EV disease, formally called epidermodysplasia verruciformis, is a rare genetic skin condition that leaves the body unable to fight off certain strains of human papillomavirus (HPV). This results in widespread, persistent wart-like growths on the skin and a significantly elevated lifetime risk of skin cancer. The condition is sometimes called “tree man syndrome” in popular media because of the extensive bark-like skin growths it can produce in severe cases.
How EV Disease Affects the Skin
People with EV develop flat, scaly lesions and papules that can appear across the trunk, neck, face, and other sun-exposed areas. The growths often look like flat warts or can resemble the patchy, discolored spots seen in a common fungal skin condition called pityriasis versicolor. Unlike ordinary warts that come and go, these lesions persist indefinitely because the immune system simply cannot clear the virus causing them.
In inherited cases, lesions can begin as early as infancy and continue spreading throughout a person’s life. They tend to cluster on areas that get regular UV exposure. Some people also develop light-colored skin patches, small visible blood vessels on the skin surface, and recurring skin infections. The appearance varies widely from person to person: some have relatively flat, subtle patches, while others develop thick, raised growths covering large areas of the body.
The Genetic Root Cause
EV is caused by mutations in two genes known as TMC6 and TMC8 (also called EVER1 and EVER2). These genes normally help skin cells regulate their defenses against certain viruses. When both copies of either gene are nonfunctional, the skin becomes selectively vulnerable to a group of HPV strains called beta-HPVs that most people’s immune systems handle without difficulty.
The condition follows an autosomal recessive inheritance pattern, meaning a child must inherit a defective copy of the gene from each parent to develop the disease. Parents who carry one defective copy typically show no symptoms themselves. Because it requires two copies, EV is rare even in families that carry the mutation.
Which HPV Strains Are Involved
EV patients are not vulnerable to every type of HPV. Their immune defect is specific to beta-HPV strains, a group that causes little to no trouble in people with normal immune function. Among these, HPV-5 and HPV-8 are the most common culprits, identified in roughly 90% of EV patients. Around 20 additional beta-HPV types have also been found in EV cases, including HPV-9, 12, 14, 15, 17, and 19, among others.
What makes HPV-5 and HPV-8 particularly concerning is their oncogenic potential: they can trigger cells to become cancerous, especially in skin that receives regular sun exposure.
Skin Cancer Risk
The most serious consequence of EV is a significantly increased lifetime risk of developing non-melanoma skin cancer, particularly squamous cell carcinoma. The combination of chronic HPV infection and UV radiation exposure creates ideal conditions for cancerous changes in the skin. These cancers typically develop on sun-exposed areas like the face, hands, and forearms.
Because the viral infection is lifelong and widespread, patients need ongoing skin monitoring throughout their lives. Early detection of cancerous changes in existing lesions is critical, since the risk accumulates over time. Lesions that change in color, texture, or size, or that begin to bleed or ulcerate, warrant prompt evaluation.
Inherited Versus Acquired Forms
Most cases of EV are inherited, but an acquired form also exists. Acquired EV develops in people whose immune systems become suppressed for other reasons, such as HIV infection or immunosuppressive medications after organ transplants. In these patients, the same beta-HPV strains take hold and produce lesions that look virtually identical to the inherited form. The key difference is timing: inherited EV typically appears in childhood, while acquired EV emerges after the immune system has been compromised.
How EV Is Diagnosed
Diagnosis starts with the appearance of the skin lesions themselves. The combination of widespread, persistent flat warts and pityriasis versicolor-like patches, especially beginning in childhood, is highly suggestive. A skin biopsy can reveal characteristic changes in the skin cells that confirm HPV involvement. Molecular testing can identify the specific beta-HPV strains present, and genetic testing can confirm mutations in TMC6 or TMC8.
Because the lesions can superficially resemble other skin conditions, including common warts, fungal infections, or seborrheic dermatitis, it is not unusual for EV to go unrecognized for years, particularly in mild cases or in regions where the condition is unfamiliar to local clinicians.
Treatment Options
There is no cure for EV. Treatment focuses on managing the skin lesions and preventing or catching cancer early. The approaches fall into a few categories.
- Retinoids: Oral retinoids (vitamin A derivatives) are the most commonly used systemic treatment. They can flatten and reduce lesions, with some patients experiencing dramatic improvement. However, lesions often return when the medication is reduced or stopped, so long-term use may be necessary.
- Physical removal: Cryotherapy (freezing), laser treatment, and surgical removal can address individual lesions, particularly those showing precancerous changes. These methods treat the lesion itself but do not prevent new ones from forming.
- Immune-boosting therapies: Topical creams that stimulate the skin’s local immune response, as well as injectable interferons (proteins that help the body fight viruses), have been used in combination with retinoids. Results vary.
- Sun protection: Because UV exposure both worsens lesion development and drives the progression toward cancer, consistent sun protection is a cornerstone of management. This means daily sunscreen, protective clothing, and minimizing time in direct sunlight.
Living With EV Long Term
EV is a lifelong condition. The lesions that appear in childhood persist and new ones continue to develop over time. For many patients, the daily reality involves managing visible skin changes that can affect self-image and social interactions, alongside the practical demands of ongoing skin surveillance and treatment cycles.
The prognosis depends largely on how well skin cancer risk is managed. With consistent monitoring and early treatment of any cancerous changes, many people with EV live full lives. The greatest danger comes from undetected squamous cell carcinomas, particularly in sun-exposed areas, which is why regular dermatological follow-up is essential from an early age.