The skin as a signal organ in the development of recent cytostatic drugs and anti-tumor strategies

It has been estimated that of all new cancers diagnosed annually in the USA almost one third originate in the skin such as basal cell carcinoma, squamous cell carcinoma, and melanoma. Much progress has been achieved in our understanding of the pathogenesis and it became clear primarily by studies of chemical carcinogenesis in murine skin that this is a stepwise process comprising at least three distinct stages: initiation, promotion, and malignant conversion or progression. This knowledge of the pathogenesis prompted to the development of chemoprevention of cancer in humans. Large clinical chemoprevention intervention studies with vitamin A, -carotene, vitamin E, and selenium are on the way. The metabolism of chemical carcinogens by cytochrome P-450 isozymes and other xenobiotica metabolizing enzymes has been proven essential in chemocarcinogenesis but it plays also a crucial role in the biotransformation of cancer themotherapeutic agents and may be of importance in influencing the efficacy as well as the side effects of these drugs in the target organ. Although our current knowledge is limited, studies of the xenobiotic metabolizing enzymes in extrahepatic tissues such as the skin demonstrate that they are possible. They may be of special importance in the near future in order to design individual therapies that will avoid unwanted toxicities and enhance therapeutic effectiveness.     

Assessing the treatment of solar urticaria. The dose-response as a quantifying approach

The weal and flare produced by monochromatic irradiation in solar urticaria may be treated as a classical dose-response. This has been used to investigate therapy with H1 and H2 antihistamines. The conventional H1 drug proved superior. But from the practical viewpoint, solar urticaria is difficult to suppress even with a relatively efficient H1 Antihistamine, chlorpheniramine; the mean protective factor in 5 patients was only 2, insufficient for satisfactory clinical management.     

Cold urticaria as a complication of cryotherapy in the treatment of viral warts

Cryotherapy with liquid nitrogen has been established as the first-line treatment for pediatric patients with viral warts. Cold-induced urticaria (CU) is a rare skin reaction triggered by cold stimuli. We present the case of a pediatric patient with viral warts who developed CU after receiving cryotherapy.     

慢性荨麻疹发病机制和治疗策略的思考

慢性荨麻疹在临床十分常见,其病因和发病机制尚不清楚,治疗以对症为主,病情容易反复而严重影响患者的生活质量.近年来,随着研究的深入,对本病的认识有了较大的变化,使治疗的理念不断更新.然而.临床上有时因不能正确把握疾病的本质,会给患者带来不必要的负担.为此,结合近年来国内外某些研究进展,就有关问题进行探讨.     

3种抗组胺药治疗慢性特发性荨麻疹的临床研究

目的:评价第2代抗组胺药咪唑斯汀、西替利嗪、氯雷他定治疗慢性特发性荨麻疹的疗效和安全性。方法:采用随机开放平行对照的方法,对96例慢性特发性荨麻疹患者进行随机分组,分别予以咪唑斯汀10mg、西替利嗪10mg、氯雷他定10mg,均每日1次口服,观察治疗第14天、第28天的临床疗效及停药1周后的复发率。结果:三者治疗慢性特发性荨麻疹第14天和第28天的有效率分别为:咪唑斯汀组90.0%和96.7%,西替利嗪组85.3%和94.2%,氯雷他定组90.6%和93.8%,三者之间差异无显著性(P>0.05)。停药1周后的复发率,咪唑斯汀组为40.0%,西替利嗪组为35.3%,氯雷他定组为28.1%。整个试验过程中均无明显严重不良反应出现。结论:咪唑斯汀、西替利嗪和氯雷他定治疗慢性特发性荨麻疹临床疗效好,安全性高,在改善临床症状及控制复发方面各有所长。     

Evidence for methotrexate as a useful treatment for steroid-dependent chronic urticaria

Chronic urticaria is a relatively common disorder that can be severe and may impair quality of life. The management of recalcitrant chronic urticaria that is not responding to histamine antagonists includes short-term systemic corticosteroids, anti-inflammatory drugs (colchicine, dapsone and sulfasalazine) and immunomodulatory agents, such as cyclosporine, methotrexate, plasmapheresis and intravenous immunoglobulin. We report here our retrospective experience with the use of methotrexate in 8 patients (2 males and 6 females) with recalcitrant chronic urticaria who were not responding to high-dose first- and second-generation antihistamines. The mean duration of the disease prior to methotrexate treatment was 12 ± 8 months. Patients were treated for a mean duration of 4.5 months with a mean dose of 15 mg methotrexate/week. A complete response was achieved in 7 out of 8 patients (87%). Five out of the 7 patients were disease-free during a period of 1-10 months follow-up after discontinuing methotrexate and prednisone therapy. No serious adverse effects were reported. Methotrexate is an effective and safe treatment for chronic urticaria in patients who are not responsive to conventional therapy.     

Doxepin in the treatment of chronic urticaria

24 patients were included in a double-blind, crossover trial to test the efficacy of doxepin (a tricyclic antidepressant) and mequitazine (a new antihistamine of the phenothiazine group). Compared to placebo treatment, both doxepin and mequitazine significantly improved the various clinical parameters evaluated. When the two active drugs were compared with each other, no significant difference in their effectiveness was found. The authors conclude that both agents are equally useful in the treatment of chronic idiopathic urticaria.     

Famotidine in the treatment of acute urticaria

Recent studies suggest that histamine H2-receptor antagonists may be useful in the treatment of urticaria. This study was conducted to determine whether famotidine, a H2 antagonist, is effective in the treatment of acute urticaria and compare its effect with that of the H1 antagonist diphenhydramine. In this prospective, double-blind, controlled trial, 25 patients with urticaria of less than 72 h duration were randomized to receive a single dose of either famotidine 20 mg i.m. or diphenhydramine 50 mg i.m. Prior to treatment and 30 min after treatment, patients rated pruritus and sedation using visual analogue scales, while physicians evaluated intensity of urticaria and percentage of body surface area involved by urticaria. Famotidine was found to reduce pruritus associated with acute urticaria, intensity of urticaria, and body surface area affected by urticaria without causing sedation. Famotidine was comparable to diphenhydramine in efficacy; however, there was a (nonsignificant) trend for diphenhydramine to be more effective than famotidine in the treatment of pruritus, and for famotidine to be more effective in the reduction of surface area of involvement. It is concluded that famotidine merits further investigation as a potential medication for treatment of urticaria.     

白癜风治疗的新进展

白癜风是常见的易诊而难治的色素障碍性皮肤病,近年来随着新技术及新方法,如窄谱中波紫外线、308nm(氯化氙)受激二聚体激光、他克莫司软膏、抗干扰素γ抗体、促黑素细胞激素、黑素细胞和角质形成细胞混悬液移植、激光脱色及中药银杏浸出液的应用,取得了很好的临床疗效,使得白癜风的治疗有了很大进展,而基因和组织工程治疗更为白癜风的治疗提供了广阔的前景。     

Class action of oral coumarins in the treatment of a patient with chronic spontaneous urticaria and delayed-pressure urticaria

Chronic spontaneous urticaria is a common condition, with a lifetime prevalence of 0.5-1.0%. It has a significant effect on quality of life, comparable to having triple-vessel coronary artery disease. Warfarin and nicoumalone are synthetic derivatives of the plant toxin coumarin. We report the first case of successful response to both warfarin and nicoumalone in the same patient, thereby demonstrating a class action of synthetic coumarins in the disease. Complete response with both coumarins occurred once an INR above 2.0 was achieved, and was maintained during a 12-month follow-up. The mechanism of action of coumarins on urticaria is not known, but may be related to decrease in thrombin production or to interference of activation of other inflammatory proteins produced during the coagulation process. Side-effects of anticoagulation can be catastrophic, and coumarin treatment currently remains reserved for restricted severe recalcitrant cases only.     

比拉斯汀在荨麻疹治疗中的应用

比拉斯汀是一种新型的H1受体拮抗剂,口服可治疗过敏性鼻炎和荨麻疹,其吸收较快,但食用食物和果汁后吸收减慢.已有数据证实,相比其他受体,比拉斯汀对H1的亲和力更高,并能降低组胺和细胞因子水平.在由组胺引起的皮肤风团和红斑上,比拉斯汀20 mg与西替利嗪10 mg相比具有等同疗效,可能有更快的抑制作用.比拉斯汀无抗胆碱作用,不影响驾驶,除此之外,比拉斯汀还具备良好的耐受性,无镇静作用、心脏毒性和肝脏毒性等优点.     

The use of a responder analysis to identify clinically meaningful differences in chronic urticaria patients following placebo- controlled treatment with rupatadine 10 and 20 mg

Background  According to the EAACI/GA²LEN/EDF guidelines for urticaria management, modern non-sedating H1-antihistamines are the first-line symptomatic treatment for chronic urticaria. Two previous randomized clinical trials demonstrated rupatadine efficacy and safety in chronic urticaria treatment. However, a responder analysis to identify clinically meaningful differences in patients with chronic urticaria has not yet been performed.
Methods  This analysis includes the pooled data from two randomized, double-blind, placebo-controlled, multicentre studies in which chronic urticaria patients were treated with rupatadine at different doses. Responder rates were defined as the percentage of patients after 4 weeks of treatment who exhibited a reduction of symptoms by at least 50% or 75% as compared to baseline. The variables analysed were as follows: Mean Pruritus Score (MPS), Mean Number of Wheals (MNW), and Mean Urticaria Activity Score (UAS).
Results  A total of 538 patients were included. This responder analysis, using different response levels, shows that the efficacy of rupatadine 10 mg and 20 mg is significantly better as compared to placebo in the treatment of chronic urticaria patients. Notably, treatment with rupatadine 20 mg daily resulted in a higher percentage of patients with response of 75% symptom reduction or better than rupatadine 10 mg.
Conclusion  Our results support the use of higher than standard doses of non sedating antihistamines in chronic urticaria. We strongly recommend performing and reporting responder analyses for established and new drugs used by patients with chronic urticaria.     

Alpha-fluoromethylhistidine in the treatment of idiopathic cold urticaria

Summary Alpha-fluoromethylhistidine (alpha-FMH), a new irreversible inhibitor of mammalian histidine decarboxylase, was tested in the treatment of idiopathic cold urticaria in 11 patients. In the initial trial with 50 mg b.i.d., a significant decrease (about 30%) in the total blood histamine level was found after 3 weeks of treatment but clinically there was no improvement in the symptoms of ten cold urticaria patients nor in the responses to the ice-cube test. In the second trial with three patients suffering from severe idiopathic cold urticaria, a higher dose of up to 500 mg b.i.d. of alpha-FMH for 3 weeks resulted in a marked decrease in the total blood histamine level as well as in an apparent inhibition of histamine synthesis in the skin previously exposed several times to cold water. The symptoms of cold urticaria and the responses in the ice-cube tests also decreased simultaneously. No clinical side effects nor changes in laboratory analysis were seen during the treatment with alpha-FMH. These results suggest that alpha-FMH may be useful in the treatment of severe cold urticaria especially in combination with histamine exhaustion of mast cells using cold water.