Dermatology Consultation Clinic and Clinical Research

咨询服务由我本人、Edward Cowen博士（专职临床医生）和Heidi Kong博士（副研究员）组成。考恩医生和我自己看了很多会诊病人，孔医生每周负责一次半天的门诊。她正在接受临床试验的培训。如前所述，我们以副调查员的身份参与其他分支机构发起的一些协议，同时我们也是我们自己协议的首席调查员。Dr. Maria L. Turner：首席研究员外用罗米地辛治疗皮肤t细胞淋巴瘤（CTCL）的一期研究；CTCL疾病自然史；UVR/UVA光毒性测试。这些都是可以累积的。副研究员（皮肤科方案）肉毒杆菌治疗疼痛的平滑肌瘤；伊马替尼治疗硬化性GVHD；黑素细胞痣和黑色素瘤；护理标准；为研究副研究员（非真皮分支发起的试验）取样皮肤和血液：遗传性肾细胞癌（HLRCC）；人源抗tac治疗成人t细胞淋巴瘤（ATL）慢性GVHD的自然史研究Ontak为ATL；LMB-2治疗CD25+ CTCLI/II期钇治疗表达恶性肿瘤的Tac；正常人类志愿者的微生物组；特应性皮炎微生物组；自身炎症性疾病患者的研究方案；利妥昔滨滨皮肌炎/多肌炎。爱德华·考恩博士：首席研究员肉毒杆菌治疗疼痛性平滑肌瘤；伊马替尼治疗硬化性慢性GVHD副研究员（皮肤科方案）与M.L. Turner副研究员（非皮肤科方案）相同；恶性淋巴瘤/白血病的低强度移植；孟鲁司特II期治疗闭塞性细支气管炎；西罗莫司治疗考登症；血液恶性肿瘤的低强度移植。孔海迪博士：副研究员（皮肤科方案）-局部罗米地辛治疗CTCL的I期研究；UVR/UVA光毒性测试；助理调查主任（非皮肤科）规程).正常人类志愿者的微生物组；我和Heidi Kong博士完成了06-C0198方案一部分的招募和组织获取。这部分方案的目的是确定具有多西环素诱导的光毒性的正常受试者对太阳模拟UVR暴露的表皮反应的转录谱，并将其反应与其CYP450谱相关联。这些样品的微阵列已经完成，结果还有待分析。Kong博士和我已经开始招募早期皮肤t细胞淋巴瘤(CTCL)/真菌样霉菌病患者，以测试局部沉积肽（一种组蛋白去乙酰化酶抑制剂）治疗早期CTCL的安全性。这是一个毒性方案，我们目前的剂量水平为3，没有证据表明有毒性或有益。我们正在提交一项修正案，允许我们尝试在25平方厘米的皮肤上增加浓度，直到达到引起轻微刺激的浓度。一旦最大耐受剂量确定，我们将在更大范围内进行应用。海蒂·孔博士现在是副研究员，在我的监督下领导两项试验。孔博士和我继续与Julie Segre博士（NHGRI和测序中心）在探索人类皮肤微生物组的项目上合作。孔医生和我为患者选择提供临床专业知识而塞格雷医生负责分子生物学部门。对5名正常受试者皮肤微生物组的初步研究结果已经发表（见出版物清单）。我们今年最大的成就是在《科学》杂志上发表了一篇关于10名正常人类志愿者在20个不同地点的微生物组的文章。我们正在招募特应性皮炎、乔布斯综合征和耐甲氧西林金黄色葡萄球菌（MRSA）感染的患者。有很强的临床迹象表明，皮肤上金黄色葡萄球菌的存在会加剧和延续特应性皮炎。抗生素的使用也能使它平静下来。这种相互关系是如何起作用的，以及如何在不需要长期抗生素治疗的情况下改变它，这只是我们打算追求的一些问题。在未来，我们计划探索为什么晚期CTCL患者会受到皮肤葡萄球菌感染，以至于它即使不是最常见的死亡原因，也是非常常见的原因。慢性移植物抗宿主病（GVHD）的合作努力继续与爱德华·考恩博士集中在皮肤方面。他领导了慢性皮肤移植物抗宿主病（GVHD）的3项试验，将在本报告的项目部分进行描述。斯特拉顿博士是一名妇科医生，我和她继续评估和治疗患有慢性GVHD外阴阴道并发症的女性。这些活动产生了若干出版物，将分别列出。Cowen博士已成为公认的GVHD皮肤表现方面的专家，并在全国各地的各种团体（哈佛大学，塔夫茨大学，宾夕法尼亚大学，美国皮肤病学会，区域皮肤病学会和世界皮肤病大会）发表了关于皮肤GVHD的报告。由于会诊服务繁忙，协同临床研究非常活跃。Cowen博士越来越多地参与这些合作努力，现在他分享了咨询服务的覆盖范围。通过查看我们每个人参与的协议列表，可以看到合作项目。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PAPA综合征、Behcets和DIRA患者的皮肤表现，并评估对治疗的反应。我们也在评估青少年皮肌病患者的皮肌炎和钙沉积之间的关系，并评估利妥昔单抗在这种疾病中的益处。Cowen博士和我积极参与了NCI乃至全国范围内多学科慢性移植物抗宿主病（GVHD）联盟的持续运作。他是研究伊马替尼在治疗与慢性GVHD相关的硬化性皮肤疾病中的有效性的新方案的首席研究员。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。黄禹锡博士离开后，我接手了CTCL的自然历史方案。我与Susan Bates博士合作，她是使用全身性抑郁肽治疗晚期CTCL/PTCL的PI，导致了depsipeptide被食品和药物管理局批准用于这一适应症

The Consult Service consists of myself, Dr. Edward Cowen (Staff Clinician) and Dr. Heidi Kong (Associate Investigator). Dr. Cowen and myself see the bulk of the consult patients with Dr. Kong taking care of a half day clinic once a week. She is in training to do clinical trials. As previously stated, we participate as Associate Investigators in some protocols initiated by other branches at the same time that we are Principal Investigators on our own protocols. Dr. Maria L. Turner: Principal Investigator Phase 1 study of topical romidepsin in Cutaneous T-Cell Lymphoma (CTCL); CTCL natural history of disease; UVR/UVA phototoxicity testing . These are all open to accrual. Associate Investigator (Dermatology Branch protocols) Botox for painful leiomyomas; Imatinib for sclerotic GVHD; Melanocytic nevi and melanoma; Standard of care; Sampling skin and blood for research Associate Investigator (non-Derm Branch initiated trials): Hereditary Renal Cell Carcinoma (HLRCC); Humanized anti-TAC for Adult T-cell Lymphoma (ATL); Natural History of Chronic GVHD; Ontak for ATL; Treatment of CD25+ CTCL with LMB-2; Phase I/II Yttrium for Tac expressing malignancies; Microbiome in normal human volunteers; Microbiome in atopic dermatitis; protocols on the study of patients with autoinflammatory diseases;Rituximabindermatomyositis/polymyositis. Dr. Edward Cowen: Principal Investigator Botox for painful leiomyomas; Imatinib for sclerotic chronic GVHD Associate Investigator (Dermatology Branch protocols) same as M.L. Turner Associate Investigator (non-Dermatology Branch protocols) Natural History of GVHD; Reduced intensity transplants for malignant lymphomas/leukemias; Phase II Montelukast for bronchiolitis obliterans; Sirolimus for Cowdens; Reduced intensity transplants for hematologic malignancies. Dr. Heidi Kong: Associate Investigator (Derm Branch protocols) - Phase I study of topical romidepsin for CTCL; UVR/UVA phototoxicity testing; Associate Investigatory (Non-Derm Br. Protocols) - Microbiome in normal human volunteers; Microbiome in atopic dermatitis Dr. Heidi Kong and I finished the recruitment and tissue acquisition for one part of protocol 06-C0198. This part of the protocol had for its aim to determine the transcriptional profile of the epidermal response to solar-simulated UVR exposure in normal subjects with doxycycline-induced phototoxicity and relating their reactions to their CYP450 profiles. The microarrays from these samples have been done and results remain to be analyzed. Dr. Kong and I have started recruiting patients with early cutaneous T-cell lymphoma (CTCL)/mycosis fungoides to a new protocol testing the safety of topical depsipeptide (a histone deacetylase inhibitor) for the treatment of early CTCL. This is a toxicity protocol and we are currently at dose level 3, with no evidence of toxicity nor benefit. We are in the process of submitting an amendment to allow us to try increasing concentrations over 25 sq cm of skin until we get to the concentration that cause mild irritation. Once the maximal tolerated dose is determined, we will proceed to applications over larger areas. Dr. Heidi Kong is now an associate investigator and is spearheading both trials under my supervision. Dr. Kong and I continue to collaborate with Dr. Julie Segre (NHGRI and Sequencing Center) on projects exploring the human cutaneous microbiome. Dr. Kong and I provide the clinical expertise for patient selection while Dr. Segre is responsible for the molecular biology arm. The results of a pilot study of the cutaneous microbiome in 5 normal subjects has already been published (see list of publications). Our biggest achievement this year was a publication in Science of the microbiome at 20 different sites in 10 normal human volunteers. We are well into recruitment of patients with atopic dermatitis, Jobs syndrome and methicillin resistant staphylococcus aureus (MRSA) infection. There are strong clinical indications that atopic dermatitis is exacerbated and perpetuated by the presence of staphylococcus aureus on the skin. It also is calmed by the administration of antibiotics. How this interrelationship works and how it can be altered without the need for long-term antibiotic therapy are just some of the questions that we intend to pursue. In the future, we plan to explore why patients with late CTCL are subject to skin staphylococcal infections such that it is a very common if not the most common cause their death. The chronic graft versus host disease (GVHD) collaborative effort continues with Dr. Edward Cowen concentrating on the cutaneous aspects. He is spearheading 3 trials on chronic cutaneous graft versus host disease (GVHD)which will be described in the project section of this report. Dr. Stratton, a gynecologist, and I continue to evaluate and treat women with vulvo-vaginal complications of chronic GVHD. These activities have resulted in several publications that will be listed separately. Dr. Cowen has become recognized as an expert on the cutaneous manifestations of GVHD publishing and giving presentations on cutaneous GVHD to various groups around the country (Harvard, Tufts, U. of Pennsylvania, the American Academy of Dermatology, regional dermatologic societies, and the World Congress of Dermatology.) Collaborative clinical research is extremely active by virtue of the busy consultation service. Dr. Cowen has become increasingly involved in these collaborative efforts, now that he shares in the coverage of the Consultation Service. Collaborative projects can be seen by looking at the list of protocols that each of us are involved in. 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 and assessing responses to treatment in patients with PAPA syndrome, Behcets and DIRA. We are also evaluating the relationship between panniculitis and calcium deposition in patients with juvenile dermatomyosistis and assessing the benefit of Rituximab in this disease. Dr. Cowen and I are actively involved in the continuing operation of the multidisciplinary chronic graft versus host disease (GVHD) consortium not only within NCI but nationally. He is the Principal Investigator on a new protocol investigating the usefulness of Imatinib in the treatment of sclerotic skin disease associated with chronic GVHD. 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. Since Dr. Hwang left, I have taken over the Natural History of CTCL protocol. My cooperative efforts with Dr. Susan Bates, who was the PI on the use of systemic depsipeptide for late CTCL/PTCL has resulted in the approval of Depsipeptide for this indication by the Food and Drug Administration