical rash may be present for 48 to 72 hours. Herpes zoster usually lasts between seven and 10 days; however, the skin lesions may take up to one month to heal.

Diagnosis
A shingles diagnosis often is made clinically but can be confirmed by immunofluorescent staining of cells from the lesion base, isolation of VZV in tissue culture, or by detection of VZV DNA by polymerase chain reaction.8 A PHN diagnosis is made when pain lasts for three months or longer after an acute attack of shingles or appears after the skin lesions have healed. No tests are necessary to diagnose PHN.

Shingles Treatment
Shingles treatment aims to limit symptom severity and pain duration, decrease viral shedding, and prevent PHN.

The first-line agents for treating shingles, acyclovir (Zovirax), valacyclovir (Valtrex), and famciclovir (Famvir), are nucleoside analogues that have been shown to quicken the healing of skin lesions and reduce the pain associated with herpes zoster.9 The recommendation is to start the antiviral agents within 48 to 72 hours of rash onset to achieve the best clinical benefit.10 It is not clear whether antiviral therapy decreases the incidence of PHN.11

Acyclovir (800 mg orally five times per day for seven to 10 days) has a poor bioavailability and needs to be taken frequently. Valacyclovir (1,000 mg orally three times per day for seven days) is a prodrug of acyclovir and has a better bioavailability than acyclovir. Famciclovir (500 mg three times per day for seven days) is a prodrug of penciclovir, which is active against VZV but has a longer duration of action.

NSAIDs and acetaminophen are useful for treating mild pain associated with herpes zoster. If the pain is moderate or more severe, opioid analgesics such as oxycodone and morphine can be prescribed.

Steroids (30 mg of prednisone orally twice a day for seven days, then tapered off) often are given with acyclovir to improve quality of life, hasten skin lesion healing, and reduce the incidence of PHN. While some trials have found a moderate improvement in quality of life,12 other trials could not identify any benefit of corticosteroids on PHN incidence or duration.13 Given the potential adverse effects of steroids, such as immunosuppression and secondary bacterial superinfection of the skin lesions, current expert opinion is to limit corticosteroid administration to those patients with severe herpes zoster pain or severe neurological involvement (facial paralysis).14 Steroids should not be administered without concurrent antiviral therapy.

Neuraxial and sympathetic blocks have been used in both herpes zoster and PHN for pain control. There is strong evidence for the beneficial effects of epidural local anesthetics and steroid administration in herpes zoster as well as intrathecal local anesthetics and steroids in PHN. Epidural injections during herpes zoster also may reduce the incidence of PHN.15

Other treatment modalities for herpes zoster pain include topical lidocaine and capsaicin.

PHN Treatment
There are several treatment options available for PHN. In clinical practice the most common challenge is to identify the combination of drugs that is best suited for each patient, as no single medication is considered the gold standard for relieving PHN.

Tricyclic antidepressants are among the main pillars of treatment for patients with PHN. These medications are very effective in providing pain relief, but they are limited by their anticholinergic side effects, such as sedation and dry mouth. One thing to remember is that it may take up to three weeks before tricyclic antidepressants develop their full effect.

Anticonvulsants are another class of drugs used for patients with PHN. Both gabapentin (Neurontin) and pregabalin (Lyrica) have been shown to be effective in reducing the neuropathic pain associated with PHN.

Opioids such as morphine are highly effective in reducing PHN pain. One randomized controlled trial showed a trend toward greater pain relief with opioids than tricyclic antidepressants.16 Opioids, however, have a higher incidence of drowsiness and gastrointestinal side effects, such as constipation.

Data for topical lidocaine patches are not as strong as for the above medications, but the relative lack of side effects compared with the systemic agents allows topical lidocaine to be a useful addition in the treatment of PHN.17 Capsaicin is another topical agent that provides moderate pain relief in PHN, but its use is limited by its burning and stinging sensation in up to one-third of patients in a clinical trial.18

Intrathecal glucocorticoids are another treatment option, particularly if none of the above measures works. Preservative-free intrathecal methylprednisolone has been shown to provide superior pain relief compared with intrathecal lidocaine19 and epidural methylprednisolone.20

Transcutaneous electrical nerve stimulation is used to treat patients with various pain disorders, such as PHN, but there still is considerable debate regarding the effectiveness of this treatment because controlled studies are lacking.

Prevention
Zostavax is an FDA-approved shingles vaccine. The Advisory Committee on Immunization Practices recommends that all patients aged 60 and older be vaccinated against shingles, including patients with a history of herpes zoster. One large randomized double-blind, placebo-controlled trial found that the herpes zoster vaccine reduced the incidence of shingles by roughly 50%. Patients who were vaccinated but still affected by herpes zoster had a roughly 66% reduction in their risk of developing PHN.21 The vaccine is not recommended to treat active shingles or PHN once it develops.

— Shengping Zou, MD, is medical director of the Center for the Study and Treatment of Pain at New York University (NYU) Langone Medical Center. He also is program director at the NYU School of Medicine Pain Medicine Fellowship and an assistant professor of anesthesiology at the NYU School of Medicine in New York City.

— Steven Ropers, MD, is a third-year resident in the department of anesthesiology at New York University Langone Medical Center School of Medicine.

References
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2. Kost RG, Straus SE. Postherpetic neuralgia—pathogenesis, treatment, and prevention. N Engl J Med. 1996;335(1):32–42.

3. Thomas SL, Hall AJ. What does epidemiology tell us about risk factors for herpes zoster? Lancet Infect Dis. 2004;4(1):26-33.

4. Shingles and chickenpox (Varicella-zoster virus) — symptoms. University of Maryland Medical Center website. http://www.umm.edu/patiented/articles/how_serious_chickenpox_shingles_000082_4.htm. Accessed March 28, 2013.

5. Helgason S, Petursson G, Gudmundsson S, Sigurdsson JA. Prevalence of postherpetic neuralgia after a first episode of herpes zoster: prospective study with long term follow up. BMJ. 2000;321:794–6.

6. Dworkin RH, Schmader KE. The epidemiology and natural history of herpes zoster and postherpetic neuralgia. In: Watson CPN, ed. Herpes Zoster and Postherpetic Neuralgia. 2nd ed. New York, NY: Elsevier Press; 2001:39–64.

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8. Fauci AS, Braunwald E, Kasper D, et al. Harrison’s Manual of Medicine. 17th ed. Baltimore, MD: McGraw-Hill Professional; 2009:570-571.

9. Shingles: treatments and drugs. Mayo Clinic website. http://www.mayoclinic.com/health/shingles/ds00098/dsection=treatments-and-drugs. Accessed March 28, 2013.

10. Li Q, Chen N, Yang J, et al. Antiviral treatment for preventing postherpetic neuralgia. Cochrane Database Syst Rev. 2009;2:CD006866.

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12. Whitley RJ, Weiss H, Gnann JW Jr, et al. Acyclovir with and without prednisone for the treatment of herpes zoster. A randomized, placebo controlled trial. The National Institute of Allergy and Infectious Diseases Collaborative Antiviral Study Group. Ann Intern Med. 1996;125(5):376–383.

13. Chen N, Yang M, He L, Zhang D, Zhou M, Zhu C. Corticosteroids for preventing postherpetic neuralgia. Cochrane Database Syst Rev. 2010;12:CD005582.

14. Dworkin RH, Johnson RW, Breuer J, et al. Recommendations for the management of herpes zoster. Clin Infect Dis. 2007;44 Suppl 1:S1-S26.

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16. Raja SN, Haythornthwaite JA, Pappagallo M, et al. Opioids versus antidepressants in postherpetic neuralgia: a randomized, placebo-controlled trial. Neurology. 2002;59(7):1015–1021.

17. Wolff RF, Bala MM, Westwood M, Kessels AG, Kleijnen J. 5% lidocaine-medicated plaster vs other relevant interventions and placebo for post-herpetic neuralgia (PHN): a systematic review. Acta Neurol Scand. 2011;123(5):295-309.

18. Watson CP, Evans RJ, Watt VR. Post-herpetic neuralgia and topical capsaicin. Pain. 1988;33(3):333–340.

19. Kotani N, Kushikata T, Hashimoto H, et al. Intrathecal methylprednisolone for intractable postherpetic neuralgia. N Engl J Med. 2000;343(21):1514–1519.

20. Kikuchi A, Kotani N, Sato T, Takamura K, Sakai I, Matsuki A. Comparative therapeutic evaluation intrathecal versus epidural methylprednisolone for long Term analgesia in patients with intractable post herpetic neuralgia. Reg Anesth Pain Med. 1999;24:287–293.

21. Oxman MN, Levin MJ, Johnson GR, et al. (2005) A vaccine to prevent herpes zoster and postherpetic neuralgia in older adults. N Engl J Med. 2005;352(22):2271–2284.