Herpes zoster: Epidemiology, natural history, and

common complications
Jeffrey M. Weinberg, MD
New York, New York

Herpes zoster is a disease associated with aging that can significantly impair quality of life for affected
individuals. Anyone infected with varicella (chickenpox) virus in childhood is at risk for reactivation of
dormant virus and the onset of zoster disease, although it occurs with increasing frequency in the elderly as
a result of waning of cell-mediated immunity. The most common complication of herpes zoster is
postherpetic neuralgia, which can cause chronic and debilitating pain. Current treatments can decrease the
severity of zoster rash and pain but cannot prevent disease onset or completely eliminate the most frequent
symptoms. The zoster vaccine may help prevent the onset of herpes zoster in the target population of those
age 60 years and older. This summary reviews the epidemiology, pathogenesis, natural history, and
common symptoms of zoster disease. ( J Am Acad Dermatol 2007;57:S130-5.)

H erpes zoster, or shingles, is a disease that
predominantly affects the elderly. It occurs
as a result of aging-related waning of cell-
mediated immunity to varicella-zoster virus (VZV),
the virus that also causes varicella and is dormant in
everyone who has ever had it.1,2 The association
between aging and vulnerability to VZV reactivation
is apparent in the epidemiology of the disease: of the
estimated 1 million cases of herpes zoster in the
United States each year, approximately 50% occur in
individuals aged 50 years or older.3 Although 10% to
20% of the US population overall will develop zoster
in their lifetimes, 50% of persons reaching age 85
years can be expected to do so4; the incidence of
herpes zoster increases dramatically, from a low of
between 1.1 and 2.9 per 1000 person-years in people
younger than 50 years to 4.6 and 6.9 per 1000 person-
years, respectively, in the age groups 50 to 59 and 60
to 69 years. The age groups 70 to 79 and 80 years or
older have the highest incidence, with 9.5 and 10.9
per 1000 person-years, respectively.5
From the Clinical Research Center, Department of Dermatology,
St. Luke’s-Roosevelt Hospital Center and Beth Israel Medical
Center, and Department of Dermatology, Columbia University
College of Physicians and Surgeons.
Supported by an educational grant from Merck & Co., Inc.
Disclosure: Dr Weinberg is a consultant and on the speakers’
bureau for Merck & Co., Inc.
Accepted for publication August 11, 2007.
Reprint requests: Jeffrey M. Weinberg, MD, Department of
Dermatology, St. Luke’s-Roosevelt Hospital Center, 1090
Amsterdam Ave, Suite 11D, New York, NY 10025. E-mail:
jmw27@columbia.edu.
0190-9622/$32.00
ª 2007 by the American Academy of Dermatology, Inc.
doi:10.1016/j.jaad.2007.08.046
Acute zoster is painful, but does not incur lasting
morbidity. However, there is a potential for neuro-
logic and inflammatory complications that cause
patientseand physiciansegreat and lasting difficulty.
The relationship between zoster infection and de-
struction of neurons and satellite cells has been well
established, with neurologic damage beginning even
before the characteristic zoster rash appears.1,6
Postherpetic neuralgia, the most frequent complica-
tion of herpes zoster, can cause debilitating pain and
impaired quality of life among the otherwise healthy
elderly.7-9 The associated pain, furthermore, can
continue long after the rash resolves, despite aggres-
sive antiviral and/or pain therapy. In addition, when
herpes zoster occurs in the first division of the
trigeminal nerve, the patient develops herpes zoster
ophthalmicus (HZO), and runs the risk of long-term
vision complications related to inflammation or
nerve damage.10
The zoster vaccine is indicated for the prevention
of herpes zoster in adults age 60 years and older, and
has been shown to reduce the incidence and severity
of zoster, and the incidence of postherpetic neural-
gia, in this population.3 However, despite the avail-
ability of a vaccine, zoster is still seen frequently in
clinical practice. This review will describe the natural
history of VZV, the usual course of zoster disease, its
common complications, and their impact on the at-
risk elderly population.
NATURAL HISTORY OF HERPES ZOSTER
VZV is a ubiquitous herpes virus that causes
chickenpox in childhood.10 On resolution of the pri-
mary varicella infection, residual provirus segments
travel from sensory nerve endings up sensory fibers,

S130
J AM ACAD DERMATOL Weinberg S131
VOLUME 57, NUMBER 6

Fig 1. Natural history of herpes zoster: primary varicella infection induces immunity via
development of antigens (not shown) and varicella-zoster virus (VZV)-specific memory T cells.
T cellemediated immunity declines with age until, below threshold point (dashed line) risk for
zoster reactivation increases. Exposure to zoster, whether as VZV reactivation or vaccination,
boosts immunity and protects against subsequent episodes. Data from Arvin A. N Engl J Med
2005;352:2266-7.

eventually lodging in the cranial or dorsal root gan-
glia. These viral fragments settle in neuronal or
satellite cell nuclei, where they are protected from
the high levels of antibody that persist in the circula-
tion in response to the primary infection. This migra-
tion and colonization of virus along the neural route
may in part explain why herpes zoster primarily
affects the sensory ganglia and its rash is distributed
locally along a sensory nerve dermatome.2
Once inside the neuronal nucleus, the virus
remains latent and does not multiply, although it
retains the ability to revert to an infectious state at any
time.2 It is unclear what induces reactivation of VZV,
but it is thought to occur when cell-mediated immu-
nity decreases below a crucial level. This conviction
is supported by evidence that, over time, even
persons with apparent immunity to varicella exhibit
T cells with reduced ability to proliferate and pro-
duce VZV-specific interferon gamma when exposed
to VZV antigen in vitro.1 Furthermore, although
memory CD4 and CD8 T cells are highly detectable
in the young, who are largely resistant to herpes
zoster, they are substantially diminished among
the elderly and in immunocompromised indiv-
iduals, groups that are more likely to develop herpes
zoster.
Periodic exposure to individuals with varicella
provides a boost in immunity to VZV. When cell-
mediated immunity declines too far, zoster results.
An episode of acute zoster does, however, boost the
Table I. Risk factors and potential risk factors for
varicella-zoster virus reactivation
Prior VZV exposure (chickenpox, vaccine)
Age [ 50 y
Immunocompromised state
Immunosuppressive drugs
HIV/AIDS
Bone-marrow or organ transplantation
Cancer
Chronic steroid therapy
Psychologic stress
Trauma
VZV, Varicella-zoster virus.
Data from Arvin.10
individual’s immunity to VZV; thus, recurrence of
zoster is rare (Fig 1).1-3,11
RISK FACTORS FOR HERPES ZOSTER
Prior varicella is a prerequisite for herpes zoster,
but other factors further increase risk (Table I).10
More than 90% of the US adult population has had
varicella, which means the pool of individuals at risk
for zoster is quite large.12 Older age further increases
risk: most zoster disease occurs after age 45 years,
and half of all cases reported are in individuals older
than 60 years.3,5 This association with advancing
years, as previously described, is a result of the age-
related decline in VZV-specific cell-mediated
S132 Weinberg
Fig 2. Herpes zoster lesions: dermatomal distribution and close-up view of vesicles. Copyright ª
2007 Photo Researchers, Inc. All rights reserved. Credit: Scott Camazine/Photo Researchers, Inc.
immunity. Childhood zoster is rare but not unheard
of, with cases reported in children as young as 4
months. The incidence of zoster in children younger
than 14 years is only 1.1 per 1000 person-years.5
Immunocompromised people or those receiving
immunosuppressive drugs are also at increased risk
for zoster.10 Thus, HIV-positive individuals have a
higher incidence of zoster disease than individuals
with a healthy immune system; one longitudinal
study reported 29.4 cases per 1000 patient-years.13
Patients undergoing bone-marrow or organ trans-
plantation and treated with immunosuppressives are
also at increased risk for herpes zoster.10
Some reports have suggested that systemic steroid
therapy can incite VZV reactivation as well, placing
persons with conditions such as rheumatoid arthritis
or lupus at increased risk.10 Finally, both trauma and
stressful life circumstances have been suggested to
play a role in development of herpes zoster.14,15
ACUTE HERPES ZOSTER: SYMPTOMS AND
DIAGNOSIS
Prodrome
The characteristic feature of herpes zoster is a
vesicular rash of unilateral distribution limited to 1 to
3 adjacent dermatomes. The onset of the rash,
however, often is preceded by a prodromal phase.16
J AM ACAD DERMATOL
DECEMBER 2007
Beginning 4 days to 2 weeks before lesions appear,
patients often note pain and paresthesia in what will
become the zoster-affected dermatome. The pain
can be intermittent or continuous, and has been
described by patients variously as throbbing, sharp,
stabbing, burning, or shooting pain.16 They may
experience abnormal skin sensations such as tingling
or itching. Malaise, dysesthesia, and itching are
frequent elements of the prodrome as well.17
Rash
Most patients exhibit thoracic distribution of zos-
ter rash, with more than 50% of cases presenting with
cutaneous lesions of the trunk.10,16 The rash gener-
ally appears proximally, then spreads distally along
the affected dermatome. The initial lesions appear as
erythematous papules, which turn into vesicles
within 12 to 24 hours (Fig 2). New lesions generally
appear over no more than 3 to 7 days, but the
duration of the rash has been correlated with patient
age (advancing age associated with longer duration)
and site of infection (face healing more rapidly than
other loci). The vesicles become pustules in about 3
days, and form scabs 7 to 10 days later.16,17 Virus
persists in the lesions for only a few days and only
infrequently spreads cutaneously, except in patients
who are immunocompromised.16
J AM ACAD DERMATOL
VOLUME 57, NUMBER 6
In 10% to 15% of cases, zoster affects the first
division of the trigeminal nerve,7 producing the char-
acteristic and usually painful zoster rash on the fore-
head, periocular area, and nose. Such a rash is known
as HZO. Ocular complications of HZO are among the
most dangerous consequences of zoster disease,
placing patients at risk for sight impairment or vision
loss caused by nerve damage or ocular pathology.12
Pain and sensation
Approximately 60% to 90% of patients with zoster
experience local neuritic pain16 and hypersensitivity
in association with the acute herpetic rash. This pain
is likely a result of an immediate nociceptive re-
sponse: local inflammation and tissue damage stim-
ulate the primary afferent neurons of the skin and
subcutaneous tissue, which manifests neurologi-
cally as pain.18 It may also be a function of direct
neurolytic injury to heavily infected axons and cell
bodies, or intraneural hemorrhage secondary to
inflammation. The pain often increases as the rash
develops but then declines as the rash begins to
heal.19 In addition, allodynia and hyperalgesia may
be present, adding to patient discomfort during acute
herpes zoster.
Pain associated with zoster disease resolves within
several days for many patients, although the degree
of pain can be variable. Acute pain is also correlated
with an increased risk of postherpetic neuralgia.19,20
Diagnosis
The features of zoster disease are so characteristic
that a diagnosis is generally made clinically, based on
the presence of prodromal pain and/or itching and
the defining zoster rash. For patients presenting in the
prodromal period, the pain and dysesthesia may
require differentiation from other pain sources, such
as trauma, myocardial ischemia, renal colic, gallblad-
der disease, or dental pain.17 Atypical lesions,
furthermore, may require laboratory confirmation,
which sometimes is obtained from viral culture (often
difficult to recover from swabs) or more readily from
direct immunofluorescence assay. Recently, nested
and real-time polymerase chain reaction testing of
samples from skin lesions have proved valuable for
identifying VZV, with more rapid amplification than
other methods and high sensitivity.21 These labora-
tory techniques are most valuable for differentiating
VZV from zosteriform herpes simplex, a herpes
simplex viral infection that mimics zoster disease.
COMPLICATIONS OF HERPES ZOSTER
Potential outcomes of zoster disease
A number of complications of zoster disease have
been described in the literature (Table II).
Weinberg S133
Table II. Potential complications of varicella-zoster
virus can contribute to chronic pain and impairment
Neurologic
Postherpetic neuralgia
Motor paralysis
Meningoencephalitis
Transverse myelitis
Cerebral vasculitis
Cranial palsy
Ocular
Lid ulceration
Conjunctivitis, keratitis, uveitis
Optic neuritis
Retinal necrosis
Secondary glaucoma
Visceral
Pneumonitis
Myocarditis
Hepatitis
Esophagitis
Data from Wood and Easterbrook.16
Encephalitis, myelitis, and nerve palsies have been
reported among patients with zoster. Motor paralysis
can be a particularly disquieting outcome, although
it is rare, occurring in less than 5% of patients.19
Ramsay Hunt syndrome can present with hearing
loss, vertigo, and facial paresis, and cerebral arteritis
leading to stroke, delayed even months after the
acute infection has been reported.17
The most common and challenging complications
of herpes zoster, however, are postherpetic neuralgia
and HZO with ocular complications. Postherpetic
neuralgia, chronic and debilitating pain that persists
long after the zoster rash has cleared, is more likely to
occur with advancing age, in patients with a painful
prodrome, in those with more severe pain or rash
during the acute phase, and in those whose rash is
distributed across multiple dermatomes.19,22,23
Postherpetic neuralgia affects up to 34% of those
with zoster in the general population, but about 60%
to 70% of patients age 60 years and older who
develop zoster.24
HZO results when VZV reactivates in the first
(ophthalmic) branch of the trigeminal (fifth) nerve.16
Of those with HZO, as many as 71% may develop
ocular complications.25 Although blindness is rare,
HZO is associated with a substantial complication
rate, and permanent ocular damage and vision loss
can occur.10 Patients with ocular involvement should
be referred to an ophthalmologist.
Postherpetic neuralgia
Postherpetic neuralgia is thought to arise when
nociceptors, sensitized during acute zoster infection,
S134 Weinberg
Table III. Postherpetic neuralgia can present with a
range of neurologic pain symptoms
Intermittent or continuous, deep or superficial
Throbbing or stabbing
Spontaneous aching or burning
Paroxysm
Allodynia
Hyperalgesia
Intense itching
Data from Johnson and Whitton.17
fail to return to their prezoster state, or when a
persistent subclinical threshold state of central hy-
persensitization develops in which neurons are more
easily stimulated than normal.18
Postherpetic neuralgia has been variously de-
fined: definitions share persistent pain post-rash,
but differ in how long the pain must persist post-rash
to be classified as postherpetic neuralgia. Cut points
used to discriminate postherpetic neuralgia have
ranged from 1 to 6 months after onset of zoster.26
The presentation of postherpetic neuralgia is
heterogeneous (Table III): patients may present
with continuous or intermittent pain, which may be
spontaneous, evoked, or evoked in response to
stimuli that are not normally painful (allodynia).
Some patients may present with intense itching.17
Postherpetic neuralgia is a chronic and debilitat-
ing condition that can seriously impair the health and
quality of life among the affected elderly. Like zoster
disease itself, the risk for postherpetic neuralgia
increases with advancing age. Choo et al22 reported
a 14.7-fold increase in prevalence of pain 30 days
after the acute rash among their patients aged 50
years and older compared with patients younger
than 50 years. Ragozzino et al7 observed that the
average age of persons with postherpetic neuralgia
in Rochester, Minn, was 67 years.
Symptoms frequently associated with posther-
petic neuralgia include chronic fatigue, anorexia,
weight loss, and insomnia.9 The persistent pain and
discomfort often interfere with activities of daily
living, limiting patients’ social interaction and ability
to work or tend to household chores. These chal-
lenges may lead to psychologic problems, including
depression and difficulty concentrating. Oster et al27
reported that 385 respondents completing a ques-
tionnaire assessing pain and its impact on life activ-
ities experienced long-standing and severe pain that
diminished their health-related quality of life, despite
the use of medication. The pain interfered moder-
ately to severely with their ability to participate in
general activities, and with their mood and enjoy-
ment of life (Fig 3). Mauskopf et al28 also related
J AM ACAD DERMATOL
DECEMBER 2007
Fig 3. Extent and degree of impact of postherpetic neu-
ralgia pain on health-related quality-of-life parameters
measured with the EuroQol scale. Reprinted from Oster
et al,27 with permission from the American Pain Society.
postherpetic neuralgia to impaired health-related
quality of life. In a study involving 1141 adults aged
50 years or older with zoster pain treated with
valacyclovir or acyclovir, this group measured im-
pact of pain on 6 dimensions of well-being using a
generic quality-of-life instrument, the Nottingham
Health Profile. It was observed that 8 weeks after
rash onset, zoster pain significantly diminished qual-
ity-of-life measures for energy, sleep, and global
quality-of-life score (P \.01).27
These consistent findings across multiple studies
establish postherpetic neuralgia as a substantial
problem among the elderly.
Herpes zoster ophthalmicus
HZO is not in and of itself sight threatening or
difficult to treat, but if the eye becomes involved, the
risk to the patient increases, and the patient should
be referred to an ophthalmologist. The ocular
sequelae can be focused at the eyelid/conjunctiva
(blepharoconjunctivitis, secondary Staphylococcus
infection), episclera/sclera (episcleritis/scleritis),
cornea (punctate epithelial keratitis, dendritic kera-
titis, anterior stromal keratitis, neurotrophic keratop-
athy), anterior chamber (uveitis), retina (necrosis), or
cranial nerves (optic neuritis, oculomotor palsies),
with different degrees of associated damage or
impairment. The most serious complications de-
velop from involvement of the nasociliary branch
of the cranial nerve, which innervates the globe.29
CONCLUSION
Herpes zoster carries significant morbidity, and is
both more common and associated with greater
harm in the elderly and/or in immunocompromised
individuals. Acute herpes zoster is painful, and a
J AM ACAD DERMATOL
VOLUME 57, NUMBER 6
substantial portion of these patients will develop
long-lasting complications associated with ongoing
pain and other morbidity. Available antiviral and
pain medications help reduce the severity of zoster
rash and diminish pain, but have limited efficacy in
preventing the complications and pain entirely; in
fact, in some cases zoster-related pain actually
worsens over time.9 Furthermore, patients with
prolonged postherpetic neuralgia have a variety of
constitutional symptoms, such as fatigue, weight
loss, and depression, and become progressively
more socially isolated as they try to cope with the
pain and limitations associated with the disease.
Chronic morbidity and ocular damage related to
ophthalmic zoster infection can lead to fear, caution,
and confinement among the already guarded el-
derly. The risk of blindness, although small, is real.
Given the current risk profile and limitations of
available symptomatic therapies, prevention may
prove to be the key to reducing the health and
economic costs of herpes zoster. As we attempt to
help patients deal with the challenges of acute and
chronic zoster disease, universal application of the
zoster vaccine to the target population may be a first
step toward reducing the burden of this terrible
disease. The vaccine has the potential to reduce the
risk of active zoster disease and thereby reduce the
challenging and life-altering sequelae that it can
leave in its wake, thereby preserving quality of life
for the increasing number of US citizens older than
60 years. Ensuring widespread vaccination among
this population is the next step in protecting against
zoster morbidity, gaining better health and emo-
tional well-being for the 35 million elderly persons in
the United States at risk for this debilitating disease.
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