GENOTYPE CORRELATES AND CLINICAL TRIALS IN INHERITED EB

遗传性大疱性表皮松解症(EB)包括那些以机械脆弱的皮肤和水泡形成倾向为特征的疾病。截至1998年5月，已描述了四个主要类型，至少23个表型独特的亚型，以及至少200个不同的基因类型。现在，3,000多名临床特征良好的EB患者已经通过国家EB注册中心收集起来，我们建议使用注册中心和K24奖的机制，试图解决几个临床相关和及时的问题，包括(1)遗传性EB的主要类型和次要类型以及亚型之间的表型-基因型相关性，以及那些具有特殊预后或治疗意义的基因类型的识别。(2)启动一项前瞻性介入性临床试验，以评估异维A酸或另一种全身性维甲酸作为化学预防药物在那些至少发展了一种此类肿瘤的RDEB-HS患者中可能的有益作用，以防止更多的鳞状细胞癌的发展；(3)启动一项或多项其他临床试验，以确定选定的内科或外科干预措施对患有较严重EB的患者的疗效(如果有的话)，包括(A)早期选择性胃造口术，(B)手夹板，(C)一种或多种局部细胞因子制剂的使用和/或较新的伤口愈合敷料，(D)局部或全身抗氧化剂的使用，以及(E)积极的营养补充；以及(4)遗传性严重全身性EB患者的基线代谢和营养参数的特点。希望这几项拟议临床研究的结果将为EB患者的管理提供新的见解，并提供一种极好的手段，使对以患者为中心的研究感兴趣的年轻研究人员能够得到指导和培训。

Inherited epidermolysis bullosa (EB) encompasses those diseases characterized by mechanically fragile skin and the tendency for blister formation. As of May 1998, four major types, at least 23 phenotypically distinctive subtypes, and at least 200 different genotypes have been described. Now that over 3,000 clinically well characterized patients with EB have been assembled via the National EB Registry, we propose to use the Registry, and the mechanism of a K24 Award, to attempt to address several clinically relevant and timely issues, to include (1) phenotype - genotype correlations across both major and minor types and subtypes of inherited EB, and the identification of those genotypes which have specific prognostic or therapeutic significance., (2) initiation of a prospective interventional clinical trial to assess the possible beneficial role of isotretinoin or another systemic retinoid as a chemopreventive agent against the development of additional squamous cell carcinomas in those patients with RDEB-HS who have developed at least one such tumor; (3) initiation of one or more other clinical trials to determine the benefit, if any, in the performance of selected medical or surgical interventions in groups of patients having more severe forms of EB, to include (a) early elective gastrostomy placement, (b) hand splinting, (c) use of one or more topical cytokine preparations and/or newer wound, healing dressings, (d) the use of topical or systemic antioxidant agents, and (e) aggressive nutritional supplementation; and (4) characterization of baseline metabolic and nutritional parameters in patients with severe generalized forms of inherited EB. It is hoped that the results of these several proposed clinical studies will provide new insights into the management of patients with EB, as well as provide an excellent means whereby young investigators interested in patient-oriented research can be mentored and trained.