Epidermodysplasia Verruciformis and Vδ2 γδ T-cell Expansion in STK4 Deficiency.

The clinical penetrance of infectious diseases varies considerably among patients with inborn errors of immunity (IEI), even for identical genetic defects. This variability is influenced by pathogen exposure, healthcare access and host-environment interactions. We describe here a patient in his thirties who presented with epidermodysplasia verruciformis (EV) due to infection with a weakly virulent beta-papillomavirus (HPV38) and CD4+ T-cell lymphopenia. The patient was born to consanguineous parents living in the United States. Exome sequencing identified a previously unknown biallelic STK4 stop-gain mutation (p.Trp425X). The patient had no relevant history of infectious disease during childhood other than mild wart-like lesion on the skin, but he developed diffuse large B-cell lymphoma (DLBCL) and EBV viremia with a low viral load in his thirties. Despite his low CD4+ T-cell count, the patient had normal counts of CD3+ cells, predominantly double-negative T cells (67.4%), which turned out to be Vδ2+ γδ T cells. γδ T-cell expansion has frequently been observed in the 33 reported cases with STK4 deficiency. The Vδ2 γδ T cells of this STK4-deficient patient are mostly CD45RA-CD27+CCR7+ central memory γδT cells, and their ability to proliferate in response to T-cell activation was impaired, as was that of CD4+ T cells. In conclusion, γδ T-cell expansion may act as a compensatory mechanism to combat viral infection, providing immune protection in immunocompromised individuals.

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.

Acquired epidermodysplasia verruciformis: clinical presentation and treatment update.

Acquired epidermodysplasia verruciformis (AEV) is a form of epidermodysplasia verruciformis (EV) that is most commonly found in immunocompromised or immunosuppressed patients. EV is commonly associated with human papillomavirus (HPV), which is often found in EV and AEV lesions. Clinical presentation of AEV in patients with organ transplantation, HIV+, congenital HIV+, hematological diseases, and other iatrogenic immunosuppression are reviewed. Treatment options include topical cidofovir, topical retinoids, topical imiquimod, topical glycolic acid, HPV 9-valent vaccine, acitretin, improving cellular immunity, and changing transplant medication to mycophenolate mofetil.

Acquired epidermodysplasia verruciformis or generalized verrucosis? A clinical and virological comparative study.

Few articles have described the difference between epidermodysplasia verruciformis (EV) and generalized verrucosis (GV). This study aimed to analyze the clinical findings and virology of the two diseases. The study enrolled patients diagnosed with EV and GV by clinical and histopathological findings. The demographic information, clinical manifestation, treatment, and therapeutic outcome were analyzed. All of the biopsy specimens of enrolled patients were sent for ß-human papillomavirus (HPV) DNA detection. A total of 13 cases were included in the present study, including five EV cases and eight GV cases. Legs and feet were significantly affected in GV cases (p = 0.035). All acquired EV cases had immunocompromised conditions, while only three GV cases could be identified as having an immunocompromised history. All EV cases were detected with ß-HPV infection, especially HPV5, but none of the GV cases were found to be infected with ß-HPV. The therapeutic response was refractory and often relapsed after discontinuation of treatment in both groups.

Acquired Epidermodysplasia Verruciformis in the Setting of Renal Transplant.

ABSTRACT: Epidermodysplasia verruciformis (EV) is a rare dermatologic condition that is clinically characterized by flat, cutaneous, verrucous papules, pityriasis versicolor-like lesions, and similar lichenoid papules. There are 2 forms of EV: a classic inherited genodermatosis and a secondary acquired form. EV predisposes individuals to infections with certain types of human papillomavirus virus and subsequently increases the risk of cutaneous squamous cell carcinoma. The acquired form occurs in immunosuppressed patients, particularly in patients infected with HIV; however, it has also been described in patients who have undergone stem cell and solid organ transplantation. We report an additional case of renal transplantation and immunosuppressive therapy-associated acquired EV (AEV) in a 78-year-old man with multiple flesh-colored to violaceous, flat-topped papules distributed on the face and trunk clinically mimicking lichen planus. Biopsy was typical for that of EV, demonstrating enlarged keratinocytes with a blue-gray cytoplasm, a thickened granular layer, acanthosis, and hyperkeratosis. Herein, we discuss an unusual presentation of an AEV-mimicking lichen planus with review of the literature.