Communicating a drug alert

In October 1990, a recall procedure was initiated for the teratogenic drug acitretin, and the recommended post-therapy contraception period after acitretin therapy was extended from 2 months to 2 years due to the possibility of its conversion to the lipophilic compound etretinate. The aim of the present study was to evaluate the communication procedures and their effects as a drug alert from the health authorities, the pharmaceutical company and professional associations of health professionals to the population at risk.A model was used to evaluate communication between three hierarchical levels. Data were obtained via semi-structured interviews and structured questionnaires. Communication procedures were evaluated according to channel characteristics and by analysis of their contents. The effect was measured as whether the drug dispensers identified acitretin users, contacted physicians, and whether physicians communicated in person with the population at risk.The penetration of direct mail from the health authorities and from the pharmaceutical company ranged from 97–98% and 65–94% at Level 2 (health professionals). The population at risk was informed via personal communication with health professionals, and/or the mass media. Of the women at risk, 19% were contacted by a dermatologist, 30% by their GP, and 39% by the pharmacist. 35% was never informed by any health professional.The Dutch health care system is adequately equipped for effective communication between health authorities, pharmaceutical industry and health professionals. Due to problems with identification in terms of past exposure, subsequent personal communication between health professionals and the population at risk was inadequate. Therefore, the role in personal communication of health professionals should be increased, as they can rapidly identify persons at risk as a result of previous exposure. In The Netherlands drug dispensers should have an important role.     

阿维A酸治疗银屑病疗效的系统评价

目的通过对阿维A酸治疗银屑病的随机对照试验研究进行系统评价，了解阿维A酸治疗银屑病的有效性。方法将观察应用阿维A酸治疗银屑病患者疗效的随机或半随机对照试验进行分析，将有效率作为观察指标。检索中英文文献应用Medline、Pubmed（1966—2004）、Ovid、TheCochrane library2004．妒、中国生物医学文献数据库（1978—2004）、Vip全文数据库（1994-2004）、解放军医学图书馆、国家科技图书文献中心的数据库进行电子检索结合手工检索国内的期刊杂志和药厂提供的资料。应用Jadad量表的质量标准进行文献评价，RevMan4．2版软件进行统计分析。用比值比（D曰）和95％CI为疗效分析统计量。采用SPSS和SAS软件制作漏斗图分析潜在的发表偏倚。结果有4个阿维A酸治疗银屑病研究的有效率的按亚组分类后，组间无异质（X^2=1．40，P=-0．71，／2=0％），用固定效应模型进行合并，结果显示应用治疗阿维A酸治疗银屑病的有效率与对照组差异有统计学意义[OR 5．93，95％CI（2．79，12．57）]。结论阿维A酸治疗银屑病是有效的，其安全性还需进一步评价，今后随着高质量的报告出现，可以不断的完善本评价。     

Capillary leak syndrome induced by acitretin

The mucocutaneous side-effects of systemic retinoids are well known. We report a patient with diffuse oedema, which is a very rare side-effect of retinoids. The pathophysiology of this condition is poorly known because of the rarity of relevant observations, but apparently corresponds to capillary leak syndrome. The outcome is invariably favourable following withdrawal of the drug, which should be definitively contraindicated in the patient.     

Oral liarozole vs. acitretin in the treatment of ichthyosis: a phase II/III multicentre, double-blind, randomized, active-controlled study

BACKGROUND: Liarozole, a retinoic acid metabolism blocking agent, has been granted orphan drug status for congenital ichthyosis by the European Commission and the U.S. Food and Drug Administration. OBJECTIVES: The purpose of this trial was to investigate the efficacy, tolerability and safety of oral liarozole vs. acitretin in patients with ichthyosis. METHODS: In this double-blind comparative trial of liarozole vs. acitretin, 32 patients with ichthyosis were randomized to be treated with either oral liarozole 75 mg in the morning and 75 mg in the evening or with acitretin 10 mg in the morning and 25 mg in the evening for 12 weeks. Clinical efficacy, tolerability and safety were monitored. RESULTS: Between-group comparisons for efficacy and tolerability revealed no statistically significant differences except for scaling on the trunk at baseline which was significantly worse in the liarozole group (P = 0.024) and showed a more pronounced improvement in this group than in the acitretin-treated patients (P = 0.047). Based on the overall evaluation of the response to treatment at endpoint, 10 of 15 patients in the liarozole group and 13 of 16 patients in the acitretin group were considered by the investigator to be at least markedly improved. The expected retinoic acid-related adverse events were mostly mild to moderate and tended to occur less frequently in the liarozole group. No serious adverse events related to the drugs occurred. CONCLUSIONS: The present study indicates that liarozole at a daily dose of 150 mg is equally effective as a treatment for ichthyosis as acitretin but shows a trend towards a more favourable tolerability profile. The results of this trial warrant further clinical trials to confirm efficacy and safety of liarozole as an orphan drug in ichthyosis.     

Successful treatment of type I adult-onset pityriasis rubra pilaris with infliximab

A 59-year-old woman presented with a painful, pruritic eruption that had commenced as an erythematous, dry patch on the upper back but progressed to erythroderma. Examination revealed orange-tinged erythroderma, scalp scaling, ectropion, palmoplantar keratoderma and nail changes. A diagnosis of type I adult-onset pityriasis rubra pilaris was made, and a subsequent skin biopsy was consistent with this. She was treated with a number of topical and systemic agents with minimal improvement or major side-effects. The patient was then treated with intravenous infliximab 5 mg/kg. She improved dramatically within 2 weeks and was no longer erythrodermic. Five further infusions resulted in additional improvement. Methotrexate was briefly added to the regime, but was ceased owing to nausea. Topical tar and keratolytics were used on the scalp. The patient was left with minimal disease activity and was maintained on emollients.     

Apolipoprotein E gene polymorphisms are associated with psoriasis but do not determine disease response to acitretin

BACKGROUND: Psoriasis is associated with abnormal plasma lipid metabolism and a high frequency of cardiovascular events. Increased lipid levels are also seen in patients with psoriasis treated with acitretin. Apolipoprotein E (ApoE) variants have been linked to hypertriglyceridaemia and hypercholesterolaemia in normal individuals. Two coding single nucleotide polymorphisms at +3937 and +4075 define the three common ApoE alleles e2, e3 and e4. OBJECTIVES: To test the hypothesis that particular ApoE polymorphism(s) are associated with psoriasis and that specific ApoE allelic variant(s) may be a marker for predicting disease response to acitretin. METHODS: DNA was genotyped for ApoE polymorphisms using a radioactive hybridization technique in cohorts of patients with psoriasis, including patients with chronic plaque psoriasis (CPP, n = 212), guttate psoriasis (GP, n = 94), palmoplantar pustulosis (PPP, n = 101), controls (n = 137), acitretin responders (n =106) and acitretin nonresponders (n = 84). RESULTS: The frequency of the e4 allele (+3937C/+4075C) was significantly higher in patients with CPP and GP than in controls (P = 0.008 and P = 0.02, respectively). There was no significant difference in allele frequencies between patients with PPP and controls. Allelic distribution was similar in acitretin responders and nonresponders. CONCLUSIONS: These data demonstrate an association between the Apo e4 allele and CPP and GP, suggesting a possible pathogenic role for ApoE in psoriasis. Our results do not support a link between disease response to acitretin and the e2, e3 or e4 allelic variants of ApoE.     

Multiple porokeratomas (porokeratotic acanthoma) coexisting with disseminated superficial porokeratosis: Clinical,dermoscopic and pathological observations,and review of published work

Porokeratoma is a recently described solitary or multiple tumor-like acanthoma, sharing the histological feature of cornoid lamellae with porokeratosis. Whether porokeratoma is a variant of porokeratosis is controversial. We report a rare case of a 53-year-old Chinese woman who presented with multiple, symmetrical, hemispherical and verrucous plaques on her lower extremities that had been present for 20 years. The clinical manifestation resembled the fungal disease of chromoblastomycosis. The diagnosis of multiple porokeratoma coexisting with disseminated superficial porokeratosis was rendered according to the clinical, dermoscopic and pathological features. Oral acitretin (30 mg/day) and laser therapy were administrated. After 6 months of treatment, the number of plaques on her limbs was significantly reduced without recurrence. From this case, we speculate that porokeratoma is a rare and special variant of porokeratosis. In complex cases with multiple lesions, oral acitretin can be combined with surgery, cryotherapy and laser therapy.     

窄谱中波紫外线照射与308nm准分子光分别联合阿维A胶囊对寻常型银屑病的疗效比较

目的比较窄谱中波紫外线照射与308 nm准分子光分别联合阿维A胶囊对寻常型银屑病的疗效。方法根据治疗方式的不同将130例寻常型银屑病患者分为A组与B组,各65例,A组予以窄谱中波紫外线照射联合维A胶囊治疗,B组予以308 nm准分子光联合维A胶囊治疗。比较两组的临床疗效、治疗前、后SCORAD、VAS、PASI、SAS、SDS评分及不良反应发生情况。结果 B组的治疗总有效率显著高于A组(P<0.05)。治疗后,两组的SCORAD、VAS和PASI评分均降低,差异具有统计学意义(P<0.05);治疗后,B组的SCORAD、VAS和PASI评分均显著低于A组,差异具有统计学意义(P<0.05)。治疗后,两组的SAS及SDS评分均降低,差异具有统计学意义(P<0.05);治疗后,B组的SAS及SDS评分略低于A组,但差异不具有统计学意义(P>0.05)。B组的不良反应总发生率显著低于A组(P<0.05)。结论 308 nm准分子光联合阿维A胶囊治疗寻常型银屑病更为安全有效,可提高患者生活质量,减少不良反应,值得推广应用。     

Cover Image,Volume 33, Issue 3

Most available options for the treatment of warts are limited by the potential for scarring, pain, lack of response, or recurrences, and the patients are often unable to tolerate and accept those experiences. The aim of this study was to evaluate the clinical efficacy and safety of oral systemic acitretin monotherapy in patients with extensive/recalcitrant cutaneous warts. The patients were given a dose of acitretin of 0.8 mg kg⁻¹ day⁻¹, and the clinical efficacy and safety of acitretin was assessed every 2 weeks for 2 months. A total of 14 patients (12 males and 2 females) were included, with an age of 14‐60 years (mean 33 ± 14.7 years) and a course of 4‐48 months (mean 21.6 ± 13.4 months). After 2 months of acitretin treatment, 42.9% (6/14) of patients (including warts of the feet, legs, and hands) exhibited complete response, 28.6% (4/14) excellent response, and 28.6% (4/14) good response. All patients demonstrated significant improvement, and the drug was well tolerated, with no patients discontinuing therapy due to side effects. Common mild side effects included dry skin and cheilitis. There were no recurrences during a follow‐up period of 6 months. Acitretin monotherapy is an effective, safe, and well‐tolerated treatment for patients with extensive/recalcitrant cutaneous warts who are unsuitable for or unwilling to accept traditional treatment methods.     

呈网状红斑改变的扁平苔藓

报告1例呈网状红斑改变的扁平苔藓。患者女,34岁。全身泛发网状红斑22年,伴瘙痒,有口腔黏膜及甲受累。皮肤科检查见全身泛发网状红斑,部分红斑消退后局部有轻度萎缩,散在水疱,尼氏征阴性。双手多个指甲甲板萎缩、吸收。上腭见片状糜烂面。组织病理检查示表皮变薄,基底细胞广泛液化变性,真皮浅层淋巴细胞呈带状浸润。诊断：扁平苔藓。给予阿维A40mg/d口服3个月后皮损明显变平,颜色变暗。