A human papillomavirus-associated disease with disseminated warts, depressed cell-mediated immunity, primary lymphedema, and anogenital dysplasia: WILD syndrome

Abstract

Background: Epidermodysplasia verruciformis (EV) is a rare genodermatosis associated with infections with specific human papillomaviruses (HPVs) belonging to the beta genus of HPV. Patients with EV usually have a selective defect in cell-mediated immunity. Although skin cancer frequently develops in the sun-exposed cutaneous lesions of patients with EV, the anogenital area is usually not affected by squamous cell carcinomas related to mucosal HPV types.

Observations: We report the case of a patient with clinical similarities to EV who also presented with primary lymphedema, anogenital dysplasias, and depressed cell-mediated immunity. Swab samples and biopsy specimens from various body sites collected over a 28-month period were screened by different protocols for DNA of the HPV groups alpha, beta, and mu/nu. Seventeen alpha-HPV types could be demonstrated. Interestingly, beta-HPVs (HPV-22 and HPV-23) were detectable only in plucked eyebrows and in 1 skin swab sample. None of the specimens from lesional biopsies carried beta-HPV. Consistently found alpha-HPV types included HPV types 6, 51, 52, 61, and 84 in the genitoanal region and HPV-57 in skin lesions. Histological and cytological evaluation revealed multifocal anogenital dysplasia and benign genital and cutaneous warts.

Conclusions: To our knowledge, only 1 other similar case of an EV-like syndrome with impaired, cell-mediated immunity and primary lymphedema has been described in the literature. Based on the characteristic clinical and virological findings in the present case and the previously published case, we speculate that both patients could have a previously unknown syndrome that has clinical similarities to EV but notably differs in the associated HPV types. We suggest the acronym WILD (warts, immunodeficiency, lymphedema, dysplasia) to characterize this syndrome.