Herpes Zoster Infection

Herpes zoster infection
Straight to the point of care
Last updated: Mar 06, 2024

Table of Contents
Overview 3
Summary 3
Definition 3
Theory 4
Epidemiology 4
Aetiology 4
Pathophysiology 4
Case history 5
Diagnosis 6
Approach 6
History and exam 9
Risk factors 9
Investigations 11
Differentials 12
Management 14
Approach 14
Treatment algorithm overview 16
Treatment algorithm 17
Emerging 25
Primary prevention 25
Secondary prevention 26
Patient discussions 27
Follow up 28
Monitoring 28
Complications 29
Prognosis 30
Guidelines 31
Treatment guidelines 31
References 32
Images 45
Disclaimer 48
Herpes zoster infection Overview
Summary
Herpes zoster (also known as shingles) typically presents with pain described as burning or stabbing,
followed by a vesicular rash in the affected dermatome; location of symptoms depends on the affected nerve.
OVERVIEW
Diagnosis is primarily based on the typical clinical symptoms, such as dermatomal pain and eruption of
grouped vesicles in the same dermatome. Confirmation can be done using polymerase chain reaction (PCR)
methods.
Treatment is primarily to reduce pain using analgesics and viral replication using antiviral medicine such as
aciclovir.
Antiviral therapy may reduce the severity of postherpetic neuralgia. Early antiviral therapy is particularly
important in ophthalmic zoster and zoster in the immunocompromised.
Definition
Herpes zoster (HZ), caused by reactivation of varicella-zoster virus (VZV) that was acquired during a primary
varicella infection, is characterised by dermatomal pain and papular rash.[1] The pain typically precedes the
rash by several days and can persist for several months after the rash resolves. The rash usually presents
in a single dermatome and typically resolves within 4 to 5 weeks. A common complication is postherpetic
pain.[2]
This PDF of the BMJ Best Practice topic is based on the web version that was last updated: Mar 06, 2024.
BMJ Best Practice topics are regularly updated and the most recent version of the topics
3
can be found on bestpractice.bmj.com . Use of this content is subject to our disclaimer (.
Use of this content is subject to our) . © BMJ Publishing Group Ltd 2024. All rights reserved.
Herpes zoster infection Theory
Epidemiology
The annual incidence of HZ in the UK is estimated between 1.85 and 3.9 cases per 1000 population.[4] It
increases with age from fewer than two cases per 1000 among people under 50 years to 11 cases per 1000
THEORY
among people aged 80 years or over.
Similar incidence rates have been reported in the US, where over 90% of adults have serological evidence
of varicella-zoster virus (VZV) infection and are therefore at risk of HZ.[5] In the Netherlands, the incidence
of HZ is 3.4 per 1000.[6] In Italy, the incidence in people >14 years of age has been estimated at 1.4 per
1000.[7] In Spain the incidence is 4.2 per 1000.[8] HZ has no seasonal variation, and there appears to be no
difference in incidence worldwide.
Incidence is higher among women.[9] The incidence is also higher in people with immunosuppression
(e.g., those with HIV or malignancies, and those on chemotherapy or corticosteroid treatment).[10] [11] [12]
The risk of shingles remains increased among people living with HIV, even if they are taking antiretroviral
therapy.[9] [13] [14] Black people appear less likely to experience HZ than other ethnicities.[15] It is unknown
if exposure to unvaccinated children offers protection.[16]
Incidence of HZ has increased over time in the US, both before and after the varicella vaccination
programme.[17] [18] Incidence has also increased in other countries such as Canada, the UK, and Japan,
where there are no varicella vaccination programmes.[19] [20] [21]
Aetiology
HZ results from reactivation of latent varicella-zoster virus (VZV) from dorsal root or cranial nerve ganglia,
present since primary infection. VZV is a double-stranded DNA herpes virus, spreading from direct person-
to-person contact with an infected individual or lesion and from air droplets. Latent infection, after primary
infection, is established by evading the immune system through the reduction of the number of genes
expressed and downregulation of the expression of major histocompatibility complex class I antigens on
the surface of the infected cells.[22] HZ and 'chicken pox' or varicella are both caused by the same virus,
but varicella usually follows the initial infection and causes a generalised rash, whereas HZ occurs after
reactivation of a previous infection and tends to be localised to a specific nerve distribution.
Pathophysiology
After a primary varicella-zoster virus (VZV) infection, the virus establishes latency in dorsal root and
cranial nerve ganglia. In immunocompetent people, the infection usually affects a single dermatome, with
rare involvement of multiple dermatomes. However, in immunocompromised people, the involvement of
several dermatomes is common. A decline in the virus-specific cell-mediated immunity as a result of HIV,
malignancies, chemotherapy, or chronic use of corticosteroids results in the reactivation of infection, which
spreads from the ganglion to the neural tissue of the affected segment and the corresponding cutaneous
dermatome.[1] The reactivation leads to ganglionitis: inflammation and destruction of neurons and supporting
cells. The virus is also carried down the axons to the areas of the skin innervated by the affected ganglion,
causing local inflammation.
Characterised by a prodromal period with burning pain for 2 to 3 days, a vesicular eruption follows in the
dermatomal distribution of the infected ganglion. Any dermatome may be affected; however, the most
4 This PDF of the BMJ Best Practice topic is based on the web version that was last updated: Mar 06, 2024.
Herpes zoster infection Theory
commonly affected dermatomes are T1 to L2.[22] Although sensory neurons are most commonly affected, in
5% to 15% of patients motor neurons are affected as well.[3]
Case history
THEORY
Case history #1
A 77-year-old man reports a 5-day history of burning and aching pain on the right side of his chest. This is
followed by the development of erythema and a maculopapular rash in this painful area, accompanied by
headache and malaise. The rash progresses to develop clusters of clear vesicles for 3 to 5 days, evolving
through stages of pustulation, ulceration, and crusting.
Case history #2
A 65-year-old woman presents with generalised headache and burning pain in her left temporal area.
Eight days after onset of the pain, several facial lesions are noted. On physical examination, she is
afebrile. An erythematous tender plaque is present on the left frontal scalp area. Three smaller similar
plaques are present on the left temple and cheek.
Other presentations
Patients may present with pain and a unilateral rash that does not cross the midline. In most, the
infection affects one dermatome. Involvement of multiple non-contiguous dermatomes is very rare in
immunocompetent people but does occur in immunosuppressed people.[3] The presence of a few
skin lesions outside the primary or adjacent dermatome is not unusual in immunocompetent people.
Approximately 20% of patients present with systemic symptoms including fever, general body malaise,
and headache.[3] Healing occurs over a period of 2 to 4 weeks, and often results in scarring and
permanent pigmentation in the affected area.
5
Herpes zoster infection Diagnosis
Approach
Diagnosis is usually clinical, not requiring tests or culture.
Signs and symptoms

A typical presentation shows dermatomal pain followed by a rash in the affected area. Approximately
70% to 80% of patients with HZ present with pain in the dermatome where skin lesions subsequently
appear.[22] The pain usually lasts 2 to 3 days before the development of a rash in the affected
dermatome. However, some patients have presented with pain for approximately 1 week before
development of a rash.[3] This pain can be constant or intermittent and is typically described as burning,
stabbing, or throbbing. The severity varies, and pain can be so severe as to interfere with sleep and
quality of life.[71] The rash initially is erythematous with a macular base and is followed rapidly by the
appearance of vesicles within 1 to 2 days, continuing for 3 to 4 days. The lesions tend to be clustered
along the branches of the cutaneous sensory nerve. Pustulation of vesicles begins within 1 week of the
onset of rash, followed 3 to 5 days later by lesion ulceration and crusting.
DIAGNOSIS
Severe herpes zoster in an immunocompromised patient involving dermatomes T1 and T2

BMJ Case Reports 2009 [doi:10.1136/bcr.07.2008.0533] Copyright © 2009 by the BMJ Publishing Group Ltd.
Severe herpes zoster in an immunocompromised patient involving dermatomes T1 and T2

DIAGNOSIS
7
Severe herpes zoster in an immunocompromised patient showing multiple groupled vesicles,

a few pustules, and extensive blackish adherent crusts with underlying erosions noted
Approximately 20% of patients present with systemic symptoms such as fever, headache, malaise, or
fatigue.[3] Rarely, pain without rash (zoster sine herpete) can occur.[72]
Laboratory evaluation
DIAGNOSIS
Polymerase chain reaction (PCR) is the most sensitive and specific test for identifying varicella-zoster
virus (VZV) DNA, but is expensive. Immunohistochemical analysis of a skin scraping is less expensive
and still has a sensitivity of 90% and specificity of 95%. Culture of the virus is very specific but has a
very low sensitivity as a result of virus lability or fragility.[3][22] In almost all cases, HZ can and should be
diagnosed by history and physical examination. Confirming the diagnosis via laboratory testing may be
necessary to differentiate genital zoster from herpes simplex, or to diagnose HZ pain without skin lesions
(zoster sine herpete).
Because HZ is an HIV indicator condition (i.e., the prevalence of undiagnosed HIV in HZ is more than
0.1%), it is strongly recommended that patients with HZ should be offered an HIV test.[73] [74]
History and exam

Key diagnostic factors
presence of risk factors (common)
• Risk factors include: >50 years of age, HIV-positive, chronic corticosteroid use, chemotherapy,
malignancies.
localised pain in a dermatome (common)

• The pain is localised, burning, stinging, itching, or tingling and ranges from mild to severe.
• Pain, localised to the affected dermatome, can precede the rash by days to weeks.
• The most commonly involved ganglia are the thoracic and trigeminal nerves.
pruritus (common)
• May present in the affected dermatome.
rash (common)
• Patients develop an erythematous maculopapular rash, which is followed by the appearance of clear
vesicles. The eruption occurs in segments innervated by the affected sensory ganglion, but does not
cross the midline. The vesicles eventually pustulate and form crusts.
corneal ulceration (common)

• If the trigeminal nerve is affected, the rash may cause corneal ulceration. Patient presents with pain in
the affected eye and reduced vision.
Other diagnostic factors

fever (uncommon)
• May be low-grade. Significant temperature elevations are rare.
DIAGNOSIS
headache (uncommon)
• About 20% of patients present with systemic symptoms.[3]
malaise (uncommon)
fatigue (uncommon)
pain without rash (uncommon)

• Patients can develop typical zoster pain (acute, chronic, or both) without ever developing a rash, a
syndrome called zoster sine herpete.[72]
Risk factors
Strong
9
>50 years of age
• The incidence increases from age 50.[23]
female sex
• Women have a higher incidence of HZ than men.[9]
HIV
• Before the availability of antiretroviral therapy (ART), HZ incidence was more than 15 times higher in
HIV-infected patients than in uninfected people.[10] [11] [24] ART has reduced the incidence of HZ in
people with HIV, though the risk is still 3 times higher compared with the general population.[13]
chronic corticosteroid use

• Chronic use causes immunosuppression, increasing the risk.[25]
chemotherapy
• These drugs cause immunosuppression and hence increase risk.
malignancies
• Lymphoproliferative malignancies in particular induce immunosuppression, thus increasing the risk of
infection.[16]
Weak
white ethnicity
• One study suggested that black people are far less likely than white people to develop HZ (odds ratio
0.25).[15]
certain acute or chronic conditions

• A range of conditions have been associated with an increased risk of HZ, including COVID-19,
rheumatoid arthritis, systemic lupus erythematosus, inflammatory bowel disease, chronic obstructive
DIAGNOSIS
pulmonary disease, asthma, chronic kidney disease, type 1 diabetes, cardiovascular conditions,
physical trauma, and psychological stress.[26] [27] [28] [29] Prior antibiotic use has also been
associated with an increased risk of subsequent herpes zoster infection.[30] Further studies are
needed to confirm associations.
vaccination against other infectious diseases

• Development of HZ following administration of vaccination against other infections, including
COVID-19, has been reported.[31] [32] [33]
Investigations
1st test to order
Test Result
clinical diagnosis typically presents with
dermatomal pain followed
• Usually does not require tests or culture.
by a rash in the affected
area
Other tests to consider
Test Result
polymerase chain reaction (PCR) positive for varicella DNA
• Detects DNA in fluids and tissues. The most sensitive and specific
method.[75]
• Samples from lesions are useful in differentiating from herpes
simplex.
• Blood PCR can be used as a diagnostic test when there is no rash
(zoster sine herpete).
• Disseminated zoster in the immunocompromised is diagnosed by
PCR on blood and lesions.
immunohistochemistry positive stain for varicella
virus
• Using a modified Tzanck technique, cells are scraped from the base
of a lesion with a scalpel blade or the bevel of a large-blade needle,
smeared on a glass slide, and stained with fluorescein-conjugated
monoclonal antibodies to detect viral glycoprotein. This method is
more sensitive than viral culture.[76] [77]
vesicular fluid culture positive varicella virus in
culture
• Recovery of the virus is dependent on the stage of the lesions and
DIAGNOSIS
quality of the specimen. This method has lower sensitivity than
immunofluorescence as a result of virus lability.[1]
HIV test positive or negative
• Because HZ is an HIV indicator condition (i.e., the prevalence
of undiagnosed HIV in HZ is more than 0.1%), it is strongly
recommended that patients with HZ should be offered an HIV
test.[73] [74]
11
Differentials
Condition Differentiating signs / Differentiating tests

symptoms
Contact dermatitis • Presents as a localised • Eliminating exposure
rash or irritation of the skin to the irritating agent
caused by contact with a usually results in symptom
foreign substance. The pain resolution.
and the rash usually occur
simultaneously.
Herpes simplex • Grouped vesicles on an • Polymerase chain reaction

erythematous base in a non- (PCR) of sample from
dermatomal pattern, often lesions.
preceded by pruritus and
pain. Oral and genital lesions
most common.
Cholecystitis • Presents with pain in the • Patients have elevated levels

right upper quadrant of the of alkaline phosphatase,
abdomen, accompanied with bilirubin, CRP, and WBCs.
nausea, vomiting, and fever. Ultrasound or CT scan may
On examination patients may show a bile duct blockage,
have Murphy's sign. gallstones, and inflammation
of the gallbladder.
Ulcerative keratitis • Symptoms depend on • Fluorescein staining would

the cause. Presents with show the presence of a
pain and redness in the dendritic ulcer if the cause is
affected eye, with visual herpes simplex virus and is
changes dependent on the unrelated to HZ.
ulcer location. Some may • A slit-lamp examination
also present with purulent would indicate other causes
discharge. The distinctive of ulcerative keratitis, such
DIAGNOSIS
feature that differentiates as a foreign body.

HZ from other causes is the
development of rash in the
affected dermatome.
Glaucoma, acute angle- • Presents with periorbital • Tonometry shows increased

closure pain, blurred vision, and intraocular pressure (>20
headache. However, there mmHg), diagnostic of
is no development of an glaucoma.
accompanying rash in the
dermatome innervated by
the eye.
Trigeminal neuralgia • Presents with an intense, • No differentiating test is

stabbing, electric shock-like available.
pain in the areas of the face
innervated by the trigeminal
nerve. Patient may locate
a trigger area for the pain.
Patients do not develop a
rash.
Condition Differentiating signs / Differentiating tests

symptoms
Appendicitis, acute • Typically presents with pain • On FBC, WBCs are often
in the right lower abdominal elevated. CT scan would
quadrant. Additionally indicate inflammation of the
presents with nausea, appendix.
vomiting, and sometimes
signs of bowel obstruction,
which are not present in
patients with HZ. There is
no accompanying rash with
these symptoms.
Renal calculi • Presents with severe • A kidney, ureter, and bladder

colicky pain and inability x-ray would show the
to lie still. Other symptoms location of the calculi.
include urinary frequency,
blood in urine, and painful
urination. Flank pain
shows on examination.
These symptoms are
not accompanied by the
development of a rash.
DIAGNOSIS
13
Herpes zoster infection Management
Approach
Infections are usually self-limiting; however, consider antivirals in all patients, especially those who have
severe disease and/or are >50 years of age. Because of a higher risk of HZ-related complications, including
postherpetic neuralgia, treatment with antivirals is strongly recommended for immunocompromised patients,
especially those living with HIV. Treatment aims are to reduce viral replication, manage pain, and reduce
postherpetic neuralgia. The treatment of HZ during pregnancy is the same as for any other HZ patient.
Among all antivirals, acyclovir has been most extensively studied among pregnant women and is the most
commonly used.
Viral replication reduction

Antivirals are used to reduce viral replication in all patients, especially those who have severe disease,
are >50 years of age, are immunocompromised, and/or have evidence of trigeminal nerve involvement.
Administration shortens the duration of viral shedding, stops the formation of new lesions, prevents ocular
complications, and reduces the severity of pain.[78] [79] [80] [81] [82] Treatment is usually with orally
administered antiviral medicines such as aciclovir, famciclovir, and valaciclovir, and is most effective when
started within 72 hours after rash onset. Use intravenous aciclovir in patients who cannot tolerate oral
medicines. Topical antivirals are not recommended.
Studies comparing the effects on cutaneous and pain end points between famciclovir and valaciclovir
found that there are no differences in the efficacy.[81] [83] A systematic review of high-quality trials has
found that famciclovir and valaciclovir are superior to aciclovir in reducing the likelihood of prolonged
pain.[84]
Some meta-analyses of randomised controlled trials have found that treating HZ patients with antiviral
therapy reduces the duration or incidence of prolonged pain.[80] [83] [85] [86] [87] [88] [89] However,
others have found contrary results.[90] [91] [92] Famciclovir, valaciclovir, and aciclovir have been shown
to be superior to placebo in reducing the amount of time to complete cessation of pain.[80] [86] [93] [94]
However, the effect of aciclovir on chronic pain has been less clear in other clinical trials.[91] [95]
Immunocompromised patients
HZ infections are more common and often more complicated in immunocompromised patients. The main
objective of treatment in these patients is to reduce the incidence of cutaneous and visceral dissemination
that can lead to life-threatening complications. It is therefore recommended that immunocompromised
patients should promptly receive antiviral therapy within 1 week of rash onset or any time before full
crusting of lesions. Treat localised disease with oral valaciclovir, famciclovir, or aciclovir, with close
outpatient follow-up. Reserve intravenous aciclovir therapy for patients with disseminated varicella zoster
virus infection, ophthalmic involvement, very severe immunosuppression, or the inability to take oral
medications.
Pain management
For all patients, analgesics work to reduce pain in the acute phase as well as postherpetic neuralgia,
MANAGEMENT
and the type administered will depend on the severity. For mild pain, analgesics such as paracetamol
and ibuprofen are appropriate. For severe pain, opioid analgesics are an option. Topically administered
lidocaine and nerve blocks have also been reported to be effective.[96] [97] [98] Lotions containing
calamine may also be used on open lesions to reduce pain and pruritus.
Postherpetic pain
The most common complication, suspected if pain persists >30 days after rash onset or cutaneous
healing. The pain usually presents as a burning sensation or itching. The severity ranges from mild
to debilitating.[2] Patients at least 50 years old have an increased risk for complication and for severe
pain.[99] Usually resolves within 6 months; however, patients older than 70 years are at greater risk for
longer pain duration.
Treatment is primarily for pain control. Patients with mild-to-moderate pain may be treated with
non-steroidal anti-inflammatory drugs or paracetamol, alone or in combination with a weak opioid
analgesic.[100] [101] [102] [103] [104] Topical capsaicin has also been shown to provide pain relief.[105]
[106] [107] [108] For patients with moderate-to-severe pain, a strong opioid analgesic may be considered.
Treatment with either a tricyclic antidepressant such as amitriptyline or an anticonvulsant such as
gabapentin or pregabalin is also effective.[109] [110] [111] [112] One meta-analysis showed no difference
in pain relief between gabapentin and tricyclic antidepressants.[113] For those intolerant of opioids
or at high risk for addiction, one or a combination of anticonvulsants, tricyclic antidepressants, or
corticosteroids are appropriate.
There are no standard guidelines on which medication to initially use for treatment.[114] These treatments
are given as single agents or in combination depending on the severity of pain and the response to
treatment.
Eye involvement
Treatment includes the use of antiviral drugs such as aciclovir, famciclovir, or valaciclovir for 7 to 10 days,
preferably started within 72 hours of rash onset. Intravenous aciclovir is given as needed for retinitis.
Oral antiviral drugs resolve acute disease and inhibit late inflammatory recurrences.[82][115] Other
treatment includes pain medicines, antibiotic ophthalmic ointment to protect the ocular surface, and
topical corticosteroids. Prompt referral to an ophthalmologist is required for all patients who have eye
manifestations. Begin antiviral treatment as soon as possible, and before referral.[3]
Therapy for chronic problems includes the following:[3]
• Lubricating, preservative-free artificial tear gels or tears

• Antibiotic ointment
• Lateral tarsorrhaphy to protect the corneas (which are often hypoaesthetic/anaesthetic as a result
of neuronal damage) from breakdown
• Continuous-wear, therapeutic soft contact lenses and antibiotic drops
• Topical corticosteroids and antibiotics for inflammatory disease (iritis, episcleritis, scleritis, and
immune keratitis)
• Dilation for iritis
• Glaucoma therapy as needed
• Surgical management as needed: for example, for amniotic membrane transplantation, tissue-
adhesive seal ulcers, keratoprosthesis, and glaucoma trabeculectomy.
Chronic pain management is generally similar to that for postherpetic neuralgia.
MANAGEMENT
15
Treatment algorithm overview

Please note that formulations/routes and doses may differ between drug names and brands, drug
formularies, or locations. Treatment recommendations are specific to patient groups: see disclaimer
Acute ( summary )
acute symptoms: immunocompetent
1st oral antiviral therapy
mild pain plus simple analgesics ± calamine lotion
moderate-to-severe pain adjunct opioid analgesics ± topical analgesic
eye involvement plus prompt referral to ophthalmologist
acute symptoms:
immunocompromised
localised disease with 1st oral antiviral therapy

no eye involvement
or not severely
immunocompromised
plus simple analgesics ± calamine lotion
adjunct opioid analgesics ± topical analgesic
2nd intravenous aciclovir
disseminated disease or 1st intravenous aciclovir

eye involvement or severe
immunosuppression
Ongoing ( summary )
postherpetic pain
mild pain 1st paracetamol or NSAID
adjunct weak opioid analgesic
2nd topical capsaicin
moderate-to-severe pain 1st strong opioid, amitriptyline, or

anticonvulsant
MANAGEMENT
Treatment algorithm
Please note that formulations/routes and doses may differ between drug names and brands, drug
formularies, or locations. Treatment recommendations are specific to patient groups: see disclaimer
Acute
acute symptoms: immunocompetent
acute symptoms: 1st oral antiviral therapy

immunocompetent
Primary options
» famciclovir: 500 mg orally every 8 hours for

7 days
OR
» valaciclovir: 1000 mg orally every 8 hours

for 7 days
Secondary options
» aciclovir: 800 mg orally five times daily for

7-10 days; 10 mg/kg intravenously every 8
hours for 7 days
» Antivirals shorten the duration of viral

shedding, stop the formation of new lesions,
and reduce pain severity. Treatment is usually
with orally administered antiviral medicines
such as aciclovir, famciclovir, and valaciclovir.
Start within 48 to 72 hours of rash onset and
administer for 7 days (up to 10 days in patients
with eye manifestations). A systematic review
of high-quality trials has found that famciclovir
and valacyclovir were superior to acyclovir in
reducing the likelihood of prolonged pain.[84]
mild pain plus simple analgesics ± calamine lotion
Treatment recommended for ALL patients in
selected patient group
Primary options
» paracetamol: 500-1000 mg orally every 4-6

hours when required, maximum 4000 mg/day
OR
» ibuprofen: 200-400 mg orally every 4-6

MANAGEMENT
Secondary options

-or-
17
Acute
--AND--
» calamine lotion topical: apply to the affected
area(s) up to four times daily when required
» The type of analgesics administered will

depend on the severity of the pain.
moderate-to-severe pain adjunct opioid analgesics ± topical analgesic
Treatment recommended for SOME patients in
Primary options
» oxycodone: 5 mg orally (immediate-release)

every 4-6 hours when required
Secondary options

--AND--
» lidocaine topical: (5% ointment) apply to the
affected area(s) two to three times daily when
required
-or-

depend on the severity of pain.
eye involvement plus prompt referral to ophthalmologist
» Prompt referral to an ophthalmologist
is required for all patients who have eye
manifestations.[3]
» Treatment includes the use of antiviral drugs

such as aciclovir, famciclovir, or valaciclovir for
7 to 10 days, preferably started within 72 hours
of rash onset. Intravenous aciclovir is given as
needed for retinitis. Oral antiviral drugs resolve
acute disease and inhibit late inflammatory
recurrences.[82][115] Other treatment includes
pain medicines, antibiotic ophthalmic ointment
to protect the ocular surface, and topical
corticosteroids. Systemic corticosteroids may be
indicated in moderate-to-severe pain, especially
MANAGEMENT
if there is oedema surrounding the orbital

area.[3]
» Therapy for chronic problems includes the

following: lubricating, preservative-free artificial
tear gels or tears; antibiotic ointment; lateral
Acute
tarsorrhaphy to protect the corneas (which are
often hypoaesthetic/anaesthetic as a result of
neuronal damage) from breakdown; continuous-
wear, therapeutic soft contact lenses and
antibiotic drops; topical corticosteroids and
antibiotics for inflammatory disease (iritis,
episcleritis, scleritis, and immune keratitis);
dilation for iritis; glaucoma therapy as needed.
» Surgical management as needed: for example,

for amniotic membrane transplantation, tissue-
adhesive seal ulcers, keratoprosthesis, and
glaucoma trabeculectomy. Chronic pain
management is generally similar to that for
postherpetic neuralgia.[3]
acute symptoms:
immunocompromised
localised disease with 1st oral antiviral therapy

no eye involvement
Primary options
or not severely
immunocompromised
» aciclovir: 800 mg orally five times daily for
7-10 days; 10 mg/kg intravenously every 8
hours for 7 days
OR
» famciclovir: 500 mg orally every 8 hours for

7 days
OR
» valaciclovir: 1000 mg orally every 8 hours

for 7 days
» Immunocompromised patients should promptly

receive antiviral therapy within 1 week of rash
onset or any time before full crusting of lesions.
Localised disease should be treated with oral
valaciclovir, famciclovir, or aciclovir, with close
outpatient follow-up.
Primary options

MANAGEMENT
OR

19
Acute
Secondary options

-or-
--AND--

Primary options

Secondary options

--AND--
required
-or-

2nd intravenous aciclovir
Primary options
» aciclovir: 10 mg/kg intravenously every 8

hours for 7 days
» If the patient is unable to tolerate oral

medication, intravenous aciclovir can be given.
MANAGEMENT
Primary options
» paracetamol: oral/rectal: 500-1000 mg

orally/rectally every 4-6 hours when required,
maximum 4000 mg/day; intravenous (<50 kg
body weight): 15 mg/kg intravenously every
Acute
4-6 hours when required, maximum 60 mg/
kg/day; intravenous (≥50 kg body weight):
1000 mg intravenously every 4-6 hours when
required, maximum 4000 mg/day (3000 mg/
day if risk factors for hepatotoxicity)
OR
» diclofenac sodium: 37.5 mg intravenously

every 6 hours when required, maximum 150
mg/day
Secondary options
» paracetamol: oral/rectal: 500-1000 mg

orally/rectally every 4-6 hours when required,
maximum 4000 mg/day; intravenous (<50 kg
body weight): 15 mg/kg intravenously every
kg/day; intravenous (≥50 kg body weight):
1000 mg intravenously every 4-6 hours when
required, maximum 4000 mg/day (3000 mg/
day if risk factors for hepatotoxicity)
-or-
» diclofenac sodium: 37.5 mg intravenously
every 6 hours when required, maximum 150
mg/day
--AND--

Primary options

Secondary options

--AND--
required
MANAGEMENT
-or-

21
Acute
disseminated disease or 1st intravenous aciclovir
eye involvement or severe
Primary options
immunosuppression
» aciclovir: 10 mg/kg intravenously every 8
hours for 7 days
» Intravenous aciclovir therapy should be

reserved for patients with disseminated
infection, ophthalmic involvement, or very severe
immunosuppression.
Primary options

Secondary options

--AND--
required
-or-

MANAGEMENT
Ongoing
postherpetic pain
mild pain 1st paracetamol or NSAID

Primary options

OR

» Patients with mild-to-moderate pain should

be treated with non-steroidal anti-inflammatory
drugs (NSAIDs) or paracetamol, alone or in
combination with a weak opioid analgesic.[100]
[101] [102] [103] [104]
adjunct weak opioid analgesic
Primary options
» codeine phosphate: 15-60 mg orally every

day
» Patients with mild-to-moderate pain should

be treated with non-steroidal anti-inflammatory
drugs or paracetamol, alone or in combination
with a weak opioid analgesic.[100] [101] [102]
[103] [104]
2nd topical capsaicin
Primary options
» capsaicin topical: (0.025 to 0.075%) apply

to the affected area(s) three to four times
daily
» Topical capsaicin has also been shown to

provide pain relief.[105] [106] [107] [108]
moderate-to-severe pain 1st strong opioid, amitriptyline, or
anticonvulsant
Primary options
» tramadol: 50-100 mg orally every 4-6 hours

MANAGEMENT
when required, maximum 400 mg/day
OR

23
Ongoing
Secondary options
» amitriptyline: 0.5 to 2 mg/kg orally once

daily at bedtime initially, increase according to
response, maximum 150 mg/day
OR
» gabapentin: 300 mg orally three times daily

initially, increase according to response,
maximum 1800 mg/day
OR
» pregabalin: 300 mg/day orally given in 2-3

divided doses
» For patients with moderate-to-severe

pain, a strong opioid analgesic may be
considered. Treatment with either a tricyclic
antidepressant such as amitriptyline or
an anticonvulsant such as gabapentin or
pregabalin is also effective.[109] [110]
[111] [112] One meta-analysis showed no
difference in pain relief between gabapentin
and tricyclic antidepressants.[113] For those
intolerant of opioids or at high risk of addiction,
one or a combination of anticonvulsants,
tricyclic antidepressants, or corticosteroids is
appropriate.
MANAGEMENT
Emerging
Brivudine
Brivudine is a thymidine nucleoside analogue with high in-vitro activity against varicella-zoster virus. It is
available for oral administration in some countries in Europe.[83]
Clinacanthus nutans
Clinacanthus nutans is a plant, belonging to the family Acantaceae, that has been used as traditional
treatment for bites and infections in Thailand, including skin rashes, and snake and insect bites. It has been
reported to have analgesic and anti-inflammatory properties, and has been shown to improve the healing
rate of HZ lesions.[116] However, more studies are needed to confirm its efficacy.
Valomaciclovir
Once-daily oral valomaciclovir, a conventional DNA polymerase inhibitor, has been shown to be non-inferior
to 3-times daily valacyclovir therapy in immunocompetent patients with HZ infection. More research is
needed to further evaluate the efficacy and safety of valomaciclovir.[117]
Primary prevention
Vaccination can help prevent HZ and HZ-related post-herpetic neuralgia.[34] [35] [36] Shingrix® is a
recombinant zoster vaccine that contains varicella-zoster virus (VZV) glycoprotein E and the AS01B adjuvant
system. Zostavax® is a lyophilised or freeze-dried preparation of the Oka/Merck strain of live, attenuated
VZV.
Zostavax® was the first vaccine approved for use in adults aged ≥50 years for the prevention of HZ and
HZ-related postherpetic neuralgia.[37] [38] [39][40] Zostavax® is given as a single subcutaneous dose
and can reduce HZ cases by 51%, post-herpetic neuralgia cases by 67%, and the overall burden of illness
by 61%.[41] Because it is a live vaccine, it is contraindicated in severely immunosuppressed people,
pregnant women, or children. It can be safely co-administered with a quadrivalent influenza virus vaccine.[42]
Importantly, the Zostavax® vaccine is less effective in older patients, and vaccine efficacy wanes completely
after approximately 10 years.[43]
In 2017 Shingrix® was approved by the US Food and Drug Administration (FDA), also for adults aged
≥50 years. Following the FDA approval, the Centers for Disease Control and Prevention (CDC) Advisory
Committee on Immunization Practices (ACIP) recommend using Shingrix® in place of Zostavax® for
preventing HZ and postherpetic neuralgia in people aged ≥50 years.[44] This represents a lowering of the
recommended vaccination age from ≥60 years. The ACIP also recommended that all patients previously
vaccinated with Zostavax® receive Shingrix® at least 2 months after their initial vaccination. Shingrix®
requires 2 intramuscular doses to be administered 2 to 6 months apart, and has a substantially higher
efficacy than Zostavax®, reducing HZ cases by 97%.[45] [46] [47] An analysis combining two large phase
3 trials of Shingrix® demonstrated that its efficacy against HZ-related complications was similar in adults
aged ≥50 years and ≥70 years, and most of the reduction in HZ-related complications was driven by the
reduction of HZ cases.[48] More importantly, the efficacy of Shingrix® declines only slightly after 7 years,
remaining at >84%.[49] However, efficacy data for the 2-dose series up to 10 years of follow-up are still
under investigation. The efficacy of a single dose is also unknown, but studies suggest a single dose
does not produce a robust immune response.[36] [50] [51] Therefore, physicians should try to ensure
that patients receive both doses. Furthermore, it is important to complete the series within 2 to 6 months
as indicated, because a series with doses 12 months apart has a lower immunogenicity.[52] There is
currently no recommendation for Shingrix® in pregnancy; delaying vaccination until after pregnancy may be
MANAGEMENT
considered.[47]
Shingrix® prevents more cases of HZ but also causes more injection-site reactions than Zostavax®.[53]
Grade 3 systemic vaccine reactions, defined as symptoms that prevent normal everyday activities, occur
in up to 17% of vaccine recipients, and are more frequent after the second dose than the first.[45] A post-
licensure safety surveillance 1 year after Shingrix® was introduced in the US found that safety data were
25
consistent with the clinical trials.[54] Shingrix® has been shown to be safe and immunogenic in patients
previously vaccinated with Zostavax®.[55] In addition, it can be safely co-administered with the influenza
vaccine without interference with the immune response.[56] Shingrix® has been shown to reduce the burden
of illness of HZ and the severity of HZ-related pain and improve the patient's overall quality of life.[57] An
analysis of Medicare claims data has found an increased risk of Guillain-Barre syndrome (GBS) among
people aged ≥65 years who received Shingrix®. Compared to Zostavax® recipients, older adults vaccinated
with Shingrix® had a more than twofold higher risk of GBS, equivalent to an attributable risk of 6.47 cases
per million doses. However, the risk-benefit balance for Shingrix® still supports its use.[58]
It is important to note that Zostavax® is administered as a single dose subcutaneously; and Shingrix®
is administered as 2 doses (2 to 6 months apart in the general population, or 1 to 2 months apart in
immunodeficient or immunosuppressed patients) intramuscularly. The need to mix two vaccine components
combined with different storage requirements and a different route of administration from Zostavax® leads
to a higher risk of errors when administering Shingrix® which has led to the CDC issuing a reminder to
physicians.[59]
Immunocompromised patients are at higher risk of HZ infection and vaccination is important.[60] One
randomised clinical trial of Shingrix® in adults who had undergone autologous haematopoietic stem cell
transplantation found that a 2-dose course of the vaccine significantly reduced the incidence of HZ compared
with placebo over a median follow-up of 21 months, with a vaccine efficacy of 68%.[61] A post-hoc analysis
of a phase 3 trial of Shingrix® in patients with hematologic malignancies showed an efficacy of 87% within 11
months of follow-up.[62] Other studies have shown that Shingrix® stimulates an immune response in kidney
transplant recipients and patients with solid tumours.[63] [64] In patients with HIV infection, two doses of
Zostavax® were shown to be safe and immunogenic in persons with CD4 counts ≥200 cells/mm³.[65] In a
phase-1/2 randomised controlled trial, Shingrix® was shown to increase humoral and cell-mediated immunity
among patients with CD4 counts <200 cells/mm³ and caused no vaccine-related severe adverse events.[66]
However, there are currently no phase 3 data for either Zostavax® or Shingrix® in patients with HIV. The
US guideline for the prevention and treatment of opportunistic infections in adults with HIV recommends
vaccination with Shingrix® for adults with HIV age ≥18 years, regardless of CD4 count.[13] The vaccine
should not be given during an acute episode of HZ and some experts would delay vaccination until the
patient is virologically suppressed on antiretroviral therapy or until CD4 count recovery to maximise response
to vaccine.[13]
The ACIP recommends Shingrix® in immunodeficient or immunosuppressed adults aged 19 and over.[67]
[68] Ideally, Shingrix® should be given before the patients become immunosuppressed or, otherwise, during
the period when the immune response is strong (i.e., during periods of lower immunosuppression and stable
disease).[69]
In the US, Zostavax® is no longer commercially available; Shingrix® is the only vaccine available for the
prevention of HZ.[69] In Europe, Shingrix® was granted marketing authorisation for preventing HZ and post-
herpetic neuralgia in persons aged ≥50 years in January 2018. In July 2020, the authorisation was extended
to include adults aged ≥18 years at increased risk of HZ. In the UK, from September 2023, Shingrix® will
be offered to immunocompetent individuals aged from 60 years (in a phased implementation over a 10-year
period starting with those turning 65 and 70 years of age) and to severely immunosuppressed individuals
aged from 50 years, replacing Zostavax®.[70]
Secondary prevention
Patients can transmit the virus through fluids from the lesions to people without a history of chicken pox
infection; therefore, direct body contact should be avoided. Covering lesions that are not usually covered by
clothing may also decrease transmission. Immunocompromised people may shed virus from lesions and
MANAGEMENT
from the respiratory tract.
In the US, post-exposure prophylaxis with the varicella vaccine or varicella-zoster immunoglobulin should
be considered if an individual who is susceptible has close exposure to someone with varicella-zoster virus
infection.[125] Varicella-zoster immunoglobulin , is recommended for patients without evidence of immunity
to varicella who are at high risk for severe varicella and complications, who have been exposed to varicella or
herpes zoster, and for whom varicella vaccine is contraindicated.[126]
In the UK, post-exposure prophylaxis is recommended for individuals who have had significant exposure
to shingles (varicella-zoster virus), are at increased risk of severe chickenpox (e.g., immunosuppressed
individuals, neonates, pregnant women), and have no antibodies to varicella-zoster virus. First-line treatment
is with an oral antiviral (e.g., aciclovir, valaciclovir). Intramuscular human varicella-zoster immunoglobulin
(VZIG) is a second-line option in those unable to take oral antivirals and a first-line treatment in susceptible
neonates exposed within 1 week of delivery. Intravenous human normal immunoglobulin is an option for
those who cannot either be given antivirals or receive VZIG.[127]
Patient discussions
Advise patients to keep the rash clean and dry, to reduce the risk of bacterial superinfection. Patients
should also avoid topical antibiotics or dressings with adhesive that may cause irritation and may delay
healing of the rash. In addition, they should avoid wearing clothing made from irritating fibres (e.g.,
wool). Counsel patients about the possible complication of postherpetic pain and offer advice on how to
psychologically manage chronic pain (e.g., with relaxation techniques and counseling). Referral to a pain
management consultant is indicated if the pain interferes with daily living.
MANAGEMENT
27
Herpes zoster infection Follow up
Monitoring
Monitoring
FOLLOW UP
Patients who still have new lesions forming and those who develop neurological, ocular, motor, and
cutaneous complications after treatment with a 7-day course of antiviral drugs should be closely
monitored to assess the need for treatment extension. Treatment for the complications might
be necessary as well. Patients with ocular complications should be referred immediately to an
ophthalmologist.
Complications
Complications Timeframe Likelihood
FOLLOW UP
HZ ophthalmicus short term high
Occurs if virus infects the trigeminal nerve. Infection may cause conjunctivitis, keratitis, corneal ulceration,
iridocyclitis, glaucoma, and blindness. All patients should be treated with antivirals. Antiviral medicine
given within 72 hours after the onset of the rash reduces the incidence of complications by 25%.[120]
Lubricating eye ointment should be given to patients when the blinking reflex has been affected, to prevent
damage to the corneal epithelium.
superinfection of skin lesions short term high
Secondary infection of the lesions, usually with staphylococcal or streptococcal bacteria. Bacterial
superinfection can cause cellulitis, osteomyelitis, or life-threatening complications such as necrotising
fasciitis and sepsis. Symptoms include pain, redness, and swelling in the affected area. Lesions may
develop pus. Antibiotics should be given to treat the infection.
encephalitis short term low
Usually occurs a few days after the rash onset, but in some cases the onset may occur several months
after an HZ episode. Presents with headache, meningismus, fever, ataxia, and seizures. Chronic
encephalitis is seen almost exclusively in immunocompromised individuals. Its onset is usually a few
months after resolution of the rash. Patients usually present with subacute symptoms including headache,
fever, and mental status changes. However, patients may have focal symptoms including hemiplegia and
aphasia. The prognosis is poor. Magnetic resonance imaging scan findings include infarcts of cortical and
sub-cortical grey and white matter and small vessel vasculitis.
HZ oticus (Ramsay Hunt syndrome) short term low
Occurs when varicella-zoster virus is reactivated in the geniculate ganglion of cranial nerve VII (facial
nerve). Occurs in <1% of zoster cases and is more common among those over 60. The classic triad of
Ramsay Hunt syndrome is otalgia, vesicular rash of the ear (herpes zoster oticus) and ipsilateral facial
paralysis. Ramsay Hunt syndrome is distinctive in having a motor component (ipsilateral facial paralysis),
which occurs due to nerves from the motor nucleus of the facial nerve passing through the geniculate
ganglion. Other symptoms can include tinnitus, hearing loss, nausea, vomiting, vertigo and nystagmus
which relates to involvement of the vestibulocochlear nerve. Combination treatment containing antiviral
agents and steroids is recommended for the treatment of Ramsay Hunt syndrome. Prompt diagnosis and
treatment (ideally within 72 hours) leads to improved outcomes.[121] [122]
transverse myelitis short term low
Common in immunocompromised people, and usually occurs after thoracic HZ. Weakness usually occurs
in the same spinal cord segment as the rash. The primary symptom is usually urinary retention. Magnetic
resonance imaging shows evidence of myelitis in the segment of infection.
varicella zoster retinitis short term low
Acute retinal necrosis can occur in immunocompetent and immunocompromised patients. It is usually
unilateral and presents as acute onset of vision loss with possible redness, photophobia, pain, floaters and
flashes. Inflammation can be severe. Progressive outer retinal necrosis generally only occurs in patients
with HIV infection and CD4 count <100 cells/mm3. It is usually bilateral and minimal inflammation is seen.
29
Complications Timeframe Likelihood

Peripheral lesions in the outer retinal layers merge, causing full-thickness retinal necrosis and possible
retinal detachment.[13] [123] [124]
FOLLOW UP
Treatment is with antivirals, and involvement of an experienced ophthalmologist is strongly recommended.
disseminated zoster short term low
Common in severely immunocompromised patients. The vesicular rash involves several dermatomes, and
visceral involvement may also occur. Patients should be treated with intravenous aciclovir until infection is
controlled, then switched to oral antiviral medicine for the remainder of the treatment course.
Prognosis
Herpes zoster rarely causes fatalities in patients who are immunocompetent, but it can be life-threatening
in immunocompromised patients. Ocular complications occur in 50% to 90% of the cases, resulting in
either temporary or permanently decreased visual acuity or blindness if untreated.[96] [118] [119] Other
complications include bacterial superinfections (1.1%), peripheral nerve palsies (1.8%), sensory loss (1.8%),
and disseminated HZ (1.7%).[41]
Herpes zoster infection Guidelines
Treatment guidelines
United Kingdom
Shingles: guidance and vaccination programme (ht tps://www.gov.uk/

government/collections/shingles-vaccination-programme)
Published by: UK Health Security Agency (formerly Public Health Last published: 2023
England)
Post exposure prophylaxis (PEP) for varicella and shingles (ht tps://
www.gov.uk/government/publications/post-exposure-prophylaxis-for-
chickenpox-and-shingles)
England)
Shingles (herpes zoster): the green book, chapter 28a (ht tps://www.gov.uk/
GUIDELINES
government/publications/shingles-herpes-zoster-the-green-book-chapter-28a)
England)
Neuropathic pain in adults: pharmacological management in non-specialist

set tings (ht tps://www.nice.org.uk/guidance/cg173)
Published by: National Institute for Health and Care Excellence Last published: 2020
North America
Recommended immunization schedule for adults aged 19 years or older:

United States, 2024 (ht tps://www.cdc.gov/vaccines/schedules/hcp/index.html)
Published by: Centers for Disease Control and Prevention Last published: 2023
Update on recommendations for use of herpes zoster vaccine (ht tps://

www.cdc.gov/vaccines/hcp/acip-recs/vacc-specific/shingles.html)
Updated recommendations for use of VariZIG - United States (ht tps://

www.cdc.gov/vaccines/hcp/acip-recs/vacc-specific/varicella.html)
Asia
Guidebook on immunization 2018-19 (ht tps://www.iapindia.org/iap-

guidebook-on-immunization)
Published by: Indian Academy of Pediatrics Last published: 2020
31
Herpes zoster infection References
Key articles
• Dworkin RH, Johnson RW, Breuer J, et al. Recommendations for the management of herpes
REFERENCES
zoster. Clin Infect Dis. 2007 Jan 1;44 Suppl 1:S1-26. Full text (https://academic.oup.com/cid/
article/44/Supplement_1/S1/334966) Abstract (http://www.ncbi.nlm.nih.gov/pubmed/17143845?
tool=bestpractice.bmj.com)
• National Institutes of Health, Centers for Disease Control and Prevention, HIV Medicine Association,
and Infectious Diseases Society of America. Panel on Guidelines for the Prevention and Treatment
of Opportunistic Infections in Adults and Adolescents with HIV. Guidelines for the prevention and
treatment of opportunistic infections in adults and adolescents with HIV: varicella-zoster virus. 2022
[internet publication]. Full text (https://clinicalinfo.hiv.gov/en/guidelines/hiv-clinical-guidelines-adult-
and-adolescent-opportunistic-infections/varicella-zoster)
• Dooling KL, Guo A, Patel M, et al. Recommendations of the Advisory Committee on Immunization
Practices for use of herpes zoster vaccines. MMWR Morb Mortal Wkly Rep. 2018 Jan
26;67(3):103-8. Full text (https://www.cdc.gov/mmwr/volumes/67/wr/mm6703a5.htm) Abstract (http://
www.ncbi.nlm.nih.gov/pubmed/29370152?tool=bestpractice.bmj.com)
• Centers for Disease Control and Prevention. Adult immunization schedule. Recommendations for ages
19 years or older, United States, 2024. Nov 2023 [internet publication] Full text (https://www.cdc.gov/
vaccines/schedules/hcp/imz/adult.html)
• Severson EA, Baratz KH, Hodge DO, et al. Herpes zoster ophthalmicus in Olmsted County,
Minnesota: have systemic antivirals made a difference? Arch Ophthalmol. 2003 Mar;121(3):386-90.
Full text (https://jamanetwork.com/journals/jamaophthalmology/fullarticle/415180) Abstract (http://
References
1. Gnann JW Jr, Whitley RJ. Herpes zoster. N Engl J Med. 2002 Aug 1;347(5):340-6. Abstract (http://
2. Roxas M. Herpes zoster and postherpetic neuralgia: diagnosis and therapeutic considerations.
Altern Med Rev. 2006 Jun;11(2):102-13. Abstract (http://www.ncbi.nlm.nih.gov/pubmed/16813460?
3. Dworkin RH, Johnson RW, Breuer J, et al. Recommendations for the management of herpes
zoster. Clin Infect Dis. 2007 Jan 1;44 Suppl 1:S1-26. Full text (https://academic.oup.com/cid/
article/44/Supplement_1/S1/334966) Abstract (http://www.ncbi.nlm.nih.gov/pubmed/17143845?
4. Kawai K, Gebremeskel BG, Acosta CJ. Systematic review of incidence and complications of
herpes zoster: towards a global perspective. BMJ Open. 2014 Jun 10;4(6):e004833. Full text
(https://bmjopen.bmj.com/content/4/6/e004833.long) Abstract (http://www.ncbi.nlm.nih.gov/
pubmed/24916088?tool=bestpractice.bmj.com)
REFERENCES
5. Choo PW, Donahue JG, Manson JE, et al. The epidemiology of varicella and its complications.
J Infect Dis. 1995 Sep;172(3):706-12. Abstract (http://www.ncbi.nlm.nih.gov/pubmed/7658062?
6. Opstelten W, Mauritz Jw, de Wit NJ, et al. Herpes zoster and postherpetic neuralgia: incidence and
risk factors using a general practice research database. Fam Pract. 2002 Oct;19(5):471-5. Full text
(https://academic.oup.com/fampra/article/19/5/471/539233) Abstract (http://www.ncbi.nlm.nih.gov/
7. Di Legami V, Gianino MM, Atti MC, et al. Epidemiology and costs of herpes zoster: background
data to estimate the impact of vaccination. Vaccine. 2007 Oct 23;25(43):7598-604. Abstract (http://
8. Garcia Cenoz M, Castilla J, Montes Y, et al. Varicella and herpes zoster incidence prior to the
introduction of systematic child vaccination in Navarre, 2005-2006. An Sist Sanit Navar 2008 Jan-
Apr;31(1):71-80. Abstract (http://www.ncbi.nlm.nih.gov/pubmed/18496581?tool=bestpractice.bmj.com)
9. Insinga RP, Itzler RF, Pellissier JM, et al. The incidence of herpes zoster in a United States
administrative database. J Gen Intern Med. 2005 Aug;20(8):748-53. Full text (https://
www.ncbi.nlm.nih.gov/pmc/articles/PMC1490195) Abstract (http://www.ncbi.nlm.nih.gov/
10. Buchbinder SP, Katz MH, Hessol NA, et al. Herpes zoster and human immunodeficiency
virus infection. J Infect Dis. 1992 Nov;166(5):1153-6. Abstract (http://www.ncbi.nlm.nih.gov/
11. Alliegro MB, Dorrucci M, Pezzotti P, et al. Herpes zoster and progression to AIDS in a cohort of
individuals who seroconverted to human immunodeficiency virus. Italian HIV Seroconversion Study.
Clin Infect Dis. 1996 Nov;23(5):990-5. Abstract (http://www.ncbi.nlm.nih.gov/pubmed/8922791?
12. Yanni EA, Ferreira G, Guennec M, et al. Burden of herpes zoster in 16 selected immunocompromised
populations in England: a cohort study in the Clinical Practice Research Datalink 2000-2012. BMJ
Open. 2018 Jun 7;8(6):e020528. Full text (https://bmjopen.bmj.com/content/8/6/e020528.long)
Abstract (http://www.ncbi.nlm.nih.gov/pubmed/29880565?tool=bestpractice.bmj.com)
13. National Institutes of Health, Centers for Disease Control and Prevention, HIV Medicine Association,
and Infectious Diseases Society of America. Panel on Guidelines for the Prevention and Treatment
of Opportunistic Infections in Adults and Adolescents with HIV. Guidelines for the prevention and
treatment of opportunistic infections in adults and adolescents with HIV: varicella-zoster virus. 2022
[internet publication]. Full text (https://clinicalinfo.hiv.gov/en/guidelines/hiv-clinical-guidelines-adult-
and-adolescent-opportunistic-infections/varicella-zoster)
14. Fleming DM, Cross KW, Cobb WA, et al. Gender difference in the incidence of shingles.
Epidemiol Infect. 2004 Jan;132(1):1-5. Full text (https://www.ncbi.nlm.nih.gov/pmc/articles/
33
PMC2870070/pdf/14979582.pdf) Abstract (http://www.ncbi.nlm.nih.gov/pubmed/14979582?
REFERENCES
15. Schmader K, George LK, Hamilton JD. Racial differences in the occurrence of herpes zoster.
J Infect Dis. 1995 Mar;171(3):701-4. Abstract (http://www.ncbi.nlm.nih.gov/pubmed/7876622?
16. Smith JB, Fenske NA. Herpes zoster and internal malignancy. South Med J. 1995 Nov;88(11):1089-92.
17. Kawai K, Yawn BP, Wollan P, et al. Increasing incidence of herpes zoster over a 60-year period from a
population-based study. Clin Infect Dis. 2016 Jul 15;63(2):221-6. Full text (https://academic.oup.com/
cid/article/63/2/221/1745553) Abstract (http://www.ncbi.nlm.nih.gov/pubmed/27161774?
18. Hales CM, Harpaz R, Joesoef MR, et al. Examination of links between herpes zoster incidence
and childhood varicella vaccination. Ann Intern Med. 2013 Dec 3;159(11):739-45. Full text
(https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5719886) Abstract (http://www.ncbi.nlm.nih.gov/
19. Russell ML, Schopflocher DP, Svenson L, et al. Secular trends in the epidemiology of shingles
in Alberta. Epidemiol Infect. 2007 Aug;135(6):908-13. Full text (https://www.ncbi.nlm.nih.gov/
pmc/articles/PMC2870667) Abstract (http://www.ncbi.nlm.nih.gov/pubmed/17291380?
20. Brisson M, Edmunds WJ, Law B, et al. Epidemiology of varicella zoster virus infection in Canada and
the United Kingdom. Epidemiol Infect. 2001 Oct;127(2):305-14. Full text (https://www.ncbi.nlm.nih.gov/
pmc/articles/PMC2869750/pdf/11693508.pdf) Abstract (http://www.ncbi.nlm.nih.gov/
21. Toyama N, Shiraki K; Society of the Miyazaki Prefecture Dermatologists. Epidemiology of herpes
zoster and its relationship to varicella in Japan: a 10-year survey of 48,388 herpes zoster cases in
Miyazaki prefecture. J Med Virol. 2009 Dec;81(12):2053-8. Abstract (http://www.ncbi.nlm.nih.gov/
22. Schmader K. Herpes zoster in older adults. Clin Infect Dis. 2001 May 15;32(10):1481-6. Abstract
(http://www.ncbi.nlm.nih.gov/pubmed/11317250?tool=bestpractice.bmj.com)
23. Donahue JG, Choo PW, Manson J, et al. The incidence of herpes zoster. Arch Intern Med.
1995 Aug 7-21;155(15):1605-9. Abstract (http://www.ncbi.nlm.nih.gov/pubmed/7618983?
24. Glesby MJ, Moore RD, Chaisson RE. Clinical spectrum of herpes zoster in adults infected with human
immunodeficiency virus. Clin Infect Dis. 1995 Aug;21(2):370-5. Abstract (http://www.ncbi.nlm.nih.gov/
25. Gupta G, Lautenbach E, Lewis JD. Incidence and risk factors for herpes zoster among patients with
inflammatory bowel disease. Clin Gastroenterol Hepatol. 2006 Dec;4(12):1483-90. Abstract (http://
REFERENCES
26. Bhavsar A, Lonnet G, Wang C, et al. Increased risk of herpes zoster in adults ≥50 years old diagnosed
with COVID-19 in the United States. Open Forum Infect Dis. 2022 May;9(5):ofac118. Full text
27. Marra F, Parhar K, Huang B, et al. Risk factors for herpes zoster infection: a meta-analysis. Open
Forum Infect Dis. 2020 Jan;7(1):ofaa005. Full text (https://www.ncbi.nlm.nih.gov/pmc/articles/
PMC6984676) Abstract (http://www.ncbi.nlm.nih.gov/pubmed/32010734?tool=bestpractice.bmj.com)
28. Forbes HJ, Bhaskaran K, Thomas SL, et al. Quantification of risk factors for herpes zoster: population
based case-control study. BMJ. 2014 May 13;348:g2911. Full text (https://www.ncbi.nlm.nih.gov/
29. Kawai K, Yawn BP. Risk factors for herpes zoster: a systematic review and meta-analysis. Mayo
Clin Proc. 2017 Dec;92(12):1806-21. Abstract (http://www.ncbi.nlm.nih.gov/pubmed/29202939?
30. Armstrong D, Dregan A, Ashworth M, et al. Prior antibiotics and risk of subsequent herpes
zoster: a population-based case control study. PLoS One. 2022;17(10):e0276807. Full text
31. Chen IL, Chiu HY. Association of herpes zoster with COVID-19 vaccination: A systematic review and
meta-analysis. J Am Acad Dermatol. 2023 Aug;89(2):370-1. Full text (https://www.ncbi.nlm.nih.gov/
pmc/articles/PMC10060010)
32. Hertel M, Heiland M, Nahles S, et al. Real-world evidence from over one million COVID-19
vaccinations is consistent with reactivation of the varicella-zoster virus. J Eur Acad Dermatol Venereol.
2022 Aug;36(8):1342-48. Full text (https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9114991) Abstract
33. Walter R, Hartmann K, Fleisch F, et al. Reactivation of herpesvirus infections after vaccinations?
Lancet. 1999 Mar 6;353(9155):810.
34. de Oliveira Gomes J, Gagliardi AM, Andriolo BN, et al. Vaccines for preventing herpes zoster
in older adults. Cochrane Database Syst Rev. 2023 Oct 2;10(10):CD008858. Abstract (http://
35. Klein NP, Bartlett J, Fireman B, et al. Effectiveness of the live zoster vaccine during the 10 years
following vaccination: real world cohort study using electronic health records. BMJ. 2023 Nov
8;383:e076321. Full text (https://www.bmj.com/content/383/bmj-2023-076321.long) Abstract (http://
35
36. Zerbo O, Bartlett J, Fireman B, et al. Effectiveness of recombinant zoster vaccine against
herpes zoster in a real-world setting. Ann Intern Med. 2024 Feb;177(2):189-95. Abstract (http://
REFERENCES
37. Sanford M, Keating GM. Zoster vaccine (Zostavax): a review of its use in preventing herpes zoster
and postherpetic neuralgia in older adults. Drugs Aging. 2010 Feb 1;27(2):159-76. Abstract (http://
38. US Food and Drug Administration. Vaccines, blood and biologics: Zostavax. Dec 2019 [internet
publication]. Full text (https://www.fda.gov/vaccines-blood-biologics/vaccines/zostavax)
39. Chen N, Li Q, Zhang Y, et al. Vaccination for preventing postherpetic neuralgia. Cochrane
Database Syst Rev. 2011 Mar 16;(3):CD007795. Full text (https://www.cochranelibrary.com/
cdsr/doi/10.1002/14651858.CD007795.pub2/full) Abstract (http://www.ncbi.nlm.nih.gov/
40. Schmader KE, Levin MJ, Gnann JW Jr, et al. Efficacy, safety, and tolerability of herpes zoster
vaccine in persons aged 50-59 years. Clin Infect Dis. 2012 Apr;54(7):922-8. Full text (https://
academic.oup.com/cid/article/54/7/922/299086) Abstract (http://www.ncbi.nlm.nih.gov/
41. Oxman MN, Levin MJ, Johnson GR, et al; Shingles Prevention Study Group. A vaccine to prevent
herpes zoster and postherpetic neuralgia in older adults. N Engl J Med. 2005 Jun 2;352(22):2271-84.
Full text (https://www.nejm.org/doi/10.1056/NEJMoa051016) Abstract (http://www.ncbi.nlm.nih.gov/
42. Levin MJ, Buchwald UK, Gardner J, et al. Immunogenicity and safety of zoster vaccine live
administered with quadrivalent influenza virus vaccine. Vaccine. 2018 Jan 2;36(1):179-85. Full text
(https://www.sciencedirect.com/science/article/pii/S0264410X17310964?via%3Dihub) Abstract
43. Morrison VA, Johnson GR, Schmader KE, et al; Shingles Prevention Study Group. Long-
term persistence of zoster vaccine efficacy. Clin Infect Dis. 2015 Mar 15;60(6):900-9. Full text
(https://academic.oup.com/cid/article/60/6/900/496651) Abstract (http://www.ncbi.nlm.nih.gov/
44. Dooling KL, Guo A, Patel M, et al. Recommendations of the Advisory Committee on Immunization
Practices for use of herpes zoster vaccines. MMWR Morb Mortal Wkly Rep. 2018 Jan
26;67(3):103-8. Full text (https://www.cdc.gov/mmwr/volumes/67/wr/mm6703a5.htm) Abstract (http://
45. Lal H, Cunningham AL, Godeaux O, et al; ZOE-50 Study Group. Efficacy of an adjuvanted herpes
zoster subunit vaccine in older adults. N Engl J Med. 2015 May 28;372(22):2087-96. Full text
(https://www.nejm.org/doi/full/10.1056/NEJMoa1501184) Abstract (http://www.ncbi.nlm.nih.gov/
46. Cunningham AL, Lal H, Kovac M, et al; ZOE-70 Study Group. Efficacy of the herpes zoster subunit
vaccine in adults 70 years of age or older. N Engl J Med. 2016 Sep 15;375(11):1019-32. Full text
(https://www.nejm.org/doi/full/10.1056/NEJMoa1603800) Abstract (http://www.ncbi.nlm.nih.gov/
REFERENCES
47. Centers for Disease Control and Prevention. Adult immunization schedule. Recommendations for ages
19 years or older, United States, 2024. Nov 2023 [internet publication] Full text (https://www.cdc.gov/
vaccines/schedules/hcp/imz/adult.html)
48. Kovac M, Lal H, Cunningham AL, et al. Complications of herpes zoster in immunocompetent older
adults: incidence in vaccine and placebo groups in two large phase 3 trials. Vaccine. 2018 Mar
14;36(12):1537-41. Full text (https://www.sciencedirect.com/science/article/pii/S0264410X18302032?
via%3Dihub) Abstract (http://www.ncbi.nlm.nih.gov/pubmed/29463421?tool=bestpractice.bmj.com)
49. Boutry C, Hastie A, Diez-Domingo J, et al. The Adjuvanted Recombinant Zoster Vaccine Confers
Long-Term Protection Against Herpes Zoster: Interim Results of an Extension Study of the Pivotal
Phase 3 Clinical Trials ZOE-50 and ZOE-70. Clin Infect Dis. 2022 Apr 28;74(8):1459-67. Full text
50. Chlibek R, Smetana J, Pauksens K, et al. Safety and immunogenicity of three different formulations of
an adjuvanted varicella-zoster virus subunit candidate vaccine in older adults: a phase II, randomized,
controlled study. Vaccine. 2014 Mar 26;32(15):1745-53. Abstract (http://www.ncbi.nlm.nih.gov/
51. Parikh R, Singer D, Chmielewski-Yee E, et al. Effectiveness and safety of recombinant zoster
vaccine: a review of real-world evidence. Hum Vaccin Immunother. 2023 Dec 15;19(3):2263979.
Full text (https://www.tandfonline.com/doi/full/10.1080/21645515.2023.2263979) Abstract (http://
52. Lal H, Poder A, Campora L, et al. Immunogenicity, reactogenicity and safety of 2 doses of an
adjuvanted herpes zoster subunit vaccine administered 2, 6 or 12 months apart in older adults: results
of a phase III, randomized, open-label, multicenter study. Vaccine. 2018 Jan 2;36(1):148-54. Full
text (https://www.sciencedirect.com/science/article/pii/S0264410X17315785?via%3Dihub) Abstract
53. Tricco AC, Zarin W, Cardoso R, et al. Efficacy, effectiveness, and safety of herpes zoster vaccines in
adults aged 50 and older: systematic review and network meta-analysis. BMJ. 2018 Oct 25;363:k4029.
Full text (https://www.bmj.com/content/363/bmj.k4029.long) Abstract (http://www.ncbi.nlm.nih.gov/
54. Hesse EM, Shimabukuro TT, Su JR, et al. Postlicensure safety surveillance of recombinant zoster
vaccine (Shingrix) - United States, October 2017 - June 2018. MMWR Morb Mortal Wkly Rep. 2019
Feb 1;68(4):91-4. Full text (https://www.cdc.gov/mmwr/volumes/68/wr/mm6804a4.htm) Abstract
55. Grupping K, Campora L, Douha M, et al. Immunogenicity and safety of the HZ/su adjuvanted
herpes zoster subunit vaccine in adults previously vaccinated with a live attenuated herpes
zoster vaccine. J Infect Dis. 2017 Dec 12;216(11):1343-51. Full text (https://academic.oup.com/
37
jid/article/216/11/1343/4209275) Abstract (http://www.ncbi.nlm.nih.gov/pubmed/2902912?
REFERENCES
56. Schwarz TF, Aggarwal N, Moeckesch B, et al. Immunogenicity and safety of an adjuvanted
herpes zoster subunit vaccine coadministered with seasonal influenza vaccine in adults aged 50
years or older. J Infect Dis. 2017 Dec 12;216(11):1352-61. Full text (https://academic.oup.com/
jid/article/216/11/1352/4191338) Abstract (http://www.ncbi.nlm.nih.gov/pubmed/29029224?
57. Curran D, Oostvogels L, Heineman T, et al; ZOE-50/70 Study Group. Quality of life impact of
an adjuvanted recombinant zoster vaccine in adults aged 50 years and older. J Gerontol A Biol
Sci Med Sci. 2019 Jul 12;74(8):1231-8. Full text (https://academic.oup.com/biomedgerontology/
article/74/8/1231/5046047) Abstract (http://www.ncbi.nlm.nih.gov/pubmed/29955836?
58. Goud R, Lufkin B, Duffy J, et al. Risk of Guillain-Barré Syndrome Following Recombinant Zoster
Vaccine in Medicare Beneficiaries. JAMA Intern Med. 2021 Dec 1;181(12):1623-30. Full text
59. Shimabukuro TT, Miller ER, Strikas RA, et al. Notes from the Field: vaccine administration errors
involving recombinant zoster vaccine — United States, 2017–2018. MMWR Morb Mortal Wkly Rep.
2018 May 25;67(20):585-6. Full text (https://www.cdc.gov/mmwr/volumes/67/wr/mm6720a4.htm)
60. Chen SY, Suaya JA, Li Q, et al. Incidence of herpes zoster in patients with altered immune function.
Infection. 2014 Apr;42(2):325-34. Full text (https://www.doi.org/10.1007/s15010-013-0550-8)
61. Bastidas A, de la Serna J, El Idrissi M, et al; ZOE-HSCT Study Group Collaborators. Effect of
recombinant zoster vaccine on incidence of herpes zoster after autologous stem cell transplantation:
a randomized clinical trial. JAMA. 2019 Jul 9;322(2):123-33. Full text (https://jamanetwork.com/
journals/jama/fullarticle/2737683) Abstract (http://www.ncbi.nlm.nih.gov/pubmed/31287523?
62. Dagnew AF, Ilhan O, Lee WS, et al. Immunogenicity and safety of the adjuvanted recombinant
zoster vaccine in adults with haematological malignancies: a phase 3, randomised, clinical
trial and post-hoc efficacy analysis. Lancet Infect Dis. 2019 Sep;19(9):988-1000. Full text
(https://www.doi.org/10.1016/S1473-3099(19)30163-X) Abstract (http://www.ncbi.nlm.nih.gov/
63. Vink P, Ramon Torrell JM, Sanchez Fructuoso A, et al. Immunogenicity and Safety of the Adjuvanted
Recombinant Zoster Vaccine in Chronically Immunosuppressed Adults Following Renal Transplant:
A Phase 3, Randomized Clinical Trial. Clin Infect Dis. 2020 Jan 2;70(2):181-190. Full text (https://
www.doi.org/10.1093/cid/ciz177) Abstract (http://www.ncbi.nlm.nih.gov/pubmed/30843046?
64. Vink P, Delgado Mingorance I, Maximiano Alonso C, et al. Immunogenicity and safety of the
adjuvanted recombinant zoster vaccine in patients with solid tumors, vaccinated before or during
chemotherapy: A randomized trial. Cancer. 2019 Apr 15;125(8):1301-12. Full text (https://
www.ncbi.nlm.nih.gov/pmc/articles/PMC6766894) Abstract (http://www.ncbi.nlm.nih.gov/
REFERENCES
65. Benson CA, Andersen JW, Macatangay BJC, et al. Safety and Immunogenicity of Zoster Vaccine
Live in Human Immunodeficiency Virus-Infected Adults With CD4+ Cell Counts >200 Cells/mL
Virologically Suppressed on Antiretroviral Therapy. Clin Infect Dis. 2018 Nov 13;67(11):1712-19. Full
text (https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6233680) Abstract (http://www.ncbi.nlm.nih.gov/
66. Berkowitz EM, Moyle G, Stellbrink HJ, et al. Safety and immunogenicity of an adjuvanted herpes
zoster subunit candidate vaccine in HIV-infected adults: a phase 1/2a randomized, placebo-controlled
study. J Infect Dis. 2015 Apr 15;211(8):1279-87. Full text (https://www.doi.org/10.1093/infdis/jiu606)
67. Centers for Disease Control and Prevention. Morbidity and Mortality Weekly Report. Use of
recombinant zoster vaccine in immunocompromised adults aged ≥ 19 Years: recommendations
of the advisory committee on immunization practices — United States, 2022. Jan 2022 [internet
publication]. Full text (https://www.cdc.gov/mmwr/volumes/71/wr/mm7103a2.htm) Abstract (http://
www.ncbi.nlm.nih.gov/pubmed/insert id?tool=bestpractice.bmj.com)
68. Centers for Disease Control and Prevention. Clinical considerations for use of recombinant zoster
vaccine (RZV, Shingrix) in immunocompromised adults aged ≥19 Years. Jan 2022 [internet
publication]. Full text (https://www.cdc.gov/shingles/vaccination/immunocompromised-adults.html)
Abstract (http://www.ncbi.nlm.nih.gov/pubmed/insert id?tool=bestpractice.bmj.com)
69. Centers for Disease Control and Prevention. Shingles (Herpes Zoster). Feb 2022 [internet publication].
Full text (https://www.cdc.gov/shingles/index.html)
70. UK Health Security Agency. Shingles vaccination: guidance for healthcare practitioners. Sep 2023
[internet publication]. Full text (https://www.gov.uk/government/publications/shingles-vaccination-
guidance-for-healthcare-professionals)
71. Katz J, Cooper EM, Walther RR, et al. Acute pain in herpes zoster and its impact on health-related
quality of life. Clin Infect Dis. 2004 Aug 1;39(3):342-8. Abstract (http://www.ncbi.nlm.nih.gov/
72. Gilden DH, Wright RR, Schneck SA, et al. Zoster sine herpete, a clinical variant. Ann Neurol. 1994
May;35(5):530-3. Abstract (http://www.ncbi.nlm.nih.gov/pubmed/8179298?tool=bestpractice.bmj.com)
73. National Institute for Health and Care Excellence. HIV testing: encouraging uptake. Sep 2017 [internet
publication]. Full text (https://www.nice.org.uk/guidance/qs157/chapter/Quality-statement-3-HIV-
indicator-conditions)
74. HIV in Europe. HIV indicator conditions - guidance for implementing HIV testing in adults in health care
settings. Jun 2016 [internet publication]. Full text (https://www.eurotest.org/testing-tools/hiv-indicator-
conditions)
39
75. Gilden DH, Kleinschmidt-DeMasters BK, LaGuardia JJ, et al. Neurologic complications of the
reactivation of varicella-zoster virus. N Engl J Med. 2000 Mar 2;342(9):635-45. Abstract (http://
REFERENCES
76. Dahl H, Marcoccia J, Linde A. Antigen detection: the method of choice in comparison with virus
isolation and serology for laboratory diagnosis of herpes zoster in human immunodeficiency
virus-infected patients. J Clin Microbiol. 1997 Feb;35(2):347-9. Full text (https://jcm.asm.org/
content/jcm/35/2/347.full.pdf) Abstract (http://www.ncbi.nlm.nih.gov/pubmed/9003593?
77. Sauerbrei A, Eichhorn U, Schacke M, et al. Laboratory diagnosis of herpes zoster. J Clin Virol. 1999
Sep;14(1):31-6. Abstract (http://www.ncbi.nlm.nih.gov/pubmed/10548128?tool=bestpractice.bmj.com)
78. Pavan-Langston D. Herpes zoster antivirals and pain management. Opthalmology. 2008 Feb;115(2
Suppl):S13-20. Abstract (http://www.ncbi.nlm.nih.gov/pubmed/18243927?tool=bestpractice.bmj.com)
79. Huff JC, Bean B, Balfour HH Jr, et al. Therapy of herpes zoster with oral acyclovir. Am J
Med. 1988 Aug 29;85(2A):84-9. Abstract (http://www.ncbi.nlm.nih.gov/pubmed/3044099?
80. Tyring S, Barbarash RA, Nahlik JE, et al; Collaborative Famciclovir Herpes Zoster Study Group.
Famciclovir for the treatment of acute herpes zoster: effects on acute disease and postherpetic
neuralgia: a randomized, double-blind, placebo-controlled trial. Ann Intern Med. 1995 Jul
15;123(2):89-96. Abstract (http://www.ncbi.nlm.nih.gov/pubmed/7778840?tool=bestpractice.bmj.com)
81. Tyring SK, Beutner KR, Tucker BA, et al. Antiviral therapy for herpes zoster: randomized, controlled
clinical trial of valacyclovir and famciclovir therapy in immunocompetent patients 50 years and older.
Arch Fam Med. 2000 Sep-Oct;9(9):863-9. Abstract (http://www.ncbi.nlm.nih.gov/pubmed/11031393?
82. Severson EA, Baratz KH, Hodge DO, et al. Herpes zoster ophthalmicus in Olmsted County,
Minnesota: have systemic antivirals made a difference? Arch Ophthalmol. 2003 Mar;121(3):386-90.
Full text (https://jamanetwork.com/journals/jamaophthalmology/fullarticle/415180) Abstract (http://
83. Wassilew SW. Brivudin compared with famciclovir in the treatment of herpes zoster: effects in acute
disease and chronic pain in immunocompetent patients. A randomized, double-blind, multinational
study. J Eur Acad Dermatol Venereol. 2005 Jan;19(1):47-55. Abstract (http://www.ncbi.nlm.nih.gov/
84. McDonald EM, de Kock J, Ram FS. Antivirals for management of herpes zoster including
ophthalmicus: a systematic review of high-quality randomized controlled trials. Antivir
Ther. 2012;17(2):255-64. Abstract (http://www.ncbi.nlm.nih.gov/pubmed/22300753?
85. Degreef H; Famciclovir Herpes Zoster Clinical Study Group. Famciclovir, a new oral antiherpes drug:
results of the first controlled clinical study demonstrating its efficacy and safety in the treatment of
uncomplicated herpes zoster in immunocompetent patients. Int J Antimicrob Agents. 1994;4(4):241-6.
REFERENCES
86. Beutner KR, Friedman DJ, Forszpaniak C, et al. Valaciclovir compared with acyclovir for improved
therapy for herpes zoster in immunocompetent adults. Antimicrob Agents Chemother. 1995
Jul;39(7):1546-53. Abstract (http://www.ncbi.nlm.nih.gov/pubmed/7492102?tool=bestpractice.bmj.com)
87. Wassilew SW, Wutzler P. Oral brivudin in comparison with acyclovir for herpes zoster: a survey study
on postherpetic neuralgia. Antiviral Res. 2003 Jun;59(1):57-60. Abstract (http://www.ncbi.nlm.nih.gov/
88. Huff JC, Drucker JL, Clemmer A, et al. Effect of oral acyclovir on pain resolution in herpes
zoster: a reanalysis. J Med Virol. 1993 Jan 1;Suppl 1:93-6. Abstract (http://www.ncbi.nlm.nih.gov/
89. Morton P, Thomson AN. Oral acyclovir in the treatment of herpes zoster in general practice. N
Z Med J. 1989 Mar 8;102(863):93-5. Abstract (http://www.ncbi.nlm.nih.gov/pubmed/2648213?
90. McKendrick MW, McGill JI, White JE, et al. Oral acyclovir in acute herpes zoster. BMJ.
1986 Dec 13;293(6561):1529-32. Abstract (http://www.ncbi.nlm.nih.gov/pubmed/3099943?
91. McKendrick MW, McGill JI, Wood MJ. Lack of effect of acyclovir on postherpetic neuralgia.
BMJ. 1989 Feb 18;298(6671):431. Abstract (http://www.ncbi.nlm.nih.gov/pubmed/2495051?
92. Wood MJ, Ogan PH, McKendrick MW, et al. Efficacy of oral acyclovir treatment of acute herpes zoster.
Am J Med. 1988 Aug 29;85(2A):79-83. Abstract (http://www.ncbi.nlm.nih.gov/pubmed/3044098?
93. Wood MJ, Kay R, Dworkin RH, et al. Oral acyclovir therapy accelerates pain resolution in patients
with herpes zoster: a meta-analysis of placebo-controlled trials. Clin Infect Dis. 1996 Feb;22(2):341-7.
94. Jackson JL, Gibbons R, Meyer G, et al. The effect of treating herpes zoster with oral acyclovir in
preventing postherpetic neuralgia: a meta-analysis. Arch Intern Med. 1997 Apr 28;157(8):909-12.
95. Whitley RJ, Weiss H, Gnann JW Jr, et al. Acyclovir with and without prednisone for the treatment of
herpes zoster: a randomized, placebo-controlled trial. Ann Intern Med. 1996 Sep 1;125(5):376-83.
96. Opstelten W, Zaal MJ. Managing ophthalmic herpes zoster in primary care. BMJ. 2005
Jul 16;331(7509):147-51. Abstract (http://www.ncbi.nlm.nih.gov/pubmed/16020856?
41
97. Kumar V, Krone K, Mathieu A. Neuraxial and sympathetic blocks in herpes zoster and postherpetic
neuralgia: an appraisal of current evidence. Reg Anesth Pain Med. 2004 Sep-Oct;29(5):454-61.
REFERENCES
98. Wolff RF, Bala MM, Westwood M, et al. 5% lidocaine-medicated plaster vs other relevant
interventions and placebo for post-herpetic neuralgia (PHN): a systematic review. Acta Neurol
Scand. 2011 May;123(5):295-309. Abstract (http://www.ncbi.nlm.nih.gov/pubmed/21039364?
99. Choo PW, Galil K, Donahue JG, et al. Risk factors for postherpetic neuralgia. Arch Intern
Med. 1997 Jun 9;157(11):1217-24. Abstract (http://www.ncbi.nlm.nih.gov/pubmed/9183233?
100. Wu CL, Marsh A, Dworkin RH. The role of sympathetic nerve blocks in herpes zoster and postherpetic
neuralgia. Pain. 2000 Aug;87(2):121-9. Abstract (http://www.ncbi.nlm.nih.gov/pubmed/10924805?
101. Rowbotham M, Harden N, Stacey B, et al. Gabapentin for the treatment of postherpetic neuralgia: a
randomized controlled trial. JAMA. 1998 Dec 2;280(21):1837-42. Full text (https://jamanetwork.com/
journals/jama/fullarticle/188226) Abstract (http://www.ncbi.nlm.nih.gov/pubmed/9846778?
102. Watson CP, Babul N. Efficacy of oxycodone in neuropathic pain: a randomized trial in postherpetic
neuralgia. Neurology. 1998 Jun;50(6):1837-41. Abstract (http://www.ncbi.nlm.nih.gov/
103. Bernstein JE, Korman NJ, Bickers DR, et al. Topical capsaicin treatment of chronic postherpetic
neuralgia. J Am Acad Dermatol. 1989 Aug;21(2 Pt 1):265-70. Abstract (http://www.ncbi.nlm.nih.gov/
104. Galer BS, Rowbotham MC, Perander J, et al. Topical lidocaine patch relieves postherpetic neuralgia
more effectively than a vehicle topical patch: results of an enriched enrollment study. Pain. 1999
Apr;80(3):533-8. Abstract (http://www.ncbi.nlm.nih.gov/pubmed/10342414?tool=bestpractice.bmj.com)
105. Backonja M, Wallace MS, Blonsky ER, et al. NGX-4010, a high-concentration capsaicin
patch, for the treatment of postherpetic neuralgia: a randomised, double-blind study. Lancet
Neurol. 2008 Dec;7(12):1106-12. Abstract (http://www.ncbi.nlm.nih.gov/pubmed/18977178?
106. Derry S, Rice AS, Cole P, et al. Topical capsaicin (high concentration) for chronic neuropathic
pain in adults. Cochrane Database Syst Rev. 2017 Jan 13;(1):CD007393. Full text (https://
www.cochranelibrary.com/cdsr/doi/10.1002/14651858.CD007393.pub4/full) Abstract (http://
107. Irving GA, Backonja MM, Dunteman E, et al. A multicenter, randomized, double-blind, controlled
study of NGX-4010, a high-concentration capsaicin patch, for the treatment of postherpetic neuralgia.
Pain Med. 2011 Jan;12(1):99-109. Abstract (http://www.ncbi.nlm.nih.gov/pubmed/21087403?
108. Webster LR, Malan TP, Tuchman MM, et al. A multicenter, randomized, double-blind, controlled dose
finding study of NGX-4010, a high-concentration capsaicin patch, for the treatment of postherpetic
neuralgia. J Pain. 2010 Oct;11(10):972-82. Abstract (http://www.ncbi.nlm.nih.gov/pubmed/20655809?
REFERENCES
109. Saarto T, Wiffen PJ. Antidepressants for neuropathic pain. Cochrane Database Syst
Rev. 2007 Oct 17;(4):CD005454. Full text (https://www.cochranelibrary.com/cdsr/
doi/10.1002/14651858.CD005454.pub2/full) Abstract (http://www.ncbi.nlm.nih.gov/
110. Roth TV, van Seventer R, Murphy TK. The effect of pregabalin on pain-related sleep interference
in diabetic peripheral neuropathy or postherpetic neuralgia: a review of nine clinical trials. Cur
Med Res Op. 2010 Oct;26(10):2411-9. Abstract (http://www.ncbi.nlm.nih.gov/pubmed/20812792?
111. Wiffen PJ, Derry S, Bell RF, et al. Gabapentin for chronic neuropathic pain in adults. Cochrane
Database Syst Rev. 2017 Jun 9;(6):CD007938. Full text (https://www.cochranelibrary.com/
cdsr/doi/10.1002/14651858.CD007938.pub4/full) Abstract (http://www.ncbi.nlm.nih.gov/
112. Semel D, Murphy TK, Zlateva G, et al. Evaluation of the safety and efficacy of pregabalin
in older patients with neuropathic pain: results from a pooled analysis of 11 clinical studies.
BMC Fam Pract. 2010 Nov 5;11:85. Full text (https://bmcfampract.biomedcentral.com/
articles/10.1186/1471-2296-11-85) Abstract (http://www.ncbi.nlm.nih.gov/pubmed/21054853?
113. Chou R, Carson S, Chan BK. Gabapentin versus tricyclic antidepressants for diabetic neuropathy
and post-herpetic neuralgia: discrepancies between direct and indirect meta-analyses of randomized
controlled trials. J Gen Intern Med. 2009 Feb;24(2):178-88. Full text (https://www.ncbi.nlm.nih.gov/
114. Edelsberg JS, Lord C, Oster G. Systematic review and meta-analysis of efficacy, safety, and
tolerability data from randomized controlled trials of drugs used to treat postherpetic neuralgia. Ann
Pharmacother. 2011 Dec;45(12):1483-90. Abstract (http://www.ncbi.nlm.nih.gov/pubmed/22085778?
115. Tyring S, Engst R, Corriveau C, et al. Famciclovir for ophthalmic zoster: a randomised aciclovir
controlled study. Br J Ophthalmol. 2001 May;85(5):576-81. Abstract (http://www.ncbi.nlm.nih.gov/
116. Kongkaew C, Chaiyakunapruk N. Efficacy of Clinacanthus nutans extracts in patients with

herpes infection: systematic review and meta-analysis of randomised clinical trials. Complement
Ther Med. 2011 Feb;19(1):47-53. Abstract (http://www.ncbi.nlm.nih.gov/pubmed/21296267?
117. Tyring SK, Plunkett S, Scribner AR, et al; Valomaciclovir Zoster Study Group. Valomaciclovir versus
valacyclovir for the treatment of acute herpes zoster in immunocompetent adults: a randomized,
43
double-blind, active-controlled trial. J Med Virol. 2012 Aug;84(8):1224-32. Abstract (http://
REFERENCES
118. Harding SP, Lipton JR, Wells JC. Natural history of herpes zoster ophthalmicus: predictors of
postherpetic neuralgia and ocular involvement. Br J Ophthalmol. 1987 May;71(5):353-8. Full text
(https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1041165/pdf/brjopthal00615-0030.pdf) Abstract
119. Shaikh S, Ta CN. Evaluation and management of Herpes Zoster ophthalmicus. Am Fam
Physician. 2002 Nov 1;66(9):1723-30. Abstract (http://www.ncbi.nlm.nih.gov/pubmed/12449270?
120. Cobo LM, Foulks GN, Liesegang T, et al. Oral acyclovir in the treatment of acute herpes zoster
ophthalmicus. Ophthalmology. 1986 Jun;93(6):763-70. Abstract (http://www.ncbi.nlm.nih.gov/
121. Sweeney CJ, Gilden DH. Ramsay Hunt syndrome. J Neurol Neurosurg Psychiatry.
2001 Aug;71(2):149-54. Abstract (http://www.ncbi.nlm.nih.gov/pubmed/11459884?
122. Uscategui T, Dorée C, Chamberlain IJ, et al. Antiviral therapy for Ramsay Hunt syndrome (herpes
zoster oticus with facial palsy) in adults. Cochrane Database Syst Rev. 2008 Oct 8;2008(4):CD006851.
Full text (https://www.cochranelibrary.com/cdsr/doi/10.1002/14651858.CD006851.pub2/full) Abstract
123. American Academy of Ophthalmology. Acute retinal necrosis. May 2023 [internet publication]. Full text
(https://eyewiki.aao.org/Acute_Retinal_Necrosis)
124. American Academy of Ophthalmology. Progressive outer retinal necrosis. Jan 2024 [internet
publication]. Full text (https://eyewiki.org/Progressive_Outer_Retinal_Necrosis)
125. Harpaz R, Ortega-Sanchez IR, Seward JF, et al. Prevention of herpes zoster: recommendations
of the Advisory Committee on Immunization Practices (ACIP). MMWR Recomm Rep. 2008 Jun
6;57(rr-5):1-30. Abstract (http://www.ncbi.nlm.nih.gov/pubmed/18528318?tool=bestpractice.bmj.com)
126. Centers for Disease Control and Prevention. Updated recommendations for use of VariZIG -
United States, 2013. MMWR Morb Mortal Wkly Rep. 2013 Jul 19;62(28):574-6. Full text (https://
www.cdc.gov/mmwr/preview/mmwrhtml/mm6228a4.htm) Abstract (http://www.ncbi.nlm.nih.gov/
127. UK Health Security Agency. Guidance: post exposure prophylaxis for chickenpox and shingles. Jan
2023 [internet publication]. Full text (https://www.gov.uk/government/publications/post-exposure-
prophylaxis-for-chickenpox-and-shingles)
Herpes zoster infection Images
Images
IMAGES
Figure 1: Severe herpes zoster in an immunocompromised patient involving dermatomes T1 and T2
45
IMAGES Herpes zoster infection Images
Figure 2: Severe herpes zoster in an immunocompromised patient involving dermatomes T1 and T2

Herpes zoster infection Images
IMAGES
Figure 3: Severe herpes zoster in an immunocompromised patient showing multiple groupled vesicles, a few
pustules, and extensive blackish adherent crusts with underlying erosions noted
47
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Contributors:
// Authors:
Phuc Le, PhD, MPH

Assistant Professor
Center for Value-Based Care Research, Medicine Institute, Cleveland Clinic, Cleveland, OH
DISCLOSURES: PL declares that she has no competing interests.
Michael Rothberg, MD, MPH

Professor
Center for Value-Based Care Research, Medicine Institute, Cleveland Clinic, Cleveland, OH
DISCLOSURES: MR declares that he has no competing interests.
// Acknowledgements:
Dr Phuc Le and Dr Michael Rothberg would like to gratefully acknowledge Dr Kenneth J. Smith and Dr
Linda Kalilani, the previous contributors to this topic.
DISCLOSURES: KJS and LK declare that they have no competing interests.
// Peer Reviewers:
Julius Atashili, MD, MPH

Department of Epidemiology
Division of General Medicine and Epidemiology, UNC at Chapel Hill, Chapel Hill, NC
DISCLOSURES: JA declares that he has no competing interests.
Ken Mut ton, MB, BS, FRCPA, FRCPath

Consultant Virologist
Manchester Royal Infirmary, Manchester, UK
DISCLOSURES: KM declares that he has no competing interests.

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Herpes zoster infection

Straight to the point of care

Last updated: Mar 06, 2024

among people aged 80 years or over.

Signs and symptoms

Severe herpes zoster in an immunocompromised patient involving dermatomes T1 and T2

Severe herpes zoster in an immunocompromised patient involving dermatomes T1 and T2

Severe herpes zoster in an immunocompromised patient showing multiple groupled vesicles,

History and exam

localised pain in a dermatome (common)

corneal ulceration (common)

Other diagnostic factors

pain without rash (uncommon)

chronic corticosteroid use

certain acute or chronic conditions

vaccination against other infectious diseases

Other tests to consider

Condition Differentiating signs / Differentiating tests

Herpes simplex • Grouped vesicles on an • Polymerase chain reaction

Cholecystitis • Presents with pain in the • Patients have elevated levels

Ulcerative keratitis • Symptoms depend on • Fluorescein staining would

feature that differentiates as a foreign body.

Glaucoma, acute angle- • Presents with periorbital • Tonometry shows increased

Trigeminal neuralgia • Presents with an intense, • No differentiating test is

Condition Differentiating signs / Differentiating tests

Renal calculi • Presents with severe • A kidney, ureter, and bladder

Viral replication reduction

Therapy for chronic problems includes the following:[3]

• Lubricating, preservative-free artificial tear gels or tears

Treatment algorithm overview

1st oral antiviral therapy

mild pain plus simple analgesics ± calamine lotion

moderate-to-severe pain adjunct opioid analgesics ± topical analgesic

eye involvement plus prompt referral to ophthalmologist

localised disease with 1st oral antiviral therapy

plus simple analgesics ± calamine lotion

adjunct opioid analgesics ± topical analgesic

2nd intravenous aciclovir

plus simple analgesics ± calamine lotion

adjunct opioid analgesics ± topical analgesic

disseminated disease or 1st intravenous aciclovir

adjunct opioid analgesics ± topical analgesic

mild pain 1st paracetamol or NSAID

adjunct weak opioid analgesic

2nd topical capsaicin

moderate-to-severe pain 1st strong opioid, amitriptyline, or

acute symptoms: 1st oral antiviral therapy

» famciclovir: 500 mg orally every 8 hours for

» valaciclovir: 1000 mg orally every 8 hours

» aciclovir: 800 mg orally five times daily for

» Antivirals shorten the duration of viral

» paracetamol: 500-1000 mg orally every 4-6

» ibuprofen: 200-400 mg orally every 4-6

» paracetamol: 500-1000 mg orally every 4-6

» The type of analgesics administered will

» oxycodone: 5 mg orally (immediate-release)

» oxycodone: 5 mg orally (immediate-release)

» The type of analgesics administered will