Risk Factors for Eczema Vaccinatum in Atopic Dermatitis

描述（由申请方提供）：重新关注天花病毒可能被用作生物恐怖剂，导致早期实施有限的疫苗接种计划。由于牛痘湿疹是牛痘疫苗的一种令人担忧的并发症，因此严格的标准将目前患有特应性皮炎（AD）或先前患有AD的人，甚至患有AD的人的密切接触者排除在疫苗接种之外。据估计，上述标准将至少50%的美国现有人口排除在自愿免疫之外。但是，在发生生物恐怖主义袭击的情况下，这种排除标准不能维持，因为必须立即开始大规模接种疫苗，以防止病毒的进一步传播。本提案的目的是根据免疫遗传学标准（流行假设）或基于表皮屏障功能异常的替代假设，确定AD的哪些临床亚组有发生牛痘并发症的风险。 已经提出了两种病理生理机制来解释AD患者发生细菌和病毒感染的倾向增加。一种假设假定AD是遗传性免疫缺陷的外部表现，而我们怀疑它可能是皮肤的抗微生物/渗透性屏障，主要是AD中病毒传播的原因。本研究将首先确定谁患牛痘性湿疹的风险最高，比较各种假定的AD临床亚组的皮肤屏障功能测量和生化参数，以确定渗透屏障状态。在相同的AD队列中，我们将同时评估一组异常TH 2细胞功能的免疫遗传标记，包括IL-4、-5、-13、-18和IFN γ的改变。这些研究的结果将首先允许医生使用一种或两种方法来确定谁是接种性湿疹的最高风险。其次，这些研究将可能使医生对患有AD或相关疾病亚组但仍需要牛痘疫苗的患者进行预治疗，以降低牛痘湿疹的风险。 总之，本研究的短期目标是确定哪些患有AD或有AD病史的人可以安全地接受牛痘疫苗;并确定皮肤预处理是否降低必须接受牛痘疫苗的高危患者的牛痘湿疹风险。本研究的长期目标是确定表皮抗菌和渗透屏障缺陷与免疫遗传异常对AD患者发生播散性病毒感染的相对贡献。

DESCRIPTION (provided by applicant): Renewed concern that smallpox virus might be employed as a bioterrorism agent has led to an early implementation of a limited vaccination program. Because eczema vaccinatum is a feared complication of the Vaccinia vaccine, stringent criteria have excluded persons who currently suffer from atopic dermatitis (AD), or who have previously suffered from AD, and even close contacts of persons who have AD, from vaccination. The above criteria are estimated to exclude at least 50% of the current US population from voluntary immunization. In the event of a bioterrorism attack, however, such exclusion criteria could not be maintained, since mass vaccination would have to be initiated immediately to prevent further spread of the virus. The goal of this proposal is to identify which clinical subgroups of AD are at risk for Vaccinia complications, based upon either immunogenetic criteria (the prevailing hypothesis), or an alternate hypothesis, based upon abnormalities in epidermal barrier function. Two pathophysiologic mechanisms have been proposed to explain the increased propensity of persons with AD to develop bacterial and viiral infections. One hypothesis postulates that AD is an external manifestation of inherited immune defects, while alternatively we suspect that it could be the skin's antimicrobial/permeability barrier that primarily account for viral dissemination in AD. This study will first determine who is at the highest risk of developing eczema vaccinatum, comparing skin barrier functional measure-ments and biochemical parameters in various putative AD clinical subgroups to determine permeability barrier status. In the same AD cohorts, we will simultaneously assess a panel of immuno-genetic markers of abnormal TH2 cell function, including alterations in IL-4, -5, -13, -18, and IFN gamma. Results of these studies will first, alllow physicians to use the one or both approaches to determine who is at the highest risk for eczema vaccinatum. Second, these studies will potentially allow physicians to pretreat patients who have AD or related disease subgroups, but still require the Vaccinia vaccine, to decrease the risk in the eczema vaccinatum. In summary, the short-term goals of this study are to determine which persons suffering from AD or a history of AD can safely receive the Vaccinia vaccine; and to determine if skin pretreatment decreases the risk of eczema vaccinatum in patients at high risk who must receive the Vacciniia vaccine. The long-term goals of this study are to determine the relative contributions of epidermal antimicrobial and permeability barrier defects vs. immunogenetic abnormalities for the development of disseminated viral infections in patients with AD.