VIRAL SKIN INFECTIONS

Rini Syahrani Harahap, T. Ibnu Alferraly

Department of Anatomical Pathology, Faculty of Medicine, University of North Sumatera

INTRODUCTION
Viral skin infections present with different patterns and must be excluded
from infections due to bacteria and fungi, and drug eruptions. Viral infections of
skin and mucosa produce a wide spectrum of clinical manifestations. Viruses such
as human papillomavirus (HPV) and molluscum contagiosum virus (MCV)
colonize the epidermis of most individuals without causing any clinical lesions.
Benign epithelial proliferations, i.e., warts and molluscum, occur in some, are
transient, and eventually resolve without therapy. In immunocompromised
individuals, however, these lesions may become extensive, persistent, and
refractory to therapy. Viruses that cause febrile illness with exanthems are herpes
viruses often have asymptomatic primary infections but are characterized by
lifelong latent infection. In the setting of immunocompromise, these viruses can
become active and cause disease with significant morbidity and mortality rates.1
Rashes caused by bacterial, fungi, and drugs are more likely to present
with erythematous–pustular patterns, whereas viral infections are more likely to
present with erythematous-vesicular patterns and be accompanied by enanthema.
Certain viruses may produce scarring, especially if acquired earlier on in
gestation, such as congenital varicella and congenital herpes simplex (e.g., aplasia
cutis congenital, scarring in a dermatomal pattern). Herpes simplex infection
produces grouped vesicles with scalloped borders, whereas varicella produces
vesicles on an erythematous base (e.g., ‘dew-drop on a rose petal’).2,3
A virus is a particle of DNA or RNA enclosed by structural proteins.
Viruses infect cells and proliferate to cause viral infections. Viral skin diseases are
classified by clinical features into three types: (1) tumorous changes in epidermal
cells (e.g., in verruca vulgaris) (2) degeneration of epidermal cells and blistering
(e.g., in herpes simplex and herpes zoster), and (3) allergic eruptions on the whole
body (e.g., in measles and rubella). The first two types are caused by viral
infection in epidermal keratinocytes; the last type is caused by systemic viral
infection (viremia).4

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LITERATURE REVIEW
TUMOROUS CHANGES IN EPIDERMAL CELLS
Verrucae (Warts)
Verrucae are common lesions of children and adolescents, although they
may be encountered in any age group. They are caused by human papillomavirus
(HPV). Transmission usually involves direct contact with an infected individual
or autoinoculation. Verrucae generally are self-limited, most often regressing
spontaneously within 6 months to 2 years.1,5,6

Figure 1. Verruca vulgaris. A, Multiple warts, with characteristic rough, pebble-like surfaces. B,
Microscopically, common warts contain zones of papillary epidermal proliferation that often
radiate symmetrically like the points of a crown (top). Nuclear pallor, prominent keratohyalin
granules, and related cytopathic changes are seen at higher magnification (bottom).5
As mentioned earlier, verrucae are caused by HPV. Some members of the
HPV family are associated with preneoplastic and invasive cancers of the
anogenital region. In contrast with HPV-associated carcinomas, most warts are
caused by low-risk HPV subtypes that lack transforming potential. Like high-risk
viruses, these low-risk viruses express viral E6 and E7 oncoproteins that lead to
dysregulated epidermal cell growth and increased survival. Why lowrisk viruses
cause warts instead of cancer is unclear; subtle functional differences due to
structural variation in E6 and E7 proteins that affect interactions with host
proteins as well as differences in the abilities of different viral strains to evade the

2
immune response have been proposed. The immune response normally limits the
growth of these tumors, and immunodeficiency often is associated with increased
numbers and larger sized verrucae.5

Figure 2. Verruca vulgaris. (a) There is a papillomatous surface and the peripheral edges of the
lesion claw in toward the center resembling a buttress. (b) The papillary dermal blood vessels are
dilated. The koilocytes have irregular nuclei and coarse keratohyaline granules7

Figure 3. Verruca plantaris. Verruca on the sole have an endophytic growth pattern, but otherwise
features typical of a verruca.7

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 Different kinds of warts are identified on the basis of their gross
appearance and location and generally are caused by distinct HPV subtypes. (1)
Verruca vulgaris (Figure 1&2), (infected by HPV 2,4,7) the most common type of
wart, can occur anywhere but is found most frequently on the hands, particularly
on the dorsal surfaces and periungual areas, where it appears as a graywhite to tan,
flat to convex, 0.1- to 1-cm papule with a rough, pebble-like surface. (2) Verruca
plantaris (figure 3) and verruca palmaris (infected by HPV 1,4) occur on the soles
and palms, respectively. These rough, scaly lesions may reach 1 to 2 cm in
diameter and then coalesce to form a surface that can be confused with ordinary
calluses. (3) Verruca plana (figure 4), or flat wart (infected by HPV 1,4), is
common on the face or dorsal surfaces of the hands. These warts are flat, smooth,
tan macules.5,6
Verruca plantaris has a thick hyperkeratotic surface. A
papillomatous architecture may be less apparent, and the lesion
is frequently partly endophytic (Figure 3). Koilocytes are present
and may be quite prominent.7

Figure 4. Verruca plana. Flat warts have less pronounced papillomatosis and do not have the
prominent peripheral buttressing.7

Verruca plana is acanthotic, but lacks pronounced

papillomatosis and the buttressed edges (Figure 4). The granular
layer is thickened and koilocytes are present, but they may be
less prominent than verruca vulgaris or plantaris.1,7

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Condyloma Accuminata (Veneral Warts)
Condyloma accuminata occurs on the penis, female genitalia, urethra, and
perianal areas. which is characterized grossly by one or several soft elevated
masses of variable size (Figure 5). Histologic features common to verrucae
include epidermal hyperplasia, which is often undulant in character (so-called
verrucous or papillomatous epidermal hyperplasia) (figure 6), and cytoplasmic
vacuolization (koilocytosis), which preferentially involves the more superficial
epidermal layers, producing halos of pallor surrounding infected nuclei. Infected
cells also may demonstrate prominent keratohyalin granules and jagged
eosinophilic intracytoplasmic protein aggregates as a result of impaired
maturation.5,8

Figure 5. Large condyloma of vulva8

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 Figure 6. Whole mount of condyloma acuminatum of vulva.8

Figure 7. Papillomatous shape of vulvar condyloma.5,6

The other form of condyloma, which is actually much more common, is

the flat condyloma (not to be confused with the condyloma latum of syphilis). The
cytologic features are similar in both forms. Koilocytosis of the malpighian
epithelium and lymphocytic infiltration of the stroma are regular features (Figure
8). Koilocytosis refers to the combination of perinuclear cytoplasmic clearing and
wrinkling of the nuclear membrane (nuclear ‘raising’). As a rule, this change is
not as florid in vulvar condylomas as it tends to be in condylomas of the cervix. A
typical condyloma shows minimal basal or parabasal cell atypia, orderly
maturation, and a smooth transition to koilocytotic intermediate and superficial
cells; mitoses may be numerous but are all typical. 9 In contrast, the lesions of VIN
(vulvar intraepithelial neoplasia) exhibit abnormal mitoses and nuclear
pleomorphism, enlargement, and hyperchromasia in the basal and parabasal cell
layers. The increased proliferative activity of condyloma (in contrast to
fibroepithelial polyp and squamous papilloma) can be easily appreciated with the
Ki-67/MIB-1 stain.10

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 Figure 8. Prominent koilocytotic changes in vulvar epithelium9
Sometimes one sees verrucopapillary vulvar lesions in children or adults
that lack the cytologic markers of condyloma; these are often referred to as
squamous papillomas and usually contain genital HPV types by polymerase chain
reaction (PCR). Conversely, there may be multinucleated atypia of the epithelial
squamous cells associated with reactive conditions in the absence of HPV
infection. Another vulvar lesion which needs to be discussed here is the process
morphologically indistinguishable from cutaneous seborrheic keratosis, which in
this particular location is frequently associated with HPV infection. 11 The
differential diagnosis of condyloma also includes a lesion characterized by
epidermolytic hyperkeratosis, which could be related to Darier disease or
represent a form of Hailey–Hailey disease.12 The acantholysis is usually
suprabasal, but we have also seen it at the level of the granular layer.9
For verruca vulgaris, the diferential diagnosis is usually not
difficult. In irritated or inflaamed lesions, koilocytes may not be as
evident. This situation can cause confusion with an irritated
seborrheic keratosis, or possibly a squamous cell carcinoma. The
papillomatous surface with hemorrhage in the stratum corneum,
dilated papillary dermal blood vessels and buttressed edges are
keys to the diagnosis. It should be pointed out that the overlap
between some cases of verruca vulgaris and irritated seborrheic
keratosis can be so signifcant that it is not always possible to
unequivocally distinguish them. Some use the term “verrucal

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keratosis” in this situation. Some reactive atypia is allowed in
irritated or inflaamed verruca vulgaris, but prominent
pleomorphism or a desmoplastic stroma are clues to the
diagnosis of squamous cell carcinoma. It should be remembered
that malignancy can arise in cutaneous warts, especially in older
patients or organ transplant patients.1,7
Verruca plantaris is not a difficult diagnosis provided there
is an adequate specimen. Too often, only the hyperkeratotic
surface is biopsied with little or no underlying dermis. In such a
situation, it is important to look for evidence of a papillomatous
architecture that can be revealed by the pattern of
hyperkeratosis and for evidence of hemorrhage in the stratum
corneum that can lead the pathologist to suggest the possibility
of a verruca (Figure 9). Verruca plana frequently comes
submitted with a clinical diagnosis of entities such as actinic
keratosis, squamous cell carcinoma, basal cell carcinoma, etc.
Recognizing the thickened granular layer with koilocytes is
crucial to the diagnosis. Verruca plana does not show signifcant
atypia.9

Figure 9. Superficially sampled verruca plantaris. Frequently, only the keratotic surface of a
verruca plantaris is sampled. The keratotic surface shows remnants of the dermal papillae with
parakeratosis and hemorrhage.7

Condyloma acuminatum can be a frustrating diagnosis. It

closely resembles seborrheic keratosis. In fact, a clue to the

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diagnosis is that it resembles a domeshaped seborrheic keratosis
on genital skin. Careful examination usually reveals some
koilocytes, though they are not as numerous as in other warts. In
cases where there is any doubt, special studies such as
chromogenic in situ hybridization should be pursued, as this
diagnosis carries important implications. I have heard stories,
perhaps apocryphal, about pathologists being successfully sued
for over diagnosis of this entity.1,7

Molluscum Contagiosum
Molluscum contagiosum is a common, self-limited viral disease of the
skin caused by a poxvirus. The virus is characteristically brick shaped, has a
dumbbell-shaped DNA core, and measures 300 nm in maximal dimension, and
thus represents the largest pathogenic poxvirus in humans and one of the largest
viruses in nature. Infection is usually spread by direct contact, particularly among
children and young adults, but may present at any age.1,8
Lesions are most common on the head and neck, followed by genitalia, the
latter is often the result of sexual transmission. Fomite transmission is the major
route of infection, accounting for the frequency in young children.
Immunosuppressed patients can have widespread lesions.1,5,6,7,8
Clinically, multiple lesions may occur on the skin and mucous membranes,
with a predilection for the trunk and anogenital areas. Individual lesions are firm,
often pruritic, pink to skin-colored umbilicated papules generally ranging in
diameter from 0.2 to 0.4 cm. Rarely, “giant” forms occur measuring up to 2 cm in
diameter. A curd-like material can be expressed from the central umbilication.
Smearing this material onto a glass slide and staining with Giemsa reagent often
shows diagnostic molluscum bodies.6
On microscopic examination, lesions show cuplike verrucous epidermal
hyperplasia, an inverted proliferation of squamous epithelium that opens to the
epidermal surface in the central portion. The diagnostically specific structure is
the molluscum body, which occurs as a large (up to 35 μm), ellipsoid,
homogeneous, cytoplasmic inclusion in cells of the stratum granulosum and the

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stratum corneum. In the H&E stain, these inclusions are eosinophilic in the blue-
purple stratum granulosum and acquire a pale blue hue in the red stratum
corneum. Numerous virions are present within molluscum bodies. Occasionally,
there can be rupture of the invaginated epithelium leading to a brisk inflammatory
response mimicking a ruptured folliculitis. In such cases, deeper levels may reveal
the characteristic viral inclusions. 1,5,7
Reed and Parkinson suggested that molluscum contagiosum arises on the
basis of follicular neogenesis, based on their findings of areas of hair bulb
differentiation at the periphery, occasionally associated with areas of sebaceous
gland differentiation. However, the disease can also appear in places where there
are no hair follicles, such as the palms, indicating that the epidermis itself may be
affected.8

Figure 10. Molluscum contagiosum. (a) In Molluscum contagiosum there is an endophytic

proliferation of epidermis. (b) The infected keratinocytes have large intracytoplasmic eosinophilic
viral inclusions.8

For typical cases, there is essentially nothing else in the differential

diagnosis due to the distinctive appearance of Molluscum contagiosum. As noted
above, some cases can be confused with a folliculitis.7

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Figure 11. Molluscum contagiosum. A focus of verrucous epidermal hyperplasia contains
numerous cells with ellipsoid cytoplasmic inclusions (molluscum bodies) within the stratum
granulosum and stratum corneum.6

DEGENERATION OF EPIDERMAL CELLS AND BLISTERING

Herpesvirus Infections

Herpesvirus infections are usually encountered in three

settings: oral lesions of Herpes simplex 1 (HSV-1), genital lesions
of Herpes simplex 2 (HSV-2), or reactivation of Varicella zoster in
the form of herpes zoster (shingles). HSV-1 infection usually
initially presents in childhood and as vesicular crusted lesions
around the mouth. Patients can have episodes of reactivation
throughout life. HSV-2 is typically acquired in adult life and is
generally the result of sexual transmission. Lesions are similar to
HSV-1 but are most common on genital or perianal skin. For
herpes zoster, there is a linear, painful vesicular eruption that
follows a dermatomal distribution. It is more frequent in older
adults but may be seen in a wide age range.7
The infection pattern of HSV is shown in Figure 12. The virus enters the
skin through a minor external injury, or through the oral mucosa, eyes or genitalia.
It travels along the sensory nerve axons to reach the trigeminal ganglia or
lumbosacral spinal cord ganglia. In 90% of cases, primary infection does not
progress beyond latency, however, symptoms may be apparent in infants or in
people with immunodeficiency. After the symptoms subside, viral DNA remains
in the gangliocytes and becomes reactivated by stress or a common cold. Some

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viruses may travel along the axons anterogradely to reach the skin and become
reactivated.4

Figure 12. Mechanism of infection by HSV and VZV. HSV: Herpes simplex virus. VZV:
Varicella zoster virus.4

Figure 13. Herpesvirus. (a) Intraepidermal vesicles with acantholysis are the classic lesion of
herpesvirus infection. (b) The virally infected cells have intranuclear steel gray inclusions with
peripheral condensation of the native chromatin. Multinucleation is common.7

Herpes labialis (cold sore)

This is the most common clinical form of herpes simplex
seen in adults. Most cases are caused by reactivated HSV-1. It

12
begins with prodromes such as itching and discomfort in the lips
and their periphery, including the anterior naris cheeks and
orbital region. After a day or two, edematous erythema appears
and small blisters with central umbilication occur and aggregate,
sometimes coalescing to form irregularly shaped blisters. The
blisters soon form pustules, erosions and crusts. They heal in
about 1 week.1,4

Herpes gingivostomatitis
This type occurs most frequently in initial infection of HSV-1 in infancy.
It begins 2 to 10 days after infection, with discomfort, fever and pharyngeal pain.
Accompanied by a high fever, multiple painful small blisters and erosions occur
in the oral mucosa, tongue and lips.1,4

Herpes genitalis (genital herpes)

This type occurs as an initial infection or recurrently. Herpes genitalis is
often transmitted through sexual activity and can be regarded as a sexually
transmitted disease (STD). Although men and women in adolescence and older
are frequently affected, it may also occur in infants in rare cases. It may be
transmitted to an infant by the hands of the mother or nurses. The causative virus
in most cases is HSV-2; however, the number of cases caused by HSV-1 has been
increasing in recent years. In initial infection, small blisters form in the glans
penis or foreskin of adult men, or in the labia or perineal region of adult women.
The blisters become severely painful small ulcers. The inguinal lymph node
becomes painful and enlarged. The lesions usually disappear spontaneously in 2 to
4 weeks; however, when the sacral nervous root is involved it may leave urinary
disturbance. The symptoms of recurrent cases are moderate.1,4

Herpetic whitlow
HSV-1 (or HSV-2 in some cases) invades the body from a minor injury in
the tip of a finger, leading to aggregated formation of painful blisters and pustules
in fingers. The blisters on the fingers are not as fragile as those on other sites of

13
the body. Infants who have a habit of finger-sucking and dentists may be infected.
It is recurrent and heals in 2 to 4 weeks.4
Essentially, all of these entities have the same histological
features. Distinction between subtypes requires culture or other
techniques (e.g., direct flauorescent antibody tests). Classically,
there is in intraepidermal vesicle with acantholysis and
degenerating keratinocytes. The diagnostic feature is the
presence of keratinocytes with intranuclear viral inclusions. The
intranuclear inclusions have an eosinophilic to steel gray
appearance with peripheral margination of the chromatin.
Frequently, the afected keratinocytes fuse, resulting in multi-
nucleation.4,7
In older lesions, the epidermis may be necrotic and it is
vital to look for evidence of viral inclusions in the necrotic
epidermis. Follicles should also be examined, as it is sometimes
possible to identify virally infected cells that are not recognizable
in the necrotic epidermis, or because the epidermal surface is
ulcerated. Finally, in some resolving lesions, no viral inclusions
are evident and the histological features are a nonspecifc
granulomatous dermatitis.7
The diagnosis is generally quite straight forward. For more
subtle cases, entities such as pemphigus or even acute
spongiotic dermatitis can be considered. Neither of these has
intranuclear viral inclusions. Once the epidermis is completely
ulcerated, it may be more difficult to recognize the presence of
the virus. If there is still some necrotic epidermis present, it may
be possible to recognize the remnants of viral nuclear inclusions. 7

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Figure 14. Histopathology of herpes simplex. There is necrotic degeneration in epidermal cells.
The giant cells contain inclusion bodies (ballooning cells).4
Repetitive replication of viral DNA leads to ballooning degeneration and
reticular degeneration of infected epidermal cells. These degenerated epidermal
cells are observed as ballooning cells containing intranuclear inclusion bodies by
smear staining of the blister contents (Figure 14).7

Figure 15. Intraepidermal vesicle produced by profound degeneration (Ballooning) of epidermal

cells. Ballooning degeneration occurs mainly at the base of viral vesicle.

15
Figure 16. Eosinophilic intranuclear bodies, surrounded by a clear halo, are usually seen in
balloon cells.

Varicella
It is commonly known as chickenpox. Infants are most frequently affected.
It is caused by primary infection of varicellazoster virus (VZV) and is highly
infectious. A fever emerges concurrently with erythematous papules on the whole
body. Eruptions progress in the course of vesicles, pustules and crusts, and
healing. New eruptions continue to occur such that preexisting eruptions appear
together with new eruptions. It heals in 7 to 10 days.4
Symptomatic treatments are helpful. Aspirin is contraindicated. After a
latency of 2 to 3 weeks, erythematous papules appear on the whole body,
accompanied by fever (37 to 38°C) and systemic fatigue. The eruptions are
accompanied by itching. They progress in the order of erythema, papules, blisters,
pustules and crusts, over the course of several days. Varicella is characterized by
small blisters that resemble insect bites and blisters that form on the scalp.
Because the eruptions continue to appear, preexisting eruptions are found together
with newly formed ones. Blistering also occurs in the oral mucosa and palpebral
conjunctiva. Varicella heals in 7 to 10 days, without scarring. If the eruptions are
scratched or secondarily infected, they heal with moderate scarring.1,4
The main complications are pneumonia, encephalitis, unilateral high-
frequency deafness (thought to be a symptom of Ramsay- Hunt syndrome), and
Reye’s syndrome (cerebritis and fatty liver).1,4,5,6

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 Varicella is caused by infection of the varicella zoster virus (VZV). This
virus enters the upper respiratory tract by droplet infection or contact infection
and proliferates in the regional lymph nodes, inducing primary viremia. The virus
further proliferates in the liver and spleen, leading to secondary viremia, and
reaches the skin, resulting in blistering. Varicella occurs most frequently between
weaning and early childhood. Ninety-five percent of children aged 9 have the
antibodies. The age of initial infection has risen in recent years; varicella in adults
is increasing.4

Figure 17. Histopathology of varicella. Multinucleated cells, some with intranuclear inclusions. 13
In adult cases, varicella is often accompanied by encephalitis and
pneumonia, and it can easily become severe.4,13
Tzanck test is useful for early diagnosis. Varicella is characterized by
balloon cells, the epidermal cells that are infected by VZV.4,13

Figure 18. Varicella and herpes zoster. A. During primary VZV infection, virus onfects sensory
ganglia. B. VZV persists in a latent phase within ganglia for the life of the individual. C. VZV re-
activates within sensory ganglia, descends through sensory nerves, and replicates in skin.1
Herpes Zoster

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 Latent VZV in the ganglia reactivate to form band-like herpetic
aggregations of small blisters on certain innervated regions. Pain is present in
areas over the involved nerves. It occurs in individuals with history of varicella
infection. Herpes zoster occurs most frequently in persons between the ages of 10
and 30 and over 50.4
Ballooning cells are observed by Tzanck test, as in herpes simplex. Tzanck
test, detection of viral antigens, and serological diagnosis are conducted, as in the
cases of herpes simplex and varicella. Cases in the elderly or with generalized
herpes zoster should be carefully observed, because there is the possibility of
malignant tumor immunodeficiency as an underlying disease. Ophthalmologic
examination is conducted on any lesions involved in the first division of the
trigeminal area.1,4,5,6
There is permanent immunity after the first infection. The pain that
persists after healing is called post-herpetic neuralgia (PHN). When the ears and
the peripheral regions are involved, hearing loss and peripheral facial paralysis
may occur (Ramsay-Hunt syndrome).4

Figure 19. Histopathology of herpes zoster. Intraepidermal vesicle, acantholysis, reticular

degeneration, underlying dermis shows edema and vasculitis.1

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Figure 20. Histopathology of herpes zoster. Multinucleated giant cells with characteristic nuclear
changes. 1

Herpes zoster symptoms are divided into cutaneous and nervous. There are
several specific types of herpes zoster. (1) Mucocutaneous symptoms. Multiple
herpetic vesicles appear in band-like patterns over certain innervated regions. The
skin over the intercostal nerve is most frequently involved, followed in frequency
by the trigeminal area of the face. Prodromes such as neuralgic pain and abnormal
paresthesia occur several days before the eruptions manifest. Later, edematous
erythema and papules occur and transform into blisters. All these blisters progress
in the same course; this differs from varicella, in which preexisting blisters are
found concurrently with newly formed ones. The blisters soon rupture and
become erosions. They heal after crust formation in 2 to 3 weeks. (2) Nervous
symptoms. Neuralgic pain is often present several days before the onset of
eruptions. The pain is severest 7 to 10 days after the eruptions occur. The severity
of pain ranges from moderate to intense, causing sensory disturbance, insomnia or
paralysis. The pain in most cases subsides with remission of the eruptions. (3)
Types of herpes zoster. Generalized herpes zoster: In patients who are
immunocompromised as a result of steroid or immuno-suppressant intake or a
primary disease, small widespread blisters resembling varicella may spread on the
whole body 4 to 5 days after manifestation of typical eruptions of herpes zoster.1,4

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Figure 21. Post-Zoster granulomatous inflammation. In some case, after the viral infection has
histologically resolved, there is a granulomatous inflammatory infiltrate. This is nonspecific, but
suggestive in a clinical setting where zoster is suspected clinically. (Courtesy of Dr. Soon
Bahrami).7

Cytodiagnosis has been used as an aid to the rapid diagnosis of numerous

skin conditions (Greek word: Kytos = hollow vessel). George Papanicolaou is
considered the father of exfoliative cytology. For dermatologic diseases, cytology
was first used by the Frenchman, Arnault Tzanck in 1947 in herpetic infections
and pemphigus. Since then, cytology has been used in the diagnosis of various
vesiculobullous, erosive, tumoral, and granulomatous diseases, and the method
has been termed the “Tzanck smear.” The Tzanck smear is a quick and reliable
tool for the evaluation of various erosive and vesiculobullous skin lesions.14

Figure 22. Tzanck smear showing Multi Nucleated Giant cells (MNGs) (pink arrow) and
Tzanck cells (red arrow) in herpetic infections.14

Variola (Synonym: Smallpox)

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 Variola is caused by infection of the upper respiratory mucosa by the
Orthopoxvirus variola virus. Infection is by droplet or contact. This pathogen is so
virulent that it used to be fatal in many cases; however, Jenner’s cowpox vaccine
made prevention possible. A smallpox eradication program was developed in
1958 by WHO, and no cases of variola have occurred since 1977. In 1980, WHO
declared the disease eradicated. The virus is kept at secure institutions in biosafety
level 4 labs in the U.S. and Russia.1,4

The typical skin vesicles observed in smallpox occur (1) viral infection of
the epidermal cell, (2) Cells in malpighian layer entering balloon degeneration,
from formation of vacuoles, (3) Cytoplasmic enlargement leading to loss
of nuclear material, Destruction of upper and middle layers of stratum spinosum,
(4) Formation of vesicles. On the other hand, in the infected mucous surfaces,
the viral proliferation and absence of the stratum corneum, lead to the formation
of ulcers. These ultimately lead to the release of greater loads of virus into
the oropharynx. Poxviruses are characterized by cytoplasmic inclusions, however,
these do not identify specifically the smallpox virus on a biopsy.15

Figure 19. Histopathology of smallpox15

The most common form of variola major, common smallpox, is associated

with a mortality rate ranging from less than 10 percent when lesions are discrete
to 50 percent to 75 percent wgen lesions are confluent. Death often occurs
between days 10 and 16 of illness. Modified smallfox is associated with less than

21
10 percent mortality. The overall mortality rate for variola major is 30 percent,
compared to less than 1 percent for variola minor. Those wh survive either disease
have lifetime immunity.1

ALLERGIC ERUPTIONS ON THE WHOLE BODY

Measles
Measles, also known as rubeola, is characterized by conjunctivitis, cough,
and coryza; and its symptoms appear 8–12 days after the exposure and presents
with classic cephalocaudal maculopapular rash 14 days after the exposure. It is a
highly communicable virus that causes infection through aerosol droplets.1,16

Figure 20. Measles skin rash1

In classic measles, cutaneous changes present as an enanthem (Koplik

spots) followed by an exanthem in a cephalocaudal distribution. Primary viremia
causes viral dissemination through lymphoid tissues and Warthin–Finkeldey giant
cells (reticuloendothelial giant cells), Epithelial giant cells with viral inclusions,
Nuclei may contain a single large Cowdry type A inclusion. Secondary viremia
involves other organs through infected lymphocytes and monocytes with
subsequent formation of SEGCs. Although most often being a self-limited illness,

22
possible complications include otitis media, pneumonia, laryngotracheobronchitis,
diarrhea, and encephalitis.16,17

Figure 21. Giant cell in measles histopathology.17

Clinical diagnosis of measles is tipically made with onset of
the characteristic rash as the prodromal symptoms can mimic
inflauenza-like illnesses. Uncomplicated measles is self-limited,
lasting 10 to 12 days. Malnutrition, immunosupression, poor
helath, and inadequate supportive care can worsen the prognosis
in any patient. In developing nations, measles is a major cause of
infant mortality.1

CONCLUSION
Viral skin infections present with different patterns. Viral skin diseases are
classified by clinical features into three types: (1) tumorous changes in epidermal
cells (e.g., in verruca vulgaris, condyloma accuminata) (2) degeneration of
epidermal cells and blistering (e.g., in herpes simplex and herpes zoster), and (3)
allergic eruptions on the whole body (e.g., in measles and rubella). The first two
types are caused by viral infection in epidermal keratinocytes; the last type is
caused by systemic viral infection (viremia). The prognostics are depend on the
diseases, clinical finding, and the immunity of the patients.

23
References
1. Wolf K, Goldsmith LA, Katz SI, et al. (2008). Fitzpatrick's Dermatology in
general medicine. 7th Ed. Vol 2. The McGraw-Hill Companies. USA. p.1845-
1940.
2. Hunt RD, Friedlander SF. (2015). Viral infections. In: Eichenfield LF, Frieden IJ,
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