爱若华在皮肤科其他疾病的应用.docx

1、爱若华在皮肤科其他疾病的应用Successful treatment of recalcitrant eczematous dermatitis with leflunomide. A. S. BoydJ Am Acad Dermatol. 2013; 69(3): e148-149.Not all patients with eczematous dermatitis respond to conservative treatment, which means that systemic therapies or light therapy must be considered. Leflu

2、nomide may be of benefit in these patients.A 49-year-old healthy white woman presented with a 14-year history of eczematous dermatitis primarily affecting her hands and feet. Her condition fluctuated, with vesicles and bullae developing on the sides of her fingers and soles. Her plantar disease was

3、variably incapacitating, with thickened, cracked, and painful skin, making walking difficult, leading to significant weight gain. She had been treated with high potency topical steroids, topical picrolimus, lactic acid and urea-containing creams, oral antibiotics, oral ketoconazole, and oral cortico

4、steroids.None elicited more than temporary relief. A biopsy specimen of her left sole was obtained, and the histopathologic results were consistent with eczematous or atopic dermatitis.An intramuscular injection of triamcinolone 40 mg was unhelpful, as were topical coal tar and ichthammol.A patch te

5、st revealed allergies to fragrance mix, nickel sulfate, balsam of Peru, cobalt chloride, and cinnamaldehyde. Avoidance of these chemicals failed to result in improvement. The patient was prescribed mycophenolate mofetil 500 mg twice daily with only mild improvement. Because no relief had ensued afte

6、r 4 months and the patient was anxious to pursue other options, the mycophenolate mofetil was discontinued and the patient was prescribed azathioprine 25 mg daily. Significant gastrointestinal upset ensued almost immediately, and she stopped taking azathioprine after 1 week. Because light therapy wa

7、s impractical, leflunomide 20 mg daily was prescribed. After 1 month, her hands were largely disease-free and her feet had improved. After 2 months, her soles were essentially clear. After 5 months of therapy, the medication was reduced to every other day. The patients blood work was unremarkable. A

8、fter 1 year of treatment, she remains disease-free and the drug is being tapered. She has resumed walking and has lost 35 pounds.Leflunomide is classified as an oral diseasemodifying antirheumatic drug and is used in the treatment of both rheumatoid and psoriatic arthritis. It also has a favorable t

9、rack record in treating cutaneous psoriasis, although it is not considered a first-line medication. The drug inhibits dihydroorotate dehydrogenase, decreasing the available intracellular pyrimidines and making activated lymphocytes unable to enter the S phase of the cell cycle. The most common side

10、effect is diarrhea, reported in 32% of rheumatoid arthritis patients. It causes transaminase elevation in 2% to 4% of patients, usually within the first 6 months of therapy. It is contraindicated in pregnant women or women of childbearing potential who are not using reliable contraception.Three pati

11、ents with recalcitrant atopic or eczematous dermatitis treated with this drug have been reported. All improved, with 1 patient being able to discontinue leflunomide. Eotaxin-3 levels and atopic dermatitis severity have been linked.There is also evidence that eotaxin release by eosinophils is inhibit

12、ed by leflunomide in vitro, leading to speculation that this represents the drugs mechanism of action in atopic dermatitis. As with psoriasis, leflunomide should not be considered a first-line treatment option; however, it does appear to be effective in some patients with recalcitrant disease.来氟米特成功

13、治疗顽固性湿疹性皮炎不是所有的湿疹性皮炎患者都对保守治疗有效，这也意味着需要考虑系统性治疗或光疗法，来氟米特或许能使这些病人受益。一名49岁的健康白人女性有14年湿疹性皮炎病史，主要累及手足，病情波动明显，双手和双侧足底出现囊泡和大泡，足底病变复杂失去功能，伴有皮肤增厚、皲裂和皮肤疼痛（如图），由于难以行走，导致体重明显增加。曾使用局部激素、吡美莫司、乳酸和尿素膏，口服抗生素、酮康唑和激素治疗，都只能暂时缓解病情，左脚底组织病理活检提示符合湿疹和特应性皮炎。肌肉注射去炎松40mg，外用煤焦油和鱼石脂病情没有改善，皮肤过敏原检测提示对芳香化合物、硫酸镍、秘鲁香胶、氯化钴和肉桂醛过敏，但避免接触这

14、些过敏原未没能使病情得到改善，使用吗替麦考酚酯500mg每日两次治疗，仅有轻微改善，由于在接下来的4个月病情没有改善，病人急于寻求其他治疗于是停用吗替麦考酚酯，并开始采用硫唑嘌呤25mg/d治疗，随即发生非常严重的胃肠道不适症状，于是在服用硫唑嘌呤一周后停药。由于光疗无法实现，所以采用来氟米特20mg治疗，治疗1个月后，双手大部分病愈，双脚也明显好转，治疗2个月后，脚底病变基本痊愈，在治疗5个月后，开始改为隔天服药，血液检查未见异常，治疗一年后病情没有反复，药物逐渐减量，她重新开始行走，并减重35磅。来氟米特作为口服病程改善抗风湿药物，被用于治疗类风湿关节炎和银屑病关节炎，在治疗银屑病方面尽管

15、不是一线治疗用药但也有很好的记录。来氟米特能抑制二氢乳清酸脱氢酶，减少细胞内嘧啶合成，抑制激活的淋巴细胞使其不能跨越细胞周期的S期，最常见的不良反应是腹泻，有报道称达到类风湿关节炎患者的32%。在2%-4%患者中会发生转氨酶升高，常发生在治疗的前6个月内，在孕妇和没有采取避孕措施的育龄期妇女中禁用。曾有报道称三名顽固性过敏性或湿疹性皮炎患者使用来氟米特治疗，均治疗好转，并且1名患者能停药。嗜酸细胞活化趋化因子3水平和过敏性皮炎严重程度相关，在体外实验中，有实验表明来氟米特能抑制嗜酸性粒细胞释放嗜酸细胞活化趋化因子，因此，这可能是治疗特应性皮炎的机制。来氟米特虽然不是治疗的一线用药，然而它确实对

16、治疗一些顽固性疾病患者有效。 来氟米特治疗前、后对比Leflunomide is a possible deactivator for vitiligo, a pilot study.S. S. AwadJournal of the European Academy of Dermatology and Venereology. 2012; 26(9): 1173.In vitiligo patients with actively progressive disease, abundant T cells were detected in the margin of lesions.Targ

17、eting the activation maturation of T cells may interfere with the autoimmune mediated destruction of melanocytes by activated T cells.This pilot study, aims to evaluate possible beneficiary effect of Leflunomide as an immune-modulator drug introduced to halt vitiligo activity. Leflunomide is an inhi

18、bitor of pyrimidine synthesis and has antiproliferative and anti-inflammatory actions. Leflunomide is known to inhibit lymphocyte activation, cell migration and proliferation. It partially reduces IL-2 production and completely inhibits proliferation of stimulated T cells principally by inhibition o

19、f T-cell responsiveness to IL-2, and by inhibition of protein Tyrosine phosphorylation in T Cells.A total of 30 active vitiligo patients were included in the study, 18 male patients and 12 female patients, with age ranging from 16 to 56 years with a mean of 29.2 (10.68 SD). The duration of vitiligo

20、varied from 2 weeks to 30 months with a mean of 7.45 months (7.23 SD). History and general examinations of the patients revealed diabetes mellitus in three patients, alopecia areata in one patient, hypertension in one patient and psychological stress in four patients. Family history of vitiligo was

21、noticed in 16 patients.All patients had non-segmental vitiligo in different parts of the body showing newly evolving lesions and or enlarging patches, within the last month, with no manifestation of stoppage onfirmed by examination and archived digital images.Fifteen patients were using systemic ste

22、roids and helio photo-therapy prior to the study to control their disease activity, but with no success, the other fifteen patients were naive and did not use any preceding systemic medications. Detailed history, clinical examination and laboratory investigations were performed at the baseline visit

23、. Blood and or liver enzymes anomalies excluded their cases from the study. Leflunomide therapy was initiated in a dose of 100 mg daily for 3 days as loading dose, followed by 20 mg daily for 6 weeks.Follow-up visits were scheduled every week, where disease progress was evaluated and adverse effects

24、 were monitored till 12th week, the end of the study. Significant stoppage of activity and progress of vitiligo was reported in 90% of cases and was as early as 2 weeks of therapy in 13 patients, 3 weeks in 11 patients, 4 weeks in two patients and 5 weeks in one patient, with a mean of 2.6 weeks (0.

25、7 SD). Significant pigmentation was also observed in many patients by the end of the study. Leflunomide could not achieve significant halting of the disease activity in only three patients (10%).During the study, 24 patients (80%) did not report any complains or show adverse effects, while only one

26、patient (3.3%) had his liver enzymes elevated at the end of 6 weeks treatment, and five patients (16.7%) had some gastric complains ranging from mild discomfort to vomiting and one of them also developed lymphopenia and hair fall.In this study, LEF also proved to manage the activity not only in naiv

27、e patients but also when systemic steroids failed and proved to be superior to the steroids in such cases. Steroids are also well known for diabetic, hypertensive and psychogenic adverse effects and could be contraindicated in many vitiligo patients, demonstrating further LEF benefits over steroids

28、in susceptible individuals.In conclusion, once daily leflunomide is an effective and convenient treatment to stop vitiligo progression with tolerability and a favourable safety profile.来氟米特可能成为治疗白癜风的减活化剂，一项试点研究活动性进展性白癜风患者，在病变的边缘可检测大量的T细胞。靶向T细胞的活化/成熟可能干预T细胞激活由自身免疫介导的黑色素细胞结构的破坏。这项试验研究旨在评估免疫调节剂来氟米特治疗活动

29、性白癜风的疗效。来氟米特是嘧啶合成抑制剂并具有抗增殖和抗炎作用。来氟米特可抑制淋巴细胞的活化，细胞迁移和增殖。它减少了部分IL-2产生并完全抑制了激活的T细胞的增殖，通过抑制活化T细胞对IL-2的反应还能抑制T细胞蛋白的酪氨酸磷酸化共有30例活动性白癜风患者被纳入研究，男18例，女12例，年龄从16 56岁，平均年龄为29.2岁（ 10.68 SD）。白癜风病程从2周到30个月，平均7.45个月（ 7.23 SD）。根据病史和查体发现糖尿病3例，斑秃患者1例，高血压1例，心理应激4例。白癜风家族史发现16例。所有患者均在身体的不同部位患有非节段型白癜风，表现为新的病变进展和斑块扩大。在过去的一

30、个月内，通过检查和影像学证实没有疾病停止进展的表现。15例病人使用全身激素之前已经使用光照治疗控制其疾病活动度，但没有成功，另外15例患者没有使用任何前述全身用药。在基线访问时详细询问病史并进行临床和实验室检查。给予来氟米特前3天100mg/d的负荷剂量，以后给予20mg/d持续6周。每周随访评估疾病进展和监测不良反应，直到第12周试验结束。90的病例白癜风的活动度和进展明显停止，治疗 2周时有13例，3周有11例，4周2例病人，5周1例，平均为2.6周（0.7SD）。研究结束时在许多患者中观察到明显的色素沉着。来氟米特也无法降低疾病活动度的只有3例（10）。 在研究中，24例（80）没有任何

31、并发症或不良事件，而只有1例病人（3.3）在治疗6周结束时肝酶升高，5例患者有一些胃部不适，从轻度不适到呕吐，其中1例患者淋巴细胞减少和脱发。在本研究中，来氟米特不仅能够控制初治，也能控制全身激素治疗失败患者，而且疗效优于类固醇激素。众所周知，激素治疗可能引起糖尿病，高血压和精神性等不事件，并可能在许多白癜风患者中被禁用，这表明在某些患者治疗中，LEF更优于激素。 总之，每日一次来氟米特是一种有效和方便的治疗，能够阻止白癜风病情的进展，并具有良好的安全性和耐受性。Conversion from tacrolimus/mycophenolic acid to tacrolimus/lefluno

32、mide to treat cutaneous warts in a series of four pediatric renal allograft recipients.Nguyen L, McClellan RB, Chaudhuri A, et alTransplantation. 2012; 94(5): 450-455.BACKGROUND: The challenge of immunosuppression in pediatric renal transplantation is to balance preventing rejection while avoiding infectious complications. A dermatological complication of immunosuppression is viral warts, which cause significant disfigurement and increase the risk of skin malignancy.METHODS: We present three pediatric and adolescent renal allograft recipients with multiple, recalcitrant verrucae v