VIRAL INFECTIONS OFSKIN AND MUCOSA II

AAU-MFDepartment of

Dermato-Venereology

• Viral infections of skin and mucosa produce awide spectrum of clinical manifestations.• Viruses that cause febrile illness with exanthemsare usually self-limited, with primary infectionconveying lifetime immunity.• Viruses such as human papillomavirus (HPV) andmolluscum contagiosum virus (MCV) colonizethe epidermis of most individuals without causingany clinical lesions.

• ▪ Benign epithelial proliferations, i.e., warts and molluscum, occur in some colonized persons, are transient, and eventually resolve without therapy.

• ▪ 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 mortality rates.

POXVIRUS INFECTIONS

• The poxvirus family is a diverse group of epitheliotropic viruses that infect humans and animals.

• The genera of poxviruses that infect humans include orthopoxvirus, parapoxvirus, molluscipoxvirus, and yatapoxvirus .

• Only smallpox virus (SPV) and molluscum contagiosum virus (MCV) cause natural disease in

humans.

• 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 infections.• 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 cowpox virus.

• 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

• Molluscum contagiosum (MC) is a self-limited• epidermal viral infection.• Risk groups• Children• Sexually active adults• Immunocompromised: HIV/AIDS, organ

transplant recipients

Etiology• 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

electron microscopy.• In many healthy adults, the epidermis andinfundibulum of hair follicle are colonized by

MCV.

Transmission: Skin-to-skin contact.Classification by Risk GroupsChildren• Mollusca commonly occur on exposed skinsites.• 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 byshaving.• With response to ART, lesions often resolve.• Without aggressive therapy in advanced HIV/AIDS, mollusca enlarge; spontaneous regressiondoes not occur.

Clinical manifestations:• Skin-colored papules; often umbilicated• Few to myriads of lesions• HIV/AIDS: large nodules; confluent• Course:• 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, molluscapersist and proliferate even after aggressivelocal therapy.Skin Symptoms• Usually none.• Cosmetic disfigurement.• Concern about having a transmissible infection.• Painful if superinfected.

Mucocutaneous Lesions• Papules (1–2 mm), nodules (5–10 mm)(rarely, giant) Pearly white or skin-colored. Round, oval, hemispherical, Umbilicated

Most larger mollusca have a central keratoticplug (Fig. 27-1A), which gives the lesion acentral dimple or umbilication, best observedafter light liquid nitrogen freeze. Gentle pressureon a molluscum causes the central plugto be extruded.• Autoinoculation is apparent in that molluscaare clustered at a site such as the axilla

Host immune response to viral antigen resultsin an inflammatory halo around MC i.e., “MC dermatitis,” which usually heralds spontaneous regression; purulencemay occur.• 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 patients

DIAGNOSISUsually made on clinical findings.Biopsy lesion in HIV-infected individual ifdisseminated invasive fungal infection is in thedifferential diagnosis.

MANAGEMENTPrevention: Avoid skin-to-skin contact with individual having mollusca. HIV-infected individuals with mollusca in the beard area should be advised to minimize shaving facial hair or grow a beard.

Supportive therapy In immunocompetent children and sexually active adults, mollusca regress spontaneously; painful aggressive therapy is not indicated.Treatment of lesionsTopical 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 PAPILLOMAVIRUS INFECTIONS

• Human papillomaviruses (HPV) are ubiquitous inhumans, causing▪ 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 thegeneral population:▪ 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, meatpackers, fish handlers.▪ Plantar warts: Common in older children andyoung adults, accounting for 30% of cutaneouswarts. Flat warts: Occur in children and adults,accounting for 4% of cutaneous warts

Mucosal warts:▪ Condyloma acuminatum (genital wart) Most prevalent sexually transmitted infection.▪ Some HPV types have a major etiologic role inthe pathogenesis of in situ as well as invasiveSCC of the anogenital epithelium.▪ During delivery, maternal genital HPV infectioncan be transmitted to the neonate, resulting in• Anogenital warts• Respiratory papillomatosis after aspiration ofthe virus into the upper respiratory tract.

HUMAN PAPILLOMAVIRUS: CUTANEOUS INFECTIONS

• Certain human HPV types commonly infect keratinized skin.

• 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.

Transmission• Skin-to-skin contact.• Minor trauma with breaks in stratum corneumfacilitates epidermal infection.• Contagion occurs in groups—small (home)or large (school gymnasium) Other Factors• Immunocompromise associated with an increasedincidence of and more widespread cutaneous warts:HIV/AIDS

Iatrogenic immunosuppression with solidorgan transplantation.• Occupational risk associated with meat handling.• Epidermodysplasia verruciformis (EDV): most commonly autosomal recessive.

CLINICAL MANIFESTATIONDuration of Lesions: Warts often persist forseveral years if not treated

.

Symptoms

• Cosmetic disfigurement.• Plantar warts act as a foreign body and can bequite painful during normal daily activities,such as walking, if located over pressure points.• More aggressive therapies such as cryosurgeryoften result in much more pain than thatcaused by the wart itself.• Bleeding, especially after shaving.

Skin LesionsVerruca Vulgaris (Common Wart)• Firm papules, 1–10 mm or rarely larger hyperkeratotic, clefted surface,with vegetations.• Palmar lesions disrupt the normal line of fingerprints. Return of finger prints is a sign of resolution of the wart.Characteristic “red or brown dots” are betterseen with hand lens and are pathognomonic,representing thrombosed capillary loops.

• Isolated lesion, scattered discrete lesions.• Linear arrangement : inoculation by scratchingAnnular warts : at sites of prior therapy .• Occur at sites of trauma: hands, fingers,knees.• Butcher’s warts : large cauliflower-like lesionson hands of meat handlers.• Filiform warts have relatively small bases,extending out with elongated cap.

Verruca vulgaris: thumb

Verruca vulgaris: hand

Verruca vulgaris: hand

Verruca Plantaris (Plantar Wart)• Early small, shiny, sharply marginated papule → plaque with rough hyperkeratoticsurface, studded with brown-black dots(thrombosed capillaries).• As with palmar warts, normal dermatoglyphicsare disrupted. Return of dermatoglyphicsis a sign of resolution of the wart.• Warts heal without scarring.• Therapies such as cryosurgery and electrosurgery can result in scarring at treatment sites.

Tenderness may be marked, especially incertain acute types and in lesions over sites ofpressure (metatarsal head).• Mosaic warts : Confluence of many small warts• “Kissing” warts : lesion may occur on opposingsurface of two toes .• Plantar foot, often solitary but may be threeto six or more.• Pressure points, heads of metatarsal, heels, toes.

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 , dorsaof hands , shins.

Verruca plana A 12-year-old male kidney transplant recipient. Multiple brown keratotic papules are seen on the forehead and scalp.

Epidermodysplasia Verruciformis• Autosomal recessive condition.• Flat-topped papules.• Pityriasis versicolor–like lesions, particularlyon the trunk. Color: skin-colored, light brown, pink, hypopigmented.• Lesions may be numerous, large, and confluent.• Seborrheic keratosis–like and actinickeratosis–like lesions.

• Linear arrangement after traumatic inoculation.• Distribution : face, dorsa of hands arms, legs, anterior trunk.• Premalignant and malignant lesions arisemost commonly on face.• SCC: in situ and invasive.

DIAGNOSIS• Usually made on clinical findings.• In the immunocompromised host, HIV inducedSCC at periungual sites or anogenitalregion should be ruled out by lesional biopsy.

MANAGEMENT Goal 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 INFECTIONS

• 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 andmucosa 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.