Atypical Cutaneous Viral Infections Reveal an Inborn Error of Immunity in 8 Patients

Abstract

Unusual viral skin infections might be the first clinical manifestation in children with an inborn error of immunity (IEI). We performed a prospective study from 1 October 2017 to 30 September 2021, at the Department of Pediatric Infectious Diseases and Clinical Immunity of Ibn Rochd University Hospital-Casablanca. During this period, on 591 patients newly diagnosed with a probable IEI, eight of them (1.3%), from six independent families, had isolated or syndromic unusual viral skin infections, which were either profuse, chronic or recurrent infections, and resistant to any treatment. The median age of disease onset was nine years old and all patients were born from a first-degree consanguineous marriage. By combining clinical, immunological and genetic investigations, we identified GATA2 deficiency in one patient with recalcitrant profuse verrucous lesions and monocytopenia (1/8) and STK4 deficiency in two families with HPV lesions, either flat or common warts, and lymphopenia (2/8), as previously reported. We also identified COPA deficiency in twin sisters with chronic profuse Molluscum contagiosum lesions, pulmonary diseases and microcytic hypochromic anemia (2/8). Finally, we also found one patient with chronic profuse MC lesions and hyper IgE syndrome, (1/8) and two patients with either recalcitrant profuse verrucous lesions or recurrent post-herpetic erythema multiforme and a combined immunodeficiency (2/8) with no genetic defect identified yet. Raising clinicians awareness that infectious skin diseases might be the consequence of an inborn error of immunity would allow for optimized diagnosis, prevention and treatment of patients and their families.