Epidermodysplasia Verruciformis

Epidermodysplasia Verruciformis (EV) is a rare inherited disease characterized by an increased susceptibility to infection by Papillomaviruses of the Beta genus (β-HPV), which mainly infect the skin. EV starts during childhood with the appearance of multiple flat warts and maculo-papular lesions in sun-exposed sites, like the forehead. During the first decades of life, such lesions can give rise to precancerous elements or even full-blown cutaneous neoplasms. EV was first described in 1922 by Levandowski and Lutz, and provides a unique model of HPV-induced skin carcinogenesis and thus a valuable opportunity to study the link between infection and carcinoma formation.

The literature reports that about 10% of EV cases are born within consanguineous marriages and that 10% of such families present more than one affected sibling. These data strongly point to a recessive autosomal inheritance of the disease. Recently, two different genetic susceptibility loci were identified; the most important loci is EV1 that comprises the genes EVER1 and EVER2, and for which many genetic mutations have been reported. EV patients frequently present a state of immunodeficiency, above all caused by defects in cell-mediated immunity (T cell immunity).

The diagnosis of EV is based purely on clinical observations, and is suspected in subjects showing numerous (either isolated or confluent) flat warts, erythemato-squamous lesions on the trunk or precancerous elements, such as multiple actinic keratoses or cutaneous neoplasms, primarily localized to sun-exposed areas.

EV provides a unique human model in which to study the various factors responsible for HPV mediated skin carcinogenesis; indeed, 100% of cutaneous tumors taken from EV patients are positive for β-HPV infection. So far, no specific diagnostic test is available for EV; the only test that can be performed is the histological examination of warty lesions.

In the Department of Clinical and Experimental Medicine in Novara, a combination of molecular assays were performed in a group of EV patients in order to properly investigate and quantify β-HPV infection. The same assays have also proved to be useful for EV diagnosis, even in paucilesional and clinically uncertain cases. These assays represent a step forward in EV diagnostics and follow-up and their aim is to increase our knowledge of this rare, orphan disease.

Precancerous and neoplastic lesions in the forehead, forearms and dorsum of the hands in patients suffering from Epidermodysplasia Verruciformis.