Abstract
Epidermodysplasia verruciformis (EV) is an autosomal recessive skin disorder with a phenotype conditional on human beta-papillomavirus (beta-HPV) infection. Such infections are common and asymptomatic in the general population, but in individuals with EV, they lead to the development of plane wart-like and red or brownish papules or pityriasis versicolor-like skin lesions, from childhood onwards. Most patients develop non-melanoma skin cancer (NMSC), mostly on areas of UV-exposed skin, from the twenties or thirties onwards. At least half of the cases of typical EV are caused by biallelic loss-of-function mutations of TMC6/EVER1 or TMC8/EVER2. The cellular and molecular basis of disease in TMC/EVER-deficient patients is unknown, but a defect of keratinocyte-intrinsic immunity to beta-HPV is suspected. Indeed, these patients are not susceptible to other infectious diseases and have apparently normal leukocyte development. In contrast, patients with an atypical form of EV due to inborn errors of T-cell immunity invariably develop clinical symptoms of EV in the context of other infectious diseases. The features of the typical and atypical forms of EV thus suggest that the control of beta-HPV infections requires both EVER1/EVER2-dependent keratinocyte-intrinsic immunity and T cell-dependent adaptive immunity.
Highlights
Epidermodysplasia verruciformis (EV) is a rare skin disease characterized by persistent disseminated flat warts and pityriasis versicolor-like lesions, associated with a high risk of nonmelanoma skin cancer (NMSC)
Frontiers in Microbiology | www.frontiersin.org de Jong et al Epidermodysplasia Verruciformis (Cockayne, 1933; Rajagopalan et al, 1972). This notion was not confirmed until 70 years later, when inactivating mutations of the EVER1/TMC6 and EVER2/TMC8 genes accounting for about 50% of all known cases of EV were identified (Ramoz et al, 2002; Orth, 2006, 2008; Imahorn et al, 2017)
Eight different mutations of TMC6/EVER1 and 11 mutations of TMC8/EVER2 have been described to date, in a total of 32 patients from 19 families and 5 ethnicities reviewed in Burger and Itin (2014) and Imahorn et al (2017)
Summary
Epidermodysplasia verruciformis (EV) is a rare skin disease characterized by persistent disseminated flat warts and pityriasis versicolor-like lesions, associated with a high risk of nonmelanoma skin cancer (NMSC). EV results from a genetically determined susceptibility to specific skin-tropic HPVs (Orth, 2006, 2008; Imahorn et al, 2017). These viruses belong to the beta-genus, and are almost ubiquitous and apparently benign in the general population. Patients with cutaneous clinical symptoms of beta-HPV infection and other infectious manifestations caused by profound T-cell defects have been reported This clinical picture is referred to as “atypical EV.”.
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