D2.352 - Epidermodysplasia verruciformis as a sign for STK4 deficiency

Introduction:Epidermodysplasia verruciformis (EV) is a rare genodermatosis characterized by pityriasis versicolor-like or flat wart-like lesions, resulting from impaired immune responses against β-papillomaviruses (β-HPVs). It is associated with an increased susceptibility to squamous cell carcinoma. In typical EV, isolated cutaneous lesions are observed, and mutations in EVER1, EVER2, and CIB1 genes have been identified. In atypical EV, accompanied by T-cell defects in addition to cutaneous β-HPV infection, mutations in RHOH, STK4, CORO1A, FLT3LG, TRAC, DCLRE1C, DOCK8, RASGRP1, LCK, TPP2, and ITK genes have been reported.

Materials and Methods:In this study, we aimed to present a patient referred to our clinic with epidermodysplasia verruciformis who was subsequently diagnosed with STK4 deficiency.

Results:A 7-year-old boy developed raised, flat, hypopigmented wart-like lesions that initially appeared on the neck three years ago and later spread to the face. Skin biopsy findings were consistent with EV, leading to referral to our clinic. The patient had no history of recurrent infections. His parents were consanguineous, and his sister had severe atopic dermatitis. Laboratory evaluation revealed lymphopenia (total lymphocyte count: 1030/mm³). Serum immunoglobulin levels were within age-appropriate reference ranges. Advanced immunological work-up revealed reduced NK cells [3% (reference: 8–28)], decreased switched memory B cells [6% (reference: 10.9–30.4)], increased γδ T cells (29%), and impaired lymphocyte activation responses to phytohemagglutinin [CD3+CD25+: 12% (reference: 46–89), CD3+CD69+: 39% (reference: 50–76)] and anti-CD3 stimulation [CD4+: 33%, CD4+25+: 12%, CD4+69+: 18%]. Genetic analysis identified a homozygous novel variant in the STK4 gene (Chr20:43625898 G→A; c.782G>A; p. Cys261Tyr).

Conclusion:All patients diagnosed with epidermodysplasia verruciformis should be evaluated for underlying primary immunodeficiencies.

Keywords: Combined immunodeficiency, epidermodysplasia verruciformis, STK4 deficiency