Epidermodysplasia Verruciformis (EV)

What causes EV

Everyone is exposed to many types of HPV. Certain "beta-HPV" types (especially HPV-5 and HPV-8) are normally harmless and kept in check by the skin's immune defenses. In classic EV, inherited changes in genes such as TMC6 (EVER1), TMC8 (EVER2) or CIB1 disrupt this control in skin cells, so these viruses spread widely in the skin.

The condition is usually autosomal recessive: a child inherits one faulty copy from each parent, who are typically healthy carriers. It is more common where parents are related. It is not contagious in the usual sense; the HPV types are everywhere, and the problem is the person's inability to control them.

Acquired EV

A similar condition can develop in people with weakened immune systems: HIV, organ transplant recipients on immune-suppressing drugs, and some other immune disorders. It is called acquired EV.

Signs and symptoms

• flat, wart-like papules similar to flat warts, on the face, hands, arms and legs
• scaly patches that are pink, red-brown or lighter than surrounding skin, resembling tinea versicolor or seborrheic keratoses, often on the trunk and neck
• lesions start in childhood (often between ages 5 and 11) and increase over years
• in rare severe forms, large horn-like growths develop on the hands and feet ("tree man syndrome")
• actinic keratoses and skin cancers on sun-exposed areas, often beginning in the 20s to 40s

Skin cancer risk

Roughly 30 to 60 percent of people with classic EV develop skin cancer during their lifetime. Most are squamous cell carcinomas in situ or invasive, mainly on the forehead, face and other sun-exposed skin. Ultraviolet light and the HPV types work together to cause these cancers. They tend to grow slowly but can become invasive and, rarely, spread.

Diagnosis

• clinical appearance of widespread flat warts and scaly patches from childhood
• skin biopsy: shows typical "EV cells", enlarged cells with bluish-gray pale cytoplasm in the upper layers of the skin
• HPV testing of skin samples
• genetic testing for TMC6, TMC8, CIB1 and other genes
• immune testing and HIV testing if acquired EV is suspected

Treatment

There is no cure. Care focuses on preventing and treating skin cancer and improving the appearance of lesions.

Sun protection

The most important measure, starting in childhood:

• broad-spectrum sunscreen SPF 30 or higher daily
• protective clothing, hats and sunglasses
• avoiding midday sun and tanning beds

Treating lesions

• topical treatments: retinoids, imiquimod, 5-fluorouracil
• cryotherapy (freezing) and curettage
• photodynamic therapy for precancerous changes
• oral retinoids (acitretin) to reduce new lesions and cancers in some patients
• surgery, including Mohs surgery, for skin cancers
• surgical debulking for the large horn-like growths in severe forms

Lesions often return after treatment because the underlying susceptibility persists.

Acquired EV

Improving immune function, for example with HIV treatment or adjusting transplant medicines, may help lesions improve.

Monitoring

• full skin checks by a dermatologist every 3 to 6 months, or as advised
• prompt biopsy of any changing lesion
• genetic counseling for families

Outlook

People with EV have a normal lifespan when skin cancers are caught and treated early. The condition is lifelong, and the burden of lesions and procedures can be significant, so psychological support helps.

Frequently asked questions

What is epidermodysplasia verruciformis?

It is a rare inherited skin condition in which certain HPV types grow widely in the skin, causing many flat, wart-like spots and scaly patches from childhood. People with EV have a high risk of skin cancer, especially on sun-exposed skin.

Is epidermodysplasia verruciformis contagious?

Not in the usual sense. The HPV types involved are common and harmless for most people. People with EV have an inherited or acquired weakness in controlling them, so others who come into contact do not develop EV.

What is tree man syndrome?

"Tree man syndrome" is a popular name for severe EV in which large, bark-like horny growths develop on the hands and feet. It is extremely rare. Surgical removal can improve function, but growths often recur.

Can epidermodysplasia verruciformis be cured?

No. The inherited susceptibility is lifelong. Treatments can remove or reduce lesions and catch skin cancers early, and sun protection lowers cancer risk. In acquired EV, improving immune function may help lesions regress.

How is skin cancer prevented in EV?

Strict sun protection from childhood is key, along with regular dermatology checks, early treatment of precancerous lesions, and sometimes oral retinoids. Any growing, bleeding or changing lesion should be biopsied promptly.