Recalcitrant Pseudotumoral Anogenital Herpes Simplex Virus Type 2 in HIV-Infected Patients: Evidence for Predominant B-Lymphoplasmocytic Infiltration and Immunomodulators as Effective Therapeutic Strategy

Background In patients with human immunodeficiency virus (HIV) infection, genital herpetic lesions may be extensive and tend to persist for longer periods; in addition, atypical hypertrophic, ulcerative, or pseudotumor forms have been reported, frequently showing resistance to acyclovir (ACV) treatment. Methods Between 2003 and 2011, 10 HIV-1-infected patients presenting with chronic pseudotumoral anogenital herpes simplex type 2 (HSV-2) infections were studied. Results All patients developed chronic, hypertrophic HSV-2 anogenital lesions with multilesional presentation in 7 cases and involvement of 2 anatomical sites in 6 of them. At the time of diagnosis, the median CD3(+)CD4(+) absolute blood count was 480.5 cells/µL (range, 165-632 cells/µL), whereas the plasma HIV load was undetectable in all cases. Histopathologic analysis of lesion biopsies showed a moderately dense dermal polytypic plasma cell infiltrate. Detection of HSV-2 by culture and/or polymerase chain reaction was positive for all patients, with evidence for ACV-resistant strains in 6 of 8 cases. In addition, viral resistance to ACV was found only in HSV-2 isolated from ulcerative lesions, whereas purely pseudotumoral ones harbored sensitive strains. Durable control was observed with HSV DNA polymerase inhibitors in only 2 cases, and the immunomodulators imiquimod and thalidomide allowed 5 patients to reach sustained complete response. Conclusions HSV-2-related pseudolymphoma in HIV-infected patients is characterized by a predominant polyclonal lymphoplasmacytic infiltration, and is frequently refractory to antiherpetic drugs. Immunomodulatory therapeutic strategies using thalidomide showed consistent efficacy, and should be considered early during the course of disease.