Acquired Epidermodysplasia Verruciformis in Patients with Iatrogenic Immunosuppression

Background: Acquired epidermodysplasia verruciformis (AEV) is a rare cutaneous disorder arising in immunocompromised individuals. AEV is characterized by flat-topped, wart-like, or hypopigmented lesions predominantly on sun-exposed areas. Unlike classic genetic EV, AEV develops in the absence of germline mutations or family history. AEV most commonly arises in patients receiving iatrogenic immunosuppressive therapy for organ transplantation, autoimmune disease, or hematologic disorders. Methods: A comprehensive literature review was conducted via the PubMed database. Case reports and case series studies describing AEV in transplant and non-transplant iatrogenic immunosuppression were identified through a literature search. There were no restrictions on language or publication year. The last search was conducted in July 2025. Reports were analyzed for patient demographics, immunosuppressive agents, HPV subtypes, clinical and histopathologic features, and treatment outcomes. Results: AEV occurs across a broad spectrum of immunosuppressive therapies, including calcineurin inhibitors, antimetabolites, biologics, tyrosine kinase inhibitors, and cytotoxic chemotherapy. β-HPV subtypes, most commonly HPV 5 and 8, drive lesion formation in the context of impaired cell-mediated immunity. Histopathology demonstrates keratinocyte vacuolization, acanthosis, and perinuclear halos. Lesions may persist despite immunosuppressive adjustment, due to viral latency and incomplete immune reconstitution. Treatment strategies are varied and include topical retinoids, immune response modifiers, systemic retinoids, and HPV vaccination, and have variable efficacy. AEV carries an elevated risk of cutaneous squamous cell carcinoma, particularly in transplant recipients, and highlights the need for proactive dermatologic management. Conclusions: AEV represents a clinically significant consequence of immunosuppression mediated by β-HPV. Early recognition, monitoring for malignant transformation, and individualized multimodal therapy are critical. Future studies should evaluate targeted interventions to enhance antiviral immunity and establish standardized treatment guidelines.