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

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.

STK4 deficiency and epidermodysplasia verruciformis-like lesions: A case report.

Serine/threonine kinase 4 deficiency (STK4 or MST1, OMIM:614868) is an autosomal recessive (AR) combined immunodeficiency that can present with skin lesions such as epidermodysplasia verruciformis-like lesions (EVLL). Herein, we describe a 17-year-old male patient born from consanguineous parents presenting with recurrent respiratory infections, verruciform plaques, poikiloderma, chronic benign lymphoproliferation, and Sjögren syndrome with suspected interstitial lymphocytic pneumonia.

Monogenic etiologies of persistent human papillomavirus infections: A comprehensive systematic review.

PURPOSE: Persistent human papillomavirus infection (PHPVI) causes cutaneous, anogenital, and mucosal warts. Cutaneous warts include common warts, Treeman syndrome, and epidermodysplasia verruciformis, among others. Although more reports of monogenic predisposition to PHPVI have been published with the development of genomic technologies, genetic testing is rarely incorporated into clinical assessments. To encourage broader molecular testing, we compiled a list of the various monogenic etiologies of PHPVI. METHODS: We conducted a systematic literature review to determine the genetic, immunological, and clinical characteristics of patients with PHPVI. RESULTS: The inclusion criteria were met by 261 of 40,687 articles. In 842 patients, 83 PHPVI-associated genes were identified, including 42, 6, and 35 genes with strong, moderate, and weak evidence for causality, respectively. Autosomal recessive inheritance predominated (69%). PHPVI onset age was 10.8 ± 8.6 years, with an interquartile range of 5 to 14 years. GATA2,IL2RG,DOCK8, CXCR4, TMC6, TMC8, and CIB1 are the most frequently reported PHPVI-associated genes with strong causality. Most genes (74 out of 83) belong to a catalog of 485 inborn errors of immunity-related genes, and 40 genes (54%) are represented in the nonsyndromic and syndromic combined immunodeficiency categories. CONCLUSION: PHPVI has at least 83 monogenic etiologies and a genetic diagnosis is essential for effective management.

Recurrent fungating tumor and a chronic rash in an immunosuppressed transgender patient: a case of Buschke-Lowenstein condyloma and epidermodysplasia verruciformis.

A transgender female in her 40s with history of HIV and testicular cancer status post-genital X-irradiation presented with a perianal mass and pruritic rash across her chest. Physical examination revealed a bulky, verrucous tumor protruding outward from the anus involving the medial buttocks. Examination of the chest and arms showed numerous guttate, pink, flat-topped papules coalescing into plaques. Clinically and histologically the lesions were consistent with Buschke-Löwenstein condyloma (BLC) and acquired epidermodysplasia verruciformis (AEDV). Buschke-Löwenstein condyloma incisional biopsy tested negative for common low- and high-risk human papillomavirus (HPV) subtypes, including 6, 11, 16, and 18, possibly implicating beta HPV subtype or a less common pathogenic subtype. The patient underwent abdominoperineal resection of the BLC, which tested positive for low-risk HPV subtypes, suggesting the possibility of multiple implicated HPV subtypes in the same tumor. This case demonstrates a possible role of beta HPV or rarer HPV subtypes in the pathogenesis of verrucous carcinoma, particularly in the setting of immunosuppression.

Epidermodisplasia verruciforme y carcinoma epidermoide - diagnóstico y tratamiento / Verruciform epidermodysplasia and epidermoid carcinoma - diagnosis and treatment

La epidermodisplasia verruciforme es una genodermatosis precancerosa de tipo autosómica recesiva, infrecuente, de distribución mundial. Los portadores de esta enfermedad presentan una inmunodepresión celular selectiva contra determinados tipos de virus papiloma humano, sobre todo con los genotipos 5 y 8, desarrollando desde edades tempranas de la vida lesiones semejantes a pitiriasis versicolor, verrugas planas y queratosis seborreicas, muy extendidas, crónicas y refractarias al tratamiento. Es habitual la aparición de carcinomas escamosos múltiples, especialmente en el contexto de cofactores carcinogénicos como el sol. Presentamos a un paciente con diagnóstico de epidermodisplasia verruciforme, que evidenciaba lesiones tipo verrugas planas, queratosis seborreicas y carcinoma escamoso, la cual fue tratada con excéresis con margen de seguridad y reconstrucción con injerto de piel parcial y colocación de sistema de aspiración sellada al vacío con buena evolución.

Verruciform epidermodysplasia is a rare, autosomal recessive precancerous genodermatosis with a worldwide distribution. Carriers of this disease present a selective cellular immunosuppression against certain types of human papilloma virus, especially with genotypes 5 and 8, developing from early ages of life lesions similar to pityriasis versicolor, flat warts and seborrheic keratoses, very widespread, chronic and refractory to treatment. Multiple squamous cell carcinomas are common, especially in the context of carcinogenic cofactors such as the sun. We present a patient with a diagnosis of verruciform epidermodysplasia, who evidenced flat wart-like lesions, seborrheic keratoses and squamous carcinoma, which was treated with excision with a margin of safety and reconstruction with partial skin graft and placement of a vacuum-sealed aspiration system with good evolution.

Claudin expression profile in flat wart and cutaneous squamous cell carcinoma in epidermodysplasia verruciformis.

Epidermodysplasia verruciformis (EV) is a genodermatosis related to human beta-papillomavirus (beta-HPV), with a high risk of cutaneous squamous cell carcinoma (cSCC). Claudins are transmembrane proteins expressed in epithelia and may be altered during carcinogenesis. For a better understanding of the role of beta-HPV in cutaneous carcinogenesis, this claudin expression study was conducted on lesions of patients with and without EV. In this study, claudins-1, -2, -3, -4, -5, -7 and -11 expressions were analyzed by applying the immunohistochemistry technique, in samples of 108 normal skin, 39 flat warts and 174 cSCC. The cSCC samples were organized in tissue microarrays. We found that claudin-1 and claudin-3 focal expressions were associated with cSCC (p < 0.001), and claudin-2 focal or negative expression with flat wart (p < 0.001), in EV and NEV (non-EV) groups. For claudin-5, EV group showed a lower chance of focal and negative expression (p < 0.001), and its negative expression was associated with flat wart (p < 0.001) and lower mean age (p < 0.001). Claudins-4, -7 and -11 showed a diffuse expression in almost all studied samples. Our findings suggest that claudin-5 increased expression observed on normal skin, flat wart and cSCC showed association with EV. Claudin-1 and -3 down expression were also observed, but they could not be related to beta-HPV infection.

Epidemiology and biology of cutaneous human papillomavirus.

Cutaneous human papillomaviruses (HPVs) include ß- and γ-HPVs, in addition to a small fraction of α-HPVs. ß-HPVs were first isolated from patients with the rare genetic disorder Epidermodysplasia verruciformis, and they are associated with the development of nonmelanoma skin cancer at sun-exposed skin sites in these individuals. Organ transplant recipients also have greater susceptibility to ß-HPV infection of the skin and an increased risk of developing nonmelanoma skin cancer. In both immunosuppressed and immunocompromised individuals, cutaneous HPVs are ubiquitously disseminated throughout healthy skin and may be an intrinsic part of the commensal flora. Functional analysis of E6 and E7 proteins of specific cutaneous HPVs has provided a mechanistic comprehension of how these viruses may induce carcinogenesis. Nevertheless, additional research is crucial to better understand the pathological implications of the broad distribution of these HPVs.

Epidemiology and biology of cutaneous human papillomavirus

Cutaneous human papillomaviruses (HPVs) include β- and γ-HPVs, in addition to a small fraction of α-HPVs. β-HPVs were first isolated from patients with the rare genetic disorder Epidermodysplasia verruciformis, and they are associated with the development of nonmelanoma skin cancer at sun-exposed skin sites in these individuals. Organ transplant recipients also have greater susceptibility to β-HPV infection of the skin and an increased risk of developing nonmelanoma skin cancer. In both immunosuppressed and immunocompromised individuals, cutaneous HPVs are ubiquitously disseminated throughout healthy skin and may be an intrinsic part of the commensal flora. Functional analysis of E6 and E7 proteins of specific cutaneous HPVs has provided a mechanistic comprehension of how these viruses may induce carcinogenesis. Nevertheless, additional research is crucial to better understand the pathological implications of the broad distribution of these HPVs.

Epidermodysplasia verruciformis associated with idiopathic CD4+ lymphopenia / Epidermodisplasia verruciforme asociada a linfopenia idiopática de CD4+

Abstract Epidermodysplasia verruciformis (EV) is an autosomal recessive disease of the skin commonly associated with EVER1 and EVER 2 mutations, and is characterized by high susceptibility to infections associated with certain types of human papillomavirus called EV-PVH. Patients have warty lesions on the skin of varying characteristics and are often associated with skin cancer, with a strong association being found with EVER1 and EVER2 mutation gene. The case presented below concerns an absolute CD4+ lymphopenia, and establishes the hypothesis of a possible mutation of the RHOH gene as its origin.

Resumen La epidermodisplasia verruciforme (EV) es una enfermedad de la piel autosómica recesiva, relacionada con la mutación EVER1 y EVER2, caracterizada por alta susceptibilidad a infecciones asociadas a ciertos tipos de papillomavirus humano llamadas EV-PVH. Los pacientes presentan lesiones verrucosas en la piel de características variadas y muchas veces asociadas a cáncer de piel no melanocítico, encontrándose una fuerte asociación con la mutación del gen EVER1 y EVER2. El caso que se presenta a continuación documenta linfopenia absoluta de CD4+ por lo que se plantea la hipótesis de una posible mutación del gen RHOH como etiología.

Comparative study of p16 protein expression in squamous cell carcinomas from patients with epidermodysplasia verruciformis and patients without the disease.

Epidermodysplasia verruciformis (EV) is a rare genodermatosis associated with susceptibility to beta-human papilloma virus (HPV) infection. EV patients develop disseminated warts and non-melanoma skin cancer, mainly squamous cell carcinomas (SCC) that are locally aggressive. EV pathogenesis is not yet fully understood, but alterations in the p16 gene play a role in the pathogenesis of neoplasms caused by high-risk genital HPV. To explore its role in EV lesions, we compared p16 expression in SCC from patients with and without EV. Tissue microarray slides composed of 27 SCC from EV patients, and 35 from non-EV patients were stained with an anti-p16 antibody. Twenty (74%) EV tumors exhibited diffuse (nuclear and cytoplasmic) p16 expression, one (4%) displayed focal expression, and six (22%) displayed no p16 staining. Eleven (31%) SCC from non-EV patients presented diffuse p16 staining, 14 (40%) displayed focal expression and 10 (29%) did not express p16. The frequency of diffuse p16 expression was higher in EV tumors than in SCC from patients without EV. The frequency of diffuse p16 expression in moderately and poorly differentiated EV-SCC was similarly higher than non-EV tumors with the same degree of differentiation. The diffuse expression of p16 in EV-SCC suggests that changes in the p16 gene, probably resulting in a functionally defective protein, may be one factor determining the locally aggressive clinical behavior of SCC in young EV patients.

Verrugosis generalizada con linfedema, inmunodeficiencia y displasia genital: síndrome WILD / Generalized verrucosis with limphoedema, immunodeficiency and genital dysplasia: WILD syndrome

La verrugosis generalizada es un rasgo común a diferentes síndromes de inmunodeficiencia, cuyo prototipo es la epidermodisplasia verruciforme (EV). Se presenta una paciente con síndrome WILD (Warts, Immunodeficiency, Lymphoedema, anogenital Dysplasia), que consultó por verrugas profusas, con displasia genital y linfedema. La presencia de DNA para los papilomavirus de los grupos I y II se reveló con hibridización molecular por captura híbrida en microplaca para detección del DNA de HPV de lesiones de cuello uterino. La inmunofenotipificación en sangre periférica demostró población linfoide con moderado aumento de poblaciones NK y TNK, sin evidencia inmunofenotípica de población B clonal. Las verrugas planas mejoraron con retinoides sistémicos e imiquimod tópico. La displasia genital desapareció luego de la vacunación para HPV con vacuna cuadrivalente (AU)

Generalized verrucosis is a common characteristic of several immunodeficiency disorders whose prototype is the epidermodysplasia verruciformis. We report a patient with WILD SYNDROME (Warts, Immunodeficiency, Lymphoedema and anogenital Dysplasia) who consulted for profuse warts, genital dysplasia and limphoedema. The presence of DNA from papillomavirus groups I and II was revealed by molecular hybridization with hybrid capture in microplate for HPV DNA detection of uterine cervical lesions. Immunophenotyping in peripheral blood showed lymphoid population with moderate increase in NK and TNK populations without immunophenotypic evidence of clonal B population. Flat warts improved with systemic retinoids and topical imiquimod. The genital dysplasia disappeared after vaccination with quadrivalent HPV vaccine (AU)

Epidermodisplasia verruciforme / Epidermodysplasia verruciformis

La epidermodisplasia verruciforme (EV) es una genodermatosis rara, caracterizada por el desarrollo de verrugas planas y lesiones similares a pitiriasis versicolor, asociada a infección crónica por Virus Papiloma Humano. Se reporta el caso de EV. Mujer de 49 años con múltiples lesiones verrucosas de larga evolución distribuidas en las cuatro extremidades y antecedente familiar de cuadro similar. Biopsia a los 19 años evidenció verrugas sin atipia. Nuevo estudio histológico informó carcinoma escamoso, decidiéndose extirpación de lesiones. La clínica inicia en edades tempranas, con elevado riesgo de transformación maligna. No existe tratamiento específico. Es esencial la fotoprotección estricta y manejo precoz de lesiones para prevención de progresión a carcinoma.

Epidermodysplasia verruciformis (EV) is a rare genodermatosis, characterized by the development of plane warts and pityriasis versicolor-like lesions, associated with chronic infection caused by the Human Papilloma virus. An EV case is reported. 49 year-old woman with multiple long standing warty lesions distributed on the four limbs and family background of similar cases. Biopsy at 19 years old evidenced warts without atypia. New histological study reported squamous cell carcinoma, deciding the removal of the lesions. The clinic begins at early age, with high risk of malignant transformation. There is no specific treatment. Strict photoprotection and early management of the lesions is essential to prevent the progression to carcinoma.

Deleterious Effect of Radiation Therapy on Epidermodysplasia Verruciformis Patients.

BACKGROUND: Epidermodysplasia verruciformis (EV) is a rare genodermatosis caused by specific human papillomavirus (HPV) types associated with the development of multiple squamous cell carcinomas (SCC). The treatment for this skin tumour may be difficult. Among the therapy options, radiotherapy (RT) should be avoided due to its deleterious effects on HPV-induced carcinogenesis. OBJECTIVE: To describe 4 patients with EV who underwent radiotherapy to treat cutaneous SCC. METHODS: This is a retrospective study. The evolution of cutaneous SCC after adjuvant radiotherapy in 4 patients with EV was observed. RESULTS: This study included 4 patients with diagnosis of EV. All 4 of the patients had cutaneous SCC. They underwent surgical resection and adjuvant radiotherapy. Over a period of up to 2 years, there was aggressive tumour recurrence. CONCLUSION: Radiotherapy might be associated with progression of SCC in patients with EV, and it is recommended that radiotherapy should be avoided in this patient population.

Acquired epidermodysplasia verruciformis in a renal transplant recipient--case report.

A 24-year-old male patient, who underwent kidney transplant six years ago due to Lupus nephritis, for the last two years presented asymptomatic erythematous scaly plaques on the abdomen and areas exposed to light. Post-transplantation immunosuppressive medications included prednisone, mycophenolate sodium and sirolimus. The histopathologic features were typical for epidermodysplasia verruciformis. Epidermodysplasia verruciformis is a rare autosomal recessive genodermatosis with increased susceptibility to specific strains of cutaneous human papilloma virus. The term ''acquired epidermodysplasia verruciformis'' was recently introduced to the literature and describes epidermodysplasia verruciformis occurring in patients with impaired cell-mediated immunity. We report an additional case associated to immunosuppression after kidney transplantation.

Acquired epidermodysplasia verruciformis in a renal transplant recipient - Case report

A 24-year-old male patient, who underwent kidney transplant six years ago due to Lupus nephritis, for the last two years presented asymptomatic erythematous scaly plaques on the abdomen and areas exposed to light. Post-transplantation immunosuppressive medications included prednisone, mycophenolate sodium and sirolimus. The histopathologic features were typical for epidermodysplasia verruciformis. Epidermodysplasia verruciformis is a rare autosomal recessive genodermatosis with increased susceptibility to specific strains of cutaneous human papilloma virus. The term ''acquired epidermodysplasia verruciformis'' was recently introduced to the literature and describes epidermodysplasia verruciformis occurring in patients with impaired cell-mediated immunity. We report an additional case associated to immunosuppression after kidney transplantation.

Epidermodysplasia verruciformis in a young man with HIV since birth--case report.

Epidermodysplasia Verruciformis is a genodermatosis characterized by susceptibility to infection by specific HPV types (HPV 3/10 and beta-HPVs). It is considered to be the first model in human carcinogenesis induced by HPV. In this report we present a rare case of Epidermodysplasia Verruciformis associated with vertical transmission of HIV. Although most patients with HIV present infections by HPV virus, the frequency of Epidermodysplasia Verruciformis is no greater in patients with HIV because in EV there is a deficiency of specific cellular immunity to infection by some types of HPV, called HPV-related Epidermodysplasia Verruciformis.

Epidermodysplasia verruciformis in a young man with HIV since birth - case report / Epidermodisplasia verruciforme em um jovem com HIV desde o nascimento - relato de caso

Epidermodysplasia Verruciformis is a genodermatosis characterized by susceptibility to infection by specific HPV types (HPV 3/10 and beta-HPVs). It is considered to be the first model in human carcinogenesis induced by HPV. In this report we present a rare case of Epidermodysplasia Verruciformis associated with vertical transmission of HIV. Although most patients with HIV present infections by HPV virus, the frequency of Epidermodysplasia Verruciformis is no greater in patients with HIV because in EV there is a deficiency of specific cellular immunity to infection by some types of HPV, called HPV-related Epidermodysplasia Verruciformis.

A Epidermodisplasia Verruciforme é uma genodermatose que se caracteriza pela susceptibilidade à infecção por tipos específicos de HPV (HPVs 3 e 10 e os beta-HPVs) e é considerada o primeiro modelo no homem de carcinogênese induzida pelo HPV. Neste artigo apresenta-se um caso raro de Epidermodisplasia Verruciforme em um paciente com HIV desde o nascimento. Apesar dos doentes com HIV apresentarem mais infecções pelos vírus HPVs, existem poucos relatos na literatura de Epidermodisplasia Verruciforme no doente com HIV. Isso se explica, pois a Epidermodisplasia Verruciforme é consequência de uma deficiência celular específica à infecção por alguns tipos distintos de HPVs, ditos HPVs relacionados a Epidermodisplasia Verruciforme.

[Student experience in providing care to a patient with epidermodysplasia verruciformis]. / Experiência discente com o cuidado a paciente portador de Epidermodisplasia Verruciforme.

Report of an experience of nursing students in providing care to a patient with epidermodysplasia verruciformis, during the internship in the discipline Nursing in Transmittable Diseases, at the dermatology ward of a teaching hospital, located in the state of São Paulo, Brazil, in 2009. This is a rare genodermatosis, susceptible to infection with different types of human papilloma viruses, that cause exacerbated physical changes that impact the psyche of the affected individual. Care delivery was based on the assistance complexity indicated by the application of the Patient Classification System proposed by Perroca. The experience allowed students to learn how to cope with a patient affected by a rare and complex disease, of difficult resolution, and to provide integral care to this individual, perceiving him beyond the lesions. One conclude that the experience has greatly contributed to the growth of the students as future professionals.

Experiência discente com o cuidado a paciente portador de Epidermodisplasia Verruciforme / Student experience in providing care to a patient with Epidermodysplasia Verruciformis / Experiencia de estudiantes con el cuidado a paciente con Epidermodisplasia Verruciforme

Relato de experiência de situação vivenciada, em 2009, por acadêmicas de enfermagem, durante estágio da disciplina Enfermagem em Doenças Transmissíveis, na enfermaria de dermatologia de um hospital de ensino do interior paulista, em que cuidaram de um paciente com Epidermodisplasia Verruciforme. Esta é uma genodermatose rara, com susceptibilidade à infecção por diferentes tipos de papiloma vírus humanos, ocasionando alterações físicas exacerbadas e impactando o psiquismo da pessoa acometida. A assistência foi baseada na complexidade assistencial indicada pela aplicação do Sistema de Classificação de Pacientes proposto por Perroca. A experiência proporcionou aprendizado no cuidado a paciente portador de doença rara, complexa e de difícil resolução, possibilitando a necessidade de assisti-lo integralmente, percebendo-o além das lesões. Conclui-se que este tipo de experiência muito contribuiu para o crescimento das acadêmicas como futuras profissionais de enfermagem.

Report of an experience of nursing students in providing care to a patient with epidermodysplasia verruciformis, during the internship in the discipline Nursing in Transmittable Diseases, at the dermatology ward of a teaching hospital, located in the state of São Paulo, Brazil, in 2009. This is a rare genodermatosis, susceptible to infection with different types of human papilloma viruses, that cause exacerbated physical changes that impact the psyche of the affected individual. Care delivery was based on the assistance complexity indicated by the application of the Patient Classification System proposed by Perroca. The experience allowed students to learn how to cope with a patient affected by a rare and complex disease, of difficult resolution, and to provide integral care to this individual, perceiving him beyond the lesions. One conclude that the experience has greatly contributed to the growth of the students as future professionals.

Relato de experiencia vivida por estudiantes de enfermería, en 2009, durante la pasantía de la disciplina de Enfermería en Enfermedades Transmisibles, en la sala de dermatología de un hospital universitario del estado de São Paulo, Brasil, donde cuidarán a uno paciente con Epidermodisplasia Verruciforme. Esta es una genodermatosis rara, con susceptibilidad para la infección por diferentes tipos de virus del papiloma humano, causando cambios físicos exasperados e impacto en la psiquis de la persona afectada. La asistencia esté basada en la complejidad de la atención, segundo la aplicación del Sistema de Clasificación de Pacientes propuesto por Perroca. A experiencia proporciono aprendizaje en el cuidado del paciente con una enfermedad rara, compleja y de difícil cura, dando la posibilidad a las estudiantes de asistirlo integralmente, más allá de las lesiones. Concluye-se que este tipo de experiencia contribuyó para el crecimiento de las estudiantes como futuros profesionales.