Generalized verrucosis caused by various human papillomaviruses in a patient with GATA2 deficiency

Dear Editor, Generalized verrucosis (GV) characterized by more than 20 lesions of cutaneous human papillomavirus (HPV) infection involving several anatomical sites is recognized as a skin manifestation of GATA2 deficiency. GATA2 belongs to a family of transcription factors that are critical in early hematopoietic differentiation, lymphatic vascular development and dendritic cell (DC) differentiation. GATA2 deficiency is clinically characterized by monocytopenia, disseminated mycobacterial disease and opportunistic fungal and viral infections. A 33-year-old Japanese man was referred to our department with a 16-year history of numerous warts on his hands and legs. The lesions were first noticed on his finger and then spread to his palms and were unresponsive to cryotherapy. His medical history included anal canal cancer which was controlled with chemoradiation therapy, and myelodysplastic syndrome. He had no history of tuberculosis or recurrent bacterial, fungal or herpes infection. His parents were non-consanguineous and had been healthy. A physical examination revealed numerous verrucous nodules spreading over the fingers and the hands (Fig. 1a). They were also seen on his forearms, lower legs and feet. A reddish tumor on the right side of the anus (Fig. 1b) and lymphedema on his lower legs were also noted (Fig. 1c). Laboratory studies showed significant findings for anemia, leukopenia and thrombocytopenia. His white blood cell count revealed lymphopenia and no monocytes. A lymphocyte subpopulation analysis showed a reversal of the CD4/CD8 T cells. The CD16CD56 natural killer (NK) cell population was high range and the NK cell activity was elevated. Immunoglobulin levels were within normal range. A skin biopsy of the warts demonstrated prominent hyperkeratosis, papillomatosis and coarse keratohyalin granules. Immunohistochemistry was positive for anti-HPV antibody. CD4 T cells were decreased compared with CD8 cells around the warts. Histologically, the anal tumor was diagnosed as anal canal cancer. A novel frame-shift GATA2 mutation, c.1017+2T>C (p.Ser340Alafs*49) was detected from his DNA and RNA extracted from white blood cells. The parents did not have the same mutation. The diagnosis of GATA2 deficiency was established. With polymerase chain reaction analysis of HPV, types 2 (cutaneous genus), 36 (epidermodysplasia verruciformis [EV]type genus b) and 105 (EV-type genus b) were detected from