Introduction
Epidermodysplasia verruciformis (EV) is an uncommon skin condition that is passed down through autosomal recessive inheritance and can lead to increased vulnerability to infections caused by human papillomavirus (HPV). Its primary symptom is the persistent appearance of brownish plaques on the skin. In some cases, a comparable condition called acquired epidermodysplasia verruciformis can occur in individuals with compromised immunity.
What Are the Causes of Epidermodysplasia Verruciformis?
EV is classified as an autosomal recessive inherited disorder, which requires two abnormal EV genes - one inherited from each parent - to manifest. In most instances, the genetic mutation causing EV is sporadic, originating during the formation of the sperm or egg, but can still be transmitted to future offspring.
Approximately 10 percent of individuals with EV have parents who share a common ancestor, and they are more susceptible to certain HPV subtypes for reasons not yet entirely understood. While there are over 70 HPV subtypes capable of causing warts, those found in individuals with EV are distinct from those typically associated with genital warts and cervical cancer. People with EV exhibit a normal immune response to non-HPV infections but may have a reduced immune response to HPV and other wart viruses. There are roughly 30 HPV subtypes linked to the development of warts and plaques in EV patients.
Although symptoms usually manifest during puberty, EV can appear at any age, and it affects males and females equally.
What Are the Symptoms of Epidermodysplasia Verruciformis?
The onset of symptoms associated with EV can occur at any age, even in infancy. However, over 50 percent of cases present symptoms in children between the age of five to 11 years, and nearly 25 percent of people with EV first develop symptoms during puberty.
The signs of EV may include a combination of various skin lesions, such as flat-topped or bumpy growths, small raised bumps known as papules, large inflamed patches of raised skin called plaques, and small brown raised lesions that resemble scabs. The presentation of symptoms can vary among individuals with EV, and a proper diagnosis by a healthcare professional is necessary.
Epidermodysplasia verruciformis (EV) is characterized by the development of wart-like growths or flat, scaly patches on the skin. These growths can appear on different body parts, including the hands, feet, face, and trunk. The lesions may vary in size, shape, and color, ranging from pale or flesh-colored to brownish in hue. Over time, the growths may coalesce and develop a scaly, wart-like appearance.
In some cases, the lesions may itch or bleed, and they can be painful if they become irritated or infected. In rare instances, EV may also affect the mucous membranes and the nails. Symptoms typically manifest during childhood or adolescence, although they may emerge at any stage of life.
Individuals with EV have an increased vulnerability to skin infections caused by human papillomavirus (HPV), which can worsen the symptoms of the condition. In certain instances, these infections can advance to squamous cell carcinoma, a form of skin cancer. Additionally, people with EV may be more vulnerable to other types of skin infections, although their immune response to non-HPV infections is usually normal.
What Is the Epidemiology of Epidermodysplasia Verruciformis?
The most comprehensive series of cases of epidermodysplasia verruciformis reported in the medical literature included 195 cases, with the majority originating from Eastern Europe, particularly Poland, and Latin America. A literature review in 2017 identified approximately 500 reported cases of the disease worldwide.
Epidermodysplasia verruciformis is not limited to any specific race and affects people of all races equally. There is no noted sexual preference for epidermodysplasia verruciformis, although sex-linked and autosomal dominant inheritance patterns have been reported.
During early childhood, patients with epidermodysplasia verruciformis typically present with flat wart-like lesions on their dorsal hands, extremities, face, and neck. The disease can occur congenitally in infancy (approximately 7.5 percent), during childhood (61.5 percent in children aged five to 11 years), or at puberty (22.5 percent). Malignant tumors usually appear during the fourth and fifth decades of life, with a reported frequency of malignant transformation ranging from 30 to 60 percent.
What Is the Diagnosis of Epidermodysplasia Verruciformis?
Epidermodysplasia verruciformis is often diagnosed based on clinical signs, such as a high number of unresponsive viral warts to treatment. A skin biopsy may confirm the presence of characteristic features (refer to epidermodysplasia verruciformis pathology).
PCR testing in certain laboratories may also allow for the identification of the specific HPV subtype involved.
What Is the Treatment of Epidermodysplasia Verruciformis?
Epidermodysplasia verruciformis is a condition that persists throughout a person's life. While individual lesions can be managed through treatment or removal, new lesions will continue to develop over time.
Currently, no treatment is available to impede the development of new lesions. Treatment of EV generally involves a combination of medical and surgical interventions, as well as counseling, education, and regular monitoring (particularly for individuals with compromised immune systems).
Highlighting the significance of sun protection measures is crucial, particularly if living at high altitudes or working outdoors. Studies have demonstrated that exposure to sunlight (both UVB and UVA) can accelerate the transformation of EV lesions into skin cancers. It is also important to encourage individuals to quit smoking.
Treatment for EV involves managing lesions as they appear using chemical treatment, cryotherapy, electrosurgery, or laser ablation, similar to other viral warts. Oral and topical retinoids such as Isotretinoin, Acitretin, Fluorouracil, and Imiquimod may be effective.
Experimental therapies for EV and skin tumors include intralesional interferon, a combination of Isotretinoin and interferon alpha, or Cholecalciferol (vitamin D) analogs. For invasive skin cancers, surgical excision and reconstruction are employed. Regular patient counseling, education, and monitoring are essential for effective EV management, especially for immunocompromised individuals. There is no current treatment available to prevent the occurrence of new lesions.
What Are the Complications of Epidermodysplasia Verruciformis?
Epidermodysplasia verruciformis patients have a major concern regarding the potential transformation of their lesions into skin cancers, with 30 to 60 percent of cases resulting in cutaneous squamous cell carcinoma and intraepidermal squamous cell carcinoma. Basal cell carcinoma and adnexal tumors are less frequent, with malignant tumors typically found in individuals between 30 to 50 years of age.
Research has shown that more than 90% of skin cancers associated with EV are linked to HPV types 5, 8, 10, and 47, whereas EV lesions caused by HPV 14, 20, 21, and 25 tend to remain non-cancerous. The risk of benign warts progressing to skin cancer is heightened by exposure to sunlight or ultraviolet radiation.
What Is the Prognosis of Epidermodysplasia Verruciformis?
The tumors associated with epidermodysplasia verruciformis tend to develop gradually over time, starting in childhood and continuing into adulthood. While it is rare, some patients have experienced fatal consequences due to invasive squamous cell carcinoma that originated in the conjunctiva. Malignant skin tumors, including seborrheic keratosis, actinic keratosis, Bowen disease, and squamous cell carcinoma, have been found to develop in around one-third of patients during their fourth or fifth decades of life. These tumors are usually noninvasive in situ carcinomas at first and progress to invasive cancers in about 30 to 60 percent of patients. Some patients have also developed cancers such as Burkitt lymphoma and EBV lymphoma. While most cancers remain localized and do not metastasize, they can be locally destructive if left untreated. No fatalities related to epidermodysplasia verruciformis have been reported.
Conclusion
Epidermodysplasia verruciformis is a rare genetic disorder that causes persistent and widespread viral warts, which can potentially develop into skin cancers in 30 to 60 percent of patients. Although there is no cure for EV, a combination of medical and surgical treatments can help manage the condition and remove lesions. Patients with EV should follow strict sun protection strategies, stop smoking, and receive regular surveillance to reduce their risk of developing skin cancer.
