Herpes Zoster: Treatment Modalities and Prevention with Zoster Vaccine

Herpes zoster (HZ), or shingles, is a neurocutaneous viral disease. HZ affects ~1 million persons in the United States each year and millions of older adults worldwide.^1-3 Although HZ can occur at any age, it most often occurs in persons aged 50-70 years.⁴ The lifetime incidence of HZ—about 20% in the general population—may rise to 50% among persons aged 85 or older.⁵ Decreased immune response is thought to render seniors more susceptible to HZ.⁶ The rate of HZ is also higher in immunocompromised persons. The most common and debilitating complication of HZ is postherpetic neuralgia (PHN). As with HZ, the most important feature of PHN, from an epidemiologic standpoint, is its marked increase in incidence and severity with aging.⁵

Herpes zoster is caused by a reactivation of the varicella-zoster virus (VZV). That is, HZ occurs in persons who were previously infected with VZV and then experienced a case of varicella (chickenpox). Once chickenpox resolves, the VZV travels up a spinal nerve and resides in the dorsal root ganglion, the area of the nerve near the spinal cord.4 The typical blistering rash of HZ can appear anywhere on the skin lying over the nerve(s) affected by the virus.⁴ This area over a nerve is called a dermatome (see Resources at end of article). 

The pattern formed by HZ on the skin is explained by the arrangement of the spinal nerves and dermatomes, with the rash appearing within an affected dermatome or two. The primary lesion is characterized by a unilateral eruption of multiple groups of vesicles, or crusted lesions. A prodrome—signs and symptoms (S/S) that often precede the appearance of the rash by several days—consists of fever, malaise, headache, and localized pain and paresthesias lasting 1-4 days.⁷ Symptoms affecting the dermatome range from superficial itching, tingling, or burning to severe, deep, boring or lancinating pain.⁷ Pain associated with the prodrome may be mistaken for trigeminal neuralgia, glaucoma, myocardial infarction, pleurisy, appendicitis, cholecystitis, renal colic, collapsed intervertebral disk, or unappreciated trauma.⁵ 

Herpes zoster in children usually occurs as a result of varicella exposure in utero; the fetus becomes infected and a latent infection is established.^8,9 Because HZ represents reactivation of a latent virus, HZ per se cannot be transmitted from one person to another. However, a person without previous exposure to VZV is at risk for developing chickenpox if exposed to someone with active HZ.^1,10

Postherpetic Neuralgia—The most common chronic, debilitating complication of HZ is PHN, which is defined as pain persisting >30 days or continuing even after the HZ rash has healed. A more common benchmark used in practice is pain continuing after 90 days.¹ Some researchers define PHN as pain persisting or appearing >90 days after HZ rash onset, which is more clearly definable than rash healing.² 

Postherpetic neuralgia occurs in 10%-20% of patients with HZ, and in 50% of those who develop HZ after age 60.^11,12 Risk factors for PHN include older age, severe HZ rash, severe acute pain, and presence of a prodrome.^1,5,13,14 Clinical trials have shown that a severe rash (>50 lesions [papules, vesicles, or crusted vesicles]), older age, and severe pain at rash onset are important risk factors for prolonged pain.¹⁵ 

Patients describe the quality of PHN pain as burning, throbbing, stabbing, shooting, sharp, aching, or gnawing. Pain severity varies from mild to excruciating, and its frequency ranges from intermittent to constant. Contact with trivial stimuli such as the wind or bedsheets can provoke pain in some patients. The chronic pain can cause mood disturbances and insomnia, interfere with work and activities of daily living, and compromise quality of life, ultimately leading to social withdrawal and depression.¹⁶

Other Complications—HZ is associated with many other complications, some lasting months to years. Herpes zoster ophthalmicus, or ophthalmic HZ, occurs in 10%-25% of patients.¹⁶ Palsies of the extraocular muscles can also occur, causing prolonged or permanent sequelae such as pain, facial scarring, and vision loss. The side and tip of the nose may be affected in 30%-40% of cases of ophthalmic HZ because of involvement of the nasociliary branch of the ophthalmic nerve;⁵ NPs need to search for eye involvement whenever S/S affect the tip of the nose. Ischemic stroke, occurring weeks to months after rash onset, is associated with ophthalmic HZ secondary to carotid arteritis.⁵ Twersky and Schmader⁵ offer this clinical pearl: When Bell’s palsy presents with pain, think HZ; if a patient presents with painful facial paresis, look in the ipsilateral ear for vesicles (Ramsey Hunt syndrome).

Because 5% of patients with HZ develop bacterial superinfection of skin lesions,¹ patients are instructed to keep the affected area clean and to avoid scratching. Bacterial superinfections, as well as neurologic complications, are more likely to occur in immunocompromised patients.16 Rare neurologic complications of HZ include myelitis, aseptic meningitis, and meningoencephalitis.¹⁶

In patients with HZ, the goal is to treat the acute viral infection to facilitate rash resolution and relieve pain. Therapy with antivirals, oral corticosteroids, and analgesics is implemented to achieve this goal. 

Nonpharmacologic Management—NPs instruct patients to keep the HZ rash clean and dry. Strategies to reduce S/S and hasten vesicle drying include:^5,17 
 

Education (see Resources at end of article), adequate nutrition, social support, and an attitude of concern are all important elements of the treatment plan for patients experiencing an HZ attack.     

Pharmacologic Management—

Antiviral therapy. The goal of first-line drug therapy with antivirals is inhibiting VZV replication.⁵ Clinical trial data have shown that all three available antivirals—acyclovir, famciclovir, and valacyclovir—are effective (see Table).⁵ Factors such as dosing frequency and cost are considered when individualizing therapy.⁵ Valacyclovir, a prodrug of acyclovir, is dosed less frequently (q8h vs q4h); famciclovir is also administered every 8 hours. Initiating antiviral therapy within 72 hours of HZ onset has been shown to significantly shorten the duration of acute pain, virus shedding, rash, and acute and late-onset complications.¹⁶ Treatment may be initiated beyond the 72-hour threshold in patients who continue to have vesicle formation and in those with ophthalmic HZ.⁵ 

Although no antiviral has been shown to prevent development of PHN, both valacyclovir and famciclovir have been shown to lessen the incidence and severity of PHN.¹⁶ The most common adverse effects of the antivirals, which are safe and generally well tolerated in older adults, are nausea, vomiting, diarrhea, and headache.⁵

Analgesics. Systemic analgesics are often necessary to treat HZ-associated acute pain.¹⁷ Whereas mild pain may be managed with acetaminophen or a nonsteroidal anti-inflammatory drug (NSAID), an opioid (eg, hydrocodone, oxycodone) may be required to treat moderate to severe pain.⁵ NPs must avoid the tendency to undertreat HZ pain. Side effects of opioids include nausea, vomiting, constipation (which is anticipated and managed with laxative/stool softener therapy), dizziness, headache, sedation, and respiratory depression; falls and confusion are of particular concern in the elderly.^5,17 Warnings regarding NSAID use include (1) increased risk for adverse cardiovascular (CV) events, including myocardial infarction and stroke; and (2) potential increased risk for gastrointestinal irritation, inflammation, ulceration, bleeding, and perforation.   

Corticosteroids. Controversy exists regarding the use of corticosteroids in treating HZ. When prescribed for their anti-inflammatory effects in patients with HZ, corticosteroids are to be used in conjunction with antiviral agents.⁵ Corticosteroids are used to treat facial paralysis and cranial polyneuritis, and to ease moderate to severe pain unrelieved by antivirals and analgesics.⁵ In one clinical trial, prednisone for HZ (unlabeled use) was dosed at 60 mg/day for 7 days, followed by 30 mg/day for 7 days and then 15 mg/day for 7 days, which facilitated sleep, return to routine activities, and cessation of analgesic therapy.^18,19 Randomized controlled trials have shown that corticosteroids, when compared with acyclovir or placebo, do not prevent PHN.5 Corticosteroids are used with caution in the elderly, especially those with diabetes, hypertension, gastritis, osteoporosis, cognitive impairment, or psychosis.5,19 Common side effects of corticosteroids include nausea, vomiting, dyspepsia, and edema.^5,19

Adjuvant agents. When antivirals in combination with oral analgesics and/or corticosteroids fail to alleviate moderate to severe acute HZ pain, these adjuvant agents are considered:⁵

Treatment for Postherpetic Neuralgia

The objective of PHN treatment is relief of pain; achieving this goal is elusive in many cases. Because of its efficacy and safety profile, the lidocaine 5% patch is recommended as a first-line therapy.²⁰ Pain management may also involve use of agents such as topical analgesics (eg, topical capsaicin), TCAs (nortriptyline and desipramine are preferred over amitriptyline because of their more favorable side-effect profile), anticonvulsants (eg, gabapentin, pregabalin), opioids (eg, oxycodone), or opioid-like analgesics (eg, tramadol). Other treatments include noninvasive therapies (eg, transcutaneous electrical nerve stimulation) and invasive therapies (eg, neural blockade, spinal cord stimulation, central nervous system drug delivery).¹⁶

The premise for the usefulness of an HZ vaccine is that if elderly patients boost their immune response to VZV, fewer of them will develop HZ.³ Research has shown that seniors who receive a zoster vaccine may also reduce their chance of developing PHN.21 Zoster Vaccine Live (Zostavax®) was approved by the FDA in 2006 and is indicated for prevention of HZ in persons aged ≥50 years.²²

According to the Shingles Prevention Study, the zoster vaccine, relative to placebo, reduced HZ incidence by 64% in persons aged 60-69, by 41% in those aged 70-79, and by 18% in those aged ≥80.²² Overall, the zoster vaccine reduced HZ risk by 51% and PHN risk by 67%.²³ Although the duration of protection against HZ beyond 4 years post-vaccination is unknown, research suggests that the zoster vaccine is effective for ≥6 years and may last much longer.²³ Studies are under way to pinpoint the duration of protection and to define the need for revaccination.^22,23

Results of a recent study suggested that rates of HZ recurrence are similar to those of first HZ occurrence in immunocompetent persons.²⁴ This finding suggests that recurrence is sufficiently common to warrant investigation of vaccine prevention in this group.²⁴ According to the CDC, persons who have had HZ in the past can still receive the zoster vaccine to help prevent future occurrences of the disease; there is no specific wait time after having HZ before receiving the vaccine. However, one should be certain that the HZ rash has disappeared before getting vaccinated.²³

A single 0.65-mL dose of zoster vaccine is administered subcutaneously (SC) in the deltoid region of the upper arm. This vaccine has been manufactured for SC use only; it is not injected intravascularly or intramuscularly.  

The most frequent adverse reactions, reported in ≥1% of study participants, were headache and injection-site reactions (redness, pain, itching, swelling, warmth, or bruising).²² Serious adverse events included asthma exacerbation, polymyalgia rheumatica, and CV events (congestive heart failure, pulmonary edema).²² Persons who develop S/S of an allergic reaction, such as difficulty breathing or swallowing, must contact their healthcare practitioner (HCP) immediately or seek emergency care.²² 

Persons allergic to gelatin or neomycin, two constituents of the zoster vaccine, should not receive the vaccine. This live, attenuated VZV vaccine can cause infection and should not be administered to anyone with an immune system weakened by disease (eg, HIV/AIDS, leukemia, lymphoma, malignant neoplasms affecting the bone marrow or lymphatic system) or drug therapy (eg, use of high-dose corticosteroids).²² The zoster vaccine is not administered to persons with acute illness, those with active untreated tuberculosis, or pregnant women.22 Also, pregnancy should be avoided for 3 months following administration of the vaccine.²² The zoster vaccine should not be given at the same time as the pneumococcal vaccine polyvalent (Pneumovax®²³).²²

Because the zoster vaccine contains weakened VZV, patients are instructed to tell their HCP if they will be in close contact with newborn infants, someone who may be pregnant and has not had chickenpox or been vaccinated against chickenpox, or someone who has problems with their immune system. HCPs and patients are encouraged to report adverse effects of vaccines to the FDA at www.fda.gov/medwatch or by calling 1-800-FDA-1088.

According to the CDC, all Medicare Part D plans cover the HZ vaccine; the amount of cost-sharing (by the patient) for vaccination varies. Medicare Part B does not cover the HZ vaccine.²³ Persons with private insurance or Medicaid may or may not be covered for the vaccine. NPs need to advise patients to contact their insurer to find out. 

In July 2009, the FDA approved a change to the prescribing information (PI) for Zoster Vaccine Live. This change defines specific conditions under which the vaccine can be stored at refrigerator temperature in connection with a change to expiry dating for the product. The HOW SUPPLIED/STORAGE AND HANDLING section of the PI was revised (see Resources at end of article). 

Every year, ~1 million persons in the United States develop HZ. Although antivirals have improved management of this disease, many patients still experience pain complications, most commonly PHN. NPs are well positioned to encourage the CDC-recommended zoster vaccine for appropriate patients. 

Dr. Zagaria is a Senior Care Consultant Pharmacist and President of MZ Associates, Inc., in Norwich, NY (www.mzassociatesinc.com). 

References

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22. Zostavax (Zoster Vaccine Live) Full Prescribing Information. Whitehouse Station, NJ: Merck & Co, Inc; March 2011.    
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