Human papillomavirus evaluation of vemurafenib‐induced skin epithelial tumors: a case series

apoptosis. Off-label uses include pemphigus vulgaris (PV), mucosal membrane pemphigoid, paraneoplastic pemphigus and chronic graft-versus-host disease. Mucosal membrane diseases can be devastatingly destructive and in some cases fatal. PV of the epiglottis treated with rituximab was recently reported. The mechanism by which rituximab improves T cell-mediated LP is difficult to explain as it suggests B cells are implicated in the pathogenesis of LP. The majority of intraepithelial lymphocytes in oral LP are CD8 cytotoxic T cells, but most lymphocytes in the lamina propria are CD4 helper T (Th) cells. CD8 cytotoxic T cells may be activated by the combination of antigen associated with major histocompatibility complex class I on basal keratinocytes and Th1 CD4 T cellderived interleukin (IL)-2 and interferon-c. In RA, Melet et al. found rituximab caused a durable, reversible depletion of peripheral CD4 and CD8 T cells. Rituximab efficacy in PV is probably due to B-cell depletion resulting in decreased desmoglein (Dsg)-specific autoantibodies. PV pathogenesis likely involves both autoreactive Th1 and Th2 cells to promote autoantibody secretion by Dsg3-reactive B cells. Dsg3-specific T cells have also been demonstrated to release IL-4, IL-6 and IL-10. Rituximab may also affect autoreactive T cells and the production of T cell-modulating cytokines, autoantigen processing and the presentation of B cells. Rituximab may exhibit a dual effect in PV by depleting CD20 autoreactive B cells as progenitors of autoantibody secreting plasma cells and indirectly by decreasing the frequency of autoreactive CD4 T cells via depletion of B cells. It was hypothesized that regulatory B cells observed postrituximab could be responsible for the downregulation of Dsg-specific CD4 T cells through the secretion of IL-10. We report two cases of erosive LP successfully treated with the RA rituximab protocol. Conversely, cases of rituximabinduced LP are reported. Further investigation in prospective clinical trials is warranted.