VIRAL INFECTIONS OF
SKIN AND MUCOSA II
• Viral infections of skin and mucosa produce a
wide spectrum of clinical manifestations.
• Viruses that cause febrile illness with exanthems
are usually self-limited, with primary infection
conveying lifetime immunity.
• 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 colonized
persons, are transient, and eventually resolve
• ▪ In immunocompromised individuals,
however, these lesions may become extensive,
persistent, and refractory to therapy.
• The eight human herpesviruses often have
asymptomatic primary infection but are
characterized by lifelong latent infection.
• ▪ In the setting of immunocompromise,
herpesviruses can become active and cause
disease with significant morbidity and
• The poxvirus family is a diverse group of
epitheliotropic viruses that infect humans and
• The genera of poxviruses that infect humans include
orthopoxvirus, parapoxvirus, molluscipoxvirus, and
• Only smallpox virus (SPV) and molluscum
contagiosum virus (MCV) cause natural disease in
• Small pox (SPV) and monkey pox virus typically
cause systemic disease with rash; other poxviruses
cause localized skin lesions.
▪ Other poxviruses are associated with zoonotic
• Poxviruses are the largest of all animal viruses and
have a double-strand DNA genome.
• They are the only DNA viruses that replicate in
cytoplasm, where accumulated viral particles form
eosinophilic inclusions, or Guarnieri bodies, visible by
light microscopy (200–400 μm).
• Poxviruses appear as brick-shaped or oval virus
particles by electron microscopy.
• The nucleosome contains double-strand DNA, which
is surrounded by a membrane.
• Smallpox, or variola, has been eradicated as a
naturally occurring infection.
• ▪ Cowpox is an infection of cattle caused by
• The origins of vaccinia virus, which is used
to immunize humans against smallpox, are
uncertain. It may be derived from variola virus,
cowpox virus, or be a hybrid of the two.
• Molluscum contagiosum (MC) is a self-limited
• epidermal viral infection.
• Risk groups
• Sexually active adults
• Immunocompromised: HIV/AIDS, organ
• Molluscum contagiosum virus.
• Four discrete viral subtypes, I, II, III, IV.
• 30% homology with smallpox virus.
• The virus has not been cultured.
• Not distinguishable from other poxviruses by
• In many healthy adults, the epidermis and
infundibulum of hair follicle are colonized by
Transmission: Skin-to-skin contact.
Classification by Risk Groups
• Mollusca commonly occur on exposed skin
• Child-to-child transmission relatively low.
• Resolve spontaneously.
Sexually Active Adults
• Occur in genital region.
• Virus transmitted during sexual activity.
• Resolve spontaneously.
HIV/AIDS: Organ Transplant Recipients
• Most commonly occur on the face, spread by
• With response to ART, lesions often resolve.
• Without aggressive therapy in advanced HIV/
AIDS, mollusca enlarge; spontaneous regression
does not occur.
• Skin-colored papules; often umbilicated
• Few to myriads of lesions
• HIV/AIDS: large nodules; confluent
• Healthy persons: MC resolves spontaneously
• HIV/AIDS: if not successfully treated with
antiretroviral therapy (ART), MC can become
huge and confluent.
CLINICAL MANIFESTATIONS and course:
Duration of Lesions
• In the normal host, mollusca usually persist up to 6
months and then undergo spontaneous regression.
• In HIV/AIDS without effective ART, mollusca
persist and proliferate even after aggressive
• Usually none.
• Cosmetic disfigurement.
• Concern about having a transmissible infection.
• Painful if superinfected.
• Papules (1–2 mm), nodules (5–10 mm)
(rarely, giant) Pearly white or skin-colored. Round, oval,
Most larger mollusca have a central keratotic
plug (Fig. 27-1A), which gives the lesion a
central dimple or umbilication, best observed
after light liquid nitrogen freeze. Gentle pressure
on a molluscum causes the central plug
to be extruded.
• Autoinoculation is apparent in that mollusca
are clustered at a site such as the axilla
Host immune response to viral antigen results
in an inflammatory halo around MC i.e., “MC dermatitis,”
which usually heralds spontaneous regression; purulence
• MC can be extensive in organ transplant recipients
• In HIV-infected males who shave, mollusca can be confined
to the beard area. Hundreds of lesions occur in HIV/AIDS
Usually made on clinical findings.
Biopsy lesion in HIV-infected individual if
disseminated invasive fungal infection is in the
Prevention: Avoid skin-to-skin contact with individual
HIV-infected individuals with mollusca in the beard area
should be advised to minimize shaving facial hair or grow a
Supportive therapy In immunocompetent children and
sexually active adults,
mollusca regress spontaneously; painful aggressive therapy is
Treatment of lesions
Topical patient-directed therapy 5% imiquimod cream applied
at bedtime 3–5 times per week for up to1–3 months.
Clinician-directed therapy (office)
These procedures are painful and traumatic, especially for
young children. EMLA cream applied to lesions 1 h before
therapy may reduce/eliminate pain.
Curettage Small mollusca can be removed with a small curette
with little discomfort or pain.
Cryosurgery Freezing lesions for 10–15 s is effective and
minimally painful, using either a cotton-tipped applicator
or liquid nitrogen spray.
Electrodesiccation For mollusca refractory to cryosurgery,
especially in HIV-infected individuals with numerous
and/or large lesions, electrodesiccation or laser surgery is
the treatment of choice.
Large lesions usually require injected lidocaine
anesthesia. Giant mollusca may require several cycles of
electrodesiccation and curettage to remove the large bulk
of lesions; these lesions may extend through the dermis
into the subcutaneous fat.
• Human papillomaviruses (HPV) are ubiquitous in
▪ Subclinical infection
▪ Wide variety of benign clinical lesions on skin
and mucous membranes.
• They also have a role in the oncogenesis of
cutaneous and mucosal premalignancies :
▪ Squamous cell carcinoma in situ (SCCIS)
▪ Invasive SCC
Cutaneous HPV infections occur commonly in the
▪ Common warts: Represent approximately 70%
of all cutaneous warts, occurring in up to 20%
of all school-age children.
• Butcher’s warts: Common in butchers, meat
packers, fish handlers.
▪ Plantar warts: Common in older children and
young adults, accounting for 30% of cutaneous
Flat warts: Occur in children and adults,
accounting for 4% of cutaneous warts
▪ Condyloma acuminatum (genital wart)
Most prevalent sexually transmitted infection.
▪ Some HPV types have a major etiologic role in
the pathogenesis of in situ as well as invasive
SCC of the anogenital epithelium.
▪ During delivery, maternal genital HPV infection
can be transmitted to the neonate, resulting in
• Anogenital warts
• Respiratory papillomatosis after aspiration of
the virus into the upper respiratory tract.
• Certain human HPV types commonly infect
• Cutaneous warts are:
▪ Discrete benign epithelial hyperplasia with varying
degrees of surface hyperkeratosis
▪ Manifested as minute papules to large plaques
Lesions may become confluent, forming a mosaic.
• The extent of lesions is determined by the immune
status of the host.
• Skin-to-skin contact.
• Minor trauma with breaks in stratum corneum
facilitates epidermal infection.
• Contagion occurs in groups—small (home)
or large (school gymnasium)
• Immunocompromise associated with an increased
incidence of and more widespread cutaneous warts:
Iatrogenic immunosuppression with solid
• Occupational risk associated with meat
• Epidermodysplasia verruciformis (EDV): most
commonly autosomal recessive.
Duration of Lesions: Warts often persist for
several years if not treated
• Cosmetic disfigurement.
• Plantar warts act as a foreign body and can be
quite painful during normal daily activities,
such as walking, if located over pressure points.
• More aggressive therapies such as cryosurgery
often result in much more pain than that
caused by the wart itself.
• Bleeding, especially after shaving.
Verruca Vulgaris (Common Wart)
• Firm papules, 1–10 mm or rarely larger
hyperkeratotic, clefted surface,with vegetations.
• Palmar lesions disrupt the normal line of
Return of finger prints is a sign of resolution of the
Characteristic “red or brown dots” are better
seen with hand lens and are pathognomonic,
representing thrombosed capillary loops.
• Isolated lesion, scattered discrete lesions.
• Linear arrangement : inoculation by scratching
Annular warts : at sites of prior therapy .
• Occur at sites of trauma: hands, fingers,
• Butcher’s warts : large cauliflower-like lesions
on hands of meat handlers.
• Filiform warts have relatively small bases,
extending out with elongated cap.
Verruca Plantaris (Plantar Wart)
• Early small, shiny, sharply marginated papule
→ plaque with rough hyperkeratotic
surface, studded with brown-black dots
• As with palmar warts, normal dermatoglyphics
are disrupted. Return of dermatoglyphics
is a sign of resolution of the wart.
• Warts heal without scarring.
• Therapies such as cryosurgery and
electrosurgery can result in scarring at treatment
Tenderness may be marked, especially in
certain acute types and in lesions over sites of
pressure (metatarsal head).
• Mosaic warts : Confluence of many small warts
• “Kissing” warts : lesion may occur on opposing
surface of two toes .
• Plantar foot, often solitary but may be three
to six or more.
• Pressure points, heads of metatarsal, heels,
Verruca Plana (Flat Wart)
• Sharply defined, flat papules (1–5 mm); “flat”
surface; the thickness of the lesion is 1–2 mm
• Skin-colored or light brown.
• Round, oval, polygonal, linear lesions
(inoculation of virus by scratching).
• Occur on face, beard area , dorsa
of hands , shins.
Verruca plana A 12-year-old male kidney transplant recipient. Multiple brown keratotic
papules are seen on the forehead and scalp.
• Autosomal recessive condition.
• Flat-topped papules.
• Pityriasis versicolor–like lesions, particularly
on the trunk.
Color: skin-colored, light brown, pink,
• Lesions may be numerous, large, and confluent.
• Seborrheic keratosis–like and actinic
• Linear arrangement after traumatic
• Distribution : face, dorsa of hands
arms, legs, anterior trunk.
• Premalignant and malignant lesions arise
most commonly on face.
• SCC: in situ and invasive.
• Usually made on clinical findings.
• In the immunocompromised host, HIV induced
SCC at periungual sites or anogenital
region should be ruled out by lesional biopsy.
Aggressive therapies, which are often quite painful and
may be followed by scarring, are usually to be avoided
because the natural history of cutaneous HPV infections is
for spontaneous resolution in months or a few years.
Plantar warts that are painful because of their location
warrant more aggressive therapies.
HUMAN PAPILLOMAVIRUS: MUCOSAL
• Mucosal HPV infections are the most common
STIs seen by the dermatologist.
• Only 1–2% of HPV-infected individuals have any
visibly detectable clinical lesion.
• HPV present in the birth canal can be transmitted
to a newborn during vaginal delivery and can cause
▪ External genital warts (EGW)
• ▪ Respiratory papillomatosis
• Warts: barely visible papules to nodules to
confluent masses occurring on:
▪ Anogenital: skin or mucosa
▪ Oral mucosa
HPV dysplasia of anogenital and oral skin and
mucosa ranging from:
▪ Mild to severe to squamous cell carcinoma
(SCC) in situ (SCCIS)
▪ Invasive SCC can arise within SCCIS
▪ Most commonly in cervix, anal canal.