management of herpes simplex and varicella-zoster infections .varicella-zoster virus infection vzv

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14 z Prescriber 5 February 2014

Herpes simplex virus (HSV) and varicella-zoster virus (VZV)are related viruses that both cause blistering rashes andare characterised by the ability to establish latent infection.

Primary infections typically involve the skin or mucous mem-branes, causing a characteristic vesicular rash. Following theresolution of active virus infection the virus establishes a clini-cally silent infection primarily in neurones within the trigeminaland dorsal root ganglia.

This latent infection is life-long and may subsequently giverise to reactivated infection in which new infectious virus is pro-duced in the ganglion and travels via the axon to the originalsite of infection or another site within the same dermatome.This in turn may give rise to a lesion, although asymptomaticshedding of reactivated HSV, particularly at mucosal sites, iscommon. Reactivation of viral replication may be triggered byphysical or psychological stress events such as sunlight, illnessor anxiety.

The immune system controls and eliminates viral replicationin both primary and reactivated infections, and those with poorimmune function are susceptible to more extensive viral repli-cation, more frequent reactivations and more severe accompa-nying symptoms.

This article reviews the clinical features of HSV and VZVinfection that are likely to be encountered in primary care,excluding genital herpes. Presenting features and complicationsare discussed, along with recommendations on when to usediagnostic tests, when to treat and when to refer for hospitalassessment or specialist services. Advice on managing contactsis also given where appropriate.

Herpes simplex virus infectionPrimary HSV infection is acquired by contact with infectioussecretions, and lesions occur at the site of initial infectionafter an incubation period of 212 days. In the UK HSV type1 more commonly infects the oral mucosa, while HSV type 2

Management of herpes simplexand varicella-zoster infectionsPeter Muir PhD, FRCPath

Herpes simplex and zoster infections arecommon and can result in significant morbidity. Our Drug review discusses thechoice of drugs available for treatment and prophylaxis, followed by sources of further information and an analysis of theprescription data.

CPD questions available for this article. See page 23


is more likely to be the cause of genital infection, althoughexceptions to this anatomical distinction are increasinglyobserved.

Rarer manifestations at other sites include meningitis,encephalitis, Bells palsy, hepatitis and, in the immunocompro-mised, pneumonitis and oesophagitis.

GingivostomatitisPrimary HSV infection in children usually involves the oralmucosa, with painful vesicles and ulcers present on the gums,lips, tongue, buccal mucosa and soft and hard palates. Feverand lymphadenopathy may also be present.

The differential diagnosis includes herpangina, aphthousulcers, erythema multiforme major and Stevens-Johnson syn-drome.

PharyngitisIn older individuals primary HSV infection more commonly pres-ents with upper respiratory symptoms. On examination pharyn-geal erythema or exudate is often present.

Pharyngitis due to HSV infection is difficult to differentiatefrom that due to other infections, including infectious mononu-cleosis, group A streptococcal infection, Mycoplasma pneumo-niae or influenza and other respiratory viruses.

Herpes labialisRecurrent HSV infection most commonly presents as cold sores(see Figure 1). A prodromal phase characterised by a tinglingsensation precedes the appearance of vesicles by several hoursup to a few days.

Vesicles occur on the lip, the margin of the lip or sometimeson other areas of the skin. They are itchy and painful, and aftera day or so coalesce to form a weeping ulcer, which then crustsand heals.

Recurrences may occur sporadically, or at regular intervals,typically two to three times a year, although a few patients sufferrecurrence at a higher frequency.

Ocular HSV infectionHSV is one of many infectious causes of keratitis. Ocular infec-tion may occur in primary HSV infection, probably due toautoinoculation, and typically involves the eyelid and conjunctiva(blepharoconjunctivitis). Recurrent infection may present as asuperficial dendritic ulcer (epithelial conjunctivitis). Symptomsinclude foreign body sensation, photophobia, blurred vision anda red eye.

Stromal keratitis involves deeper layers of the cornea andmay lead to scarring of the cornea that results in visual impair-ment. Acute retinal necrosis may occur in the elderly or immuno-compromised patient.

Herpetic whitlowHSV infection of the finger (see Figure 2) may result fromautoinoculation, for example thumb sucking in children,although dentists and other healthcare workers may acquirethis infection from direct contact with infected patients. The

infected finger appears swollen, red and tender, with small vesi-cles during the early stage.

Eczema herpeticumIn individuals with atopic eczema HSV infection may spread overlarge areas of skin, particularly on the face and neck. Fever andlymphadenopathy may be present. Affected areas of skin arepainful and contain fluid-filled blisters that break down and thencrust over.

A similar condition may be seen more rarely in eczema patientswith other vesicular rashes, including varicella, zoster or enterovirusinfections. The rash may also be confused with impetigo.

Neonatal HSV infectionBabies born to women who have active HSV infection at the time of delivery may become infected and this may be

Viral skin infections l DRUG REVIEW n

Prescriber 5 February 2014 z

Figure 1. Topical antiviral treatment may by adequate for mild HSVinfections such as cold sores

Figure 2. HSV infection of the finger, or whitlow, is often seen inhealthcare workers who come into contact with infected patients;the lesions usually heal in two to three weeks


life-threatening, particularly when the mother has primary HSVtype 2 infection and has not yet developed antibody by the timeof delivery.

Infection may be limited to the skin, eyes and mucous mem-branes, while more serious systemic infection, with or withouta rash, may lead to rapid multiorgan failure and death. Babiestypically present in the first two weeks of life, initially with fever,irritability and poor feeding.

The differential diagnosis includes invasive group B strep-tococcal infection, Listeria spp., E. coli or neonatal enterovirusinfection.

Infants who survive neonatal HSV infection may experiencetroublesome mucocutaneous recurrence during childhood.

Varicella-zoster virus infectionVZV causes two major diseases: varicella (chickenpox) is asso-ciated with primary infection, whereas zoster (shingles) is theclinical manifestation of reactivated VZV infection.

VaricellaVaricella is an itchy rash that frequently covers the entirebody (see Figure 3). The incubation period is 1021 days,and the rash is often preceded by fever and nonspecificinfluenza-like symptoms. The spots are initially red, usuallybegin on the face and scalp and continue to appear in waves,spreading over the trunk and limbs. The spots become fluid-filled vesicles, then pustules, and finally crust over and heal.The illness is more severe in adolescents and adults than inchildren.

The breakdown in the integrity of the skin may allow skinflora such as Staphylococcus aureus to enter the blood-stream, resulting in secondary bacterial infection. Other com-plications include varicella pneumonitis, particularly insmokers, pregnant women and immunocompromisedpatients, and meningitis or rarely encephalitis. Ataxia mayoccur as a postinfectious complication 710 days after chick-enpox onset.

Chickenpox during the first trimester of pregnancy carriesa small risk of congenital varicella syndrome, resulting from con-genital infection and subsequent in-utero reactivation of thevirus infection. At birth the infected infant may present withmicrocephaly and brain damage, chorioretinitis, limb hypoplasiaand skin lesions. Mortality is high.

When maternal chickenpox occurs during the last fewweeks of pregnancy or the week after delivery, neonatal vari-cella may be present at birth or may develop in the first twoweeks of life. Neonatal varicella carries a risk of pneumonitisand other complications and is life-threatening, particularlywhen maternal varicella occurs during the week before or theweek after delivery, due to the lack of transplacentally acquiredmaternal antibody.

ZosterFollowing chickenpox, viral reactivation leads to zoster, whichmay occur at any age but is more common with increasingage due to the decline of cellular immune functions that serve

n DRUG REVIEW l Viral skin infections

16 z Prescriber 5 February 2014

Figure 3. In chickenpox oral aciclovir should be started within 24hours of the rash appearing

Figure 4. Oral aciclovir started within 72 hours of the rash appearingin shingles reduces the risk of postherpetic neuralgia



to eliminate viral reactivation before it becomes clinicallyapparent.

The zoster rash is vesicular and is usually limited to the der-matome served by the spinal nerve in which the virus has reac-tivated (see Figure 4), although lesions may cross thedermatome border and satellite lesions may appear in otherdermatomes. Multidermatomal or disseminated (varicelliform)zoster suggests underlying immunodeficiency, as does recurrentzoster, which unlike recurrent HSV infection is rare.

The rash is often itchy or painful; indeed, pain and tinglingmay precede the rash and persist after i


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