Dermatology Consultation Clinic and Clinical Research

皮肤科会诊服务在2004年评估了1800名患者。所有接受评估的患者都参加了NIH活跃的临床研究方案。许多患者存在由药物或其他干预措施引起的与协议相关的皮肤问题。对于其他患者，皮肤表现为综合征或与疾病相关。很少有患者表现出与礼仪无关的皮肤病急性加重。咨询服务照顾的大多数患者患有罕见疾病和/或正在参与创新的1期或2期试验。因此，临床上遇到的皮肤问题往往是不寻常的，往往是复杂的。时间上的聚集和患者的新颖性为教育和临床研究努力提供了丰富和独特的资源。考恩博士和我平等地分享咨询服务的覆盖范围。由于忙碌的咨询服务，协作临床研究非常活跃。虽然目前大多数项目都涉及我，但主要是考恩博士，因为他分担了咨询的监督责任，所以他将越来越多地参与其中。合作项目包括对家族性肾细胞癌患者的皮肤表现进行持续研究，如纤维滤泡瘤和肌瘤。我们还确定了可能与几种罕见的遗传性骨髓衰竭综合征相关的皮肤损害的特征，包括钻石-布莱克范、范可尼贫血和先天性角化不良患者。我们继续研究原发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(约伯氏综合征)和与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吡喃基因突变，以及对由此产生的自体炎症疾病有效的生物疗法的可获得性，将一组新的患者引入临床。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。我们还在评估青少年皮肌炎患者脂膜炎与钙沉积的关系，并评估强化系统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内部，而且在全国范围内。这种参与显然表明，缺乏可用于衡量皮肤病的程度和进展/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会导致女性生殖道严重受累。我在外阴阴道疾病方面的专业知识使我能够研究外阴移植物抗宿主病的表现和治疗。黄博士和我参加了一个多学科的CTCL兴趣小组，导致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，可以量化两个患者群体中皮肤病的程度和严重程度，强调可供非皮肤科医生和皮肤科医生使用的工具，并将被参与多中心试验的外部研究人员接受和实施。皮肤科发起的项目由皮肤科主要研究人员带头。Hwang博士正在通过名为“皮肤T细胞淋巴瘤的发病机制和病程”的方案对CTCL患者进行评估(04-C-0081)。Hwang博士和Cowen博士发起了一项研究，以确定是否可以在肿瘤分期为CTCL(03-C-0228)的患者中识别血清蛋白质组特征。

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)