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Herpes Zoster Overview:

Natural History and Incidence

Bethany A. Weaver, DO, MPH

The varicella-zoster virus (VZV) causes two diseases. The primary


VZV infection, known as chickenpox, typically occurs during child-
hood. Herpes zoster infection results later in life from reactivation
of VZV in the dorsal root ganglia. Herpes zoster characteristically
results in a rash with a unilateral dermatomal distribution, which
usually resolves within 2 to 4 weeks. If the infection does not
resolve after its acute phase, long-term complications, such as
postherpetic neuralgia, may develop. The author discusses the
natural history and incidence of primary VZV infection and herpes
zoster and details the epidemiology, clinical manifestation, diag-
nosis, and complications of this disease.
J Am Osteopath Assoc. 2009;109(suppl 2):S2-S6

clinical manifestation, diagnosis, and tion revised the criteria for evidence of
T he varicella-zoster virus (VZV) is a
single virus that causes two diseases
(Figure 1). The primary VZV infection,
complications of herpes zoster are exam-
ined in detail.
VZV immunity in 2006.2 The criteria for
evidence of immunity now include doc-
also known as chickenpox, typically umentation of age-appropriate admin-
occurs during childhood. However, Varicella-Zoster Virus istration of the live attenuated VZV vac-
VZV infection persists for the infected The primary mode of VZV transmission cine, which should be given in one dose
individuals lifetime, and viral latency is via droplets or airborne particles. Thus, to children aged 12 months to 12 years,
subsequently develops along the spinal a child can spread the infection by simply and in two doses to adolescents and
cord in dorsal root ganglia. Later in life, coughing or breathing. In a typical house- adults. Evidence of immunity also
the virus reactivatesusually in a der- hold, there is an 85% risk of transmis- includes laboratory test results indicating
matomal distributioncausing the sec- sion of chickenpox to a susceptible sib- immunity or confirmation of chickenpox;
ondary infection known as herpes ling.2 The infection is characterized by diagnosis of chickenpox or verification
zoster, which is also called shingles.1 fever, malaise, and the typical diffuse of history of chickenpox by a healthcare
In the present article, the natural his- rash. The average time from virus expo- provider; or verification of history of
tory and incidence of varicella zoster sure to development of the rash is 14 to herpes zoster based on diagnosis by a
(ie, primary VZV infection) and herpes 15 days, though the time can be as short healthcare provider. Such a diagnosis of
zoster are discussed. The epidemiology, as 10 days or as long as 20 days.2 herpes zoster should include a fairly
The child or young adult becomes accurate description of the rash.
infectious approximately 48 hours An individual may also be consid-
This article was developed in part from an expert before the onset of vesicle eruption and ered immune to VZV if he or she was
panel discussion held October 29, 2008, during may remain infectious for 4 to 5 days born in the United States before 1980
the American Osteopathic Associations 113th after vesicle eruption. Approximately unless that individual is pregnant or a
Annual Convention and Scientific Seminar in Las
Vegas, Nev.A video of the discussion is posted 10% of patients older than 15 years are healthcare worker.2
at http://www.docmeonline.com under the considered susceptible for primary VZV
Featured CME tab. infection.2 Herpes Zoster
Dr Weaver is medical director and infectious
disease consultant at Armor Correctional Health The Advisory Committee on Immu- Epidemiology
Services in Tampa, Fla. nization Practices of the United States Herpes zoster occurs as a more sporadic
Dr Weaver reports that she has no relevant Centers for Disease Control and Preven- disease than does primary VZV infec-
financial relationships to disclose.
Address correspondence to Bethany A.
Weaver, DO, MPH, PO Box 89069, Tampa, FL
33689-0401. This supplement is supported by an independent educational grant from Merck & Co, Inc.
E-mail: bethanyg@u.washington.edu, bethanyg
@myuw.net

S2 JAOA Supplement 2 Vol 109 No 6 June 2009 Weaver Herpes Zoster Overview
Reactivation

VZV Latency
in Dorsal Root Ganglia

Spinal Cord

Herpes Zoster

Primary VZV Infection

Figure 1. Primary varicella-zoster virus (VZV) infection Knipe DM, Howley PM, eds. Fields Virology. Vol 2. 4th ed.
(ie, chickenpox) typically occurs during childhood. Viral latency Philadelphia, Pa: Lippincott Williams & Wilkins (http://www
subsequently develops along the spinal cord in dorsal root gan- .lww.com); 2001:2731-2767; Straus SE, Oxman MN. Varicella
glia. Later in life, the virus reactivatesusually in a dermatomal and herpes zoster. In: Freedberg IM, Eisen AZ, Wolff K, et al, eds.
distributioncausing the secondary infection known as herpes Fitzpatricks Dermatology in General Medicine. Vol 2. 5th ed.
zoster (ie, shingles). Sources: Arvin AM. Varicella-zoster virus. In: New York, NY: McGraw-Hill; 1999:2427-2450.

tion. Primary VZV is transmitted from mated 4% of patients will experience a In addition to the role played by
person to person by direct contact, inhala- second episode of shingles, and third advancing age, immunosuppression
tion of aerosols from vesicular fluid of episodes are even rarer.5 increases the risk for development of
skin lesions, or infected respiratory tract The incidence and severity of herpes herpes zoster. In fact, herpes zoster is the
secretions that are aerosolized. Herpes zoster increase with advancing age earliest opportunistic infection observed
zoster is typically transmitted person to (Figure 2).5 Approximately 40% to 50% in patients with human immunodefi-
person by direct contact. Because of its of the 1 million new cases that occur each ciency virus (HIV)/AIDS as their CD4 T-
respiratory transmission, VZV can cause year develop in individuals who are at cell count declines. Patients who are
an epidemic among susceptible hosts. least 60 years of age.5 Among individ- immunocompromised have earlier and
In the United States, more than 90% uals who reach age 85 years, as many as increased manifestations of herpes zoster
of adults are susceptible to herpes zoster 50% will have experienced at least one infection than those who are not
infection, and there is no way to pre- episode of herpes zoster.4,6 With each immunocompromised.8-12
dict in whom the infection will reacti- decade of life, the incidence rate of herpes The management of HIV/AIDS or
vate.1 The lifetime risk for development zoster per thousand person-years steadily other immunocompromising diseases
of herpes zoster is estimated to be increases. may also contribute to herpes zoster
approximately 30%meaning that the The increased risk of herpes zoster development. For example, one of the
illness will occur in about one in three associated with advancing age is at least most powerful risk factors for herpes
adults.3,4 partly caused by immunosenescence, the zoster infection is the use of systemic cor-
An estimated 1 million new cases gradual deterioration of the immune ticosteroids, which are part of the stan-
of herpes zoster occur each year in the system that is part of the natural aging dard management of most autoimmune
United States,5 resulting in 50,000 to process. Specific age-related decline in diseases.
60,000 hospitalizations. Recurrence of cell-mediated immunity to VZV also con- Despite the increased risk of herpes
shingles is uncommon. Only an esti- tributes to this increased risk.7 zoster associated with immunosuppres-

Weaver Herpes Zoster Overview JAOA Supplement 2 Vol 109 No 6 June 2009 S3
Figure 2. Age-specific incidence rates (across
16 both sexes) of herpes zoster from a healthcare
claims database of more than 2.8 million indi-
Rate per 1000 person-years* (95% CI)

14 viduals for the years 2000-2001, sex-adjusted


12 to the 2000 United States population. Approx-
imately 40% to 50% of the 1 million new
10 cases of herpes zoster that occur each year
develop in individuals who are 60 years of
8 age or older. Source: Insinga RP, et al. The inci-
6
dence of herpes zoster in a United States
administrative database. J Gen Intern Med.
4 2005;20:748-753.5

0
0-14 15-29 30-39 40-49 50-59 60-69 70-79 80 from collected lesion material. However,
this technique is not widely available.
Age Group, y
Direct fluorescent antibody staining
of VZV-infected cells obtained by
scraping the base of the lesion is a rapid
sion, 70% to 80% of patients hospitalized In some cases, patients experience the and sensitive method for diagnosis of
for this condition are immunocompe- allodynia, pain, itching, and burning herpes zoster. This technique is useful
tent.8-12 without a rash ever developinga con- for evaluation of atypical skin lesions to
dition known as zoster sine herpete. Ini- guide early treatment decisions.
Clinical Manifestations tially, the rash is erythematous and mac- When the symptoms of allodynia,
As previously mentioned, herpes zoster ulopapular, but it progresses to take the pain, burning, and itching manifest
is the consequence of the primary VZV form of coalescing clusters of clear vesi- without the rash, herpes zoster is espe-
infection reactivating after a period of cles containing high concentrations of cially difficult to diagnose. As a result of
dormancy in the dorsal root ganglia. VZV.4,13 its localization, pain is often misdiag-
Herpes zoster is characterized by a uni- The rash typically lasts 7 to 10 days nosed as a gallbladder attack or appen-
lateral vesicular eruption in a der- and fully heals within 2 to 4 weeks. How- dicitis and is mismanaged until a rash
matomal distribution, with thoracic and ever, permanent scarring and altered pig- develops.
cranial and cervical distributions being mentation occur in some cases. If the Results of recent studies15,16 suggest
the most common. Zoster lesions con- infection does not resolve after the acute that PCR can be used to positively iden-
tain high concentrations of VZV, which phase, complications, such as posther- tify VZV DNA in patients blood before
can be spread to susceptible individuals petic neuralgia (PHN), may develop.4,13 symptoms manifest. Thus, PCR has
by direct contact with the lesions. Local- potential application as a diagnostic tool
ized herpes zoster is contagious from the Diagnosis for identifying patients who are in the
time of rash eruption until the time of A diagnosis of herpes zoster is often prodromal phase of herpes zoster and
lesion crusting. The rate of transmission made based on the localization and mor- patients who have zoster sine herpete,
of herpes zoster infection is lower than phologic characteristics of the rash. How- allowing these individuals to receive
that of primary VZV infection.13 ever, the rash associated with herpes treatment before rash and nerve damage
Figure 3 displays the stages of clinical zoster is sometimes confused with that of develop.
manifestation of herpes zoster. In the ini- herpes simplex virus (HSV). Physicians
tial stage of herpes zoster infection, should keep in mind that a rash that is Complications
known as the prodromal phase, patients recurrent in the same dermatome is most Postherpetic neuralgia is a common and
may report such symptoms as headache, likely HSV. A comparison of VZV and potentially debilitating complication of
pain, malaise, and acute photophobia HSV is available elsewhere in this sup- herpes zoster that is difficult to manage.
before the rash appears. After the pro- plement to JAOAThe Journal of the It is characterized by pain or dysesthesia
dromal phase, the acute phase is char- American Osteopathic Association.14 that persists after resolution of the rash.
acterized by the dermatomal rash. The The varicella-zoster virus can be col- Postherpetic neuralgia occurs in 10% to
herpes zoster rash is typically unilateral, lected from lesions and identified using 18% of patients with herpes zoster, and
not crossing the midline of the body.4,13 tissue culture, but this is a time-con- the risk for development of this compli-
The rash may be accompanied by suming process, and false-negative cation increases with advancing age.17
unbearable itching, altered sensitivity to results may occur because viable virus The severity of pain in PHN ranges
touch, or allodynia (ie, pain at the site is difficult to obtain from cutaneous from mild to excruciating, and it can be
provoked by innocuous stimuli). Pain lesions. Polymerase chain reaction (PCR) constant, intermittent, or triggered by
may also be felt before the rash develops. can be used to detect the DNA of VZV such stimuli as clothes touching the skin.

S4 JAOA Supplement 2 Vol 109 No 6 June 2009 Weaver Herpes Zoster Overview
Prodromal PhaseAcute photophobia, pain,
headache, malaise

Acute PhaseDermatomal rash, pain,


Resolution
unbearable itching, altered sensitivity to touch

ComplicationsMay or may not occur; common


complication is postherpetic neuralgia.

Figure 3. Clinical manifestations of herpes zoster. In the initial stage of manifestations of herpes zoster. In: Arvin AM, Gershon AA, eds. Vari-
herpes zoster (ie, prodromal phase), patients may experience headache, cella-Zoster Virus: Virology and Clinical Management. Cambridge, Eng-
pain, malaise, and acute photophobia before the rash appears. After land: Cambridge University Press; 2000:246-275.13 Copyright 2000 Cam-
the prodromal phase, the acute phase is characterized by the der- bridge University Press. Reprinted with permission. Harpaz R, et al.
matomal rash, as well as by pain, unbearable itching, and altered sen- Prevention of herpes zoster: recommendations of the Advisory Com-
sitivity to touch. The rash typically heals within 2 to 4 weeks. If the infec- mittee on Immunization Practices (ACIP). MMWR Recomm Rep.
tion does not resolve after the acute phase, complications, such as 2008;57(RR-5):1-30,CE2-4.4
postherpetic neuralgia, may develop. Sources: Oxman MN. Clinical

Although allodynia affects 45% to 55% of innervations in the affected region. have long-term sequelae, including vision
patients with herpes zoster, it may affect In addition to PHN, other neurologic loss and pain related to the location of
as many as 90% of those with PHN.18 complications that can result from herpes the rash, stemming from herpes zoster
The pain associated with herpes zoster or zoster include chronic sensory loss at the ophthalmicus. Keratitis occurs in approx-
PHN may last for a few minutes or occur site of the rash, limb weakness, and auto- imately two-thirds of patients with
as chronic pain. The duration of PHN nomic dysfunction related to the site of herpes zoster ophthalmicus.4
has been found to be inconsistent, the rash (eg, bladder dysfunction if the
ranging from 30 days to 6 months or rash has sacral dermatomal distribution). Conclusion
longer after rash onset. In some cases, More severe neurologic complications Herpes zoster infection results from the
the pain persists for years.18-20 include encephalitis, meningitis, and reactivation of VZV in the dorsal root
Postherpetic neuralgia adversely myelitis. Bacterial superinfection, par- ganglia. It typically results in a rash with
affects the patients quality of life as a ticularly with methicillin-resistant Staphy- a unilateral dermatomal distribution,
result of its potential to interfere with lococcus aureus, can also occur. Dissemi- which usually resolves within 2 to
sleep, work, and other activities of daily nated disease, with a mortality rate as 4 weeks. Herpes zoster may or may not
living, leading to social withdrawal and high as 40%, is a complication that is lead to PHN or other long-term compli-
depression.4 In a study by Katz and observed mainly in patients who are cations, depending on the case.
Melzack,21 in which patients were asked immunosuppressed.4
to compare the pain associated with Herpes zoster ophthalmicus, which References
PHN with other types of pain they had is prevalent in 10% to 25% of patients 1. Gnann Jr JW, Whitley RJ. Clinical practice. Herpes
experienced, pain associated with PHN with herpes zoster, can occur when reac- zoster [review]. N Engl J Med. 2002;347:340-346.
was ranked as more severe than labor tivation of latent VZV involves the first 2. Marin M, Guris D, Chaves SS, Schmid S, Seward JF;
pain, postsurgical pain, arthritis pain, division of the trigeminal nerve.4 Oph- Advisory Committee on Immunization Practices
(ACIP). Prevention of varicella: recommendations
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Pathologic mechanisms believed to plication that is difficult to manage. tices (ACIP). MMWR Recomm Rep. 2007;56(RR-4):1-
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Kurland MJ, Sy LS. A population-based study of
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J Hosp Infect. 1991;18(suppl A):317-329.

Video of Supplements Content Available Online

The contents of this supplement to JAOAThe Journal of the American Osteopathic Asso-
ciation were developed mainly from an expert panel discussion held October 29, 2008,
during the American Osteopathic Associations 113th Annual Convention and Sci-
entific Seminar in Las Vegas, Nev.
A video of the discussion is posted at http://www.docmeonline.com under the
Featured CME tab. Members of the AOA can access the video using their AOA
identification numbers and DO-Online passwords.
Alternatively, registered users of CE Medicus can access the video at
http://www.cecity.com/ce-bin/owa/ainch?tid=14415&ccd=MCK. Healthcare
professionals who are not registered on CE Medicus can obtain a user name and pass-
word by clicking on the Register Free Now link at http://www.cemedicus.com.

S6 JAOA Supplement 2 Vol 109 No 6 June 2009 Weaver Herpes Zoster Overview

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