Diagnostic and treatment landscape of pyoderma gangrenosum

坏疽脓皮病(PG)是一种罕见的慢性炎症性疾病，以疼痛的皮肤溃疡为表现。它 会导致毁容，对生活质量产生负面影响，并增加死亡率。尽管是一种疾病， 尽管它具有重大的生理和心理影响，但仍未得到充分的研究。中国临床研究的匮乏 这可能是由于诊断方面的挑战和未知的治疗结果造成的。误诊，据报道 在高达39%的患者中，一直是正确实施和登记临床的主要障碍之一 审判。由于分子诊断仍需数年时间，研究人员依靠临床标准进行诊断。三 现有的诊断框架是基于临床结果的，但它们并没有被广泛应用或接受。 此外，PG的主要治疗方法是免疫抑制。全身糖皮质激素的单一治疗 或环孢素是经典的初始治疗方法，只有少数临床试验评估了其有效性 以及生物制剂等新的治疗替代品的安全性。此外，联合或伴随治疗 在没有高质量数据的情况下，经典的免疫抑制和生物制品已被采纳为新的护理标准。 目前的治疗方法是基于专家意见指南，这增加了治疗的难度 实施临床试验，阻碍FDA对潜在药物的审批过程。 我们的建议与我们研究小组的总体长期目标一致：推动诊断和治疗 PG领域的创新--这是一种研究严重不足的疾病，增加了医疗负担。我们的 短期目标包括：1)确定哪个诊断框架在多机构中执行得最好 协作研究，支持其在医疗实践和临床试验中的适用性；2)分析当前 临床实践中的治疗结果。我们寻求通过以下具体措施来实现我们的短期目标 目的：目的1)在一项多中心前瞻性研究中，比较和评估三种诊断框架。 确定诊断为PG和PG样疾病的患者的队列，以确定他们在诊断中的表现， 和目标2)确定当前作为护理标准使用的现实世界治疗方法的有效性 在PG患者的多中心队列中。 我们在OHSU建立的PG研究团队有能力实施多机构合作努力 以确保这项提议的成功。总体而言，该项目的结果将填补诊断和治疗 知识上的差距，并定义了美国PG的现状。

Pyoderma gangrenosum (PG) is a rare, chronic, inflammatory disorder that presents with painful skin ulcers. It causes disfiguration, negatively impacts quality of life, and increases mortality. Despite being a disease with significant physical and psychological impact, it remains understudied. The paucity of clinical research in the field is likely due to challenges in diagnosis and unknown treatment outcomes. Misdiagnosis, which is reported in up to 39% of patients, has been one of the main obstacles to proper implementation and enrollment in clinical trials. Because molecular diagnostics remain years away, researchers rely on clinical criteria for diagnosis. Three diagnostic frameworks exist based on clinical findings, however they are not widely applied or accepted. Moreover, the mainstay of treatment for PG is immunosuppression. Monotherapy with systemic corticosteroids or cyclosporine is the classical initial treatment, and only a few clinical trials have evaluated the effectiveness and safety of new therapeutic alternatives such as biologics. Further, combination or concomitant therapy of classic immunosuppression and biologics has been adopted as a new standard of care without high-quality data. Current therapeutic approaches are based on expert opinion guidelines creating additional difficulty in implementing clinical trials and hampering the FDA approval process of potential drugs. Our proposal aligns with the overall long-term goals of our research group: to drive diagnostic and therapeutic innovation in the field of PG – a significantly understudied disease with an increased healthcare burden. Our short-term goals include: 1) to establish which diagnostic framework best performs in a multi-institutional collaborative study, supporting its applicability in medical practice and clinical trials, and 2) to analyze current treatment outcomes in clinical practice. We seek to accomplish our short-term goals utilizing the following specific aims: Aim 1) compare and assess the three diagnostic frameworks in a multi-center prospective study of a well- defined cohort of patients diagnosed with PG and PG-like conditions to determine their performance in diagnosis, and Aim 2) determine the effectiveness of real-world therapeutic approaches currently used as standard of care in a multi-center cohort of patients with PG. Our established PG research team at OHSU has the ability to implement a multi-institutional collaborative effort to ensure the success of this proposal. Collectively, the results of this project will fill the diagnostic and therapeutic gaps in knowledge and define the current landscape of PG in the United States.