The molecular basis for inherited bullous diseases

In the past 5 years enormous progress have been made in our understanding of the molecular basis for a number of inherited skin diseases characterized by easy blistering of the skin and the mucous membranes after minor physical trauma. This increased fragility of the skin or its appendages is due to molecular defects in genes coding for different intra- and extracellular structural proteins which are responsible for mechanical strength at their sites of expression. These diseases encompass the group of epidermolysis bullosa and disorders of cornification such as bullous forms of ichthyosis, palmoplantar keratoderma, and pachyonychia congenita. On the basis of clinical, morphological, and ultrastructural observations the epidermolysis bullosa group has been divided into three major categories. In epidermolysis bullosa simplex blister formation appears within the basal cell layer of the epidermis, and many mutations have been found in the genes of keratin 5 and 14 which are both expressed in basal keratinocytes. Epidermolytic hyperkeratosis leads to an epidermal separation in the suprabasal cell layers. In these patients numerous point mutations have now been described in the suprabasally expressed genes of keratin 1 and 10. In ichthyosis bullosa of Siemens blisters occur in the more upper suprabasal epidermis coincidental with the expression of keratin 2e, and mutations have been detected in the corresponding gene. In epidermolytic palmoplantar hyperkeratosis the suprabasal epidermal splitting is restricted to palms and soles of the patient. In keratin 9, which reveals such an exclusive expression pattern, molecular defects have indeed been recognized. Most recently in two different clinical subtypes of pachyonychia congenita, which is characterized by defective nails and focal palmoplantar hyperkeratosis, point mutations have been found in the genes coding for keratins 6, 16, and 17. In junctional epidermolysis bullosa the separation takes place within the dermal-epidermal basement membrane at the level of the lamina lucida, and mutations have been found in three genes coding for different laminin chains, in the ₄ gene of ₆₄ integrin, and in the gene of collagen XVII. In dystrophic epidermolysis bullosa the tissue separation occurs beneath the basement membrane within the papillary dermis at the level of the anchoring fibrils, and several mutations have been identified in the collagen VII gene. The rapid unraveling of molecular defects in these disabling or even lethal inherited skin diseases makes possible a more precise and earlier prenatal diagnosis, creates new options for suitable therapeutic regimens, and even offers the hope of curing these diseases by means of somatic cell gene therapy.Abbreviations BM Basement membrane - BPAg Bullous pemphigoid antigen - DEB Dystrophic epidermolysis bullosa - EB Epidermolysis bullosa - EBS Epidermolysis bullosa simplex - EHK Epidermolytic hyperkeratosis - EPPK Epidermolytic palmoplantar keratoderma - IBS Ichthyosis bullosa of Siemens - JEB Junctional epidermolysis bullosa - KIF Keratin intermediate filaments - NC Noncollagenous domain - NEPPK Nonepidermolytic palmoplantar keratoderma - PC Pachyonychia congenita     

紫外线联合中医辨证对掌跖脓疱病外周血T细胞亚群的影响

目的 观察中药泡洗联合窄谱紫外线治疗掌跖脓疱病的临床疗效及对外周血T淋巴细胞亚群的影响.方法 64例掌跖脓疱病患者随机分为2组,中药组单纯外用自制中药治疗,联合组用中药泡洗联合紫外线治疗,治疗4周为1个疗程,连续治疗8周,治疗4周、8周后分别判定疗效.治疗前后及时检测外周血T淋巴细胞表型中CD3+,CD4+,CD8+细胞的表达情况及判定疗效.结果 治疗4周后,中药组有效率为53.13%,联合组有效率为71.88%,2组比较差异有统计学意义(P<0.05);治疗8周后,中药组有效率为68.75%;联合组有效率为90.63%,2组比较差异有统计学意义(P<0.05).治疗8周后联合组CD4+细胞、CD4+/CD8+细胞比值均明显高于中药组,差异有统计学意义(P<0.05).结论 中药泡洗联合紫外线治疗掌跖脓疱病的临床疗效明显,且不良反应少,安全性高.     

表皮松解性掌跖角化病1例

报告1例表皮松解性掌跖角化病。患者女,26岁。双侧掌跖角化20余年。皮肤科检查见双侧掌跖对称性角化性斑块。皮损组织病理检查示表皮角化过度,颗粒层增厚,棘层及颗粒层中有较多裂隙,裂隙处细胞界限不清,由淡染物质或透明角质颗粒组成。组织病理改变符合表皮松解性掌跖角化病诊断。采用阿维A治疗后皮损明显改善。     

308nm单频准分子光治疗寻常性银屑病和掌跖银屑病临床疗效观察

目的:评估308nm单频准分子光局部照射治疗寻常性银屑病和掌跖银屑病的临床疗效及安全性。方法:采用单频准分子光局部照射治疗35例寻常性银屑病和15例掌跖银屑病患者皮损,每周照射1次或2次,每2周评估疗效1次,并记录不良反应。结果:30例寻常性银屑病患者经16次照射,有效率达70%,慢性斑块型疗效较好。15例掌跖银屑病患者经25次照射,有效率为53.3%。单频准分子光局部照射主要不良反应为瘙痒,局部出现红斑,偶有水疱。结论:308nm单频准分子光局部照射治疗寻常性银屑病和掌跖银屑病见效快,疗程短,且不良反应少。     

他克莫司联合311 nm窄谱中波紫外线治疗掌跖脓疱病疗效与安全性分析

目的 观察他克莫司联合311 nm窄谱中波紫外线治疗掌跖脓疱病的疗效与安全性。方法 99例掌跖脓疱病患者随机分为2组:治疗组皮损处使用311 nm窄谱中波紫外线光疗仪照射,同时外用0.1%他克莫司软膏;对照组仅给予窄谱中波紫外线照射。在治疗后2周、4周、6周、8周判定疗效,记录不良反应。结果 治疗后8周治疗组与对照疗组皮疹总积分为(2.61±1.48)与(3.75±1.99),差异有统计学意义(P＜0.05).治疗组脓疱、红斑积分下降明显。治疗组不良反应发生率13.7%,对照组不良反应8.3%,不良反应发生率无差别(P＞0.05).结论 他克莫司联合311 nm窄谱中波紫外线治疗掌跖脓疱病安全、有效。     

点状掌跖角化病伴高血压-家系遗传分析

目的:对一伴高血压的点状掌跖角化病家系进行分析.方法:对患者家系进行家系调查和分析,观察患者症状,对患者进行医院常规检查.结果:家系中有11人为点状掌跖角化病患者,所有患者皮损均局限于手足部位,发病年龄28岁到55岁,5人伴有高血压及多汗.结论:点状掌跖角化病是一种具有高度外显率的常染色体显性遗传性皮肤病.发病年龄10...     

Palmoplantar keratosis in oculodentodigital dysplasia with a GJA1 point mutation out of the C‐terminal region of connexin 43

Gap junction proteins are composed of 21 genes of the connexin (Cx) family. They play important roles in cell–cell contact by exchange of small molecules through hemichannels. Hence, mutations of Cx family genes affect various tissues of a body. The mutation of the GJA1 gene, which codes Cx43, causes oculodentodigital dysplasia (ODDD), commonly in an autosomal dominant manner with phenotypic variability. It has been believed that gene mutations causing truncation of the Cx43 C‐terminus is necessary and sufficient for palmoplantar keratosis (PPK) development in ODDD patients. Here, we report a case of an ODDD patient developing PPK with a GJA1 gene mutation (c.412G>A/p.Gly138Ser), which was previously reported in a case of ODDD without PPK and expected not to result in C‐terminal truncation of Cx43. This case suggests not only C‐terminal truncation, but also that a point mutation in the cytoplasmic region of Cx43 can cause PPK in ODDD patients.     

Successful treatment of severe Reiter’s syndrome with etretinate

Abstract

The management of a hyperkeratoitic cutaneous lesion in Reiter’s syndrome (RS) is often unrewarding. Recently, several reports have demonstrated that treatment with etretinate was especially beneficial for severe cutaneous lesion in RS or RS associated with human immunodeficiency virus. We describe a patient with RS whose skin lesions as well as arthritis were successfully treated with oral etretinate.     

Low‐dose etretinate shows promise in management of punctate palmoplantar keratoderma type 1: Case report and review of the published work

Punctate palmoplantar keratoderma type 1 (PPKP1) is a rare autosomal dominant disorder of keratinization, clinically characterized by punctate keratotic papules affecting the palmoplantar skin. Loss‐of‐function mutations in AAGAB have recently been reported as a cause of PPKP1. Despite the discovery of the genetic cause of PPKP1, pathogenesis‐based therapies are still unavailable. Moreover, little is known about the effectiveness of treatments for PPKP1. In this study, we analyzed a Japanese woman with PPKP1 and identified a novel frame‐shift mutation c.195_198del4 (p.Lys66Phefs*43) in AAGAB. Moreover, low‐dose etretinate was effective in improving the PPKP1 lesions in our patient. Our published work review identified only eight cases of PPKP1 with successful response to topical or systemic treatments. Notably, six of the cases were successfully treated with systemic retinoids. Thus, this study clearly provides further evidence that PPKP1 is caused by AAGAB mutations and that systemic retinoids are the most promising current treatment for PPKP1.