Acquired epidermodysplasia verruciformis syndrome in HIV-infected patients: a systematic review

Abstract

Congenital epidermodysplasia verruciformis (CEV) is a Genodermatosis linked to different inheritance patterns and mutations of the EVER1/TMC6 and EVER2/TMC8 genes. There is an acquired form (AEV) associated with immunodeficiency states, including human immunodeficiency virus (HIV) infection; however, the literature about AEV is limited and imprecise, so a systematic review was performed. A search of the main databases from 1975 to 2021 identified 126 studies, of which 80 met the inclusion criteria. The diagnosis of AEV is complex due to atypical manifestations and locations, it requires a mean follow-up of 7 years, and the lesions do not change with ART therapy, CD4 count, or viral load. Histopathological findings are variable depending on the location of the lesions. HPV 5 remains the serotype most frequently associated with AEV and CEV, although HPV 20 is more frequent than HPV 8 in AEV. Most treatments have low efficacy, the most described are glycolic acid 15%, 5-fluorouracil 5%, imiquimod 5%, and topical retinoids all of them in monotherapy or combined with cryotherapy. Other alternatives include topical cidofovir and systemic retinoids with variable results. The oncologic prognosis is still inconclusive; however, the development of squamous cell carcinoma and melanoma are frankly lower concerning CEV. This review opens new opportunities for future research. Additionally, we provide clear and useful key points for the practice of dermatologists and all professionals treating HIV patients around the world.

Keywords: Epidermodysplasia verruciformis; HIV; HPV; Skin cancer.

Fig. 1

PRISMA 2020 flow diagram for new systematic reviews. The search time, filtering, statistical application p < 0.05, and hypothesis verification by Shapiro Wilk test was 1 year. (ʃ) First stage of exclusion, the title or abstract does not match the case description and does not meet the inclusion criteria. (++) Grey literature (+) Title or abstract does not meet eligibility criteria (Δ) Old Documents or Unavailable Sources). (ʎ) Lack of Response (Ω) Different Format. (ɸ) Cases that included AEV-related keywords but did not meet the inclusion criteria. (*) Records identified from each database or register searched (rather than the total number across all databases/registers). (**) If automation tools were used, indicate how many records were excluded by a human and how many were excluded by automation tools. According to MJ, McKenzie JE, Bossuyt PM, Boutron I, Hoffmann TC, Mulrow CD, et al. The PRISMA 2020 statement: an updated guideline for reporting systematic reviews. BMJ2021;372:n71. DOI: 10.1136/bmj.n71

Fig. 2

Histopathological findings in acquired epidermodysplasia verruciformis. H&E 80x (a) and 60x (b). Courtesy of Dr. Mariam Rolón