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Janus Kinase Inhibitors: A Review of Their Emerging Applications in Dermatology Janus激酶抑制剂:在皮肤病学中的新应用综述
Q1 Medicine Pub Date : 2018-05-01
A Cinats, E Heck, L Robertson

The class of medications known as Janus kinase inhibitors block cytokine-mediated signaling via the Janus kinase-signal transducer and activator of transcription (JAK-STAT) pathway, which plays an important role in immunoregulation and normal cell growth. This class includes the drugs tofacitinib, approved for the treatment of rheumatoid arthritis, and ruxolitinib, approved for the treatment of myelofibrosis and polycythemia rubra vera. The most common adverse events (AEs) reported in patients taking tofacitinib are infections, whereas the most common AEs in patients taking ruxolitinib are anemia and thrombocytopenia. Both first and second generation Janus kinase inhibitors have become promising treatment modalities for dermatologic conditions such as psoriasis, atopic dermatitis, alopecia areata, vilitigo, dermatomyositis, and graft-versus-host disease. Future promising areas of investigation include treatment of cutaneous lupus, cutaneous T-cell lymphoma, melanoma, allergic contact dermatitis, and lichen planus.

一类被称为Janus激酶抑制剂的药物通过Janus激酶信号转导和转录激活因子(JAK-STAT)途径阻断细胞因子介导的信号传导,该途径在免疫调节和正常细胞生长中起重要作用。这类药物包括被批准用于治疗类风湿性关节炎的托法替尼(tofacitinib)和被批准用于治疗骨髓纤维化和真性红细胞增多症的ruxolitinib。服用托法替尼的患者报告的最常见不良事件(ae)是感染,而服用鲁索利替尼的患者最常见的ae是贫血和血小板减少症。第一代和第二代Janus激酶抑制剂已经成为皮肤病如牛皮癣、特应性皮炎、斑秃、白癜风、皮肌炎和移植物抗宿主病的有希望的治疗方式。未来有前景的研究领域包括皮肤狼疮、皮肤t细胞淋巴瘤、黑色素瘤、过敏性接触性皮炎和扁平苔藓的治疗。
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引用次数: 0
Chronic Urticaria: Following Practice Guidelines. 慢性荨麻疹:遵循实践指南。
Q1 Medicine Pub Date : 2018-05-01
E P Westby, C Lynde, G Sussman

Histamine is a key inflammatory player in the pathogenesis of urticaria, a mast-cell-driven disease characterized clinically by the development of wheals, angioedema, or both. Changes to the management of chronic spontaneous urticaria have recently been adopted due to increasing literature surrounding the efficacy and safety of up-dosing modern second-generation H1-antihistamines and the use of omalizamub, a biologic agent, as a third-line treatment. Given the prevalence of chronic urticaria and its impact on quality of life, this editorial aims to provide a summary of the proposed updated guidelines for the management of chronic urticaria as agreed upon at the 5th Consensus Conference on the Update and Revision of the EAACI/GA2LEN/EDF/WAO Guideline for Urticaria in Berlin in December 2016. The chronic urticaria treatment algorithm outlined here reflects the updates and revisions made by 43 international experts representing 40 societies from 25 countries. These guidelines have yet to be published and therefore will require approval by respective national and international boards before adoption.

组胺是荨麻疹发病机制中的关键炎症因子,荨麻疹是一种肥大细胞驱动的疾病,临床表现为荨麻疹、血管性水肿或两者兼而有之。由于越来越多的文献报道了增加剂量的现代第二代h1 -抗组胺药的有效性和安全性,以及使用生物制剂omalizamub作为三线治疗,慢性自发性荨麻疹的管理方法已经改变。鉴于慢性荨麻疹的流行及其对生活质量的影响,本社论旨在总结2016年12月在柏林举行的第五次EAACI/GA2LEN/EDF/WAO荨麻疹指南更新和修订共识会议上商定的拟议的慢性荨麻疹管理更新指南。这里概述的慢性荨麻疹治疗算法反映了代表25个国家40个学会的43名国际专家所做的更新和修订。这些准则尚未公布,因此在通过之前需要得到各自国家和国际委员会的批准。
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引用次数: 0
Brodalumab: A Review of Safety. Brodalumab:安全性综述。
Q1 Medicine Pub Date : 2018-03-01
S Rusta-Sallehy, M Gooderham, K Papp

Interleukin (IL)-17 is important in the pathophysiology of psoriasis and has proven to be an effective therapeutic target. Brodalumab, the third commercially available IL-17 antagonist, was approved by the US FDA in February 2017 for the treatment of moderate-tosevere plaque psoriasis. As brodalumab enters the marketplace, it is imperative to investigate its safety profile. We conducted a safety assessment of brodalumab using publically available adverse event data from phase II and III clinical trials. The most common adverse events were nasopharyngitis, upper respiratory tract infection, and candidiasis. The FDA issued a black box warning after six patients treated with brodalumab across four clinical trials committed suicide, but no causal relationship was identified. Current evidence suggests a similar safety profile for brodalumab compared to other IL-17 antagonists used to treat moderate-to-severe plaque psoriasis.

白介素(IL)-17在银屑病的病理生理中起重要作用,已被证明是一种有效的治疗靶点。Brodalumab是第三种市售IL-17拮抗剂,于2017年2月获得美国FDA批准,用于治疗中度至重度斑块性银屑病。随着brodalumab进入市场,对其安全性进行调查势在必行。我们使用公开的II期和III期临床试验不良事件数据对brodalumab进行了安全性评估。最常见的不良反应是鼻咽炎、上呼吸道感染和念珠菌病。FDA在4项临床试验中6名接受brodalumab治疗的患者自杀后发布了黑盒警告,但没有确定因果关系。目前的证据表明,与用于治疗中度至重度斑块型银屑病的其他IL-17拮抗剂相比,brodalumab具有相似的安全性。
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引用次数: 0
A Review of Fabry Disease. 法布里病综述。
Q1 Medicine Pub Date : 2018-03-01
B Chan, D N Adam

Fabry disease (FD) is an X-linked lysosomal storage disease. A lack of alpha-galactosidase activity results in the accumulation of globotriaosylceramide in cells of various systems, leading to multi-systemic effects. The cutaneous hallmark of FD is a specific distribution of angiokeratoma. Other common symptoms include cornea verticillata, acroparesthesia, and sweating abnormalities. FD-specific symptoms, history, as well as examination of angiokeratoma can assist in the differential diagnosis. Enzyme replacement therapy is the current mainstay of treatment.

法布里病(FD)是一种x连锁溶酶体贮积病。α -半乳糖苷酶活性的缺乏会导致球三烷基神经酰胺在不同系统的细胞中积累,从而导致多系统效应。FD的皮肤特征是血管角质瘤的特定分布。其他常见的症状包括角膜鸡斑、肢端感觉异常和出汗异常。fd特异性症状、病史以及血管角化瘤检查有助于鉴别诊断。酶替代疗法是目前主要的治疗方法。
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引用次数: 0
New Treatments for Hereditary Angioedema. 遗传性血管性水肿的新疗法。
Q1 Medicine Pub Date : 2018-01-01
Nathan M Johnson, Mariana A Phillips

Hereditary angioedema is characterized by severe, episodic edema of the subcutaneous and mucosal tissue. The disease carries significant morbidity and mortality due to involvement of the gastrointestinal tract and upper airway. Recent advances in the treatment of hereditary angioedema include new techniques used to isolate and purify human-derived C1 inhibitor, the production of a recombinant form of C1 inhibitor, and the development of drugs that target the kallikrein-kinin pathway. This paper reviews the mechanisms, efficacy, and adverse reactions associated with these medications.

遗传性血管性水肿的特点是皮下和粘膜组织严重的、发作性水肿。由于累及胃肠道和上呼吸道,该病具有显著的发病率和死亡率。遗传性血管性水肿治疗的最新进展包括用于分离和纯化人源性C1抑制剂的新技术,C1抑制剂重组形式的生产,以及针对钾likrein-kinin通路的药物的开发。本文综述了这些药物的作用机制、疗效和不良反应。
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引用次数: 0
Skin and Diet: An Update on the Role of Dietary Change as a Treatment Strategy for Skin Disease. 皮肤与饮食:饮食改变作为皮肤病治疗策略的最新进展
Q1 Medicine Pub Date : 2018-01-01
Rajani Katta, Mary Jo Kramer

An increasing body of research indicates that dietary change may serve as a component of therapy for certain skin conditions. This includes conditions such as acne, atopic dermatitis, aging skin, psoriasis, and rosacea. Certain nutrients, foods, or dietary patterns may act as disease "triggers", while others may prove beneficial. Avoidance or elimination diets may be helpful in some conditions, although testing may be recommended first. In terms of beneficial effects, an eating pattern that emphasizes the consumption of whole foods over highly processed foods may help in the treatment of certain skin conditions, and will certainly help in the prevention of associated co-morbidities.

越来越多的研究表明,饮食改变可以作为治疗某些皮肤状况的一个组成部分。这包括痤疮、特应性皮炎、皮肤老化、牛皮癣和酒渣鼻等病症。某些营养素、食物或饮食模式可能是疾病的“诱因”,而另一些可能是有益的。在某些情况下,避免或消除饮食可能会有所帮助,尽管可能建议先进行测试。就有益效果而言,强调食用天然食品而不是高度加工食品的饮食模式可能有助于治疗某些皮肤状况,并且肯定有助于预防相关的合并症。
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引用次数: 0
Real-World Efficacy of Azelaic Acid 15% Gel for the Reduction of Inflammatory Lesions of Rosacea. 15%壬二酸凝胶减少酒渣鼻炎性病变的实际疗效。
Q1 Medicine Pub Date : 2017-11-01
P J Wirth, M H Henderson Berg, N Sadick

Approximately 16 million Americans have rosacea, an inflammatory cutaneous disorder with central facial erythema, papules, pustules, telangiectasia, flushing, and swelling being among the more commonly recognized features. Overexpression of cathelicidin peptide LL-37 has been implicated in the pathophysiology of rosacea. Azelaic acid has been found to inhibit the pathologic expression of cathelicidin, as well as the hyperactive protease activity that cleaves cathelicidin into LL-37. Given these findings, a small prospective, open-label, interventional trial was undertaken to assess the effects of azelaic acid 15% gel on inflammatory lesions of papulopustular rosacea in a real-world setting. Use of azelaic acid was associated with a significant reduction in inflammatory lesions, which persisted beyond the active treatment phase. Overall, azelaic acid 15% gel is an appropriate initial topical therapy for the treatment of moderate facial rosacea.

大约1600万美国人患有酒渣鼻,这是一种炎症性皮肤疾病,常见的特征包括面部红斑、丘疹、脓疱、毛细血管扩张、潮红和肿胀。cathelicidin肽LL-37的过度表达与酒渣鼻的病理生理有关。已经发现壬二酸可以抑制cathelicidin的病理表达,也可以抑制将cathelicidin切割成LL-37的过度活跃的蛋白酶活性。鉴于这些发现,我们进行了一项小型的前瞻性、开放标签、干预性试验,以评估15%壬二酸凝胶对丘疹性酒渣鼻炎症病变的影响。使用壬二酸与炎性病变的显著减少有关,炎症病变持续超过积极治疗阶段。总的来说,15%壬二酸凝胶是一种适当的初始局部治疗中度面部酒渣鼻。
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引用次数: 0
Dupilumab for Moderate-to-Severe Atopic Dermatitis. Dupilumab用于中重度特应性皮炎。
Q1 Medicine Pub Date : 2017-11-01
R Vangipuram, S K Tyring

Atopic dermatitis (AD) is the most common chronic inflammatory disease affecting 2-10% of adults and up to 15-30% of children. Despite a rising prevalence, effective and safe therapeutics for patients with moderate-to-severe AD are limited due to toxicity and side effects. Dupilumab, an interleukin (IL)-4 and IL-13 antagonist that limits type 2 T helper (Th2) driven inflammatory activity, is a promising therapeutic option. In clinical trials, it has demonstrated efficacy by reducing clinical activity and symptoms, and showed improvement in the AD genomic phenotype, including a significant reduction in Th2 chemokines and reversal of key epidermal markers of AD. It also has a favorable safety profile. This review discusses the role of dupilumab in treating Th2 related inflammation, and its efficacy and safety, as demonstrated in clinical trials. Dupilumab (Dupixent®) recently gained US FDA approval for patients with moderate-to-severe AD, and is poised to revolutionize the management of this chronic, relapsing condition.

特应性皮炎(AD)是最常见的慢性炎症性疾病,影响2-10%的成年人和高达15-30%的儿童。尽管患病率不断上升,但由于毒性和副作用,对中重度AD患者有效和安全的治疗方法有限。Dupilumab是一种白细胞介素(IL)-4和IL-13拮抗剂,可限制2型T辅助(Th2)驱动的炎症活性,是一种很有前景的治疗选择。在临床试验中,它通过降低临床活动和症状证明了疗效,并显示了AD基因组表型的改善,包括Th2趋化因子的显著降低和AD关键表皮标志物的逆转。它还具有良好的安全性。这篇综述讨论了dupilumab在治疗Th2相关炎症中的作用,以及临床试验证明的dupilumab的有效性和安全性。Dupilumab (Dupixent®)最近获得了美国FDA批准用于中重度AD患者,并准备彻底改变这种慢性复发性疾病的管理。
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引用次数: 0
Epidermal Growth Factor Receptor Inhibitors: Cutaneous Side Effects and Their Management. 表皮生长因子受体抑制剂:皮肤副作用及其处理。
Q1 Medicine Pub Date : 2017-09-01
S Monjazeb, J Wilson

Epidermal growth factor receptor (EGFR) inhibitors are part of an emerging class of anticancer medicines known as "targeted therapy," which target pathways more specific to neoplastic proliferation than traditional chemotherapeutic agents. Adverse effects of such treatments are thought to be less severe, but can still be significant. Because EGFR is preferentially expressed in epithelial tissues, including the skin and hair follicle, cutaneous side effects of these agents are quite common. Not only can these toxicities severely affect patients' quality of life, but in some specific instances, they can be associated with increased response to therapy. It is of paramount importance that clinicians familiarize themselves with and understand the basic management of the range of cutaneous adverse effects caused by these drugs.

表皮生长因子受体(EGFR)抑制剂是一类新兴的抗癌药物的一部分,被称为“靶向治疗”,它比传统的化疗药物更针对肿瘤增殖的特异性途径。这种治疗的副作用被认为不那么严重,但仍然可能很严重。由于EGFR优先在上皮组织中表达,包括皮肤和毛囊,这些药物的皮肤副作用是很常见的。这些毒性不仅会严重影响患者的生活质量,而且在某些特定情况下,它们可能与对治疗的反应增加有关。临床医生熟悉和了解这些药物引起的一系列皮肤不良反应的基本管理是至关重要的。
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引用次数: 0
Vitamin B Derivative (Nicotinamide)Appears to Reduce Skin Cancer Risk. 维生素B衍生物(烟酰胺)似乎可以降低皮肤癌的风险。
Q1 Medicine Pub Date : 2017-09-01
S Nazarali, P Kuzel

Nicotinamide, an amide form of vitamin B3, has shown the potential to treat a variety of dermatological conditions, including acne, rosacea, and atopic dermatitis. Recent studies have demonstrated the role of nicotinamide, in both topical and oral forms, as a chemopreventive agent against skin cancer. Its anti-carcinogenic role may be due to its ability to enhance DNA repair and prevent ultraviolet (UV)-induced immunosuppression, which is known to contribute to the progression of pre-malignant lesions. Furthermore, nicotinamide is a precursor of essential coenzymes for many important reactions in the body, including the production of nicotinamide adenine dinucleotide (NAD). NAD is a key coenzyme in the synthesis of adenosine triphosphate (ATP), which transports chemical energy within cells. Therefore, nicotinamide plays a significant role in supporting energy-dependent cellular processes, including DNA repair.

烟酰胺是维生素B3的一种酰胺形式,已经显示出治疗多种皮肤病的潜力,包括痤疮、酒渣鼻和特应性皮炎。最近的研究已经证明了烟酰胺的作用,在局部和口服形式,作为一种化学预防剂对皮肤癌。其抗癌作用可能是由于其增强DNA修复和防止紫外线(UV)诱导的免疫抑制的能力,这是已知的有助于恶性病变的进展。此外,烟酰胺是体内许多重要反应必需辅酶的前体,包括烟酰胺腺嘌呤二核苷酸(NAD)的产生。NAD是合成三磷酸腺苷(ATP)的关键辅酶,ATP在细胞内运输化学能。因此,烟酰胺在支持能量依赖的细胞过程中起着重要作用,包括DNA修复。
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引用次数: 0
期刊
Skin therapy letter
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