ERYTHEMA MULTIFORME; A CLINICAL PATHOGENETIC STUDY

我们以前对红斑的临床和病理研究 多形性(EM)已证明单纯疱疹病毒是 与EM密切相关的疱疹相关性EM(Hem)是 最常见的EM形式。我们进一步模糊了 复发的EM几乎总是与单纯疱疹病毒相关。在皮肤里 从EM的活动性病变中获得的我们检测到了HSV 特定的抗原。这种抗原，糖蛋白B(GB)是在 人角质形成细胞(HK)，这是血液中的损伤部位。 我们现在建议将我们的临床和病理研究扩展到 分子水平；使用分子病毒学技术 探讨单纯疱疹病毒在子宫内膜异位症中的作用。我们建议确定是否 单纯疱疹病毒通过检查受试者的黄褐色大衣在血液中传播， 内异症发作前、发作中和发作后。我们也希望 通过以下方法确定血肿患者皮肤中是否存在HSV潜伏 EM皮损和既往受累皮肤的检查 EM清理后的站点。为了完成这些研究，我们 已经准备了一种包括病毒DNA区域的核探针 这是对GB的编码。该探针是HSV特异性的，并且高度 对皮克级敏感。我们将使用机器人探测器在 原位杂交技术和斑点杂交技术 识别HSV。 我们假设皮肤损伤不仅仅是非 之前认为的特异性超敏反应，但是HSV特异性的 涉及宿主对在HK上表达的HSV抗原的反应。我们 建议使用几种模型来研究损伤的机制 细胞毒性。最后，我们建议研究 使用抗单纯疱疹病毒药物阿昔洛韦治疗EM 以抑制EM。

Our previous clinical and pathologic investigations of erythema multiforme (EM) have demonstrated that herpes simplex virus is closely linked to EM and that herpes-associated EM (HAEM) is the most commonly observed form of EM. We have further obsrved that recurrent EM is virtually always HSV associated. In the skin obtained from active lesions of EM we have detected a HSV specific antigen. The antigen, glycoprotein B (gB) is found within human keratinocytes (HK), which is the site of injury in HAEM. We now propose to extend our clinical and pathologic studies to the molecular level; using molecular virology techniques to investigate the role of HSV in EM. We propose to determine if HSV disseminates in HAEM by examining buffy coats of subjects, before, during and after episodes of EM. We also wish to determine if HSV is latent in the skin of patients with HAEM by examination of EM skin lesions and of previously involved skin sites after the EM has cleared. To complete these studies we have prepared a riboprobe which includes the region of viral DNA that encodes for gB. The probe is HSV-specific and highly sensitive to the picogram level. We will use the roboprobe for in situ hybridization techniques and dot-blot hybridization to identify HSV. We hypothesize that the cutaneous injury is not merely non- specific hypersensitivity as previously thought, but HSV-specific involving the host response to HSV antigens expressed on HK. We proposed to examine the mechanism of injury using several models of cytotoxicity. Finally, we propose to study the effect of therapeutic intervention in EM using an anti-HSV drug, acyclovir, to suppress EM.