Epidermodysplasia verruciformis: a little-suspected inborn error of immunity

Abstract

Epidermodysplasia verruciformis is a rare, autosomal recessive, intrinsic and innate immune disorder characterized by verrucous skin lesions caused by ubiquitous, non-pathogenic serotypes of the human papillomavirus (beta group 1).
75% of cases are associated with TMC6/8 deficiency, which encodes EVER1/2, with onset before age 23. These serotypes form complexes with CIB1 in keratinocytes and interact with other cutaneous serotypes via E5 and E8 proteins to prevent their transcription; these proteins are not synthesized by the beta group. The remaining 25% have T-cell defects, with diverse clinical expression. One-third of patients may develop cancer after age 24 from the initial dermatosis.
We treated a female patient who, since the age of 2, had experienced generalized, recurrent common warts (Figure 1). She received topical and surgical treatment without response. At age 18, she was referred to the Dermatology service, where a biopsy of her common warts was performed. Superinfections were found, and prophylaxis with moxifloxacin and clarithromycin was initiated. She was then referred to the Allergy and Clinical Immunology service. Lymphocyte subpopulation analysis showed no abnormalities. Genetic testing is still pending, and she has been discharged with a probable EVER1/2 defect.
The diagnosis of this type of disorder is both clinical and genetic. It requires a multidisciplinary approach to identify any inborn errors of immunity, along with frequent follow-up appointments for timely detection of malignancy and treatment of skin lesions. This approach has a positive impact on the quality of life and life expectancy of patients.