Annals of Long-Term Care: Clinical Care and Aging. 2014;22(3):25-27.
Herpes zoster, also known as shingles, develops when the varicella zoster virus (VZV) is reactivated in the dorsal ganglia and migrates to adjacent sensory dermatomes, causing a rash and pain. An estimated 90% of adults in the United States carry VZV, and the risk of reactivation increases with age. Vaccination among older adults is key to preventing serious VZV-related complications, such as postherpetic neuralgia (PHN). Many older adults who neglect getting the vaccine may eventually become institutionalized for these complications, compromising patient quality of life and increasing healthcare burden and costs.
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Annals of Long-Term Care® (ALTC) had the opportunity to discuss shingles with geriatric pharmacist Kenneth Cohen, PharmD, PhD, CGP, associate professor, Department of Pharmacy and Health Outcomes, Touro College of Pharmacy, New York, NY. ALTC asked him to review the evidence-based recommendations for vaccination and management of shingles-related pain in complex older patients, as well as discuss some of the issues under investigation, such as management of secondary infections and use of novel treatments.
ALTC: What are the current evidence-based recommendations for shingles vaccination?
Cohen: A live attenuated VZV vaccine (Zostavax) is available to prevent reactivation of VZV in adults older than 60 years. Oxman and colleagues demonstrated that the vaccine significantly reduced the incidence of herpes zoster, the burden of the illness on quality of life, and incidence of associated PHN.
The current recommendations for administration of herpes zoster vaccine published by the Centers for Disease Control and Prevention Advisory Committee on Immunization Practices advise routine vaccination with one dose of zoster vaccine in individuals older than 60 years. Individuals reporting a previous episode of zoster can be vaccinated if there are no contraindications. It is not necessary to obtain a history of chickenpox or to test for varicella immunity.
It is interesting to note that the herpes zoster vaccination is not recommended for individuals of any age who have received the varicella vaccine; however, since vaccination against varicella did not begin until 1995 in the United States, the geriatric population is not impacted. Patients taking antivirals, such as acyclovir, famciclovir, or valacyclovir, should discontinue these medications at least 24 hours prior to administration of zoster vaccine, if possible, and should not be restarted until at least 14 days after the vaccination. These agents may interfere with replication of the live VZV-based zoster vaccine.
What are the major goals and considerations for treating shingles in older adults?
Goals of treatment include quicker healing of skin lesions, reducing the risk of complications, and decreasing the risk of viral dissemination. These goals are best achieved through the use of antiviral drugs.
Antivirals must be started immediately, and any prescribed ophthalmic steroids should be reduced. If ophthalmic symptoms occur, an immediate referral to an ophthalmologist is key. It is also desirable to limit the severity and duration of acute and chronic pain and to differentiate therapy between the two.
In the elderly, you need to monitor for many different complications. In the “walking well” elderly patient, it is not uncommon to see constipation, confusion, and instability secondary to narcotic analgesic use. Also, monitoring for anticholinergic effects of tricyclic antidepressants (TCAs) is important, as is monitoring for any interactions with patients’ regular medication regimens. Adverse effects may interfere with their normal activities of daily living and result in their requiring a higher level of care.
For the long-term care patient, participation in regular care programs could be disrupted, and there could be an increase in instability—including vertigo in both the prodromal stage and as a long-term complication—resulting in increased risk for falls. Careful titration of pain medications is important to balance the need for analgesia with the risks of adverse effects, such as lethargy and constipation, from these drugs.
What are the considerations before prescribing an oral antiviral to an older patient?
The oral antiviral agents acyclovir, valacyclovir, and famciclovir have been shown to reduce the severity and duration of VZV infection. These agents are administered systemically. Topical antiviral agents are ineffective and are not recommended.
Early antiviral intervention provides a greater likelihood of a clinical response. Most trials enrolled patients within 72 hours of the onset of symptoms, but acyclovir is most effective when administered within 48 hours of the onset of the VZV rash.
Acyclovir is considered the mainstay of treatment; however, its clinical use in the elderly is limited by its multiple dosing schedule (five times daily) and less favorable pharmacokinetic profile when compared with valacyclovir and famciclovir. Valacyclovir is the oral prodrug of acyclovir and is only required to be administered three times daily. Studies indicate that valacyclovir accelerated the resolution of herpes zoster–associated pain when compared with acyclovir. However, the rash subsided at the same rate.
Famciclovir has a longer half-life than acyclovir and allows three times daily dosing, but the drugs are equivalent in efficacy and speed of resolution. Foscarnet is useful in acyclovir-resistant viruses. It appears to be useful in the HIV population but has toxic effects on the kidneys and gastrointestinal tract.
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How is chronic shingles pain best managed in older adults?
If the pain persists for more than 3 weeks or further related complications develop, such as allodynia (ie, pain initiated by normally non-noxious stimulus, such as dragging clothing across the skin), consider adding TCAs, such as amitriptyline and nortriptyline, or gabapentin. It is important to continue long-term support and monitoring for this population to ensure preparation and treatment for possible complications.
Therapy for chronic pain should be individualized for each patient. To treat pain and to provide effective treatment for PHN, it is often necessary to administer drug combinations for long-term periods. Acetaminophen and nonsteroidal anti-inflammatory drugs (NSAIDS), including aspirin, may provide some benefit for mild to moderate PHN. For optimal pain control, these medications must be administered continuously rather than as needed.
Controlled studies indicate that opiates may be effective in chronic neuropathic pain, such as PHN. Patients with moderate to severe PHN and related sleep disturbances may benefit from the use of opiates as a part of their treatment plan. The dose of opiates must be titrated to achieve optimal pain relief while limiting side effects. Utilizing a pain relief measurement instrument and a treatment plan with monitoring for side effects is beneficial. The use of a prophylactic laxative is important to prevent constipation. One should consider the use of a controlled-release opiate that could be augmented with short-acting analgesics to control breakthrough pain. Tramadol, a centrally acting opioid, is useful in treatment of polyneuropathy.
TCAs have been found helpful in the treatment of neuropathic pain. Amitryptilyine is usually the first-line drug, however, nortriptyline should be considered because of fewer side effects. The anticholinergic side effects associated with TCAs must be closely monitored. Anticonvulsants, such as gabapentin and pregabalin, are also useful in PHN treatment. Topical therapy with lidocaine and capsaicin is often useful because of their local action and fewer systemic side effects.
Monitoring for adverse effects in the long-term care population centers around those directly associated with analgesics, such as constipation, urinary retention, dry mouth, lethargy, and confusion. Indirectly, these effects may reduce patients’ abilities to participate in cognitive and physical activities. Worsening of underlying chronic conditions may be noted, and care must be taken when reviewing regular drug regimens for these individuals.
How is acute shingles pain best managed in older adults?
Although chronic pain control is emphasized, the treatment of acute pain of herpes zoster has a profound effect on health-related quality of life. The prompt treatment with antiviral agents within 72 hours will reduce the severity of acute pain. Acute pain should also be treated starting with acetaminophen and increasing the analgesic effect as needed to include codeine, oxycodone, and morphine, depending on the effectiveness of treatment, severity of pain, and side effects of the analgesics. Oral analgesics should be used to treat ocular involvement, but topical ocular anesthetics should be avoided.
Elderly patients may not be able to tolerate high-dose opioids because of the side effects. In these situations, the balance between pain relief using a tolerated dose of analgesics, along with combinations of NSAIDs and treatment of common side effects, should be attempted. One has to be cognizant of the other medications the patient may be taking and potential interactions of these drugs.
The use of corticosteroids to treat the acute pain of herpes zoster is controversial. They may offer slight benefit, but the risks associated with systemic corticosteroid use should be considered. If corticosteroids are used, they should be administered in combination with antiviral agents. Adverse effects associated with both the short-term and long-term use of corticosteroids (eg, glucose metabolism, psychosis, and other related effects) should be taken into consideration before prescribing.
What are some of the limitations of existing therapies for herpes zoster?
Multiple daily dosing is a major limitation of the oral antiviral agents that are currently available. The risk of patient nonadherence increases with the more times per day a drug is dosed. Adherence to an antiviral regimen is more of a concern in the community setting, where a patient is self-administering medications, because nonadherence may increase risk of PHN. Because of the limitations of existing therapies, prevention moves to the forefront. Although expensive ($200+ per dose), vaccination has the potential to reduce risk and preserve the quality of life of many geriatric patients.
Are there any promising new therapies for treating shingles?
The US Food and Drug Administration has approved Qutenza (capsaicin 8%) patch for relief of PHN pain. The patch must be applied by a healthcare professional, as patch placement may be quite painful. Local topical anesthetics, ice, and pain relievers may be required to treat the pain associated with the patch placement. The patient must be monitored for hypertension for 1 hour after the patch is placed.
FV 100, also known as CF1743, is a novel oral nucleoside with antiviral activity, which may be effective against VZV. A phase 2 study was performed comparing this drug with valacyclovir. CF1743 showed up favorably in reducing the severity of shingles-associated pain during the course of the condition and decreased the development of PHN.
Brivudin (bromovinyl deoxyuridine) is a highly potent thymidine nucleoside analogue with selective activity against herpes simplex virus-1 and VZV. The mechanism of action of bromovinyl deoxyuridine appears to be through the inhibition of the viral DNA polymerase. The drug is well-absorbed after oral administration and has a favorable pharmacokinetic profile that permits once-daily dosing.
Are there any alternative therapies that have been shown to reduce shingles-related pain in older adults?
Proteolytic enzymes, which are found in foods like papaya and pineapple, are naturally produced in the pancreas to digest dietary protein. Supplements derived from papaya (ie, papain) and from pineapple (ie, bromelain) are marketed as digestive enzyme supplements. In one small study, 100 people took proteolytic enzymes and 100 people took acyclovir. Both groups experienced similar pain relief and skin improvement. The group taking enzymes had significantly fewer side effects. Potential interactions occur between proteolytic enzymes when anticoagulants are used concomitantly.
Lemon balm, licorice, and mint tea (as a drinkable tea or as a topical therapy) may provide some symptomatic relief. Red pepper (with the active ingredient capsaicin) has become a more conventional treatment for pain associated with VZV. Echinacea, taken in high doses, has been used to help control shingles pain. In addition, it has been shown to boost the immune system and may prevent a herpes zoster outbreak.
St. John’s wort, an herbal supplement commonly used for depression, is also helpful in alleviating some of the painful symptoms of herpes zoster. Vervain (verbena), lavender, chamomile, and marjoram also help to relieve inflammation.
Tai chi may improve immune function and health in older adults at risk for shingles. Acupuncture, neural therapy, and meditation may also reduce pain symptoms when used in conjunction with conventional medicine.
What are some other complications associated with herpes zoster in older adults?
Ocular involvement may occur and may be predicted by the Hutchinson’s sign (ie, lesion on the tip of the nose). Herpes zoster ophthalmicus is caused by virus reactivation in the ophthalmic division of the trigeminal nerve and is found in increasing incidence with age. Edema and inflammation of the outer eyelids and the mucus layer are also present. More than half of these patients go on to develop keratitis (corneal inflammation). Inflammation of the iris (uveitis) can also occur. Mild uveitis can elevate intraocular pressure, resulting in glaucoma and cataracts.
Other risks include zoster oticus, a dermatological eruption in the external auditory canal. The combination of facial muscular weakness and zoster oticus is referred to as Ramsay Hunt syndrome. Additionally, further involvement of the cranial nerves can lead to tinnitus, hearing loss, and vertigo, which would be accompanied by nausea, vomiting, and nystagmus (involuntary eye movements).
Inflammation of the cerebral arteries, potentially resulting in stroke, may be a long-term effect of VZV infection, particularly in older adults. This may be due to the infection, its associated immunological reaction, or a post-infection inflammatory process.
What should healthcare providers understand about the risks and complications of secondary VZV infection?
There is a common belief that if a person comes into contact with a patient who has shingles, he or she can get shingles. Although the virus is shedding from open lesions, the only people susceptible to infection are those who have no prior history of primary varicella infection or no varicella vaccination.
Secondary infections can occur if the blisters associated with the rash are not kept clean. These infections are usually caused by Group A Streptococcus or Staphylococcus bacteria. Physicians and healthcare care providers caring for long-term care residents must be cognizant of antiseptic practices with patients in these circumstances, especially when lesions are in areas that are difficult to keep clean.
The incidence of secondary VZV infection is higher in patients with HIV infection than in the overall population. These immunocompromised patients may experience an extensive visceral dissemination of the VZV that affects the lungs, liver, and brain.
There is an association between VZV and Guillain-Barré syndrome, which is typically associated with weakness in the extremities, but may also involve the face. In severe cases, there can be pain and eventual paralysis that may require hospitalization for monitoring and support. The condition typically resolves on its own in a few weeks.
Bell’s palsy, a partial paralysis involving the face, may be associated with a reactivation of VZV, even if no rash is noted. This may require separate treatment to avoid permanent facial paralysis and other complications associated with paralysis of the eyelids and ocular effects.
Jerry Frank, MD, clinical assistant professor, Department of Family Medicine, SUNY Stony Brook School of Medicine, Stony Brook, NY, and Rebecca L. Salbu, PharmD, CGP, associate professor, Touro College of Pharmacy, New York, NY, contributed to the responses.