Dermatology Consultation Clinic and Clinical Research

2004年，皮肤科分支咨询服务评估了1 800名患者。所有接受评估的患者均参加了积极的NIH临床研究方案。许多患者存在由药物或其他干预引起的方案相关皮肤问题。对于其他患者，皮肤表现是综合征或疾病相关的。很少有患者出现与研究方案无关的皮肤病急性加重。大多数接受咨询服务的患者患有罕见疾病和/或正在参加创新的1期或2期试验。因此，在临床上遇到的皮肤问题往往是不寻常的，往往是复杂的。在时间上的聚类和所看到的患者的新奇为教育和临床研究工作提供了丰富而独特的资源。Cowen博士和我同样分享咨询服务的覆盖范围。凭借忙碌咨询服务，合作临床研究非常活跃。虽然大多数项目目前涉及我，主要是，考恩博士将越来越多地参与，现在他分担监督责任的咨询。合作项目包括对家族性肾细胞癌患者的皮肤发现如纤维毛囊瘤和平滑肌瘤的持续研究。我们也在研究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综合征）和NEMO基因突变相关免疫缺陷。在患有几种周期性发热综合征的患者中新发现的pyrin基因突变，以及在所产生的自身炎症性疾病中有效的生物疗法的可用性，为临床引入了一组新的患者。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。我们也在评估幼年型皮肌炎患者脂膜炎和钙沉积之间的关系，并评估强化全身治疗在预防阴燃性肌肉疾病和最终钙化方面的益处。Cowen博士和我不仅在NCI内部，而且在全国范围内积极参与多学科慢性GVHD联盟的开发和运营。这种参与使得可用于测量皮肤疾病的程度和进展/消退以及对治疗的反应的可重复和经验证的评估工具的缺乏变得明显。直到最近才认识到慢性GVHD导致女性生殖道的显著受累。我在外阴阴道疾病方面的专业知识使我能够研究外阴阴道GVHD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，得出了类似的结论，即缺乏评估工具。我们正在开发这样的工具，将允许量化的程度和严重程度的皮肤病在两个病人群体，强调工具，可以利用非皮肤科医生以及皮肤科医生，将拥抱和实施的校外研究人员参加多中心试验。皮肤科发起的项目是由分支主要研究者带头。Hwang博士正在通过题为“皮肤T细胞淋巴瘤的发病机制和病程”的方案（04-C-0081）评估CTCL患者。Hwang和Cowen博士已经启动了一项研究，以确定是否可以在肿瘤分期CTCL患者中识别血清蛋白质组特征（03-C-0228）

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)