Atypical Human Papillomavirus Types Causing Epidermodysplasia Verruciformis in Association with X-linked Primary Immunodeficiency-50

Abstract Epidermodysplasia verruciformis (EV) is a rare autosomal recessive genodermatosis characterized by increased susceptibility to human papillomavirus (HPV) infections, often leading to malignant transformation. While HPV types 5 and 8 are commonly implicated, we hereby report a case of EV associated with the atypical HPV types 6, 11, and 66 in conjunction with X-linked primary immunodeficiency-50 (IMD-50), an association not previously reported in the literature. A 10-year-old male with a history of recurrent respiratory infections and persistent cough presented with multiple skin-colored papules on the face, neck, trunk, and upper arms. Histopathology revealed koilocytes, and HPV typing confirmed HPV 6, 11, and 66. Immunological assessment demonstrated low CD4 count, reduced natural killer and B cells, and hypogammaglobulinemia. Whole-genome sequencing identified a hemizygous pathogenic variant in the moesin gene confirming IMD-50. Given the increased risk of malignant transformation in EV, the patient was started on oral acitretin and advised photoprotection. This case highlights the novel association of EV with IMD-50 and an atypical HPV profile, underscoring the need for immunological evaluation in EV patients with recurrent infections and widespread lesions.