Topical Calcineurin Inhibitors in the Treatment of Atopic Dermatitis

Purpose: To summarize success rates of the topical calcineurin inhibitors tacrolimus and pimecrolimus in treating atopic dermatitis. Methods: Randomized controlled trials (RCTs) comparing either drug to themselves (i.e. dose-ranging studies), each other, the vehicle (or placebo), or corticosteroids were obtained from Medline, EMBASE, and Cochrane databases. Two reviewers identified studies and extracted data, a third reviewer adjudicated disagreements. Outcomes included success, as defined by 90%, 75%, or 50% reductions from baseline in Eczema Area and Severity Index (EASI) scores or equivalent at 1, 3, 6, and 12 months, and also the difference between drug and vehicle (placebo). Rates were combined using a random effects meta-analytic model. Results: Of 180 articles identified, 165 were rejected (142 not RCTs/inappropriate outcome, 23 inappropriate/unextractable data). We included 15 articles reporting on 16 trials (nine tacrolimus and seven pimecrolimus trials) involving a total of 5301 patients, of whom 2107 received tacrolimus, 1225 received pimecrolimus and 1969 patients were controls. Tacrolimus reduced EASI scores by 65.6% at 1 month and 73.0% at 3 months; pimecrolimus reduced scores by 61.5% at 1 month, 60.3% at 6 months, and 61.9% at 12 months. When the difference in EASI score reductions were compared between active drug and placebo, tacrolimus success was 51.5% above placebo at 1 month and pimecrolimus was 45.9% higher at 1 month, 24.9% at 6 months, and 16.1% at 12 months. Conclusions: Success rates for tacrolimus and pimecrolimus were statistically similar. However, tacrolimus rates were consistently higher numerically than those for pimecrolimus, and tacrolimus was used in patients with more severe disease. A head-to-head RCT is required to determine if true differences exist between these drugs.     

The Role of Topical Calcineurin Inhibitors for Skin Diseases Other Than Atopic Dermatitis

The topical calcineurin inhibitors (TCIs) pimecrolimus and tacrolimus are approved for atopic dermatitis but have additional potential in other inflammatory skin diseases. This article reviews their clinical use in non-atopic dermatitis diseases. In seborrheic dermatitis, asteatotic eczema, and contact dermatitis, TCIs are of great benefit and can compete with topical corticosteroids. In psoriasis, TCIs have shown clinical efficacy and safety in facial and intertriginous lesions. Further investigations into possible combinations of TCIs with other established treatments such as UVB irradiation in this disorder are necessary. Initial studies in cutaneous lupus erythematosus have been promising, whereas the response in rosacea and rosacea-like eruptions has been mixed. TCIs have been associated with good clinical responses in oral lichen planus and anogenital lichen sclerosus et atrophicus. In vitiligo, TCIs are associated with some degree of repigmentation, with better results being seen in children and in facial and neck areas. TCIs have a synergistic effect with UVB irradiation in vitiligo. There is a long list of small series and case reports documenting use of TCIs in various other skin conditions that warrant further validation. Although the established mode of action of TCIs is T-cell control, other effects also need to be considered. Specifically, TCIs reduce pruritus and erythema, which cannot be explained by T-cell interactions, and further investigations are needed in these fields.     

Calcineurin Inhibitors in Pediatric Atopic Dermatitis

Atopic dermatitis (AD) is a common, chronic inflammatory dermatosis with a prevalence of 7-21% in school-aged children. Childhood AD has a profound impact on the social, personal, emotional, and financial perspectives of families. For the last half-century, topical corticosteroids of different potencies have been the mainstay of topical therapy. In recent years, two topical calcineurin inhibitors (TCIs), tacrolimus and pimecrolimus, have become available for the treatment of AD. Both tacrolimus and pimecrolimus have been extensively evaluated in the management of pediatric AD. Trials comparing them with placebo, topical corticosteroids, and each other have shown them to be effective and safe for continuous short-term use, and for noncontinuous use for up to 4 years. Long-term safety of TCIs is not known as they have been in clinical use for less than a decade.     

Role of Topical Calcineurin Inhibitors in the Treatment of Seborrheic Dermatitis

Seborrheic dermatitis (SD) is characterized by erythematous pruritic patches and plaques with greasy scale that occur in sebaceous areas. It is common, affecting up to 3% of the population. Past treatments have relied on a wide variety of anti-inflammatory and antifungal agents, but corticosteroids have limited use because of long-term adverse effects. Topical calcineurin inhibitors provide a safe alternative for the treatment of SD, as these drugs block the inflammatory cascade involved in the disease process and pose no risk of skin atrophy. Studies of topical pimecrolimus and tacrolimus in the treatment of SD have found that improvement occurred within 2 weeks, and if SD recurred after stopping treatment, it was significantly less severe. There have been no studies of the comparative efficacy of pimecrolimus versus tacrolimus for the treatment of SD. Common adverse effects of mild burning and irritation have been associated with the use of both of these agents. Safety profile studies are limited to studies of atopic dermatitis, which show no increase in infection rate, photocarcinogenicity, or signs of immunosuppression in patients using topical calcineurin inhibitors for long-term treatment. This article reviews the clinical trials of pimecrolimus and tacrolimus in the treatment of SD, focusing on efficacy and safety.     

Impact of Topical Calcineurin Inhibitors on Quality of Life in Patients with Atopic Dermatitis

This review considers randomized trials of topical calcineurin inhibitors in atopic dermatitis that have included quality-of-life (QOL) data. Relatively few trials were identified and several different QOL measures have been used, partly because trial subjects included adults, children, and the parents of affected infants. Tacrolimus 0.1% and 0.03% ointment and pimecrolimus 1% cream were found to be superior to vehicle treatment in terms of QOL for active AD. In adults, tacrolimus 0.1% ointment provided a greater improvement in QOL than the 0.03% strength. Pimecrolimus 1% cream was superior to vehicle treatment for flare prevention in the studies that contained QOL outcomes but no data are available for tacrolimus ointment in this regard. QOL data comparing topical calcineurin inhibitors with other active treatments such as topical corticosteroids are sparse and it would be useful for future randomized trials to include QOL measures as a primary outcome.     

Efficacy Versus Systemic Effects of Six Topical Steroids in the Treatment of Atopic Dermatitis of Childhood

Six groups of children suffering from widespread atopic dermatitis were treated once daily with six topical steroids of different potency. Systemic effects were measured by the morning estimation of plasma cortisol. A clear relationship was demonstrated between clinical efficacy of the steroid treatment and degree of reduced adrenal function. This study demonstrated that a rapid and marked therapeutic effect can be obtained with potent topical steroids applied once daily without occlusion, but in children is accompanied by a fall in plasma cortisol.     

湿包裹治疗儿童重度特应性皮炎的疗效观察

目的 观察湿包裹(WWT)治疗儿童重度特应性皮炎(AD)的疗效和安全性.方法 2018年9月-2019年9月在南京儿童医院皮肤科门诊诊断为重度AD的患儿(符合Williams诊断标准,SCORAD ＞50分)40例,随机分为WWT组(n =20)和传统治疗组(n=20).WWT组采用0.1％糠酸莫米松乳膏联合2％莫匹罗...     

莫匹罗星局部抗菌治疗特应性皮炎的临床研究

目的探讨莫匹罗星局部抗菌治疗在特应性皮炎(AD)中的作用。方法采用随机双盲对照试验将48例AD患者分为2组,前2周分别给予莫匹罗星+来可得与莫匹罗星基质+来可得外用对比治疗;后2周改为开放试验,所有患者均给予莫匹罗星+来可得治疗。结果治疗后第1周、第2周2组患者总有效率分别为:研究组74.07％、88.88％,对照组25％、60％,经统计学检验研究组总有效率优于对照组(P<0.01,P<0.05);治疗后第4周2组总有效率分别为:研究组92.59％,对照组95％,经统计学检验2组总有效率无差异(P>0.05)。治疗后第1、2、4周时细菌学清除率2组相比统计学无差异(P>0.05)。结论局部抗菌药物与皮质类固醇联合应用治疗AD疗效优于单用皮质类固醇。     

JAK Inhibitors for Atopic Dermatitis: An Update

American Journal of Clinical Dermatology - Atopic dermatitis (AD) is one of the most common inflammatory skin diseases. AD is driven by barrier dysfunction and abnormal immune activation of...     

Topical Therapy in Atopic Dermatitis in Children

Atopic dermatitis (AD) is a common, chronic childhood skin disorder caused by complex genetic, immunological, and environmental interactions. It significantly impairs quality of life for both child and family. Treatment is complex and must be tailored to the individual taking into account personal, social, and emotional factors, as well as disease severity. This review covers the management of AD in children with topical treatments, focusing on: education and empowerment of patients and caregivers, avoidance of trigger factors, repair and maintenance of the skin barrier by correct use of emollients, control of inflammation with topical corticosteroids and calcineurin inhibitors, minimizing infection, and the use of bandages and body suits.     

Atopic Dermatitis: Studies of Skin Permeability and Effectiveness of Topical PUVA Treatment

Ultraviolet light is effective treatment for patients with atopic dermatitis that is resistant to conservative therapy, or complicated by adverse effects of extended steroid use. We designed a protocol using topical psoralen chemotherapy with ultraviolet A (PUVA) to treat atopic dermatitis in 114 patients. Clinical results were excellent, with complete clearing in 50% of patients receiving daily treatment. Histologic and immunologic values correlated with the clinical response, including reduced epidermal thickness, and decreased numbers of epidermal Langerhans cells and dermal mast and mononuclear cell infiltrates. The pattern of keratin 14-positive keratinocytes returned toward normal. In addition, the water-holding capacity of the stratum corneum increased to near normal levels. We also studied stratum corneum permeability in lesional and nonlesional skin using the dimethyl sulfoxide whealing test and theophylline absorption studies. Compared with controls, permeability was markedly increased in lesional skin and mildly increased in nonlesional skin in patients with atopic dermatitis. These results suggest that immune abnormalities and barrier dysfunction participate in the pathogenesis of atopic dermatitis.     

他克莫司软膏治疗成人特应性皮炎疗效和安全性研究

目的 评价0.1%和0.03%他克莫司软膏治疗成人中、重度特应性皮炎的疗效和安全性。方法 采用多中心、随机双盲、赋形剂平行对照的临床研究,受试者每日2次外搽0.1%或0.03%他克莫司软膏或赋形剂。疗程3周,于治疗前及治疗后第1、2、3周各访视1次,进行疗效和安全性评价。结果 6个中心共有211例中、重度特应性皮炎患者纳入疗效分析。治疗结束时,0.1%和0.03%他克莫司软膏组治疗有效率分别为88.4%和77.8%,均明显高于赋形剂组的30.0%(P<0.001)。治疗后第1、2、3周,0.1%和0.03%他克莫司软膏组湿疹面积与严重度指数、皮损受累面积百分比、症状/体征总评分、研究者对治疗临床反应总评、患者对瘙痒自我评分均明显优于赋形剂组,且多于治疗后第1周始即明显改善(P=0.002-P<0.001),0.1%他克莫司软膏组疗效优于0.03%他克莫司软膏组。0.1%和0.03%他克莫司软膏组药物相关性不良反应发生率分别为47.3%和40.0%,均高于赋形剂组的28.2%,主要表现为皮肤灼热、瘙痒/瘙痒加重或刺痛等局部刺激反应。结论 0.1%和0.03%他克莫司软膏对治疗成人特应性皮炎具有良好的疗效和安全性。     

龙牡汤治疗特应性皮炎的临床疗效评价

目的 观察龙牡汤治疗血虚风燥型特应性皮炎的临床疗效、安全性及对患者生活质量的改善情况、复发情况.方法 采用随机对照方法将64例患者随机分配到试验组(龙牡汤内服加外洗组)和对照组(氯雷他定片和丁酸氢化可的松乳膏组),疗程8周.于治疗前、治疗第2周、第4周、第8周记录皮肤病变面积、皮损严重程度、瘙痒及患者的生活质量、用药情况、不良反应等,并在疗程结束后第3、6个月记录复发情况.结果 试验组治疗前后症状体征积分比较有显著性差异,与对照组疗效相当;两组治疗前后生活质量评分比较无显著性差异;两组复发情况比较差异有显著性,对照组6个月的复发风险是试验组的3.14倍.结论 龙牡汤内外合治特应性皮炎,有一定临床疗效.     

Spotlight on Topical Pimecrolimus in Pediatric Atopic Dermatitis

Topical pimecrolimus 1% cream (Elidel®) [hereafter referred to as topical pimecrolimus] is a nonsteroidal alternative in the treatment of pediatric atopic dermatitis. In vehicle-controlled, short-term, continuous-use trials in pediatric patients with mild to moderate atopic dermatitis, topical pimecrolimus was effective in treating disease symptoms. Topical pimecrolimus was effective in preventing disease flares and reducing the need for topical corticosteroids in longer term, intermittent-use trials. In addition, topical pimecrolimus was associated with improvements in the health-related quality of life of pediatric patients with atopic dermatitis and their parents. In vehicle-controlled trials, topical pimecrolimus was generally as well tolerated as vehicle. Topical pimecrolimus showed similar efficacy to topical tacrolimus 0.03% ointment in a short-term, continuous-use trial and the two agents had a generally similar tolerability profile. Although comparative data between topical pimecrolimus and topical corticosteroids are lacking in pediatric patients, and the long-term tolerability (beyond 1–2 years) of topical pimecrolimus is yet to be established, topical pimecrolimus is a useful agent in the management of pediatric patients with mild to moderate atopic dermatitis who do not achieve satisfactory treatment with other topical pharmacologic treatments, including topical corticosteroids.     

他克莫司软膏治疗儿童特应性皮炎疗效和安全性研究

目的评价0．03％他克莫司软膏治疗儿童中、重度特应性皮炎的疗效和安全性。方法采用多中心．随机、双肓、赋形剂平行对照的临床研究,受试者每日2次外搽0.03％他克莫司软膏或赋形剂,疗程3周,于治疗前及治疗后第1、2、3周各随访1次,进行疗效和安全性评价。结果 5个中心共有139例中、重度儿童特应性皮炎患者纳入疗效分析。治疗结束时,0.03％他克莫司软膏组治疗有效率为84.6％,明显高于赋形剂组的29.0％(P<0．001)。其他疗效评估指标包括湿疹面积与严重度指数、皮损受累面积百分比、症状/体征总评分、研究者对治疗临床反应总评、患者／监护人对瘙痒自我评分。在治疗后第1、2、3周0.03％他克莫司软膏组明显优于赋形剂组,且均于治疗后第1周始即明显改善(P=0.002～P<0．001)。0.03％他克莫司软膏组药物相关不良反应发生率为32.9％,赋形剂组为37.7％,主要表现为皮肤灼热、瘙痒／瘙痒加重或刺痛等局部刺激反应。结论 0.03％他克莫司软膏对治疗儿童特应性皮炎具有良好的疗效和安全性。     

Cancer Concerns with Topical Immunomodulators in Atopic Dermatitis

The topical immunomodulators tacrolimus and pimecrolimus were approved for the treatment of atopic dermatitis in 2000 and 2001, respectively. However, on 20 January 2006, the US FDA approved a 'black box' warning for these agents because of concerns regarding a possible link to development of malignancy. These concerns were based upon the known mechanism of action of this drug class, the results of animal studies, and case reports. This article provides an overview of the data that led to the approval by the FDA of a 'black box' warning and concludes that physicians, patients, and caregivers should feel confident about using tacrolimus and pimecrolimus for atopic dermatitis so long as they follow the FDA guidelines.     

复方苦参颗粒对重度特应性皮炎51例的治疗效果

目的 评估复方苦参颗粒治疗重度特应性皮炎的疗效及安全性.方法 51例门诊病人参加此次研究.记录治疗前后的湿疹评分,以及治疗前后的嗜酸粒细胞(EOS)和血清总IgE值.复方苦参颗粒口服1～2g/次,3次/d,外用方1患部外洗1～2次,d,外用方2惠部外用2～5 R/d.结果 治疗后特应性皮炎患者症状明显改善,治疗前全部极重度,治疗后94.1%的患者改善为中度以下.瘙痒也明显改善,治疗前全部患者约76.9%有日常生活障碍,治疗后全部患者改善为日常生活没有障碍水平.皮疹和瘙痒的评分,与治疗前比较差异均有显著性(P<0.01).患者EOS和血清总IgE值治疗后都有显著下降,与治疗前比较差异有显著性(P<0.01).有效率94.1%.结论 复方苦参颗粒治疗重度特应性皮炎安全有效.