In Vivo Skin Penetration of Acitretin in Volunteers Using Three Sampling Techniques

Etretinate and acitretin are given orally to treat psoriasis and various keratinization disorders. Acitretin, the main active metabolite of etretinate, has the pharmacokinetic advantage of being rapidly eliminated, but it shares etretinate's toxicologic profile. Thus a topical delivery of acitretin with no or reduced systemic adverse effects is desirable. To characterize the therapeutic potential of topically delivered acitretin, we quantitatively assessed its percutaneous penetration in healthy human volunteers. Additionally, three skin sampling techniques, the punch biopsy, the shave biopsy, and the suction blister technique, were validated to quantitate acitretin in the skin. The results suggest that topical delivery of acitretin renders skin concentrations which exceed those reported after oral administration of etretinate or acitretin. However, because of possible interlaminate drug contamination, drug localization within a particular skin compartment cannot be determined.     

Efficacy of acitretin in the treatment of reactive neutrophilic dermatoses in adult-onset immunodeficiency due to interferon-gamma autoantibody

Reactive neutrophilic dermatoses in adult-onset immunodeficiency due to interferon-γ autoantibody (AOID) are usually associated with concomitant active opportunistic infections. Data focusing on the treatment of these dermatoses with non-immunosuppressive drugs are still lacking. The aim of this study was to assess the efficacy and safety of acitretin treatment of reactive neutrophilic dermatoses in AOID. We conducted a retrospective review of all patients with AOID who had reactive neutrophilic dermatoses and had been treated with acitretin from January 2008 to December 2018. In total, 23 patients had been diagnosed with AOID, with 27 episodes of reactive neutrophilic dermatoses (20 episodes of Sweet syndrome and seven episodes of generalized pustular eruption) and treated with acitretin. The median effective dose of acitretin was 10 mg/day. The mean initial response was 5.6 ± 2.3 days. The rash had almost or completely cleared within 2 weeks in 70.4% of patients. One case had developed a reversible acitretin-induced liver injury with hepatocellular pattern. The median total duration of treatment was 3 months. In conclusion, this study demonstrates the potential role of acitretin as one of the treatments of choice for reactive neutrophilic dermatoses in AOID, attributable to its favorable response and good tolerability.     

Case of punctate palmoplantar keratoderma type I treated with combination of low‐dose oral acitretin and topical salicylic acid and steroid

Palmoplantar keratodermas (PPK) are heterogeneous disorders characterized by abnormal keratinization. Especially, punctate PPK (PPPK), one of the subtypes of hereditary PPK, is a rare punctate keratoderma characterized by tiny “raindrop” keratoses having a tendency to coalesce on the edge of soles, which are exposed to sustained pressure. If typical punctate lesions are confined to the palms and soles and the patient has a family history and late onset, it can be considered as PPPK type I (PPKP1), also called Buschke–Fisher–Brauer disease. The exact etiology of PPPK has not been fully understood. Furthermore, no standardized treatment for PPPK has been established and treatment options are limited. Above all, traditional systemic retinoids have been used in several cases, but dose‐related adverse effects are common. Therefore, combination of low‐dose systemic retinoids and adjuvant topical therapy can be an alternative treatment option for PPPK. Herein, we report a case of PPKP1 treated with combination of low‐dose oral acitretin (10 mg/day) and topical salicylic acid and steroid. Despite low capacity, low‐dose acitretin showed excellent regression of the lesions by combined use of topical ointments. The supplementary topical therapy may be useful in reducing the dose of systemic retinoids and preventing potential toxicity.     

桐油联合阿维A酸对银屑病的疗效及其对IL-23/Th17信号通路的影响

目的 观察桐油联合阿维A酸对轻、中度寻常型银屑病的疗效及其对IL-23/Th17信号通路的影响。方法 将196例寻常型银屑病患者随机分为桐油组及对照组,每组98例,对照组患者均给予阿维A酸联合窄谱中波紫外线（NB-UVB）治疗,桐油组患者在对照组治疗基础上给予桐油外敷。以银屑病皮损面积和严重程度指数（psoriasis area and severity index,PASI）评价桐油组及对照组疗效。酶联免疫吸附试验法（ELISA）检测治疗前后2组皮损组织中IL-17、IL-22、TNF-α和IL-23水平变化。免疫组织化学法分析治疗前后2组皮损组织中Th17细胞含量变化。结果 桐油组的总有效率（94.90%）显著高于对照组（76.53%）（P<0.05）。与治疗前相比,治疗后2组PASI评分均显著降低（P<0.01）,且治疗后桐油组显著低于对照组（P<0.05）。与治疗前相比,治疗后2组皮损中IL-23、IL-17、IL-22和TNF-α水平均显著降低（P<0.05）,且治疗后桐油组显著低于对照组（P<0.05）。治疗后2组患者皮损组织中Th17细胞百分比显著低于治疗前,且桐油组显著低于对照组（P<0.05）。桐油组不良反应发生率（14.29%）略高低于对照组（10.20%）,但差异不具有统计学意义。结论 桐油外敷联合阿维A酸治疗轻、中度寻常型银屑病有较好的疗效,其机制可能与抑制患者皮损组织中IL-23/Th17信号通路的活性有关。     

Retinoic acid for treatment of systemic sclerosis and morphea: A literature review

Systemic sclerosis and morphea are connective tissue diseases characterized by tightening, thickening, and hardening of the skin, leading to significant morbidity. Unfortunately, current treatment options have limited efficacy for many patients. Cutaneous manifestations of these diseases arise from excess collagen deposition and fibrosis in the skin, through pathogenic mechanisms which have yet to be extensively detailed at the causal immune and cellular levels. Research elucidating the mechanism of action of retinoic acid on collagen production in the skin and case series highlighting the success of retinoic acid on the skin manifestations of systemic sclerosis and on morphea demonstrate its promise as a treatment. Herein they will briefly review the treatment options for both systemic sclerosis and morphea, and will discuss the potential of retinoic acid as a therapy and the supporting evidence from the literature, highlighting the previously published basic science and clinical studies investigating the role of retinoic acid in the treatment of sclerotic skin diseases.     

Acitretin in erosive penile lichen planus

Lichen planus (LP) is an incompletely understood T‐cell mediated auto‐immune dermatosis. When LP involves the genitalia it may present as painful, pruritic erosions that can be exquisitely tender, causing distress and genitourinary and sexual dysfunction. Management of erosive genital LP is often suboptimal. Despite higher order evidence demonstrating the efficacy of oral acitretin in the management of cutaneous and oral LP, it still features below other immunosuppressive and immunomodulatory therapies in many clinicians’ therapeutic ladder. We present a case of severe erosive penile LP, successfully treated with oral acitretin after topical and oral corticosteroids failed to induce remission.     

Optimizing acitretin use in patients with plaque psoriasis

Acitretin is one of the systemic agents used for the treatment of psoriasis. Because different acitretin dosages resulted therapeutically successful, there is no general agreement on the optimal dose regimen. To report acitretin efficacy and safety in a real‐life setting, wherein patient‐tailored dose regimen is usually prescribed, a retrospective analysis evaluating charts of all plaque‐type psoriasis patients treated with acitretin from the clinic database was performed. PASI score improvement, as well as PASI 50, 75, 90, and 100 responses were assessed throughout the observational period. Overall, 52% PASI score reduction and a satisfactory safety profile were detected. PASI 50, 75, 90, and 100 response was achieved by 53%, 48%, 28%, and 14%, respectively. Treatment consisted on a mean daily acitretin dose of 25.01 mg. The initial dose was increased (51.2% of cases) or decreased (48.8%) prescribing a mean daily dose of 29.8 mg and 20.02 mg, respectively. This study proposed a dose regimen customized on clinical response and patient's needs, to optimized acitretin benefit.     

维A酸在银屑病患者中的应用

银屑病为常见的慢性复发性皮肤病,维A酸已成功应用于该疾病的治疗。本文重点介绍两种代表性药物——阿维A酸与他扎罗汀在银屑病临床治疗中的有关情况。口服阿维A酸对脓疱型及红皮病型银屑病最为有效,与光疗联合对中、重度斑块性银屑病疗效显著;而他扎罗汀作为第一个受体选择性外用维A酸,不论单用或联合治疗,对寻常型银屑病均有显著疗效。