ReviewRe-evaluation of epidermodysplasia verruciformis: Reconciling more than 90 years of debate
Section snippets
Back to the beginning
Heritage was known to be important in EV almost since the first time this identity was described by Lewandowsky and Lutz in 192230; many cases of EV are familial and 10% of patients originate from consanguineous families.31 This observation enabled Cockayne et al in 1933 to hypothesise that EV could be inherited as an autosomal recessive trait. This hypothesis was confirmed almost 90 years later, with the discovery of the first 2 genetic etiologies of EV, inactivating nonsense homozygous
New discoveries
All of these newly discovered mutations do not proclaim EV stricto sensu. The proteins encoded by RHOH, MST-1, and CORO1A are found on hematopoietic cells only and are absent from keratinocytes. RHOH encodes an atypical, hematopoietic cell–specific Rho GTPase,47 which lacks GTPase activity and remains locked in guanosine triphosphate–bound conformation. Therefore, it is unable to function as an intracellular switch and conduct signals from T and B cell membrane receptors.48, 49 CORO1A encodes
Exogenous immunodeficiency
The term AEV—also referred to as secondary EV, immunodeficient EV, and EV-like—was recently introduced57 to describe EV occurring in patients with defective cell-mediated immunity. This can be caused by infection (eg, HIV infection with severe immunosuppression with CD4+ counts <200 cells/μL),58, 59, 60 non–Hodgkin lymphoma,61 lepromatous leprosy,62 lipoid proteinosis,63 or medications (eg, bendamustine64 and cyclosporine for atopic dermatitis65). Sometimes, medications and immune dysregulation
Generalized verrucosis—A different entity
Generalized verrucosis (GV) has recently been defined as a progressive, chronic cutaneous HPV infection. On harsher scrutiny, 2 GV types might be distinguished; the first features a distribution pattern in which >20 lesions are located in >1 arbitrary region of the body, and the second features an acral distribution pattern that affects the majority of digits and additionally impairs the individual's ability to function independently.43, 81 It manifests clinically as verrucous papules and
Conclusions and clinical perspectives
We believe that dermatologists, geneticists, immunologists, and all the other specialists that are involved in research concerning EV and AEV can agree that well-established distinctive measures to differentiate between GV, EV, and AEV are lacking. Before the discovery of new mutations, the situation was much clearer, and the separation of exogenous (occurring in immunocompromised hosts) and endogenous (caused by homozygous frameshift, nonsense, or splice-site TMC6 and TMC8 mutations) EV was
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Supported in part by the Israel Cancer Association (20150020) and the Hadassah–Hebrew University Joint Research Fund (6070803).
Conflicts of interest: None declared.
Reprints not available from the authors.