Viral Infections of SKIN AND
• Human herpesviruses (HHVs) (family Herpesviridae)
are defined by the architecture of the virion,which has:
Core containing a linear double-strand DNA
• Icosahedral capsid 100–110 nm in diameter
composed of 162 capsomers Envelope containing viral
glycoprotein spikes on the surface.
• Worldwide, 60–90% of the population is infected
with one or more HHVs.
Eight HHVs have been identified:
▪ Herpes simplex virus (HSV)-1 (HHV-1)
▪ HSV-2 (HHV-2)
▪ Varicella-zoster virus (VZ V, or HHV-3)
▪ Epstein-Barr virus (EBV, or HHV-4)
▪ Cytomegalovirus (CMV, or HHV-5)
▪ HHV-8 (Kaposi sarcoma–associated virus).
• Primary HHV infections are usually asymptomatic
with the exception of VZV, which nearly always
presents with symptomatic varicella.
After primary infection, HHVs remain latent in neural or
lymphoid cells and reactivate if an adequate immune
response does not exist.
HHVs are categorized into three groups: Alpha, beta, and
▪ Alpha Herpesviridae : HSV-1, HSV-2, VZV are
characterized by a variable host range, relatively short
reproductive cycle, rapid spread in culture, rapid
destruction of infected cells, and latent
infection primarily, but not exclusively, of sensory ganglia.
Beta Herpesviridae : CMV has a restricted host
range and spreads slowly in cultures.
Gamma Herpesviridae : EBV, HHV-6, HHV-7,
HHV-8, and herpes virus saimiri are lymphotropic,
specific for either T or B lymphocytes.
The HHV-8 DNA sequences are closely homologous
to minor capsid and tegument protein genes of
gamma herpesviridae EBV and herpesvirus
HERPES SIMPLEX VIRUS (HSV)
• Whether first-symptomatic or recurrent, may
“typically” present clinically with grouped vesicles
arising on an erythematous base on keratinized
skin or mucous membrane.
• Most HSV infections are “atypical,” with
patch(es) of erythema, small erosions, fissures, or
subclinical lesions that shed HSV.
• Once an individual is infected, HSV persists in
sensory ganglia for the life of the patient,
recurring with lessening in immunity.
• Age of Onset Most commonly young adults;
• range, infancy to senescence.
• Etiology HSV-1, HSV-2.
• Labialis: HSV-1 (80–90%), HSV-2 (10–20%).
• Urogenital: HSV-2 (70–90%), HSV-1 (10–30%).
• Herpetic whitlow: <20 years of age usually
HSV-1; >20 years of age, usually HSV-2.
• Neonatal: HSV-2 (70%), HSV-1 (30%).
• Most transmission occurs when persons shed
virus but lack lesions.
• Usually skin-skin, skin-mucosa, mucosa-skin
Herpes gladiatorum transmitted by skin to-skin
contact in wrestlers.
• Increased HSV-1 transmission associated
with crowded living conditions and lower
• Primary HSV infection occurs through close contact
with a person shedding virus at a peripheral site,
mucosal surface, or secretion.
• HSV is inactivated promptly at room temperature;
aerosol or fomitic spread unlikely.
• Infection occurs via inoculation onto susceptible
mucosal surface or break in skin.
• After exposure to HSV, the virus replicates in epithelial
cells, causing lysis of infected cells, vesicle formation,
and local inflammation.
After primary infection at inoculation site, HSV
ascends peripheral sensory nerves and enters
sensory or autonomic nerve root (vagal)
ganglia, where latency is established.
• Retrograde transport of HSV among nerves
and establishment of latency are not
dependent on viral réplication in skin or
neurons; neurons can be infected in the
absence of symptoms
• Latency can occur after both symptomatic
and asymptomatic primary infection.
Periodically, HSV may reactivate from its latent state and
virus particles then travel along sensory neurons to skin
and mucosal sites to cause recurrent disease episodes.
• Recurrent mucocutaneous shedding can be associated
with or without (asymptomatic shedding) lesions; virus
can be transmitted to a new host when shedding occurs.
• Direct Microscopy Tzanck Smear
• Optimally, fluid from intact vesicle is smeared
thinly on a microscope slide, dried, and
stained with either Wright or Giemsa stain.
Positive, if acantholytic keratinocytes or
multinucleated giant acantholytic
keratinocytes are detected.
• Positive in 75% of early cases, either primary
Antigen Detection DFA Monoclonal antibodies,
specific for HSV-1 and HSV-2 antigens, detect and
differentiate HSV antigens on smear
Cultures: Positive HSV cultures from involved
mucocutaneous site or tissue biopsy specimens.
• Antibodies to glycoprotein (g)G1 and (g)G2
detect and differentiate past HSV-1 and HSV-2
• Primary HSV infection can be documented
by demonstration of seroconversion.
• Recurring herpes can be ruled out if
seronegative for HSV antibodies.
Polymerase Chain Reaction: To determine
HSV-DNA sequences in tissue, smears, or
Clinical suspicion confirmed by viral culture
or antigen detection. Cultures used for
diagnosing first-episode infections since
antibodies to (g)H1 or (g)G2 may take 2–6
weeks to develop.
• Prevention:- Skin-to-skin contact should be avoided
during outbreak of cutaneous HSV infection.
• Topical Antiviral Therapy:-
• Approved for herpes labialis; minimal efficacy.
• Acyclovir 5% ointment Apply q3h, 6 times daily for 7
days. Approved for initial genital herpes and limited
mucocutaneous HSV infections in
• Penciclovir 1% cream Apply q2h while awake for
recurrent orolabial infection in immunocompetent
Oral Antiviral Therapy
• Drugs for oral HSV therapy include acyclovir,
valacyclovir, and famciclovir. Valacyclovir, the
prodrug of acyclovir, has a better
bioavailability and is nearly 85% absorbed
after oral administration. Famciclovir is
equally effective for cutaneous HSV infections.
Antiviral agents more effective in treating
primary infections than recurrences
Acyclovir 400 mg 3 times daily or 200 mg 5 times
daily for 7–10 days
Valacyclovir 1 g twice daily for 7–10 days
Famciclovir 250 mg 3 times daily for 5–10 days
Recurrences Most episodes of recurrent herpes do
not benefit from pulse therapy with oral
acyclovir. In severe recurrent disease, patients
who start therapy at the beginning of the
prodrome or within 2 days after onset of lesions
may benefit from therapy by shortening and
reducing severity of eruption; however,
recurrences cannot be prevented.
Chronic suppression:- Decreases frequency of
symptomatic recurrences and asymptomatic HSV
shedding. After 1 year of continuous daily
suppressive therapy, acyclovir should
be discontinued to determine the recurrence rate.
Acyclovir 400 mg twice daily
Valacyclovir 500–1000 mg per day
Famciclovir 250 mg twice daily
Mucocutaneous disease in immunocompromised:-
Patients with herpes who do not respond to the
individuals recommended dose of acyclovir may
require a higher oral dose of acyclovir,
IV acyclovir, or be infected with an acyclovir-
resistant HSV strain, requiring IV
foscarnet. Acyclovir 5 mg/kg IV q8h for 7–14 days,
or 400 mg 5 times daily for 7–14 days
Acyclovir 20 mg/kg IV q8h for 14–21 days
Herpes simplex virus infection: eczema herpeticum on eyelids
VARICELLA ZOSTER VIRUS INFECTIONS
• Varicella zoster virus (VZV) is a human
herpesvirus that infects 98% of adult
• Primary VZV infection (varicella or
chickenpox) is nearly always symptomatic and
characterized by disseminated pruritic
• During primary infection, VZV establishes
lifelong infection in sensory ganglia.
When immunity to VZV declines, VZV reactivates
within the nerve cell, traveling down the neuron
to the skin, where it erupts in a dermatomal
pattern, i.e., herpes zoster (HZ), or shingles.
In the immunocompromised host, primary and
reactivated VZV infection is often more severe,
associated with higher morbidity rates and some
VZV vaccine has reduced the incidence of
varicella and herpes zoster.
Age of Onset
• Without immunization, 90% of cases occur in
children <10 years, <5% in persons older than
• With immunization (Varivax), the incidence
is markedly reduced.
• VZV, a herpesvirus.
• Structurally similar to other herpesviruses:
Lipid envelope surrounding nucleocapsid with
Centrally located double-strand DNA with
a molecular weight of 80 million
• Airborne droplets as well as direct contact
• Indirect contact uncommon
• Patients are contagious several days before
varicella exanthem appears and until last crop
• Crusts are not infectious.
• VZV can be aerosolized from skin of individuals
with herpes zoster, which is about
one-third as contagious as varicella, causing
varicella in susceptible contacts.
• In varicella, VZV is thought to enter through
mucosa of upper respiratory tract and oropharynx.
• Followed by local replication and primary viremia.
• VZV then replicates in cells of reticuloendothelial
system with subsequent secondary viremia and
dissemination to skin and mucous membranes.
• Localization of VZV in the basal cell layer
is followed by virus replication, ballooning
degeneration of epithelial cells, and accumulation
of edema fluid.
• Second episodes of varicella have been documented
but are rare.
• VZV Antigen Detection DFA
Smear of vesicle fluid or scraping from ulcer
• fluorescent antibody (DFA) test detects VZV
• Viral Cultures: Isolation of virus on viral
culture (human fibroblast monolayers) from
vesicular skin lesions, biopsy specimens, corneal
scraping, and CSF is possible but more difficult
than for HSV.
Cytology of fluid or scraping
from base of vesicle or pustule shows
both giant and multinucleated acantholytic
epidermal cells (as does that of HSV infections)
Seroconversion documents primary VZV infection.
Incubation Period 14 days (range, 10–23 days).
• Characteristically absent or mild.
• Uncommon in children, more common in
adults: headache, general aches and pains,
severe backache, malaise.
• Exanthem appears within 2–3 days.
Skin Symptoms Exanthem usually quite pruritic.
In most children, illness begins with appearance
• Vesicular lesions evident in successive
• Often single, discrete lesions or scanty in number in
children and much more dense in adults.
• Initial lesions are papules (often not observed) that may
appear as wheals and quickly evolve to vesicles and
initially appear as small “drops of water” or “dewdrops
on a rose petal”, superficial and thin-walled with
• Vesicles become umbilicated and rapidly evolve to
pustules and crusts over an 8- to 12-h period.
• With subsequent crops, all stages of evolution may be
noted simultaneously, i.e., papules, vesicles, pustules,
crusts, i.e., polymorphic.
• Crusts fall off in 1–3 weeks, leaving a pink, somewhat
• Characteristic punched-out permanent scars
• Uncommonly, hemorrhage into pustular lesion occurs
in otherwise healthy children, i.e., hemorrhagic varicella
First lesions begin on face and scalp, spreading inferiorly to
trunk and extremities.
• Most profuse in areas least exposed to pressure,
i.e., back between shoulder blades, flanks, axillae, popliteal
and anticubital fossae
• Density highest on trunk and face, less on extremities
• Palms and soles usually spared
Mucous Membranes Vesicles (not often
observed) and subsequent shallow erosions (2–3 mm)
• Most common on palate
• Mucosa of nose, conjunctivae, pharynx, larynx,
trachea, GI tract, urinary tract, vagina
Super infection by methicillin-sensitive S . aureus (MSSA),
methicillin-resistant S . aureus (MRSA), or GAS
Impetigo, furuncles, cellulitis, and gangrene In children 5–
11 years of age, the most common complications are
varicella encephalitis and Reye syndrome.
• In adults, prodromal symptoms are common and may be
Exanthem may last for a week or more, with prolonged
period of recovery.
• The mortality rate in adults was 15 per 50,000 cases
(U.S.); 25% of varicella associated deaths did occur in
Primary varicella pneumonia, which presents 1–6 days
after appearance of rash, is relatively common in adults:
16% of adults show x-ray evidence of pneumonitis, but
only 4% have clinical signs of pneumonitis. Women have a
10% risk of severe VZV pneumonitis.
VZV encephalitis may also complicate varicella
• Less common complications of varicella include viral
arthritis, uveitis, conjunctivitis, carditis, inappropriate
antidiuretic hormone syndrome, nephritis, and orchitis.
• Maternal varicella during the first trimester of
Fetus: Fetal varicella syndrome (limb hypoplasia,
eye and brain damage, skin lesions) in 2% of exposed
Neonatal varicella has higher associated incidence of
pneumonitis and encephalitis than occurs in older
• Immunocompromised or glucocorticoid treated
patients with varicella may manifest dissemination,
hepatitis, encephalitis, and hemorrhagic
• If varicella occurs at an early age when maternal
antibody is still present, an individual can
have a second episode of varicella.
Usually made on clinical findings alone.
Immunization VZV immunization is now available (Varivax)
and is 80% effective in preventing symptomatic primary
VZV infection. Those at high risk for varicella, who should
be immunized, include: normal VZV-negative adults,
children with leukemia, and immunocompromised
individuals (immunosuppressive treatment, HIV
Lotions Directed at reducing pruritus.
Oral antihistamines Application gives short-term relief of
Caution re antipyretic agents Antipyretic administration is
of concern because of a possible link between aspirin
and Reye syndrome in children with varicella.
Otherwise healthy patients If begun within 24 h after
onset of varicella, decreases the severity of varicella and
reduces secondary cases.
Acyclovir∗ 20 mg/kg (800 maximum) four times daily for 5
Valacyclovir Effective but not an approved use; dosing
same as for herpes zoster.