Topical retinoids in the management of photodamaged skin: from theory to evidence‐based practical approach

Skin, being exposed directly to the environment, represents a unique model for demonstrating the synergistic effects of intrinsic and extrinsic factors on the ageing process. Ultraviolet radiation (UVR) is the major factor among exogenous stressors responsible for premature skin ageing. The problem of skin ageing has captured public attention and has an important social impact. Different therapeutic approaches have been developed to treat cutaneous ageing and to diminish or prevent the negative effects of UVR. Topical retinoids represent an important and powerful class of molecules in the dermatologist’s hands for the treatment of photodamaged skin. Since their introduction more than 20 years ago, topical retinoids have shown beneficial efficacy and good safety profiles in the management of photodamaged skin, and as therapeutic anti‐ageing agents. This review provides a brief retrospective of the development of topical retinoids in the treatment of photodamaged skin, elucidates their mechanism of action, delineates their use and addresses clinical, pharmaceutical and regulatory issues in connection with their intended use.     

0.1%他扎罗汀乳膏短时接触治疗寻常痤疮的疗效观察

［目的］对比观察及评价0.1%他扎罗汀乳膏短时接触治疗与常规每日一次治疗轻中度寻常型痤疮的疗效和安全性。［方法］采用前瞻性开放性对照观察,选用重庆华邦公司0.1%他扎罗汀乳膏局部外用面部轻中度痤疮,短时接触疗法为每晚1次,5分钟后洗去,常规疗法为每晚1次过夜,疗程均为8周,于第1、2、4、8周进行复诊随访。短时接触治疗组为52例,常规治疗组为49例。［结果］第8周时0.1%他扎罗汀短时接触治疗组有效率为69.1%,常规治疗组有效率为75.1%,X2=6.501,P=0.09＞0.05,两组疗效之间无显著统计学差异。不良反应发生率短时接触治疗组为21.2%,常规治疗组为44.9%,X2=8.538,P=0.036＜0.05,两组不良反应发生率有显著统计学差异,短时接触治疗组明显低于常规治疗组。［结论］他扎罗汀短时接触治疗寻常型痤疮安全、有效,值得临床推广应用。     

NB-UVB联合他扎罗汀凝胶外用治疗中重度寻常型银屑病疗效观察

目的观察窄谱中波紫外线(NB-UVB)联合他扎罗汀凝胶外用治疗寻常型银屑病的疗效及安全性。方法对50例中重度患者采用NB-UVB每周3次照射配合0.05%他扎罗汀凝胶每晚1次外用,共治疗8周,用PASI积分评价疗效。结果 治疗开始后1~2周出现疗效,随着治疗时间的延长,有效率逐渐提高,疗程结束时治愈率92%,有效率达100%,8例发生皮肤刺激反应,占16%。结论 NB-UVB照射联合他扎罗汀凝胶外用治疗寻常型银屑病具有良好疗效及安全性。     

Pharmacokinetics of tazarotene and acitretin in psoriasis

Introduction: Psoriasis is a prevalent cutaneous condition with severe physical and psychological manifestations. Since the advent of biologics, clinical outcomes in psoriasis have improved. However, retinoids are useful in the correct clinical context. Tazarotene and acitretin are currently the only US Food and Drug Administration approved retinoids for treatment of psoriasis. Both topical tazarotene and oral acitretin act on retinoic acid receptors and retinoid-X-receptors, resulting in altered gene expression of inflammatory cytokines and inhibition of keratinocyte proliferation.

Areas covered: This article provides an in-depth pharmacologic and clinical review on the use of tazarotene and acitretin in psoriasis. The PubMed database was searched using combinations of keywords: acitretin, bioavailability, dosing, efficacy, etretinate, interactions, mechanism, pharmacodynamics, pharmacokinetics, pharmacogenetics, psoriasis, safety, tazarotene, tolerability, and toxicity.

Expert opinion: Tazarotene and acitretin are effective treatments for psoriasis. Benefits include lack of immunosuppression and success treating inflammatory psoriasis. When combined with other topical and systemic agents, both retinoids improve clinical efficacy while lowering the treatment threshold. However, topical adherence and bothersome side effects can limit retinoid use. Acitretin and tazarotene both improve outcomes through a unique mechanism that especially benefits subsets of patients, despite side effects and limitations.     

Histological effects of tazarotene 0.1% cream vs. vehicle on photodamaged skin: a 6-month, multicentre, double-blind, randomized, vehicle-controlled study in patients with photodamaged facial skin

BACKGROUND: Topical tazarotene has been shown to offer efficacy in ameliorating multiple effects of photodamage. OBJECTIVES: To evaluate the histological effects of tazarotene cream on photodamaged skin. METHODS: In this multicentre, double-blind, randomized, vehicle-controlled study, 50 patients with photodamaged facial skin (at least mild fine wrinkling and mottled hyperpigmentation, with at least one of these being moderate) were randomized to apply tazarotene 0.1% cream or vehicle cream to their face, once daily for 24 weeks. RESULTS: Blinded assessments showed that tazarotene was less likely than vehicle to be associated with an increase in keratinocytic and melanocytic atypia, and more likely than vehicle to be associated with a reduction in atypia. Between-group comparisons in distribution of change from baseline categories of severity were in favour of tazarotene (P = 0.055 for keratinocytic atypia, P = 0.034 for melanocytic atypia, and P < 0.001 for the number of granular cell layers). Compared with vehicle, tazarotene was associated with an increase in epidermal polarity (P = 0.008) and epidermal thickness (P = 0.012), and a tendency for stratum corneum compaction. Tazarotene was also associated with widened intercellular spaces (reported as epidermal oedema) relative to vehicle (P < 0.001). CONCLUSIONS: Treatment of photodamaged skin with tazarotene is associated with an amelioration of keratinocytic and melanocytic atypia, an improvement in epidermal polarity, and an increase in epidermal thickness.     

5 - 氮杂 - 2’ - 脱氧胞苷对食管鳞癌 ECa109 细胞增殖及 TIG1 基因表达与甲基化状态的影响

目的：探讨5-氮杂-2＇-脱氧胞苷（5-aza-2＇-deoxy-cytidine,5-aza-CdR）对食管鳞癌细胞株ECa109增殖抑制作用,以及对ECa109中TIG1基因甲基化状态及其mRNA表达的影响.方法：实验组分别使用10、20、50、100μmol/L的5-aza-CdR处理ECa109细胞,对照组用不添加5-aza-CdR培养基培养;采用MTT法检测两组细胞生存率的变化;MSP检测TIG1基因的甲基化状态;RT-PCR法检测TIG1基因mRNA表达水平.结果：5-aza-CdR可以显著抑制ECa109的生长,实验组细胞生存率显著低于对照组,差异有统计学意义（P＜0.01）.实验组同种药物浓度,作用时间延长,生存率显著降低,差异有统计学意义（P＜0.01）;同一作用时间,随着药物浓度增加,细胞生存率降低,差异有统计学意义（P＜0.01）.对照组ECa109细胞TIG1基因处于高甲基化状态,经过10μmol/L及20μmol/L的5-aza-CdR处理细胞株120h后,TIG1基因的甲基化部分解除.对照组ECa109细胞中无TIG1 mRNA表达,采用10μmol/L及20μmol/L浓度药物处理72、120、168h后细胞株中TIG1 mRNA恢复表达,且20μmol/L处理组细胞较10μmol/L组TIG1 mRNA表达增强.结论：5-aza-CdR可以抑制ECa109细胞生长,且具有剂量及时间依赖性;ECa109中TIG1基因甲基化阳性,其mRNA的表达缺失;经5-aza-CdR干预后可使TIG1基因发生去甲基化修饰,恢复表达,去甲基化修饰具有时间及剂量依赖效应.     

Combination therapy with tazarotene plus a topical corticosteroid for the treatment of plaque psoriasis

Although tazarotene monotherapy is generally efficacious and well tolerated, studies show that both the efficacy and the tolerability of tazarotene therapy can be further improved when it is used in combination with certain topical corticosteroids. The studies reported here evaluate the usefulness of two potential combination regimens. In one regimen, a corticosteroid is added to tazarotene treatment. In the other regimen, corticosteroid treatment alternates on a daily basis with tazarotene treatment. The results of the first study, which involved 300 patients, showed that additive combination therapy using tazarotene plus a mid- or high-potency topical corticosteroid significantly increased the percentage of plaques achieving treatment success at the end of the treatment period, compared with tazarotene plus placebo (91% and 95% vs. 80%, respectively; P  < 0.05 for both). Similarly, tazarotene plus a mid- or high-potency topical corticosteroid reduced the incidence of patient withdrawals compared with tazarotene plus placebo (5.5% and 9.6% vs. 13.3%). The results of the second study, which involved 398 patients, showed that a combination regimen that alternates between tazarotene and a high-potency topical corticosteroid treatment each day, significantly increased the treatment success rate compared with regimens using tazarotene alternating with a mid-potency corticosteroid or placebo (75% vs. 55% and 54%, respectively, at the end of the treatment period; P  < 0.05 for both). In addition, there was a trend towards a lower incidence of treatment-related adverse events as corticosteroid potency increased (from 42% with tazarotene plus placebo to 36%, 32%, and 31% with tazarotene plus the low-, mid-, and high-potency corticosteroid, respectively). Both treatment regimens are potentially useful and offer a rational approach to optimizing the efficacy and tolerability of tazarotene treatment for plaque psoriasis.     

Photocarcinogenesis of topical tazarotene and isotretinoin alone and in combination with valproic acid in hairless mice

Retinoids and the histone deacetylase inhibitor valproic acid have shown anticancer properties, but the photocarcinogenic or photoprotective effect is unclear. Therefore, we investigated whether a topical formulation of valproic acid is photocarcinogenic or photoprotective in hairless female C3.Cg/TifBomTac immunocompetent mice exposed to simulated solar radiation (SSR) and whether valproic acid changes the effect of the retinoids: tazarotene and isotretinoin. The products were applied on the dorsal skin of 400 mice (five times weekly) followed by SSR (three times weekly) 3-4 h after the application. This was performed during 12 months or until death. Tumors appeared sooner in groups treated with tazarotene and isotretinoin compared with that of the group treated with valproic acid and the control group. The present study shows that valproic acid alone is not photocarcinogenic or photoprotective in hairless mice. When valproic acid is combined with tazarotene or isotretinoin, it does not change their photocarcinogenicity significantly.     

他扎罗汀凝胶与卡泊三醇软膏治疗斑块型银屑病的比较

目的 :观察他扎罗汀凝胶治疗斑块型银屑病的疗效与安全性 ,并与卡泊三醇软膏比较。方法 :71例斑块型银屑病病人分为 2组 ,他扎罗汀组 36例 ,每晚外涂 1次 ;卡泊三醇组 35例 ,早、晚各外涂1次 ,2组疗程均为 12wk。结果 :2组的总有效率分别为 83%和 79% ,差异无显著意义 (P >0 .0 5 )。结论 :他扎罗汀凝胶治疗斑块型银屑病安全有效 ,与卡泊三醇相仿     

TIG2在皮肤鳞癌中的表达及意义

目的:研究TIG2(tazarotene induced gene-2)在皮肤鳞癌中的作用机制.方法:用免疫组化和原位杂交的方法检测正常皮肤组织,未受累组织及鳞癌皮损中TIG2蛋白和mRNA的表达变化.结果:TIG2蛋白和mRNA表达于正常组织及未受累组织的表皮全层;在鳞癌的边缘皮损中,可见TIG2表达于角质层,棘层上中部,而不表达于棘层下部及基底层;在Ⅰ-Ⅱ期鳞癌中,TIG2可轻度表达于分化较好的角化珠周围;而在Ⅲ～Ⅳ期鳞癌中无表达.在正常组织和未受累皮肤中,TIG2的表达高丁鳞癌组织中的表达(P<0.01);边缘皮损基底层中的表达低于正常组织及未受累组织基底层中的表达(P<0.01);在Ⅲ～Ⅳ期鳞癌中的表达明显低于鳞癌边缘皮损中的表达(P<0.01).结论:TIG2可能参与鳞癌的发生和发展.