Herpes Zoster Treatment & Management

Episodes of herpes zoster are generally self-limited and resolve without intervention. However, effective treatments do exist and can reduce the extent and duration of symptoms, and possibly the risk of chronic sequelae (ie, postherpetic neuralgia) as well. Treatment is of most benefit in those patient populations at risk for prolonged or severe symptoms, specifically, immunocompromised people and persons older than 50 years. The benefit of treating younger and healthier populations is unclear.

Uncomplicated zoster does not require inpatient care. Patients at high risk for disseminated zoster may benefit from intravenous (IV) acyclovir. Patients with disseminated zoster usually require admission for IV acyclovir. Inpatient care is also recommended for any patient demonstrating disseminated disease or ophthalmic or meningoencephalopathic involvement.

Go to Pediatric Herpes Zoster for complete information on this topic.

The majority of patients with acute herpes zoster experience pain. Primary treatments for acute zoster-associated pain include narcotic and non-narcotic analgesics (both systemic and topical), neuroactive agents, and anticonvulsant agents. While the efficacy of these treatments for general neuropathic pain has been well established, only a few of these modalities have been evaluated specifically for acute zoster-associated pain in controlled studies.

The oral narcotic oxycodone and the oral anticonvulsant gabapentin, as well as the topical analgesics aspirin and lidocaine, have all demonstrated the ability to reduce acute zoster-associated pain in double-blind, placebo-controlled studies.^{[18, 19, 20, 21, 22]} On the other hand, the oral anticonvulsant pregabalin failed to show any statistically significant effect in relieving acute zoster pain in a small double-blind, placebo-controlled study. Although, it should be noted this medication has demonstrated efficacy in treating the pain of postherpetic neuralgia in other controlled studies.^[23]

Antivirals and corticosteroids have also been shown to accelerate resolution of zoster-associated pain.^{[9, 16, 24, 25, 26, 27, 28, 29]}

Nonpharmacologic therapies for acute zoster-associated pain include sympathetic, intrathecal, and epidural nerve blocks and percutaneous electrical nerve stimulation. Although well-controlled studies are few, meta-analyses and clinical trials suggest these treatments are effective in treating acute zoster-associated pain.^{[1, 30, 31]}

The goals of antiviral therapy in herpes zoster are to decrease pain, inhibit viral replication and shedding, promote healing of skin lesions, and prevent or reduce the severity of postherpetic neuralgia. Three antiviral agents, acyclovir, valacyclovir, and famciclovir, have been approved for treatment of herpes zoster in the United States. The mechanism of action for all of these agents is the prevention of varicella-zoster virus (VZV) replication through inhibition of the viral DNA polymerase.^{[10, 32]}

Oral forms of all 3 agents have been shown in clinical trials to reduce viral shedding and accelerate resolution of symptoms, including pain, in uncomplicated herpes zoster. Some studies have suggested superiority of valacyclovir and famciclovir compared with acyclovir in terms of resolution of pain and acceleration of cutaneous healing. In addition, both valacyclovir and famciclovir have increased bioavailability over acyclovir and, as a result, require less frequent dosing.^{[9, 16, 24, 25, 26, 27]}

The controlled studies of antiviral use in herpes zoster have only evaluated the efficacy of initiation of therapy within 48-72 hours of rash onset, and they have demonstrated no loss of effectiveness when medications are started at any point during that period.^[32] Several observational studies have shown antiviral therapy capable of reducing zoster pain, even when started beyond the traditional 72-hour therapeutic window.^{[33, 34]} Thus, antiviral therapy should be considered for acute zoster treatment regimens, regardless of the time of presentation.

The duration of antiviral treatment in studies has varied from 7-21 days. Based on current literature, for immunocompetent patients, acyclovir for 7-10 days or a 7-day course of the newer agents is appropriate. Longer courses may be needed in immunocompromised patients.

The use of steroids in conjunction with an antiviral for uncomplicated herpes zoster is controversial.

The addition of oral corticosteroids has been evaluated in patients treated with acyclovir in 2 controlled studies.^{[28, 35]} Steroids were found to accelerate the resolution of acute neuritis and provide a clear improvement in quality-of-life measures in comparison to those patients treated with antivirals alone. The use of oral steroids had no effect on the development or duration of postherpetic neuralgia. Oral steroids have not been studied with valacyclovir or famciclovir, so the benefit is unknown.

Nonoral forms of adjunctive steroid therapy in acute herpes zoster have also been studied. A study involving a single epidural injection of steroids and local anesthetics given in conjunction with a standard regimen of oral antivirals and analgesics was found to modestly improve zoster-associated pain for 1 month over treatment without steroids. As above, no effect in preventing postherpetic neuralgia was noted.^[36]

In light of the potential adverse effects of and contraindications to corticosteroid use, current expert opinion suggests limiting their involvement to cases of moderate to severe zoster pain, or in which significant neurological symptoms (such as facial paralysis) or CNS involvement is present (and use of corticosteroids is not otherwise contraindicated).^[16]

The optimal duration of steroid therapy is not known. If prescribed, it seems reasonable for steroids to be used concurrently with antiviral therapy. The duration of steroid use should not extend beyond the period of antiviral therapy. Steroids should not be given alone (without antiviral therapy), owing to concern about the promotion of viral replication.

Individuals with altered cell-mediated immunity, due to an immunosuppressive condition (eg, HIV, cancer) or treatment (eg, extended corticosteroid use), are at increased risk for herpes zoster. Further, herpes zoster presentations in the immunocompromised population can be complicated by disseminated disease and visceral organ involvement.^{[16, 37]}

Antiviral therapy has been demonstrated to halt progression and dissemination of acute herpes zoster in immunocompromised patients, even when initiated more than 72 hours after rash onset.^[38] As such, current expert opinion recommends the use of antiviral therapy in all immunocompromised zoster patients who present prior to full crusting of all lesions.

Intravenous acyclovir remains the drug of choice for selected populations of immunocompromised patients, as follows:

• Patients with evidence of disseminated disease or visceral organ involvement
• Patients with ophthalmic involvement
• Patients with advanced HIV/AIDS with active opportunistic infections or prominent wasting
• Transplant recipients soon after transplantation or when being treated for rejection

Patients without such risk factors can be treated with oral antivirals. Data on adjunctive therapy with corticosteroids are lacking, and this therapy is not currently recommended. Antiviral therapy should be continued until resolution of all lesions.^[38]

Two trials comparing oral acyclovir to famciclovir or valacyclovir in patients with ophthalmic zoster showed comparable outcomes with any of the regimens.^{[39, 40]} Patients with diagnosed or suspected ophthalmic zoster should receive antivirals and be referred promptly to an ophthalmologist.

Go to Herpes Zoster Ophthalmicus for complete information on this topic.

Varicella-zoster immune globulin (VZIG) prevents or modifies clinical illness in susceptible persons who are exposed to varicella or zoster. It should be reserved for patients at risk for severe disease and complications, such as neonates and patients who are immunocompromised or pregnant.^[41]

Primary treatments for postherpetic neuralgia include neuroactive agents, such as tricyclic antidepressants; anticonvulsant agents, such as gabapentin and pregabalin; and narcotic and non-narcotic analgesics, both systemic, such as opioids, and topical, such as capsaicin. No standard treatment plans or protocols exist for treating the pain associated with postherpetic neuralgia. Consultation with pain specialists may be required.^{[2, 42, 43, 44]}

Placebo-controlled trials of various antiviral agents in treating herpes zoster have shown clear reductions in the intensity and duration of acute zoster-associated pain among treated populations. However, whether the use of antivirals in acute zoster reduces the incidence or duration of postherpetic neuralgia is less clear. Meta-analyses and studies have given conflicting results, and the subject is still under debate in the literature.^{[25, 26, 27, 45, 46, 47, 48]} Treating established postherpetic neuralgia with antivirals has not been shown to be beneficial.^[49]

The use of oral or epidural corticosteroids in conjunction with antiviral therapy has been found to be beneficial in treating moderate-to-severe acute zoster, but to have no effect on the development or duration of postherpetic neuralgia.^{[28, 29, 36]}

Intrathecal administration of corticosteroids has also been attempted. A trial involving a series of 4 intrathecal injections of methylprednisolone and lidocaine in patients with established postherpetic neuralgia demonstrated a significant and persistent reduction in pain among corticosteroid-treated patients when compared with untreated patients or those treated with intrathecal lidocaine alone.^[50] However, as these results have not received independent confirmation, and there are significant safety concerns with administration of intrathecal steroids, this treatment modality is not recommended.

Surgical care is not generally indicated for the treatment of herpes zoster. Rhizotomy (surgical separation of pain fibers) may be considered in cases of extreme, intractable pain.

Herpes zoster results from reactivation of a previous infection with varicella-zoster virus (VZV) due to altered cell-mediated immunity in the patient. As such, prevention of herpes zoster can be achieved by either avoiding initial infection, or, post infection, maintaining sufficient cell-mediated immunity against VZV to suppress reactivation of the virus. Currently, multiple vaccines are approved and used in the United States that address each of these pathways to prevention.^{[12, 41]}

In regard to prevention of initial infection, multiple live, attenuated VZV vaccines, based on the Oka vaccine strain have been used for routine childhood immunization in the United States since 1995. This has led to a remarkable reduction in the incidence of primary varicella infection. Further, vaccinated children have demonstrated lower rates of herpes zoster than those infected with wild-type VZV.^[51] However, the effect of childhood vaccination on the incidence of herpes zoster in adult populations is still unclear.

Other methods of prevention of initial infection include contact and respiratory isolation of infected patients until full crusting of lesions is achieved, as well as post-exposure prophylaxis in select populations with varicella-zoster immune globulin (VZIG).

Another live, attenuated varicella-zoster vaccine (Zostavax) has been approved and used in the United States since 2006 for the prevention of herpes zoster and its complications in older adults. In a large, placebo-controlled trial, this vaccine demonstrated a reduction in the incidence of acute herpes zoster by more than 50% and a reduction in the incidence of postherpetic neuralgia by 67% in the treated population. The Advisory Committee on Immunization Practices (ACIP) has recommended that nonimmunocompromised, nonpregnant adults aged 60 years or older receive the vaccine, regardless of zoster history.^{[12, 52]}

In March 2011, the Food and Drug Administration (FDA) lowered the approved age for use of Zostavax to 50-59 years. Zostavax was already approved for use in individuals aged 60 years or older. Annually, in the United States, shingles affects approximately 200,000 healthy people aged 50-59 years. Approval was based on a multicenter study, the Zostavax Efficacy and Safety Trial (ZEST).^[53] The trial was conducted in the United States and 4 other countries in 22,439 people aged 50-59 years. Participants were randomized in a 1:1 ratio to receive either Zostavax or placebo. Participants were monitored for at least 1 year to see if shingles developed. Compared with placebo, Zostavax significantly reduced the risk of developing zoster by approximately 70%.

No specific dietary changes are recommended.

Patients with shingles can perform activities as tolerated.

During the acute phase, patients should be counseled to avoid direct skin contact with immunocompromised persons, pregnant women, and individuals with no history of chickenpox infection. If the patient is hospitalized, contact isolation measures should be considered.

Patients with disseminated disease or severe immunosuppression or who are unresponsive to therapy should be transferred to a higher level of care.

If consultation is required but not available at the initial facility, patients should be transferred to a tertiary care medical center.

Consultation is not generally needed in cases of uncomplicated zoster. Consultation with an infectious disease or other appropriate specialist should be considered in cases of disseminated zoster, zoster with visceral involvement, or zoster in an immunocompromised patient. Patients in whom ophthalmic zoster is present or cannot be confidently ruled out should usually be referred to an ophthalmologist.

Follow up until symptoms resolve.

Inform patients about the natural progression of herpes zoster and its potential complications.

Pain relief should be a primary concern.

Patients who develop postherpetic neuralgia should be seen regularly and should receive emotional support in addition to medical therapy.