甲氨蝶呤治疗银屑病的临床合理化用药

甲氨蝶呤(MTX)被美国食品药品监督管理局(FDA)正式批准用于银屑病的治疗已有近半个世纪,是目前多国指南推荐的一线系统药物。临床研究表明,综合疗效、安全性及价格等方面,MTX具有一定优势。但在治疗剂量下,用药后出现的个体差异及不良反应在一定程度上限制了该药在治疗银屑病中的应用。该文对MTX在银屑病治疗中的规范化及合理化应用作一综述。     

银屑病患者亚甲基四氢叶酸还原酶基因C677T多态性及与MTX疗效、毒副作用的关系

目的:确定亚甲基四氢叶酸还原酶(MTHFB)基因C677T多态性与银屑病患者的关系.方法:对108例银屑病患者和102名正常对照个体采用PCR- RFLP方法检测C677T位点基因型,分析银屑病患者基因型分布与正常对照者的差异.分析62例接受甲氨蝶呤(MTX)治疗的不同基因型银屑病患者的临床疗效及毒副作用.结果:银屑病患者MTHFRC677位点T等位基因频率为28.7％,C等位基因频率为71.3％,对照组T等位基因频率为35.78％,C等位基因频率为64.22％,两组间无统计学差异.62例接受MTX治疗的患者中61例有效,TT基因型患者组MTX治疗毒副作用的发生率为55.56％,高于CC基因型(24.24％)和CT基因型(25％),有统计学差异(P=0.04).结论:MTHFR基因C677T多态位点与银屑病的易感性无相关,MTHFR的TT基因型与MTX不良反应作用可能相关.     

寻常性银屑病患者血清sCD40L水平及甲氨蝶呤的干预作用

目的研究可溶性CD40配体(sCD40L)在寻常性银屑病发病中的作用及甲氨蝶呤(MTX)对其的调节作用,探讨MTX治疗银屑病的机制。方法应用双抗体夹心酶联免疫吸附法(ELISA)检测30例寻常性银屑病患者经MTX治疗前、后外周血清中sCD40L的水平变化。结果寻常性银屑病患者血清中sCD40L的水平显著高于经MTX治疗后及正常人对照组(P<0.05),其中进行期患者组显著高于静止期(P<0.05),且血清sCD40L浓度变化与寻常性银屑病严重程度指数PASI有相关性(r=0.435,P<0.05)。结论检测血清sCD40L水平有助于判断寻常性银屑病病情的严重程度,MTX可通过降低血清sCD40L水平而起到治疗作用。     

甲氨蝶呤皮下注射治疗银屑病专家指导意见

甲氨蝶呤(MTX)是目前治疗银屑病最有效的传统药物之一，已被广泛用于各型中重度银屑病的治疗。近年相关研究显示，与口服MTX相比，皮下注射MTX给药具有明确的优势，其生物利用度及疗效更佳，且显著减少胃肠道等不良反应。以皮下注射MTX的药理作用机制、用于银屑病治疗的临床数据及研究现状为依据，中华医学会皮肤性病学分会银屑病专业委员会召集相关专家制定本指导意见，目的是为规范、合理、安全、有效地使用MTX皮下注射治疗银屑病。     

银屑病的细胞动力学和化学疗法

银屑病化学疗法的历史开始在1/4个世纪以前,首先报告了白血宁对银屑病的应用,此后关于白血宁及氨甲喋昤(MTX)在治疗中各方面问题的报告详述了不同投药方法所增加的效果以及与毒性的关系。MTX仍为严重银屑病全身化学疗法的主要药物。作为MTX治疗成功的副产品,很大地促进了对银屑病基础生物学和生物化学特性的研究。在银屑病病人的表皮观察中,注意到有极为大量的核分裂,用同位素测量方法发现细胞周期加快。放射自显影术测定银屑病的细胞周期是37.5小时,而正常细胞为     

氨甲喋呤用于银屑病

氨甲喋呤(MTX)广泛用于治疗银屑病。1975年据估计在美国有25000名银屑病患者用MTX治疗,近来调查,有52%美国皮科医生用它治疗银屑病。本文作者对MTX的适应症,用法及并发症作了简要的综述。关于MTX对肝的毒性,由于用药方案,总剂量的不同以及素质因素如酒精中毒、糖尿病和肥胖病等影响,很难估计患者发生危险的确定的百分比。根据至今积累的大量资料MTX对肝的毒性有如下特点: 1.间歇投药方案比连续方案较少产生肝中毒反应。看来是肝细胞接触药物的时间长短,而不是每次接触药物的浓度决定此中毒反应。因此,每周口服一次或36小时内分次服比每日小量连服毒性要     

MTX长疗程治疗银屑病作用的回顾

MTX是治疗严重银屑病的一种有效的系统性药物。作者对局部疗法、光疗以及口服维甲酸类无效的严重银屑病患者采用MTX治疗进行了回顾。治疗开始用MTX 3×5mg/w或3×2.5mg/w,以后逐渐调整到令人满意的最小维持量。最大剂量为15mg/w。MTX治疗前进行肝功(包括转氨酶、碱性磷酸酶和γ-谷氨酰转肽酶)、血清肌酸、血细胞计数以及胸部X线检查。禁忌证为饮酒者、严重肝脏疾病、肾衰及胃溃疡患者。血细胞减少、肝功能异常、同时服用可与MTX相互作用的药物者、传染性疾病患者以及准备怀孕的妇女不用MTX治疗。 结果:①一般资料:113例病人(66例女性,     

甲氨蝶呤治疗寻常性银屑病的药物基因组学研究进展

银屑病是一种由遗传、环境及免疫等多种因素参与的慢性炎症性疾病,其发病原因尚未完全明确,主要受遗传因素和环境因素的影响［1］。甲氨蝶呤（MTX）自1971年开始应用于银屑病的治疗,是中重度寻常性银屑病的主要治疗手段之一。MTX是一种叶酸代谢拮抗剂,能抑制淋巴细胞或上皮细胞的增殖,具有免疫抑制活性。临床长期应用于中重度寻常性银屑病的治疗［2］,也适用于关节病性、红皮病性等其他特殊类型银屑病的治疗,有着疗效持久、具有一定安全性和低成本的优点。但临床应用MTX治疗中,有许多相关的药物不良反应,轻度反应有黏膜炎和胃肠道不耐受;重度反应有骨髓抑制、肝毒性和肺毒性［3］。在因不良反应停用MTX的患者中,约有30%发生了肝毒性［3?4］。目前尚无法对MTX治疗后的疗效和可能发生的不良反应进行准确的预测……     

甲氨蝶呤治疗银屑病的临床应用

银屑病是反复发作的、T淋巴细胞介导的慢性炎症性皮肤病.自1972年美国食品药品监督管理局(FDA)批准甲氨蝶呤(MTX)治疗银屑病以来,已有40多年历史.临床调查资料显示,约有44%的中重度银屑病患者系统使用过MTX治疗[1],在2009年美国银屑病基金会共识会议上仍推荐为治疗银屑病相对安全有效的药物,主要适用于外用药及其他系统治疗如PUVA或维A酸效果不佳的中至重度寻常性银屑病,即皮损累及面积>10%(患者10个手掌面积)、或银屑病指数评分(PASI)>10、或皮肤病生活质量指数(DLOI)>10 [2].     

甲氨蝶呤对寻常性银屑病患者血清金属蛋白酶-9及其组织抑制剂-1的影响研究

目的:研究基质金属蛋白酶-9(MMP-9)及金属蛋白酶组织抑制剂-1(TIMP-1)在寻常性银屑病发病中的作用,以及甲氨蝶呤(MTX)对它的调节作用,以探讨MTX治疗银屑病的机制.方法:应用双抗体夹心酶联免疫吸附法(ELISA)检测35例寻常性银屑病患者经MTX治疗前、后外周血清中MMP-9及TIMP-1的水平.结果:寻常性银屑病患者血清中MMP-9、TIMP-1、MMP-9/TIMP-1的水平较正常人对照组显著增高(P＜0.05).治疗后血清中MMP-9、TIMP-1、MMP-9/TIMP-1较治疗前显著下降(P＜0.05).结论:MTX可能通过降低血清MMP-9、升高TIMP-1水平而起治疗作用.     

New fillers for the new man

ABSTRACT:  Two new collagen-based lidocaine-containing dermal fillers, ArteSense™/ArteFill™ (Artes Medical, San Diego, CA) and Evolence® (Colbar LifeScience Ltd., Herzliya, Israel), have proved to be of particular interest to men, many of whom seek a long-lasting or permanent correction. ArteFill™ has been available in the United States since 2006, and it is expected that Evolence® will reach the American market in 2008. The properties of the two products will be described, and experience based on the administration of many hundreds of syringes of both products by a Canadian dermatologist will be detailed here, with tips and precautions to optimize patient outcomes.     

Outcomes and adverse effects of ablative vs nonablative lasers for skin resurfacing: A systematic review of 1093 patients

It is generally believed that ablative laser therapies result in prolonged healing and greater adverse events when compared with nonablative lasers for skin resurfacing. To evaluate the efficacy of ablative laser use for skin resurfacing and adverse events as a consequence of treatment in comparison to other modalities, a PRISMA‐compliant systematic review (Systematic Review Registration Number: 204016) of twelve electronic databases was conducted for the terms “ablative laser” and “skin resurfacing” from March 2002 until July 2020. Studies included meta‐analyses, randomized control trials, cohort studies, and case reports to facilitate evaluation of the data. All articles were evaluated for bias. The search strategy produced 34 studies. Of 1093 patients included in the studies of interest, adverse events were reported in a total of 106 patients (9.7%). Higher rates of adverse events were described in nonablative therapies (12.2% ± 2.19%, 31 events) when compared with ablative therapy (8.28% ± 2.46%, 81 events). 147 patients (13.4%) reported no side effects, 68 (6.22%) reported expected, transient self‐resolving events, and five (0.046%) presented with hypertrophic scarring. Excluding transient events, ablative lasers had fewer complications overall when compared with nonablative lasers (2.56% ± 2.19% vs 7.48% ± 3.29%). This systematic review suggests ablative laser use for skin resurfacing is a safe and effective modality to treat a range of pathologies from photodamage and acne scars to hidradenitis suppurativa and posttraumatic scarring from basal cell carcinoma excision. Further studies are needed, but these results suggest that ablative lasers are a superior, safe, and effective modality to treat damaged skin.     

Genetic alterations in RAS‐regulated pathway in acral lentiginous melanoma

Studies integrating clinicopathological and genetic features have revealed distinct patterns of genomic aberrations in Melanoma. Distributions of BRAF or NRAS mutations and gains of several oncogenes differ among melanoma subgroups, while 9p21 deletions are found in all melanoma subtypes. In the study, status of genes involved in cell cycle progression and apoptosis was evaluated in a panel of 17 frozen primary acral melanomas. NRAS mutations were found in 17% of the tumors. In contrast, BRAF mutations were not found. Gains of AURKA gene (20q13.3) were detected in 37.5% of samples, gains of CCND1 gene (11q13) or TERT gene (5p15.33) in 31.2% and gains of NRAS gene (1p13.2) in 25%. Alterations in 9p21 were identified in 69% of tumors. Gains of 11q13 and 20q13 were mutually exclusive, and 1p13.2 gain was associated with 5p15.33. Our findings showed that alterations in RAS‐related pathways are present in 87.5% of acral lentiginous melanomas.     

Self‐resolving superficial primary cutaneous mucormycosis in a 7‐week‐old infant

A 7‐week‐old girl, born at 30 weeks' gestational age, presented to clinic for evaluation of a crop of vesicular lesions that were noted after removal of a bandage that had been in place for 4 days. A punch biopsy of the lesion revealed fungal elements that were later identified as Rhizopus spp. The lesion began to self‐resolve, and no further treatment was needed, with full resolution of the lesion by 1 month after presentation. Clinicians should be aware of the variable presentations of mucormycosis and consider fungal infection in the differential diagnosis when evaluating vulnerable patients with skin eruptions.     

Pathogenic role of IL-17 in psoriasis and psoriatic arthritis

Psoriasis is a chronic inflammatory skin disorder resulting from a complex network of cytokines and chemokines produced by various immune cell types and tissue cells. Emerging evidence suggests a central role of IL-17 and IL-23/T17 axis in the pathogenesis of psoriasis, giving a rationale for using IL-17-blocking agents as therapeutics.Three agents targeting IL-17 signaling are being studied in Phase III clinical trials: secukinumab and ixekizumab (IL-17 neutralizing agents), and brodalumab (IL-17 receptor antagonist). Preliminary results are highly promising for all anti-IL17 agents, creating fair expectations on this class of agents as the new effective therapeutic approach for the treatment of psoriasis.