Targeting Complex Cutaneous Viral Infections in Search of Inborn Errors of Immunity

Inborn errors of immunity are rare diseases and 50-80% present with dermatological manifestations. This study evaluated difficult-to-treat cutaneous human papillomavirus infections and their associations with immunological defects. Patients were recruited from the Dermatological Outpatient Clinic over 2 years. Patients reporting persistent common warts and/or a combination of molluscum contagiosum or more than 2 flat warts, with a clinical assessment of severe or persistent skin infection, met the clinical severity criteria for inclusion. Resistance to several therapies was also considered. A total of 632 patient records were analysed to clinically characterize the warts, laboratory data, treatments used and their responses, comorbidities, and family history. Among these, 459 cases were initially excluded from further evaluation. A questionnaire was provided by phone to 173 patients, among whom 47 patients were selected for an in-person consultation. Of these, 6 met the criteria for further evaluation. Immunological tests revealed neutropenia, low levels of immunoglobulin isotypes (IgA, IgM, and IgG), and reduced frequency of lymphocyte subsets. Family history, flat warts, and associated recurrent viral infections suggested the need for further immunological evaluation. Criteria are proposed for identifying patients with cutaneous warts that warrant additional evaluation for potential inborn errors of immunity.