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Treatment of herpes zoster

Treatment of herpes zoster
Literature review current through: Jan 2024.
This topic last updated: Nov 29, 2023.

INTRODUCTION — Varicella-zoster virus (VZV) infection causes two diseases. Primary infection with VZV results in varicella, also known as chickenpox, characterized by vesicular lesions on an erythematous base in different stages of development on the face, trunk, and extremities. During varicella, VZV establishes a latent infection in sensory ganglia.

Herpes zoster, also known as shingles, results from activation of latent VZV from a sensory ganglion. The virus then travels down the associated sensory nerve to the skin, leading to a characteristic dermatomal rash, usually in association with dermatomal pain. Although herpes zoster can occur at any age, it is more commonly a disease of adults >50 years of age. In addition, the severity and complications of herpes zoster are much more common in this age group.

The treatment of herpes zoster will be reviewed here. The epidemiology, clinical manifestations, diagnosis, and prevention of herpes zoster are discussed elsewhere. (See "Epidemiology, clinical manifestations, and diagnosis of herpes zoster" and "Varicella-zoster virus infection in pregnancy" and "Vaccination for the prevention of shingles (herpes zoster)" and "Prevention and control of varicella-zoster virus in hospitals".)

DETERMINING EXTENT OF INFECTION — Most patients with herpes zoster present with a dermatomal vesicular rash and acute neuritis; acute neuritis commonly precedes ("prodromal pain") the rash by one to three days. (See "Epidemiology, clinical manifestations, and diagnosis of herpes zoster", section on 'Common findings'.)

During the initial evaluation of a patient with herpes zoster, it is important to exclude signs and symptoms of complicated zoster. This includes disseminated disease or involvement of the eye, ear, or central nervous system (table 1). As an example, if cutaneous lesions are present on the tip or side of the nose, patients are at risk for herpes zoster ophthalmicus. Such patients should be evaluated for any signs or symptoms of eye involvement (eg, tearing, ocular pain, blurred vision, conjunctival injection, swelling/erythema of the lid and periorbital structures); if these clinical features are present, the patient should be evaluated by an ophthalmologist. (See "Epidemiology, clinical manifestations, and diagnosis of herpes zoster", section on 'Complications' and 'Ocular disease' below.)

It is also important to rule out other etiologies that cause similar syndromes, such as herpes simplex virus infection. (See "Epidemiology, clinical manifestations, and diagnosis of genital herpes simplex virus infection" and "Epidemiology, clinical manifestations, and diagnosis of herpes simplex virus type 1 infection".)

UNCOMPLICATED DERMATOMAL RASH — In patients with uncomplicated dermatomal zoster, the rash is usually limited to one dermatome, although contiguous dermatomes can be involved. (See "Epidemiology, clinical manifestations, and diagnosis of herpes zoster".)

Antiviral therapy

Goals of therapy — The management of uncomplicated herpes zoster includes:

Antiviral therapy to hasten healing of cutaneous lesions, decrease the duration and severity of acute neuritis, and prevent new lesion formation [1,2]. (See 'Antiviral therapy' above.)

Analgesia for patients with moderate to severe acute neuritis. (See 'Management of acute neuritis' below.)

Several lines of evidence suggest that antiviral therapy hastens resolution of cutaneous lesions and the pain of herpes zoster [3-5]. Antiviral therapy likely decreases viral shedding and may reduce the risk of transmission of varicella-zoster virus (VZV).

However, it is unclear if antiviral therapy prevents postherpetic neuralgia (PHN) because of conflicting study results, which are due in part to different methodologies of pain assessment, definitions of PHN, and length of follow-up [3-6]. The treatment of established PHN is discussed elsewhere. (See "Postherpetic neuralgia", section on 'Treatment'.)

Indications — The indications for treatment depend upon duration of symptoms and the presence or absence of comorbid conditions.

Patients who present within 72 hours of onset — We recommend antiviral therapy for all patients with herpes zoster who present within 72 hours of clinical signs and symptoms (algorithm 1). Antiviral therapy should be initiated as soon as possible to maximize the potential benefits of treatment. (See 'Regimen selection' below.)

The benefit of antiviral therapy appears to be greatest in patients older than 50 years of age, in whom the pain of herpes zoster is generally greater and persists longer and in whom complications of herpes zoster are more likely [3,7]. Although the efficacy of antiviral therapy in immune-competent patients less than 50 years of age has not been as well studied, the risk of adverse events secondary to antiviral therapy is very low. Efficacy has been demonstrated in younger patients who are immune compromised.

More detailed information on the efficacy of antiviral therapy is found below. (See 'Approach for most patients' below and 'Immunocompromised patients' below.)

Selected patients who present after 72 hours — We suggest antiviral therapy in certain patients with herpes zoster even if >72 hours have passed (algorithm 1). This primarily includes persons who have, or are likely to have, an impaired immune response to VZV infection. However, there is no benefit of antiviral therapy after all the lesions have crusted, regardless of the patient's underlying condition.

These patients include:

Immunocompromised persons – We administer antiviral therapy to immunocompromised patients who present after 72 hours of symptoms, particularly those at risk for disseminated disease. This includes hematopoietic cell transplant or solid organ transplant recipients, persons with hematologic malignancies, those with solid tumor malignancies receiving chemotherapy, persons with advanced HIV infection (eg. CD4 count <200 cells/microL, especially those not receiving antiretroviral therapy), persons receiving high-dose glucocorticoids (eg, >20 mg/day of prednisone for more than two weeks) or immunomodulatory therapy (eg, rituximab or TNF inhibitors) [8,9].

Selected immunocompetent persons – We treat certain immunocompetent persons, even if they present after 72 hours. These include:

Patients with lesions at a site associated with an increased risk of complications. As an example, patients with involvement of the V1 dermatome are at increased risk of future ocular involvement even if they do not have overt ocular involvement at presentation.

Patients who have advanced age (eg, >65) or those who are forming new crops of lesions after 72 hours. These groups of patients likely have decreased immunity to VZV [10].

Although the utility of initiating antiviral therapy more than 72 hours after the onset of lesions in such persons is unknown since clinical trials did not evaluate the efficacy of treatment initiated beyond this time period [3], treatment may be of some benefit.

Regimen selection

Approach for most patients

Choice of agent – The nucleoside analogues acyclovir, valacyclovir, and famciclovir are the preferred antivirals for treatment of herpes zoster (algorithm 1). For most patients, oral therapy is sufficient. Intravenous treatment is reserved for patients who have complications of herpes zoster (eg, acute retinal necrosis, encephalitis) or severe immune compromise. (See 'Complicated zoster' below and 'Immunocompromised patients' below.)

Of the available agents, we generally prefer valacyclovir or famciclovir given their superior bioavailability and the need for less frequent dosing compared with acyclovir, although small comparative trials do not support the efficacy of one over the other [11-13]. However, acyclovir is often preferred in persons who are pregnant. (See 'Pregnancy' below.)

Brivudine is another effective antiviral against VZV that is not available in the United States but is often used in other countries. It is a nucleoside analog that is mono-phosphorylated by a unique VZV-specified enzyme and changed into the triphosphate by cellular enzymes. Brivudine triphosphate is incorporated into VZV DNA and also is a competitive inhibitor of VZV DNA synthesis. However, the primary metabolic product of brivudine is bromovinyluracil, which inhibits enzymes degrading other fluoropyrimidines (eg, 5 fluorouracil and other bone marrow-suppressing chemotherapeutic drugs), and thus could be extremely toxic in certain clinical situations when these agents are used.

Dosing – The doses used for oral treatment of herpes zoster are:

Valacyclovir: 1000 mg three times daily

Famciclovir: 500 mg three times daily

Acyclovir: 800 mg five times daily

The typical course of treatment is seven days. (See 'Expected response to treatment' below.)

Acyclovir and its analogues are dependent upon renal function for clearance, and dose adjustment is needed in moderate to severe renal insufficiency. Dosing information can be found in the Lexicomp drug information topics within UpToDate.

The doses used to treat herpes zoster infection are higher than those typically required for herpes simplex virus since VZV is less sensitive to nucleoside analogs. However, these nucleoside analogs have well-established safety records at the currently recommended doses. Adverse events are uncommon, but when present typically include nausea, diarrhea, or headache. More detailed information about the individual agents is found elsewhere. (See "Acyclovir: An overview" and "Valacyclovir: An overview" and "Famciclovir: An overview".)

Efficacy – Data supporting the efficacy of these agents for the treatment of herpes zoster include:

Oral acyclovir – Oral acyclovir was the first nucleoside analogue available for the treatment of herpes simplex and herpes zoster. (See "Acyclovir: An overview".)

In a meta-analysis of four placebo-controlled trials involving 691 patients (mean age 62 years), those who received acyclovir (800 mg five times daily) administered within 48 to 72 hours of the onset of rash were more likely to have resolution of moderate/severe acute neuritis (hazard ratio [HR] 1.46; 95% CI 1.1-1.93) and PHN, defined as the presence of pain at three and six months after resolution of the rash (HR 1.8; 95% CI 1.35-2.43) [3]. In a subsequent meta-analysis, which included one additional placebo-controlled trial, antiviral therapy decreased the risk of PHN (as defined by any pain at six months) by 46 percent [4].

Valacyclovir – The limited bioavailability of acyclovir necessitated frequent daily dosing (800 mg five times daily), prompting the development of a prodrug with improved absorption (valacyclovir). Valacyclovir is well absorbed from the gastrointestinal tract and rapidly converted to acyclovir in vivo, thereby providing a three- to fivefold increase in acyclovir bioavailability. This results in improved pharmacokinetics and less frequent dosing. (See "Valacyclovir: An overview" and "Valacyclovir: An overview", section on 'Basic pharmacokinetics'.)

A randomized, double-blind trial compared valacyclovir (1000 mg orally three times daily for 7 or 14 days) with acyclovir (800 mg orally five times daily for seven days) for treatment of herpes zoster in 1141 immunocompetent adults (mean age 68 years) [14]. Cutaneous lesions resolved at similar rates in all treatment groups; however, valacyclovir for 7 or 14 days accelerated the resolution of acute neuritis compared with acyclovir (median duration of pain 38 and 44 days for the 7 and 14 day course of valacyclovir, respectively, compared with 51 days for acyclovir).

Famciclovir – Famciclovir, the prodrug of penciclovir, is well absorbed from the gastrointestinal tract and rapidly converted in the intestinal wall and liver to penciclovir, which has good activity against VZV [7,15]. (See "Famciclovir: An overview", section on 'Mechanism of action'.)

A placebo-controlled clinical trial was conducted in 419 immunocompetent adults (mean age 50 years) with uncomplicated zoster to evaluate the efficacy of standard-dose and high-dose famciclovir (500 or 750 mg three times daily) with placebo [7]. All patients initiated therapy within 72 hours of rash onset and were treated for seven days. Famciclovir was associated with a modest improvement in lesion-healing rates compared with placebo (median five to six versus seven days). While there was no difference in the incidence of PHN among the three treatment arms, the use of famciclovir therapy, regardless of dose, conferred a selective reduction in the median duration of PHN compared with placebo (62 and 55 days with low- and high-dose famciclovir, respectively versus 119 days).

Pregnancy — We prefer oral acyclovir (800 mg five times daily) rather than other antiviral agents during pregnancy since there is the most experience with this medication in pregnancy. Although there are no clinical trials evaluating specific antiviral agents in pregnant women with herpes zoster, experience with acyclovir in both herpes simplex infection and varicella pneumonia, which is supported by a large registry of acyclovir exposure during pregnancy, suggests that this drug is safe in pregnancy. (See "Acyclovir: An overview", section on 'Use in pregnancy' and "Varicella-zoster virus infection in pregnancy" and "Genital herpes simplex virus infection and pregnancy", section on 'Drug choice, dose, and safety'.)

Immunocompromised patients — Regimen selection in immunocompromised patients depends upon the degree of immunocompromise and the subsequent risk of dissemination.

Patients at high risk for dissemination – Intravenous (IV) acyclovir (10 mg/kg every eight hours) is used as initial therapy in patients who are at high risk for dissemination [2]. This includes hematopoietic cell (HCT) or organ transplant recipients with significant immunosuppression (eg, HCT recipients in the pre- or post-transplant period, those with graft versus host disease, or cancer patients with leukopenia). Small clinical trials have found that IV acyclovir substantially reduces the risk for cutaneous and visceral dissemination in highly immunocompromised patients [16-20].

After initial clinical improvement, patients may be switched to an oral agent with good bioavailability, such as valacyclovir or famciclovir. Patients should be treated until all lesions have crusted (typically 7 to 14 days).

Other immunocompromised patients – For other immunocompromised patients, oral therapy with valacyclovir (1 g three times daily) can be used. In a randomized trial of 87 immunocompromised patients with clinical evidence of localized herpes zoster, patients who received this regimen had the same median time to full crusting of lesions as those who received valacyclovir 2 g three times daily [21].

Expected response to treatment — The expected response to treatment is for new vesicles to stop forming within five to seven days of therapy. (See 'Regimen selection' above.)

If there is a delayed response to treatment, antiviral therapy treatment should be extended until new vesicle formation has ceased. In some cases, transition to intravenous acyclovir is appropriate (eg, immunocompromised patients with new vesicle formation despite several days of oral therapy).

The patient should also be evaluated to ensure there are no complications associated with herpes zoster (eg, secondary bacterial infection). (See 'Secondary bacterial infection' below.)

Patients with a delayed response to treatment generally have decreased immunity to VZV infection. Thus, when evaluating the patient, clinicians should assess for clinical manifestations that would suggest underlying immune suppression. We do not routinely do additional work-up to search for immunocompromising conditions unless the initial clinical evaluation is suggestive of a certain disease.

Limited role for adjunctive therapies — For patients with uncomplicated zoster, we suggest against the routine use of adjunctive agents (eg, gabapentin, tricyclic antidepressants, or glucocorticoids) in the acute setting. However, some of these agents may have a role in select patients with acute neuritis, as discussed below. (See 'Management of acute neuritis' below.)

There are no definitive data to suggest these adjunctive agents prevent PHN from developing [22], and the risk of adverse events can be increased by adjunctive agents in elderly patients. Although some early trials suggested glucocorticoids in addition to acyclovir made people feel better sooner [23-27], a subsequent meta-analysis did not demonstrate any benefit of combination therapy on quality of life or the incidence of PHN [24]. In addition, their role in hastening the resolution of the rash is unclear.

Assessing and managing pain

Patient monitoring — After treatment for herpes zoster has been initiated, patients should be assessed for improvement in their clinical symptoms, including worsening or persisting pain. Serial patient monitoring should include standardized pain measures and frequent follow-up to assess efficacy in relief of symptoms [2].

Approximately 10 to 15 percent of patients may develop PHN, defined as pain (defined as severity of 3 out of 10) which interferes with daily activity that is present 90 days after the onset of rash (or begins after this interval) in the distribution of the documented episode of acute herpes zoster. This a more frequent problem in patients over the age of 60 years [28].

Management of acute neuritis — Although antiviral therapy reduces pain associated with acute neuritis, pain syndromes associated with herpes zoster can still be severe. Thus, certain interventions may be needed in addition to antiviral therapy.

Management of acute neuritis must be individualized and requires the same principles as managing any pain: use of standardized pain measures, scheduled analgesia, and consistent and frequent monitoring to adjust dosing to the needs of the patient and to avoid side effects.

For all patients, nonsteroidal anti-inflammatory drugs and acetaminophen can be useful agents to alleviate pain.

For those with severe pain, management is more difficult, and additional agents may be needed. The choice of treatment is based upon the patient's comorbidities, concurrent medications, pain intensity, and preferences.

Options include [29]:

Short-acting opioid analgesics – Short-acting opioid analgesics (eg, oxycodone) are often the first option because of their efficacy in managing severe acute pain and evidence supporting their use in acute zoster neuritis [22]. We use the lowest effective dose for the shortest duration possible because of associated side effects, especially in older patients. (See "Management of acute pain in opioid naïve adults in the ambulatory setting" and "Geriatric health maintenance".)

Corticosteroids – If the patient has severe pain despite a short-acting opioid, a short course of corticosteroids may offer some benefit (eg, 10- to 14-day tapering course of oral prednisone starting at 40 mg/day). Limited data suggest that corticosteroids in addition to acyclovir may improve overall well-being and/or improve acute pain [23,25,30,31]. However, corticosteroids should generally be avoided in patients with certain comorbid conditions (eg, diabetes mellitus).

Gabapentin – Gabapentin may reduce acute pain in some patients [22,32,33], although the evidence is mixed [34-36]. By contrast, this agent is frequently used for management of post-herpetic neuralgia. (See "Postherpetic neuralgia", section on 'Gabapentinoids for most patients with moderate or severe pain'.)

For patients with unrelenting pain, neural blockade with a long acting agent like bupivacaine can also be considered [29,37].

Management of postherpetic neuralgia — PHN (pain which interferes with daily activity that is present 90 days after the onset of rash in the distribution of the documented episode of acute herpes zoster) can be difficult to treat, and some patients require multimodal therapy for symptomatic management as well as referral to a pain management center, if available. The approach to treatment of PHN should be individualized according to severity and location of pain, comorbid conditions, medication side effect profile, treatment cost and availability, and patient values and preferences. This is discussed in detail in a separate topic review. (See "Postherpetic neuralgia".)

Additional considerations

Secondary bacterial infection — Although uncommon, secondary bacterial infections of the zoster rash can occur. Patients should be counseled to contact their clinician if they observe increased erythema, warmth, and/or purulence surrounding any lesions, which could suggest secondary bacterial skin infection.

Should a bacterial infection be suspected at the time of the initial evaluation or during follow-up visits, the patient should receive appropriate antibiotic coverage in addition to antiviral therapy; regimens should include coverage for both staphylococcal and streptococcal species. (See "Acute cellulitis and erysipelas in adults: Treatment".)

Treatment failure — On rare occasion, a patient may have persistence or progression of lesions on treatment. There is no standard approach to managing treatment failure. In this setting, the lesions should be cultured and the virus isolated should be sent for resistance testing. If drug resistant virus is present, alternative agents can be used (eg, foscarnet). Such patients should be managed in conjunction with an infectious diseases specialist.

Recurrent zoster — Patients with recurrent zoster should be treated with antiviral therapy using the recommended dose and duration for treatment of an initial episode of herpes zoster. (See 'Antiviral therapy' above.)

Since episodes of recurrent zoster are uncommon, it is important that clinicians assess the patient to determine the certainty of the diagnosis [38-40]. A common error is to mistake recurrent herpes simplex for herpes zoster when the lesions are in the perioral or perigenital area, including the buttock. If the diagnosis is uncertain, confirmatory testing is warranted. (See "Epidemiology, clinical manifestations, and diagnosis of herpes zoster", section on 'Recurrent herpes zoster'.)

In addition, clinicians should assess patients with recurrent zoster for clinical features that would suggest underlying immune suppression. However, we do not routinely do additional work-up to search for immunocompromising conditions unless the initial clinical evaluation is suggestive of a certain disease.

COMPLICATED ZOSTER — Certain patients with herpes zoster will have ocular, otic, or neurologic manifestations. Such patients may require intravenous (IV) and/or prolonged therapy. In addition, there may be a role for adjunctive glucocorticoids in certain conditions.

Disseminated infection — Disseminated zoster includes extensive cutaneous involvement (eg, >2 contiguous dermatomes, lesions involving both sides of the body or non-contiguous dermatomes), and/or visceral involvement (table 1). Disseminated zoster almost always occurs in those who are immunocompromised. (See "Epidemiology, clinical manifestations, and diagnosis of herpes zoster", section on 'Special considerations in immunocompromised hosts'.)

In such patients, IV acyclovir (10 mg/kg every eight hours) should be initiated. When lesions are improving the patient can be transitioned to oral treatment such as valacyclovir (1 g three times daily). The duration of therapy is typically 10 to 14 days but may need to be extended in those with ongoing symptoms. The use of IV therapy is based upon early data that found IV acyclovir accelerates the rate of clearance of virus from vesicles, as compared with no therapy or therapy with vidarabine [18,41]. Studies comparing oral therapy versus IV acyclovir for disseminated disease have not been conducted.

Patients with disseminated infection are typically managed in the hospital setting. For such persons, appropriate infection control precautions (eg, standard, droplet, and airborne) should be implemented. (See "Prevention and control of varicella-zoster virus in hospitals", section on 'Infection control measures'.)

Ocular disease — Ocular manifestations of herpes zoster include herpes zoster ophthalmicus (HZO) and acute retinal necrosis (ARN). (See "Epidemiology, clinical manifestations, and diagnosis of herpes zoster", section on 'Herpes zoster ophthalmicus' and "Epidemiology, clinical manifestations, and diagnosis of herpes zoster", section on 'Acute retinal necrosis'.)

Patients with these conditions should be managed in conjunction with an ophthalmologist. Immediate treatment is required since they can be associated with loss of vision. Treatment includes antiviral therapy, and in some cases, additional therapies may be warranted (eg, corticosteroids for selected patients with HZO or intravitreal foscarnet for ARN) [42,43].

Ramsay Hunt syndrome — The major otologic complication of varicella-zoster virus (VZV) reactivation is the Ramsay Hunt syndrome, which typically includes the triad of ipsilateral facial paralysis, ear pain, and vesicles in the auditory canal and/or auricle. Other clinical manifestations may include tinnitus or nystagmus. (See "Epidemiology, clinical manifestations, and diagnosis of herpes zoster", section on 'Ramsay Hunt syndrome (herpes zoster oticus)'.)

For most patients, we administer valacyclovir (1 g three times per day) for 7 to 10 days and prednisone (1 mg/kg for five days, without a taper).

In severe cases (eg, vertigo, tinnitus, or hearing loss), IV therapy can be initiated, and the patient can then be transitioned to an oral antiviral agent when the lesions begin to crust.

There are few data to guide treatment decisions about management of this complication. Although a systematic review found no evidence that antiviral agents have a beneficial effect on outcomes in Ramsay Hunt syndrome [44], a subsequent retrospective review of 101 patients found that patients who received acyclovir and glucocorticoids recovered significantly more than those who had only one or no pharmacologic treatment [45].

Neurologic complications — IV acyclovir (10 mg/kg IV every eight hours) should be administered to patients with neurologic complications where viral replication likely plays an important role (eg, symptomatic meningitis, encephalitis, and myelitis) [2]. Treatment is generally administered for 10 to 14 days. This approach is supported by expert opinion. An additional discussion of the neurologic manifestations of VZV is found elsewhere. (See "Varicella zoster virus vasculopathy".)

PREVENTING TRANSMISSION TO OTHERS — Patients with herpes zoster can transmit varicella-zoster virus (VZV) to individuals who have not had varicella and have not received the varicella vaccine. VZV is transmitted by direct contact or by aerosolization of virus from skin lesions. In general, VZV is much less transmissible from a person presenting with herpes zoster than from a person presenting with varicella (chickenpox). (See "Epidemiology, clinical manifestations, and diagnosis of herpes zoster", section on 'Transmission'.)

Patients with localized zoster (ie, a dermatomal rash) are not infectious before vesicles appear and are no longer infectious when the lesions have crusted. Patients should be counseled about the risk of viral transmission to others [2]. In addition, until the rash has fully crusted, patients should be advised to:

Keep the rash covered to reduce the risk of spreading the virus to others.

Avoid contact with immunocompromised individuals as well as those who have never had chickenpox or the varicella vaccine [46].

More detailed discussions of how to prevent transmission of VZV are found elsewhere. (See "Prevention and control of varicella-zoster virus in hospitals" and "Post-exposure prophylaxis against varicella-zoster virus infection".)

SOCIETY GUIDELINE LINKS — Links to society and government-sponsored guidelines from selected countries and regions around the world are provided separately. (See "Society guideline links: Varicella-zoster virus".)

INFORMATION FOR PATIENTS — UpToDate offers two types of patient education materials, "The Basics" and "Beyond the Basics." The Basics patient education pieces are written in plain language, at the 5th to 6th grade reading level, and they answer the four or five key questions a patient might have about a given condition. These articles are best for patients who want a general overview and who prefer short, easy-to-read materials. Beyond the Basics patient education pieces are longer, more sophisticated, and more detailed. These articles are written at the 10th to 12th grade reading level and are best for patients who want in-depth information and are comfortable with some medical jargon.

Here are the patient education articles that are relevant to this topic. We encourage you to print or e-mail these topics to your patients. (You can also locate patient education articles on a variety of subjects by searching on "patient info" and the keyword(s) of interest.)

Basics topic (see "Patient education: Shingles (The Basics)")

Beyond the Basics topic (see "Patient education: Shingles (Beyond the Basics)")

SUMMARY AND RECOMMENDATIONS

Uncomplicated dermatomal zoster – Uncomplicated herpes zoster typically presents with prodromal pain, a dermatomal vesicular rash, and dermatomal pain (acute neuritis). (See 'Determining extent of infection' above.)

Uncomplicated herpes zoster excludes patients with signs and symptoms of disseminated disease or involvement of the eye, ear, or central nervous system (table 1). (See 'Complicated zoster' above.)

Indications for antiviral treatment – For patients with uncomplicated zoster, the benefit of antiviral treatment depends on the duration of symptoms and other factors (algorithm 1):

-Within 72 hours of symptom onset – For patients who present within 72 hours of symptom onset and have uncrusted lesions, we recommend antiviral therapy (Grade 1B). Antivirals promote healing of skin lesions, lessen the severity and duration of acute neuritis, and reduce the incidence or severity of chronic pain (ie, postherpetic neuralgia). (See 'Patients who present within 72 hours of onset' above.)

-Beyond 72 hours of symptom onset – For selected patients who present beyond 72 hours of symptoms and have uncrusted lesions, we also suggest antiviral therapy (Grade 2C). This includes: immunocompromised patients, patients with lesions in locations associated with complications (eg, V1 dermatome), patients age >65 years, and patients forming new crops of lesions. (See 'Selected patients who present after 72 hours' above.)

There is no benefit of antiviral therapy once all lesions have crusted.

Antiviral therapy selection and duration: Immunocompetent patients – For most immunocompetent patients, we suggest oral valacyclovir (1000 mg three times daily) or famciclovir (500 mg three times daily) (algorithm 1) (Grade 2C). These agents are dosed less frequently than acyclovir (800 mg five times daily). (See 'Approach for most patients' above.)

For pregnant patients, we prefer oral acyclovir since there is the most experience with this medication in pregnancy and extensive safety experience. (See 'Pregnancy' above.)

We continue treatment until new vesicle formation has ceased; the typical duration is seven days. For patients with delayed response to therapy, we assess for clinical manifestations that would suggest underlying immune compromise. (See 'Expected response to treatment' above.)

Antiviral therapy selection and duration: Immunocompromised patients – For immunocompromised patients at high risk for dissemination, we suggest intravenous (IV) acyclovir (10 mg/kg every eight hours) (algorithm 1) (Grade 2C). Examples include hematopoietic cell or organ transplant recipients in the pre- or early post-engraftment period or those with graft-versus-host disease, and patients with cancer and leukopenia. After initial clinical improvement, patients may be switched to an oral agent until all lesions have crusted (typically 7 to 14 days). (See 'Immunocompromised patients' above.)

For other immunocompromised patients (eg, persons with HIV and CD4 <200 cells/microL, persons receiving chronic corticosteroids or biologic agents for autoimmune conditions), we prefer oral valacyclovir (1000 mg three times daily) or famciclovir (500 mg three times daily) rather than oral acyclovir. Transition to IV acyclovir is appropriate if new vesicle formation continues despite several days of oral therapy. (See 'Expected response to treatment' above.)

Limited role of adjunctive therapies – In patients with uncomplicated zoster, we suggest against the routine use of adjunctive therapies, such as gabapentin, tricyclic antidepressants, or glucocorticoids (Grade 2C). The clinical benefit of these agents in reducing the risk of acute neuritis has not been clearly demonstrated and there are significant risks associated with these medications. (See 'Limited role for adjunctive therapies' above.)

Acute pain management (acute neuritis) – Pain associated with herpes zoster can be severe, and may require specific interventions in addition to antiviral therapy.

For all patients with acute pain, we offer nonsteroidal anti-inflammatory drugs and/or acetaminophen.

For those with severe pain, additional agents may be needed; the choice of agent depends in part on patient comorbidities and preferences. (See 'Management of acute neuritis' above.)

-Opioid analgesics – Short-acting opioid analgesics (eg, oxycodone) are often the first option because of their efficacy in managing severe acute pain and evidence supporting their use in acute zoster neuritis. We use the lowest effective dose for the shortest duration possible because of associated side effects, especially in older patients.

-Corticosteroids – If the patient has severe pain despite a short-acting opioid, a short course of corticosteroids may offer some benefit (eg, 10- to 14-day tapering course of oral prednisone starting at 40 mg/day). Limited data suggest the addition of corticosteroids to acyclovir may improve overall well-being and/or improve acute pain. However, we try to avoid corticosteroids in those with certain comorbid conditions (eg, diabetes mellitus).

-Other agents – If short-acting opioids and/or corticosteroids are unsuccessful, we offer treatments that are used for the management of postherpetic neuralgia (eg, gabapentin).

Secondary bacterial infections – If a secondary bacterial infection occurs, patients should receive an antibiotic regimen that includes coverage for both staphylococcal and streptococcal species. (See 'Secondary bacterial infection' above.)

Management of complicated disease – Patients with herpes zoster can present with disseminated infection and/or localized ocular, otic, or neurologic manifestations. (See 'Complicated zoster' above.)

Some patients may require IV therapy. As an example, in patients with disseminated infection, we suggest initial treatment with IV acyclovir rather than oral therapy (Grade 2C). (See 'Disseminated infection' above.)

We also administer adjunctive therapies in certain settings. As an example, in patients with Ramsay Hunt syndrome, we suggest adjunctive glucocorticoids in addition to antiviral therapy (Grade 2C). (See 'Ramsay Hunt syndrome' above.)

Patients with ocular disease (eg, herpes zoster ophthalmicus, acute retinal necrosis) should be managed in conjunction with an ophthalmologist. Immediate treatment is required since these conditions can be associated with loss of vision. (See 'Ocular disease' above.)

Preventing transmission to others – For patients with dermatomal zoster, varicella-zoster virus (VZV) is transmitted by direct contact or by aerosolization of virus from skin lesions.

To reduce the risk of transmitting VZV to others, patients should keep the rash covered until all lesions have crusted. (See 'Preventing transmission to others' above.)

They should also avoid contact with individuals who may be at risk for acquiring VZV. This includes:

All immunocompromised individuals

Immunocompetent individuals who have neither had varicella (chickenpox) nor received the varicella vaccine

Additional precautions are needed for those with disseminated disease. (See "Prevention and control of varicella-zoster virus in hospitals".)

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Topic 8293 Version 37.0

References

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