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中光敏性的遗传学（由VA Merit Review支持），以及LE新疗法开发所需的基本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测量方法。我们目前发表的针对少数患者和皮肤科医生的研究表明，皮肤红斑狼疮疾病活动性和严重程度指数（CLASI）测量皮肤红斑狼疮活动性和损伤，具有良好的患者间和患者内变异性。重要的是扩大目前已经完成的研究，以纳入更多的患者，包括那些皮肤急性LE改变的患者，与更多的皮肤科医生一起验证CLASI，并将研究扩展到风湿病学家。拟议的研究将允许进展到Aim II，除了生活质量研究和POR转化研究外，还包括使用CLASI来评估大量皮肤LE患者的转诊人群。目的二世。需要新干预措施的皮肤红斑狼疮临床严重程度的患病率，皮肤LE的生活质量（QOL）测量以及CLASI与QOL测量的相关性。目前有许多新的治疗方法应该在皮肤LE患者中进行试验。我们最近完成的一项前瞻性研究显示，在药物干预后，CLASI的反应性很好。CLASI的改善与患者和医生整体皮肤健康指标的改善相关。随着该仪器最近的可用性，可以量化皮肤特异性LE疾病的活动性和损伤，以及皮肤特异性的生活质量（QOL）指数（Skindex 29），并且在Aim I中提出的进一步验证研究之后，现在可以评估使用现有药物的患者的疾病严重程度。因此，在本应用中，建议使用量化皮肤病活动性和生活质量测量的工具来横断面评估皮肤LE亚群。目的是检查皮肤LE的不同亚群的严重程度，它们的生活质量，以及生活质量测量与CLASI的相关性。特别是，有必要评估目前有多少严重皮肤LE患者在使用现有药物的情况下仍出现严重疾病，以便评估新疗法的需求并设计新药物的试验。这将有助于未来的遗传，重点微阵列和PCR研究，以及与皮肤红斑狼疮亚群相关的机制研究。这些研究将允许进一步仔细验证CLASI，并有助于规划未来的试验。

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.