Dermatology Consultation Clinic and Clinical Research

2004年，皮肤科会诊服务评估了1800名患者。所有被评估的患者都参加了活跃的NIH临床研究方案。许多患者存在由药物或其他干预措施引起的与方案相关的皮肤问题。对于其他患者，皮肤表现是综合征或疾病相关的。很少有患者表现出与治疗方案无关的皮肤病急性加重。咨询服务所照顾的大多数患者都患有罕见疾病和/或正在参加创新的1期或2期试验。因此，在诊所遇到的皮肤问题往往是不寻常的，往往是复杂的。时间的聚类和患者的新颖性为教育和临床研究提供了丰富而独特的资源。我和考恩医生平分咨询部的工作。由于会诊服务繁忙，协同临床研究非常活跃。虽然目前大多数项目主要由我参与，但考恩博士将越来越多地参与其中，因为他将分担咨询的监督责任。合作项目包括继续研究家族性肾细胞癌患者的皮肤表现，如纤维滤泡瘤和平滑肌瘤。我们还描述了可能与几种罕见的遗传性骨髓衰竭综合征相关的皮肤病变，包括Diamond-Blackfan、Fanconi贫血和先天性角化不良患者。我们继续研究原发性免疫缺陷患者的皮肤表现和治疗并发症，如慢性肉芽肿病、高ige综合征（Job’s综合征）和NEMO基因突变相关的免疫缺陷。在几种周期性发热综合征患者中新发现的pyrin基因突变，以及对由此产生的自身炎症性疾病有效的生物疗法的可用性，将一组新的患者引入了临床。我们现在正在系统地描述这些患者的皮肤表现，并评估对治疗的反应。我们还评估了青少年皮肌炎患者的全身膜炎和钙沉积之间的关系，并评估了强化全身治疗在预防阴燃肌肉疾病和最终钙化方面的益处。Cowen博士和我积极参与了一个多学科慢性GVHD联盟的发展和运作不仅在NCI，而且在全国范围内。这种参与显然缺乏可用于测量皮肤病的程度、进展/消退以及对治疗的反应的可重复和有效的评估工具。直到最近，人们才认识到慢性GVHD会严重影响女性生殖道。我在外阴阴道疾病方面的专业知识使我能够研究外阴阴道GVHD的表现和治疗。黄博士和我参加了一个多学科CTCL兴趣小组，得出了关于缺乏评估工具的类似结论。我们正在开发这样的工具，以便在两种患者群体中量化皮肤病的程度和严重程度，强调非皮肤科医生和皮肤科医生都可以使用的工具，并将被参与多中心试验的校外研究人员所接受和实施。皮肤科分部发起的项目由分部的首席研究员带头。Hwang博士正在通过一项名为“皮肤t细胞淋巴瘤的发病机制和病程”（04-C-0081）的方案评估CTCL患者。Drs。黄禹锡和考恩开始了一项研究，以确定是否可以在肿瘤期CTCL （03-C-0228）患者中识别血清蛋白质组学特征。

The Dermatology Branch consultation service evaluated 1800 patients in 2004. All patients evaluated are enrolled in active NIH clinical research protocols. Many patients present with protocol-associated cutaneous problems caused by drugs or other interventions. For other patients, cutaneous manifestations are syndromic or disease-associated. Rarely, patients exhibit acute exacerbations of skin diseases that are not protocol-related. Most patients cared for by the consultation service have rare diseases and/or are participating in innovative Phase 1 or 2 trials. Thus, skin problems encountered in the clinic tend to be unusual and are often complicated. The clustering in time and the novelty of patients that are seen provide a rich and unique resource for both educational and clinical research endeavors. Dr. Cowen and I share coverage of the Consult Service equally.Collaborative clinical research is extremely active by virtue of the busy consultation service. Although most projects currently involve me,predominantly, Dr. Cowen will become increasingly involved now that he shares supervisory responsibility for consultations. Collaborative projects include continuing studies of cutaneous findings such as fibrofolliculomas and leiomyomas in patients with familial renal cell carcinoma. We are also characterizing cutaneous lesions that may be associated with several rare inherited bone marrow failure syndromes, including patients with Diamond-Blackfan, Fanconi's anemia, and dyskeratosis congenita. We continue to study cutaneous manifestations and complications of therapy that are encountered in patients with primary immunodeficiencies such as chronic granulomatous disease, hyper-IgE syndrome (Job's syndrome), and immunodeficiency related to mutations in the NEMO gene. The newly discovered mutations in pyrin genes in patients with several periodic fever syndromes, and the availability of biologic therapies that have efficacy in the resulting autoinflammatory diseases have introduced a new group of patients to the clinic. We are now systematically characterizing cutaneous manifestations in these patients and assessing responses to treatment. We are also evaluating the relationship between panniculitis and calcium deposition in patients with juvenile dermatomyosistis and assessing the benefit of intensive systemic therapy in the prevention of smoldering muscle disease and eventual calcification. Dr. Cowen and I are actively involved in the development and operation of a multidisciplinary chronic GVHD consortium not only within NCI but nationally. This involvement has made obvious the lack of reproducible and validated assessment tools that can be used to measure extent and progression/regression of cutaneous disease and response to therapy. Only lately has it been recognized that chronic GVHD results in significant involvement in the female genital tract. My expertise in vulvovaginal diseases has enabled me to study the manifestations and treatment of vulvovginal GVHD. Dr. Hwang's and my participation in a multidisciplinary CTCL interest group has led to similar conclusions regarding the lack of assessment tools. We are in the process of developing such tools that will allow quantification of extent and severity of cutaneous disease in both patient populations, emphasizing tools that can be utilized by non-dermatologists as well as dermatologists and that will be embraced and implemented by extramural investigators participating in multi-center trials.Dermatology Branch-initiated projects are spearheaded by Branch principal investigators. Dr. Hwang is evaluating CTCL patients via a protocol entitled "Pathogenesis and course of cutaneous T-cell lymphoma" (04-C-0081). Drs. Hwang and Cowen have initiated a study to determine if serum proteomic signatures can be identified in patients who have tumor stage CTCL (03-C-0228).