Acquired EDV also may be associated with other conditions including renal transplantation, IgM deficiency, severe combined immunodeficiency, common variable immunodeficiency, systemic lupus erythematosus, and myasthenia gravis.2 Hematologic malignancies such as Hodgkin disease,4 natural killer/T-cell lymphoma,5 cutaneous T-cell lymphoma,6 adult T-cell leukemia,7 intestinal diffuse large B-cell lymphoma,8,9 transformed acute myelogenous lymphoma,10 and chronic myelogenous leukemia11 also may be associated with EDV. In the inherited form, integral membrane proteins of the endoplasmic reticulum encoded by the genes EVER1 and EVER2 on chromosome 17 are thought to act as restriction factors for certain types of HPV.2,3 Inactivating mutations in EVER1 and EVER2 result in defects in cell-mediated immunity, rendering patients susceptible to both benign and oncogenic verrucous infections.2,3 Currently, it is believed that immunosuppressed states may result in defects in cell-mediated immunity that make patients similarly susceptible to these virulent strains of HPV, resulting in an acquired form of EDV.3 Interestingly, the clinical and histologic presentation is identical for acquired EDV and genetic EDV.
Due to the general resistance of EDV to treatment, a variety of options for acquired EDV have been explored including topical and systemic retinoids, cryotherapy, interferon alfa‐2a, zidovudine, ketoconazole, corticosteroids, podophyllotoxin, imiquimod, cidofovir, electrosurgery, 5‐fluorouracil, glycolic acid, temporized diathermy, and methyl aminolevulinate photodynamic therapy.3 Highly active antiretroviral therapy has been proposed as a potential treatment modality for HIV-associated cases; however, acquired EDV has been reported to develop as an immune reconstitution inflammatory syndrome after the initiation of highly active antiretroviral therapy.15
Combination therapy consisting of a systemic retinoid, immunotherapy, and cryotherapy was initiated for our patient. Human papillomavirus infection is marked by epithelial hyperplasia, and retinoids induce antiproliferation through the control of epithelial cell differentiation.16 The specific mechanism of action of retinoids in EDV treatment is unknown; however, the beneficial effects may result from the modification of terminal differentiation, a direct antiviral action, or the enhancement of killer T cells.17 Immunotherapy with C albicans antigen initiates an inflammatory reaction that leads to an immune response directed against the virus, thus reducing the number of warts.2 Cryotherapy aims to destroy the lesion but not the virus.2 The combination of systemic retinoids, immunotherapy, and destruction may target EDV via multiple potentially synergistic mechanisms. Thus, a multimodal approach can be beneficial in patients with recalcitrant acquired EDV.
The occurrence of EDV is rare, and data on treatment are limited in number resulting in general uncertainty about the efficacy of therapies. Elucidation of the specific mechanism of immunosuppression and its effects on T lymphocytes in acquired EDV may shed light on the most effective treatments. We present this novel case of a patient with HIV-associated acquired EDV who responded favorably to a combination treatment of acitretin, intralesional C albicans antigen, and cryotherapy.