Varicella-zoster virus (VZV) is the agent causing varicella, otherwise known as chickenpox, the common childhood infection. Following resolution of chickenpox, VZV lies dormant in the spinal dorsal root ganglia until a decrease in cellular immunity triggers the reactivation of the virus, resulting in herpes zoster, otherwise known as shingles. (See Etiology.)
Shingles is a syndrome characterized by a painful, vesicular rash that is usually restricted to a unilateral dermatomal distribution. At times, especially in the immunosuppressed patient, the infection may spread and produce severe systemic illness, with involvement of multiple visceral organs and multiple dermatomes (disseminated zoster). The shingles-associated rash is seen in the images below. (See Etiology and Pathophysiology.)
View Image | Herpes zoster on the neck. |
View Image | Herpes zoster on the lateral part of the abdomen. |
Shingles usually has a benign course, but complications may occur, ranging from mild to life threatening. In properly selected patients, early treatment with antivirals and corticosteroids has been shown to decrease the duration of symptoms and to possibly prevent or ameliorate some complications. (See Pathophysiology and Treatment and Management.)
The clinical manifestations of herpes zoster can be divided into the preeruptive phase (preherpetic neuralgia), acute eruptive phase, and chronic phase (postherpetic neuralgia). (See Etiology.)
Go to Pediatric Herpes Zoster for more complete information on this topic.
This phase is characterized by unusual skin sensations or pain within the affected dermatome that heralds the onset of lesions by 48-72 hours.
During this time, patients may also experience other symptoms, such as malaise, myalgia, headache, photophobia, and, uncommonly, fever.
This phase is marked by the emergence of vesicular eruptions. As in the preeruptive phase, patients may also experience such symptoms as malaise, myalgia, headache, and fever. Lesions begin as erythematous macules and papules (seen in the image below) that quickly develop into vesicles. New lesions tend to form over a period of 3-5 days, sometimes coalescing to form bullae.
View Image | Maculopapular rash due to herpes zoster in a child with a history of leukemia. Courtesy of the CDC. |
After they form vesicles, lesions progress through stages in which they rupture, release their contents, ulcerate, and finally crust over and become dry.
Almost all adult patients experience pain (ie, acute neuritis) during the eruptive phase. A few experience severe pain without any evidence of a vesicular eruption (ie, zoster sine herpete), and a small number of patients have a characteristic eruption but do not experience pain.
Symptoms and lesions in the eruptive phase tend to resolve over 10-15 days. However, lesions may require up to a month to completely heal, and the associated pain may become chronic.
Patients are infectious until the lesions have dried. Anyone who has not previously had varicella is at risk of acquiring this readily transmitted virus. Pregnant women and immunosuppressed patients have the highest risk of serious sequelae.
Postherpetic neuralgia is persistent or recurring pain lasting 30 or more days after the acute infection or after all lesions have crusted. It is the most frequent complication of herpes zoster, observed in 9-45% of all cases of zoster.[1]
Most people report a deep burning or aching pain, paresthesia, dysesthesia, hyperesthesia, or electric shock–like pains. The pain can be severe and incapacitating.
Resolution of the pain may require an extended period of time. Pain lasting longer than 12 months has been described in nearly 50% of patients older than 70 years.[2]
The prevalence of postherpetic neuralgia in herpes zoster cases increases with age, with a 14.7-fold higher prevalence in patients older than 50 years compared with their younger counterparts.[3]
VZV reactivation causes inflammation in the dorsal root ganglion, accompanied by hemorrhagic necrosis of nerve cells. The result is neuronal loss and fibrosis. The distribution of the rash corresponds to the sensory fields of the infected neurons within a specific ganglion. The anatomic location of the involved dermatome often determines the specific manifestations (eg, herpes zoster ophthalmicus [HZO], causing ocular complications, when the trigeminal ganglion is involved).
While zoster is classically described in sensory (dorsal root) ganglia, it can spread to affect any portion of the nervous system.
Involvement of the anterior horn cells can produce muscular weakness, cranial nerve palsies, diaphragmatic paralysis, neurogenic bladder, and colon pseudo-obstruction.
Wider involvement of the spinal cord can produce Guillain-Barré syndrome, transverse myelitis, and myositis.
In severely ill or immunocompromised patients, general central nervous system (CNS) involvement can be observed in the form of meningoencephalitis or encephalitis. Such presentations are indistinguishable from other forms of meningoencephalitis, although other evidence of acute zoster usually is present.[4] Cerebrospinal fluid (CSF) studies frequently reveal pleocytosis without elevated protein. These infections can be life threatening.
This is potentially the most devastating form of acute zoster.
Herpes zoster ophthalmicus (HZO) results from the reactivation of varicella-zoster virus (VZV) in the trigeminal (fifth cranial) nerve. Any branch of the nerve may be affected, although the frontal branch within the first division of the trigeminal nerve is most commonly involved. This branch innervates nearly all of the ocular and periocular structures.
Polymerase chain reaction (PCR) nerve studies have shown latent trigeminal VZV in up to 87% of patients.[5] Clinical disease has been reported in as few as 8% and as many as 56% of patients in studies focused on ophthalmic involvement.[6]
Also known as herpes zoster oticus, geniculate neuralgia, or herpes zoster auricularis, Ramsay-Hunt syndrome is caused by VZV reactivation involving the facial and auditory nerves. Go to Herpes Zoster Oticus for more complete information on this topic.
Vesicular eruptions may manifest on the pinna, tragus, or tympanic membrane or in the auditory canal, as well as anywhere in the facial nerve distribution.
The patient may experience hearing impairment, nystagmus, vertigo, or facial nerve palsy (mimicking Bell palsy).[7] Patients may lose taste sensation in the anterior two thirds of the tongue.[7]
Ramsay Hunt syndrome may go unnoticed and be difficult to diagnose, especially in elderly patients.
VZV is an enveloped, double-stranded deoxyribonucleic acid (DNA) virus belonging to the Herpesviridae family. In humans, primary infection with VZV occurs when the virus comes into contact with the mucosa of the respiratory tract or conjunctiva. From these sites, it is distributed throughout the body via mononuclear cells in the blood stream. In tissue, VZV spreads from cell to cell via direct contact to produce its effects.
After primary infection, the virus migrates along sensory nerve fibers to the satellite cells of dorsal root ganglia where it becomes dormant. This dormancy may be permanent, or the virus may become reactivated by conditions of decreased cellular immunity, resulting in herpes zoster.
Exactly why VZV reactivates from latency is not fully understood. However, cell-mediated, VZV-specific immunity has been shown to be a major factor in determining reactivation of VZV. Cell-mediated, VZV-specific immunity decreases with age and in patients with certain malignancies. These groups have much higher rates of herpes zoster. Patients with hypogammaglobulinemia (a defect of humoral, but not cellular, immunity) do not have a higher rate of zoster. This supports the concept of an important role for cell-mediated immunity in the pathogenesis of VZV infection.
No identifiable environmental, genetic, or social risk factors exist for the development of the reactivation of VZV.
Approximately 95% of adults, and 99.5% of adults aged 40 years or older, in the United States have antibodies to VZV and are vulnerable to reactivation of infection.[8] A person of any age with a prior varicella infection may develop zoster, but incidence increases with advancing age due to declining immunity. Approximately 4% of patients with zoster will develop a recurrent episode later in life.[9]
Prior to the advent of widespread vaccination, an estimated 4 million cases of primary VZV infection occurred annually in the United States alone.[8] Infection was nearly universal by the end of the teenage years, with studies showing only 10% of persons older than age 15 years remaining susceptible to infection.[9] Cumulative over a lifetime, 10-20% of those with primary infections went on to experience episodes of herpes zoster.[10] High-risk groups, such as elderly populations and immunocompromised people, might experience cumulative incidences as great as 50%.[11] The estimated annual number of herpes zoster cases in the United States is approximately 1 million.[12]
Widespread vaccination for varicella has reduced the incidence of primary VZV infection in the United States by up to 90% since its introduction in 1995.[8] However, the effect of both this vaccination, and the more recently approved vaccination for herpes zoster, on the current and future incidence of herpes zoster is still uncertain.
Epidemiological data is limited, but the international incidence appears similar to that in the United States.[13]
Research indicates that blacks are one-fourth as likely as whites to develop herpes zoster.
Retrospective and prospective research has indicated that elderly black adults are up to 75% less likely to develop herpes zoster than elderly white adults.[11] Similar findings have been demonstrated in children.[14] Conversely, in a meta-analysis of controlled herpes zoster clinical trials in a nonwhite racial group was found to be associated with a younger age at zoster onset.[15]
The incidence of herpes zoster increases with age. In the general population, the lifetime incidence rate of herpes zoster is 10-20%, which rises to 50% in those individuals surviving to age 85 years.[11]
The rash usually resolves within 10-15 days. The prognosis for younger and otherwise healthy patients is excellent. Elderly people have a significantly increased risk of complications, including postherpetic neuralgia, bacterial infections, and scarring.
A common complication of herpes zoster is postherpetic neuralgia, which is pain that persists for longer than 1 month following resolution of the vesicular rash. Its incidence increases dramatically with age (ie, 3-4% in those aged 30-50 y; 34% in those >80 y).[11] }
Postherpetic neuralgia may develop as a continuation of pain that accompanies acute zoster, or it may develop following apparent resolution of the initial zoster reactivation. The pain of postherpetic neuralgia may extend for months to years.[2]
Herpes zoster may be associated with a secondary bacterial infection at the site of the rash (typically streptococcal or staphylococcal).
Herpes zoster involving the ophthalmic branch of the trigeminal nerve may be associated with conjunctivitis, keratitis, corneal ulceration, iridocyclitis, glaucoma, and blindness.
Complications of the Ramsay Hunt syndrome (zoster involving cranial nerves V, IX, and X) may include peripheral facial nerve weakness and deafness.
Meningoencephalitis secondary to herpes zoster is more likely to be seen in immunocompromised patients than in immunocompetent patients. Other CNS complications may include myelitis, cranial nerve palsies, and granulomatous angiitis. Granulomatous angiitis may result in the development of a cerebrovascular accident.
Disseminated zoster may be seen in immunocompromised patients. In such cases, hematogenous spread may result in the involvement of multiple dermatomes. Visceral involvement can also occur.
Herpes zoster rarely causes fatalities in patients who are immunocompetent, but it can be life threatening in immunocompromised patients. Disseminated zoster in immunocompromised patients can lead to death from encephalitis, hepatitis, or pneumonitis. Patients with active lymphoproliferative malignancies are at particular risk. The mortality rate from disseminated herpes zoster is between 5% and 15%.[10]
Inform patients about the natural progression of herpes zoster and its potential complications.
During the acute phase, patients are infective to others and should be instructed to avoid contact with elderly people, people who are immunocompromised, pregnant women, or people with no history of chickenpox infection.
Patients should be instructed to not scratch the lesions, which may predispose them to secondary bacterial infections.
For patient education information, visit eMedicineHealth's Bacterial and Viral Infections Center, as well as Shingles and Chickenpox.
Prodromal pain precedes the rash in approximately 70-80% of patients; it is typically confined to the same dermatomal distribution as the rash. In immunocompetent patients, herpes zoster is generally restricted to one dermatome, with possible limited involvement of adjacent dermatomes due to normal variations in innervation. Many patients describe the pain as "burning," "throbbing," or "stabbing." It may be severe, mild, constant, rare, or felt as another sensation such as pruritus. The involved area may be tender to palpation.[16]
After 48-72 hours, or longer in some cases, the rash develops. Initially, and briefly, maculopapular lesions rapidly transition to vesicles in 1-2 days. New vesicles tend to form over 3-5 days, sometimes coalescing to form bullae. The lesions then rupture and release their contents, ulcerate, crust over, and dry, over 7-10 days. As with chickenpox, once crusting occurs, the lesions are no longer infectious.
Depending on the dermatome involved, additional physical examination findings may include the following:
Symptomatic involvement of multiple dermatomes or bilateral aspects of the same dermatome (ie, crossing the midline) may indicate disseminated disease or another etiology such as herpes simplex virus (HSV) infection.
Symptoms and lesions tend to resolve over 10-15 days. However, lesions may require up to 1 month to completely heal. Scarring and hyperpigmentation or hypopigmentation at lesion sites may persist for a long period or may be permanent. Pain duration is variable but is usually less than 1 month. Pain lasting longer than 1 month is referred to, by definition, as postherpetic neuralgia.
Less than 20% of patients have systemic symptoms, such as headache, fever, malaise, or fatigue, at any point during a case of herpes zoster.[16]
Herpes zoster may develop without the typical rash, as aseptic meningitis or zoster sine herpete, which is a condition defined as pain and paresthesias along a dermatome without the development of visible cutaneous involvement.
The primary physical finding is a rash in a unilateral dermatomal distribution. The rash may be erythematous, maculopapular, vesicular, pustular, or crusting, depending on the stage of disease. Note the images below.
View Image | Herpes zoster on the neck. |
View Image | Suspected Zoster of the Hand |
Lesions on the tip of the nose signify involvement of the nasociliary nerve. This finding mandates slit-lamp examination with fluorescein stain to look for the dendritic corneal lesions of herpetic keratitis.
As previously mentioned, in an uncertain number of cases, zoster may manifest without rash or vesicles, with only pain in a dermatomal distribution (ie, zoster sine herpete).
Presentations of HZO are diverse. In addition to the classic symptoms and lesions of herpes zoster, other common manifestations include conjunctivitis, scleritis, episcleritis, keratitis iridocyclitis, Argyll-Robertson pupil, glaucoma, retinitis, choroiditis, optic neuritis, optic atrophy, retrobulbar neuritis, exophthalmos, lid retraction, ptosis, and extraocular muscle palsies.
HZO may appear weeks to months after the resolution of other symptoms.
Postherpetic neuralgia and long-term sequelae may result.
When the nasociliary branch is involved, vesicles may appear on the tip or side of the nose (Hutchinson sign). Such a presentation is a predictor for possible serious complications, such as ocular inflammation and corneal denervation.
Diagnosis of herpes zoster is based primarily on history and physical examination, specifically the characteristic location and appearance of the skin eruption in association with localized pain. In most patients, confirming the diagnosis via laboratory testing usually has no utility, because most tests are time consuming, lack specificity, or are unavailable outside of research facilities. In select patient populations, however, the presentation of herpes zoster can be atypical and may require additional testing. This is particularly true in immunocompromised patients.
No imaging tests are indicated in typical cases of cutaneous herpes zoster infection.
One of the least expensive and simplest laboratory diagnostic methods for varicella-zoster virus (VZV) and other herpesviruses is the Tzanck smear. The Tzanck smear is performed by obtaining a scraping from the base of a fresh vesicular lesion after it has been unroofed, spreading and drying the collected material on a glass slide, staining the result with Giemsa, and examining the material with a microscope for the characteristic presence of multinucleated giant cells.
The Tzanck smear cannot differentiate between VZV and other herpesviruses. Further, this test has a limited sensitivity compared with other diagnostic methods such as polymerase chain reaction (PCR). Therefore, a negative result does not rule out a herpes virus infection and should not preclude empiric treatment in patients.[17]
When acute diagnostic confirmation is desired, modern tests, such as the direct immunofluorescence with fluorescein-tagged antibody (DFA) or PCR (if available), are preferred over the old standard Tzanck smear. These tests have far greater sensitivity and specificity than the Tzanck smear and allow differentiation between herpes simplex virus (HSV) and VZV infections.
VZV can be cultured successfully, but culturing has limited use in the acute clinical setting, owing to the long time required for viral growth.
Other tests may include monoclonal antibody tests and blood mononuclear cell testing for viral DNA (research).
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 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 effective duration of this vaccination is not yet known. However, ongoing follow-up of a portion of the study population has demonstrated that benefits persist for at least 5 years following vaccination, though with some decline in magnitude over time.[52] 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, 53]
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).[54] 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%.
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.
The goals of therapy in herpes zoster infection are to (1) shorten the clinical course, (2) provide analgesia, (3) prevent complications, and (4) decrease the incidence of postherpetic neuralgia. Meta-analyses and randomized controlled trials suggest that the oral antiviral agents acyclovir, famciclovir, and valacyclovir, started within 72 hours of the onset of rash, reduce the severity and duration of acute pain, as well as the incidence of postherpetic neuralgia.
Clinical Context: Acyclovir is a guanine derivative that prevents varicella-zoster virus (VZV) replication through inhibition of the viral DNA polymerase. It reduces the duration of symptomatic lesions.
Clinical Context: After ingestion, famciclovir is rapidly biotransformed into the active compound penciclovir and phosphorylated by viral thymidine kinase. By competition with deoxyguanosine triphosphate, penciclovir triphosphate inhibits viral polymerase. Adjust the dose in patients with renal insufficiency or hepatic disease.
Clinical Context: Valacyclovir is a prodrug that is rapidly converted to acyclovir before exerting its antiviral activity.
The goals of antiviral therapy are to decrease pain, inhibit viral replication and shedding, promote healing of skin lesions, and prevent or reduce the severity of postherpetic neuralgia. Acyclovir may also decrease the incidence of postherpetic neuralgia. Famciclovir and valacyclovir (antiviral agents with properties similar to those of acyclovir) offer more convenient dosing regimens than acyclovir. They also have been less studied and are more expensive.
Clinical Context: The addition of oral corticosteroids has been evaluated in zoster patients treated with acyclovir in 2 controlled studies. 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.
These agents have anti-inflammatory properties and cause profound and varied metabolic effects. Corticosteroids modify the body's immune response to diverse stimuli. 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 been shown to produce a significant reduction in postherpetic neuralgia.[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.
Clinical Context: Oxycodone is a narcotic analgesic that is indicated for the relief of moderate to severe pain. Patients with herpes zoster usually experience pain. Antiviral and steroid therapies provide relatively minor relief of pain, and narcotic analgesics are often needed.
Clinical Context: This is the drug of choice for the treatment of pain in patients who (1) have documented hypersensitivity to aspirin or NSAIDs, (2) have upper GI disease, or (3) are taking oral anticoagulants. Acetaminophen reduces fever by direct action on hypothalamic heat-regulating centers, which increases dissipation of body heat via vasodilation and sweating.
Clinical Context: Ibuprofen is the drug of choice for the treatment of mild to moderately severe pain, if no contraindications exist. It inhibits inflammatory reactions and pain, probably by decreasing the activity of the enzyme cyclooxygenase, which, in turn, inhibits prostaglandin synthesis. Ibuprofen is one of the few NSAIDs that are indicated for fever reduction.
Clinical Context: Naproxen is commonly used for the relief of mild to moderate pain. It inhibits inflammatory reactions and pain by decreasing activity of cyclooxygenase, which results in a decrease of prostaglandin synthesis.
Pain control is essential to quality patient care. Analgesics ensure patient comfort, promote pulmonary toilet, and enable physical therapy regimens. Most oral narcotic analgesics have sedating properties that are beneficial for patients who have skin lesions. Topical analgesics that contain capsaicin have been shown to be effective for neuropathic pain associated with postherpetic neuralgia.
Clinical Context: Capsaicin is derived from plants of the Solanaceae family. It is a transient receptor potential vanilloid-1 (TRPV1) agonist indicated for neuropathic pain associated with postherpetic neuralgia. TRPV1 is an ion channel–receptor complex expressed on nociceptive skin nerve fibers. Topical capsaicin causes initial TRPV1 stimulation that may cause pain, followed by pain relief via a reduction in TRPV1-expressing nociceptive nerve endings. Neuropathic pain may gradually recur over several months; this recurrence is thought to be caused by TRPV1 nerve fiber reinnervation of the treated area.
Clinical Context: This is a transient receptor potential vanilloid-1 (TRPV1) agonist indicated for neuropathic pain associated with postherpetic neuralgia. TRPV1 is an ion channel–receptor complex expressed on nociceptive skin nerve fibers. Topical capsaicin causes initial TRPV1 stimulation that may cause pain, followed by pain relief via a reduction in TRPV1-expressing nociceptive nerve endings. Neuropathic pain may gradually recur over several months; this recurrence is thought to be caused by TRPV1 nerve fiber reinnervation of the treated area.
Clinical Context: This is a lyophilized preparation of the Oka/Merck strain of live, attenuated varicella-zoster virus (VZV). It has been shown to boost immunity against herpes zoster virus (shingles) in older patients. It reduces the occurrence of shingles in individuals older than 60 years by about 50%. For individuals aged 60-69 years, it reduces the occurrence by 64%. In the ZEST trial, the vaccine significantly reduced the risk by 70% in subjects aged 50-59 years. It also slightly reduces pain compared with no vaccination in those who develop shingles. It is indicated for the prevention of herpes zoster in patients who have no contraindications.
These agents elicit active immunization to increase resistance to infection. Vaccines consist of attenuated microorganisms or cellular components, which act as antigens. Administration stimulates antibody production with specific protective properties.
Clinical Context: Gabapentin is a membrane stabilizer, a structural analogue of the inhibitory neurotransmitter gamma-amino butyric acid (GABA), which paradoxically is thought not to exert effect on GABA receptors. Gabapentin appears to exert action via the alpha2delta1 and alpha2delta2 auxiliary subunits of voltage-gated calcium channels. It is used to manage pain and provide sedation in neuropathic pain. Gabapentin is primarily used for the treatment of postherpetic neuralgia. It has also been used to treatment the pain of acute zoster.
Clinical Context: Pregabalin is a structural derivative of GABA. It binds with high affinity to the alpha2-delta site (a calcium channel subunit). In vitro, it reduces calcium-dependent release of several neurotransmitters, possibly by modulating calcium channel function. It is FDA approved for neuropathic pain associated with diabetic peripheral neuropathy or postherpetic neuralgia and as adjunctive therapy in partial-onset seizures.
Most often used as antiepileptics, certain anticonvulsants are also effective for treating neuropathic pain.
Clinical Context: This agent blocks the reuptake of norepinephrine and serotonin. It decreases pain by inhibiting spinal neurons involved in pain perception.
Clinical Context: Desipramine is a tricyclic antidepressant that has the least adverse effects amongst the first generation tricyclic antidepressants. These agents have been found to be effective in providing relief of postherpetic neuralgia.
Tricyclic antidepressants have been shown to have a role in the treatment of postherpetic neuralgia.