Patient-oriented research in skin autoimmune disease

描述（由申请人提供）：本提案的科学重点是红斑狼疮（LE）的患者导向研究（POR）。我们的实验室研究LE光敏性的遗传学（由VA Merit Review支持），以及开发LE新疗法所需的基本POR（当前提案）。我们最近的研究正在开发和验证测量皮肤LE活动和严重程度所需的结果指标。艾姆岛评估者间和评估者内验证研究的扩展我们目前发表的对少数患者和评估皮肤科医生的研究表明，皮肤红斑狼疮疾病活动和严重程度指数（CLASI）测量皮肤LE活动和损伤具有良好的评估者间和评估者内变异性。重要的是要扩大目前已经完成的研究，以包括更多的患者，包括那些急性LE变化的皮肤，以验证CLASI与更多的皮肤科医生，并扩大研究，包括风湿病学家。拟议的研究将允许进展到目标II，除了生活质量研究和POR转化研究外，还包括使用CLASI评价大量皮肤LE患者的转诊人群。Aim II.需要新干预的皮肤红斑狼疮临床严重程度的患病率、皮肤红斑狼疮的生活质量（QOL）测量以及CLASI与QOL测量的相关性。目前有许多新的疗法，应测试皮肤LE患者。我们最近完成的一项前瞻性研究显示，药物干预后CLASI的反应性极佳。CLASI的改善与患者和医生的皮肤健康总体指标的改善相关。随着该仪器最近可用于量化皮肤特异性LE疾病活动和损伤，以及皮肤特异性生活质量（QOL）指数（Skindex 29），以及在目标I中提出的进一步验证研究后，现在可以评估使用当前可用药物的患者的疾病严重程度。因此，在本申请中提出使用用于量化皮肤疾病活动和QOL测量的工具来横截面评估皮肤LE的子集。其目的是检查皮肤LE的各种子集的严重程度、其QOL以及QOL测量与CLASI的相关性。特别是，有必要评估有多少严重皮肤LE患者目前正在经历重大疾病，尽管使用现有的药物，以评估新的治疗方法的需要，并设计新的药物试验。这将有利于未来的遗传，集中的微阵列和PCR研究，以及机制的研究有关的皮肤红斑狼疮的子集。这些研究将允许进一步仔细验证CLASI，并帮助规划未来的试验。

DESCRIPTION (provided by applicant): The scientific focus of this proposal is patient-oriented research (POR) in lupus erythematosus (LE). Our laboratory studies the genetics of photosensitivity in LE (supported by a VA Merit Review), as well as fundamental POR needed for development of new therapies in LE (the current proposal). Our recent studies are developing and validating outcome measures needed for measuring cutaneous LE activity and severity. Aim I. Expansion of inter-rater and intra-rater validation studies Our current published studies with a small number of patients and evaluating dermatologists suggest excellent inter-rater and intra-rater variability with the cutaneous lupus erythematosus disease activity and severity index (CLASI) measure of cutaneous LE activity and damage. It is important to expand the current studies that have been done to include more patients, including those with acute LE changes in the skin, to validate the CLASI with both more dermatologists, and to extend the studies to include rheumatologists. The proposed studies will allow progression to Aim II, which involves use of the CLASI to evaluate large referral populations of cutaneous LE patients, in addition to quality of life studies and POR translational studies. Aim II. Prevalence of clinical severity of cutaneous lupus erythematosus requiring novel interventions, quality of life (QOL) measurement of cutaneous LE and the correlation of the CLASI with QOL measurement. There are currently a number of new therapies that should be tested in patients with cutaneous LE. A prospective study we recently completed showed excellent responsiveness of the CLASI after drug intervention. Improvement in the CLASI correlated with improvement in both patient and physician global measures of skin health. With the recent availability of this instrument to quantify skin-specific LE disease activity and damage, as well as a quality of life (QOL) index specific to skin (Skindex 29), and after further validation studies proposed in Aim I, it is now possible to evaluate the severity of disease in patients who are using currently available drugs. Thus, it is proposed in this application to use tools for quantifying skin disease activity and QOL measurements to cross-sectionally evaluate subsets of cutaneous LE. The purpose will be to examine the severity of various subsets of cutaneous LE, their QOL, and the correlation of the QOL measures with the CLASI. In particular, it is necessary to evaluate how many patients with severe cutaneous LE are currently experiencing significant disease despite use of available agents, in order to assess the need for new therapies and to design trials of new agents. This will facilitate future genetic, focused microarray and PCR studies, as well as mechanistic studies related to subsets of cutaneous lupus erythematosus. These studies will allow further careful validation of the CLASI, as well as aid in planning of future trials.