“Tree Man Syndrome” is the widely recognized term for the extremely rare genetic skin disorder medically known as Epidermodysplasia Verruciformis (EV). This inherited condition causes a lifelong susceptibility to common skin viruses, leading to disfiguring growths. Despite its visual severity, EV is an extremely infrequent condition, with only a few hundred cases reported in medical literature globally since its initial description in 1922.
Defining Epidermodysplasia Verruciformis
Epidermodysplasia Verruciformis is a genodermatosis, a genetic disorder affecting the skin. It is characterized by a chronic, widespread eruption of lesions that resemble both flat warts and reddish-brown plaques similar to tinea versicolor. The underlying issue is a defect in the immune system’s ability to control certain strains of the Human Papillomavirus (HPV). This inability leads to a persistent and uncontrolled proliferation of infected skin cells. The lesions typically begin to appear during childhood or early adolescence and will continue to develop throughout a person’s life. EV is classified as an autosomal recessive disorder, meaning an individual must inherit an abnormal gene from both parents to develop the condition.
Genetic Predisposition and Viral Triggers
The core cause of Epidermodysplasia Verruciformis is a combination of genetic predisposition and a viral trigger. In over half of cases, the syndrome is linked to loss-of-function mutations in the TMC6 or TMC8 genes. These genes are also known as EVER1 and EVER2 and are located adjacent to each other on chromosome 17q25. The proteins produced by these genes are thought to be involved in regulating the intrinsic immunity of skin cells against HPV infection, potentially through mechanisms involving zinc homeostasis. A defect in the TMC/EVER proteins prevents the keratinocytes from effectively controlling the viral replication and spread within the epidermal layers.
This genetic susceptibility makes patients vulnerable to infection by specific types of “beta-HPV” (β-HPV), such as HPV types 5, 8, 14, and 20. These beta-HPV strains are common in the general population. However, in an individual with EV, these viruses cause severe, chronic infection and drive the excessive growth of the skin lesions. The underlying genetic mutation essentially disarms the skin’s local defense mechanism, allowing the otherwise innocuous beta-HPV to become a persistent and pathogenic force.
Clinical Presentation and Associated Cancer Risk
The clinical presentation of Epidermodysplasia Verruciformis is characterized by two main types of lesions. The first type consists of flat, slightly scaly macules and plaques that range in color from flesh-toned to reddish-brown, often resembling pityriasis versicolor. The second, more visually dramatic type, are the hyperkeratotic, verrucous lesions that form the characteristic growths. These growths are most commonly found on sun-exposed areas, including the face, neck, trunk, and the backs of the hands and feet.
A significant concern for individuals with EV is the risk of developing non-melanoma skin cancers. Between 30% and 60% of patients will develop malignancies, most commonly squamous cell carcinoma, typically after the age of 30. Malignant transformation almost exclusively occurs in lesions that are exposed to ultraviolet (UV) radiation. The interaction between the oncogenic beta-HPV types, such as HPV-5 and HPV-8, and UV light is thought to accelerate the process of turning a benign lesion into a cancerous one. Regular dermatological surveillance is therefore essential for long-term care to catch any changes early.
Current Treatment and Management Strategies
There is currently no definitive cure for Epidermodysplasia Verruciformis, so treatment focuses on managing the chronic lesions and mitigating cancer risk. Surgical management is the primary approach for removing problematic growths, which includes excision, cryotherapy, or laser ablation. While these procedures can remove large, disfiguring, or cancerous lesions, the underlying viral infection persists, leading to a high rate of recurrence.
Medical management uses systemic treatments to slow the growth of new lesions and reduce the risk of malignancy. Oral retinoids, such as acitretin, work by affecting skin cell growth and differentiation, thereby suppressing the condition. Other treatments include topical agents like imiquimod or 5-fluorouracil.
Preventative care is essential. Since UV exposure is a powerful co-factor in the development of skin cancer, rigorous sun avoidance and the consistent use of broad-spectrum sunscreens are recommended. This strict photoprotection is a lifelong necessity to reduce the likelihood of malignant transformation in the HPV-infected lesions. Management requires a multidisciplinary team approach to ensure continuous monitoring and timely intervention for any suspicious growths.