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Open Journal of Pediatrics, 2015, 5, **-**
Published Online March 2015 in SciRes. http://www.scirp.org/journal/ojped
doi
How to cite this paper: Author 1, Author 2 and Author 3 (2015) Paper Title. Open Journal of Pediatrics, 5, **-**.
http://dx.doi.org/10.4236/***.2015.*****
Herpes Zoster in Childhood
Alexander K. C. Leung1,2*, Benjamin Barankin3
1University of Calgary, Calgary, Canada
2Alberta Children’s Hospital, Calgary, Canada
3Toronto Dermatology Centre, Toronto, Canada
Email: *aleung@ucalgary.ca
Received **** 2015
Copyright © 2015 by authors and Scientific Research Publishing Inc.
This work is licensed under the Creative Commons Attribution International License (CC BY).
http://creativecommons.org/licenses/by/4.0/
Abstract
Herpes zoster is caused by reactivation of latent varicella-zoster virus that resides in a dorsal
root ganglion. Herpes zoster can develop any time after a primary infection or varicella vaccina-
tion. The incidence among children is approximately 110 per 100,000 person-years. Clinically,
herpes zoster is characterized by a painful, unilateral vesicular eruption in a restricted derma-
tomal distribution. In young children, herpes zoster has a predilection for areas supplied by the
cervical and sacral dermatomes. Herpes zoster tends to be milder in children than in adults. Al-
so, vaccine-associated herpes zoster is milder than herpes zoster after wild-type varicella. The
diagnosis of herpes zoster is mainly made clinically, based on a distinct clinical appearance. The
most common complications are secondary bacterial infection, depigmentation, and scarring.
Chickenpox may develop in susceptible individuals exposed to herpes zoster. Oral acyclovir
should be considered for uncomplicated herpes zoster in immunocompetent children. Intra-
venous acyclovir is the treatment of choice for immunocompromised children who are at risk
for disseminated disease. The medication should be administered ideally within 72 hours of
rash onset.
Keywords
Varicella-Zoster Virus, Reactivation, Vesicular Eruption, Dermatome, Acyclovir
1. Introduction
Herpes zoster, also known as shingles, is caused by reactivation of endogenous latent varicella-zoster virus that
resides in a sensory dorsal root ganglion usually after primary infection with varicella-zoster virus (i.e., varicella
*Corresponding author.
A. K. C. Leung, B. Barankin
2
or chickenpox) [1]. Herpes zoster can develop any time after a primary infection or varicella vaccination [1].
The activated virus travels back down the corresponding cutaneous nerve to the adjacent skin, causing a painful,
unilateral vesicular eruption in a restricted dermatomal distribution.
2. Epidemiology
Herpes zoster occurs more commonly after varicella infection than after varicella vaccination [2]. Herpes zoster
usually occurs in persons with relative cell-mediated immunologic compromise such as elderly individuals or pa-
tients with an immunosuppressive illness or receiving immunosuppressive therapy [3]. The cumulative lifetime
incidence among the general population is approximately 10% to 30%, with the risk increasing sharply after 50
years of age [4]-[6]. In the study by Insigna et al, the overall age- and sex-adjusted incidence of herpes zoster was
320 per 100,000 person-years in the United States from 2000 to 2001 [7]. The rate was higher among females
(390 per 100,000 person-years) than among males (260 per 100,000 person-years).The incidence among children
aged 0 to 14 years was 110 per 100,000 person-years [7]. Kawai et al performed a systematic review of 63 studies
from 22 countries on the incidence of herpes zoster [4]. The authors found the incidence rate of herpes zoster
ranged between 300 to 500 per 100,000 person-years in the general population in North America, Europe, and
Asia-Pacific, based on studies using prospective surveillance, electronic medical record data or administrative da-
ta with medical record review. The incidence is twice in whites when compared to blacks [8]. Immunocompro-
mised individuals have a 20 to 100 times greater risk than immunocompetent individuals of the same age [9] [10].
In general, herpes zoster is uncommon in individuals younger than 10 years of age and rare in infants [3] [5].
The younger a child is when he/she has varicella, the greater the likelihood that herpes zoster will develop in
childhood or early adulthood.[6] In this regard, infantile herpes zoster is more commonly associated with intra-
uterine varicella-zoster virus infection than postnatal infection. In approximately 2% of children exposed to va-
ricella-zoster virus in utero, subclinical varicella develops, and therefore they are at risk for herpes zoster after
birth [3]. Enders et al prospectively followed 1373 women who had varicella during the first 36 weeks of gesta-
tion [11]. Herpes zoster in infancy or early childhood was reported in 10 children who were asymptomatic at
birth. The observed risk of herpes zoster after maternal varicella between 13 and 24 weeks and between 25 and
36 weeks was 4/477 (0.8%) and 6/345 (1.7%), respectively. Eight of these children had herpes zoster during the
first year of life.
At times, herpes zoster may result from varicella vaccination as the vaccine strain of varicella-zoster virus
may become latent and later reactivate to cause herpes zoster [3] [12] [13]. In one study, the incidence of herpes
zoster among varicella vaccine recipients is about 14 cases per 100,000 person-years, compared with 20 to 63
cases per 100,000 person-years after natural varicella infection [14]. In another study, the incidence of laborato-
ry-confirmed herpes zoster was 48 cases per 100,000 person-years in vaccinated children (wild type and vac-
cine-strain) and 230 cases per 100,000 person-years in unvaccinated children (wild type only) [15]. Several stu-
dies have shown that the incidence of herpes zoster in both healthy and immunocompromised children who re-
ceived varicella vaccine is less than that experienced by healthy and immunocompromised children who expe-
rienced natural varicella infection, respectively [12] [15]-[17]. The lower incidence may be related to a lower
rate of reactivation of the attenuated vaccine strain of varicella-zoster virus and the lower rate of rash following
vaccination compared with wild-type varicella [12].
3. Pathogenesis
A primary infection with either wild-type or vaccine-type varicella-zoster virus is a prerequisite for herpes zoster
[3]. Activation of latent varicella-zoster virus in a partially immune host results in herpes zoster. Defects in im-
munity, especially cell-mediated immunity, resulting from an immunosuppressive illness or immunosuppressive
therapy are important factors in the pathogenesis. Predisposing factors include increasing age, fatigue, and emo-
tional stress. In children, asthma is a risk factor for herpes zoster [18].
The vaccine-type virus strain is known to establish a latent infection in the dorsal root ganglia [14]. The virus
reaches the sensory ganglia through sensory nerves at the injection site. The relative risk of herpes zoster devel-
oping in a vaccine recipient is higher in individuals who had a vaccine-associated rash or breakthrough infection
[14]. In the majority of cases, the zoster lesions occur on the same side as the vaccine injection site [3]. Varicella
vaccine is composed of a mixture of varicella zoster virus strains. Viruses sampled from herpes zoster vesicles
are single clones, suggesting that a single strain is selected between the time of inoculation and development of
A. K. C. Leung, B. Barankin
3
the rash [19].
4. Clinical Manifestations
The onset of disease may be heralded by pain within the dermatome and precedes the lesions by 48 to 72
hours [1] [12]. The pain is due to acute neuritis and is related to viral replication, inflammation, and cytokine
production leading to neuronal destruction and increased sensitivity of pain receptors [20]. At times, there
may be paresthesia, burning, or itching in the affected area [12]. An area of erythema might follow and pre-
cede the development of a group of vesicles in the distribution of the dermatome that corresponds to the in-
fected dorsal root ganglion (Figure 1) [12]. Usually 1 or, less commonly, 2 or 3 adjacent dermatomes are af-
fected [5] [20]. In young children, herpes zoster has a predilection for areas supplied by the cervical and sa-
cral dermatomes [21]. In adults, the lesions are more common in the lower thoracic and upper lumbar derma-
tomes and may involve the trigeminal nerve [12]. In both children and adults, the lesions usually do not cross
the midline [12]. Vesicles may coalesce to form bullous lesions [1]. The vesicular and bullous lesions may
become pustular or occasionally hemorrhagic and ultimately crust in 7 to 10 days [20]. There may be regional
lymphadenopathy [12].
Herpes zoster may involve the eyelids when the ophthalmic branch of the trigeminal nerve is affected. Ap-
pearance of skin lesions at the side of the nose represents involvement of the nasociliary branch of ophthalmic
nerve (Hutchinson's sign) and predicts a higher likelihood of ocular involvement [11] [22].
Herpes zoster tends to be milder in children than in adults [2] [3] [5]. Also, vaccine-associated herpes zoster is
milder than herpes zoster after wild-type varicella [2] [3].
In individuals with immunodeficiency, the lesions may involve multiple contiguous, non-contiguous, bilateral,
Figure 1. Multiple grouped papules and vesicles on an erythematous base, present unilaterally on the right
flank in a dermatomal distribution.
A. K. C. Leung, B. Barankin
4
or unusual dermatomes [4] [12]. The lesions may disseminate to other organs such as the liver, kidneys, lungs,
and central nervous system. Also, the illness is more severe and prolonged.
5. Complications
The most common complications are secondary bacterial infection, post-inflammatory depigmentation, and
scarring [12]. Necrotizing fasciitis is a potential complication if there is secondary bacterial infection [12].
Herpes zoster ophthalmicus may lead to severe eye pain, conjunctivitis, lid ulceration, retinal necrosis, ophthal-
moparesis/plegia, sclerokeratitis, anterior uveitis, and optic neuritis [23]. Postherpetic neuralgia, which represents
a continuum of pain that does not resolve following the acute episode of herpes zoster, is uncommon in children
[1] [2] [5]. Other rare complications include Ramsay Hunt syndrome, Guillain-Barré syndrome, pneumonia,
aseptic meningitis, encephalitis, meningoencephalitis, ventriculitis, transverse myelitis, granulomatous cerebral
angiitis, cranial nerve paresis/palsies, and peripheral nerve paresis/palsies [17] [20] [24] [25]. Inflammatory skin
lesions following herpes zoster may occur within the same dermatome (Wolf's isotopic phenomenon) [12].
Complications are uncommon in vaccine-induced herpes zoster in healthy children. In contrast, in immuno-
compromised patients, complications are more common and severe.
6. Diagnosis
The diagnosis of herpes zoster is mainly made clinically, based on the distinctive clinical appearance and symp-
tomatology. Laboratory tests usually are not necessary. A Tzanck smear, performed by scraping the base of the
lesion, can demonstrate giant cells [1]. The diagnosis can be confirmed if necessary by the demonstration of
specific viral antigens in skin scrapings or vesicles using direct fluorescent (FDA) assay. Viral DNA analysis of
the lesion by polymerase chain reaction (PCR) can be used to distinguish between wild-type and vaccine-type
viruses (genotyping) [14].
7. Differential Diagnosis
Herpes zoster should be differentiated from zosteriform herpes simplex. In zosteriform herpes simplex, there is
no painful prodrome, small vesicles of almost uniform size, less number of grouped vesicles, and more likely to
recur. Other differential diagnoses include zosteriform lichen planus, drug eruption, insect bites, folliculitis,
hand-foot-mouth disease, contact dermatitis, atopic dermatitis, phytophotodermatitis, and dermatitis herpetifor-
mis.
8. Prognosis
Recurrence is uncommon in the immunocompetent individual. Approximately 5% of immunocompetent patients
have a second episode of herpes zoster [5]. Three or more episodes are rare [5] [20].
9. Management
Affected patients are contagious because the virus can be transmitted by direct contact with herpes zoster lesions
and, less commonly, by airborne spread from aerosolization of virus from skin lesions [11] [14]. Affected child-
ren should be kept out of school or day care until crusting appears and contact with pregnant women in particu-
lar is to be avoided [1]. Chickenpox may develop in susceptible individuals exposed to herpes zoster [1]. Gener-
al preventive measures include good personal hygiene, with particular emphasis on hand washing, proper cloth-
ing, and covering exposed lesions with bandages. Fingernails should be trimmed to reduce injury from scrat-
ching. If secondary bacterial infection occurs, topical or systemic antibiotic therapy is indicated.
The goals of antiviral therapy are to reduce viral shedding, hasten healing of cutaneous lesions, prevent new
lesion formation, reduce the pain associated with acute neuritis and possibly decrease complications from the
disease [11] [20]. Oral acyclovir (20 mg/kg/dose, maximum 800 mg/dose) five times per day for 5 to 7 days
should be considered for uncomplicated herpes zoster in immunocompetent children [5]. Intravenous acyclovir
(10 mg/kg or 500 mg/m2 every 8 hours) for 7 to 10 days is the treatment of choice for immunocompromised
children who are at risk for disseminated disease [1] [5]. The medication should be administered ideally within
72 hours of rash onset [20]. Relapse of herpes zoster can be treated with a second course of acyclovir with simi-
lar dosing and duration as for a primary episode.
A. K. C. Leung, B. Barankin
5
10. Prevention
It is known that vaccine-associated herpes zoster is milder than herpes zoster after wild type-varicella [26]. As
such, there is need for prevention of varicella-zoster virus infection though universal childhood immunization
[26] [27]. The Advisory Committee for Immunization Practices of the Centers for Disease Control and Preven-
tion and the American Academy of Pediatrics recommend a routine two-dose varicella vaccination program for
children, with the first dose administered at 12 to 18 months and the second dose at 4 to 6 years of age [2]. The
Advisory Committee on Immunization Practices further recommends two doses of varicella vaccine, 4 to 8
weeks apart, for all susceptible adolescents and adults and a catch-up second dose for everyone who receives
one dose of varicella vaccine previously [28].
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