Vulvar Vestibulitis Syndrome (VVS) is a chronic inflammatory condition affecting the vestibular epithelium of the vulva, which has been estimated to affect 15% of the female population (Goetsch, 1991 ). Many studies have attempted unsuccessfully, to elucidate the cause of this condition, and few advances have been made towards the understanding of the associated inflammatory response. The initial, and principal aim of this investigation was to characterise normal vestibular epithelium using electron microscopy. The ultrastructural characteristics of normal vestibular epithelium were compared with closely related epithelia, and with vestibular epithelia from VVS patients. Other aims included an investigation of the epidemiological characteristics of VVS; an assessment of vulvar sensitivity over several months, and an evaluation of ketoconazole as a non-invasive treatment for VVS. Transmission electron microscopy, confirmed that vestibular epithelium was non-keratinised, and closely resembled oral and vaginal mucosae. Intermediate cells were predominant, characterised by pale staining cytokeratin filaments and glycogen deposits. Leukocytes were present in small numbers. Using SEM, superficial cells were characterised by an interlacing network of rounded microridges. By comparison, vestibular epithelium from VVS patients demonstrated the presence of numerous, intensely staining, apoptotic-like cells. These cells were associated with membrane bound cytoplasmic lobules and leukocytes of varying types. A similar ultrastructural appearance was observed in post-treatment biopsies. However, apoptotic-like cells appeared heavily vacuolated, and the number of cytoplasmic bodies present was increased. Mature plasma cells, NK-like cells and macrophages were common in the dermis. Leukocyte counts, demonstrated a significantly greater number of leukocytes in the VVS biopsies compared with the controls, however, there was no statistical difference in the number of leukocytes in pre and post-treatment samples. The presence of apoptotic-like cells accompanied by a significant inflammatory cell infiltrate, may suggest a cell signalling defect, resulting in the pain associated with VVS. Treatment with ketoconazole cream was found to have very little effect on either the number of leukocytes or the frequency of apoptotic-like cells as quantified using image analysis. The epidemiological characteristics of VVS patients were investigated using a structured questionnaire interview. All of the VVS patients interviewed fulfilled the diagnostic criteria established by Friedrich ( 1987), and epidemiological findings were generally consistent with previous epidemiological reports. Unique to this study, HPV infections were rare, however recurrent Candida infections and cystitis were commonly reported. The 'Vulvar Algesiometer', was designed and developed in Plymouth, to assist diagnosis and assessment of VVS patients. Using this equipment, VVS patients demonstrate heightened vestibular sensitivity when compared with control patients. The utilisation of a pain measuring device the 'Vulvar Algesiometer', in accordance with the questionnaire and ultrastructural investigation has formed a novel and balanced approach to the study of VVS. This study has demonstrated several distinct features of VVS which have not previously been described, features which may be important in elucidating the cause of this condition. These features centre around the presence of apoptotic-like cells and associated cytoplasmic bodies which have not previously been described in association with VVS.

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