Thalidomide in the management of epidermolysis bullosa pruriginosa

Epidermolysis bullosa (EB) pruriginosa is a distinctive clinical subtype of dystrophic EB. We report a patient with dominant dystrophic EB pruriginosa, who had an excellent response to systemic thalidomide treatment. The mechanism of action of thalidomide in the management of pruriginous disorders is not yet completely understood. Most recent studies point towards an immunomodulatory action of thalidomide that may suppress excessive production of tumour necrosis factor-alpha and may downregulate certain cell surface adhesion molecules involved in leucocyte migration.     

Clinical and immunological studies for 105 Japanese seropositive patients of epidermolysis bullosa acquisita examined at Kurume University

Objectives: Using our serological diagnostic criteria, we selected 105 Japanese patients with epidermolysis bullosa acquisita (EBA), an autoimmune bullous disease (AIBD) reacting with type VII collagen, from our cohort of 5063 AIBD patients.

Methods: We examined the patients clinically and immunologically.

Results: We found diversity of clinical manifestations in both cutaneous and oral mucosal lesions and a high rate of inflammatory-type EBA patients in Japan. Common treatments were systemic steroids, followed by immunosuppressives, DDS, tetracycline/minocycline and colchicine. Immunological studies revealed that indirect immunofluorescence of 1M-NaCl-split skin, immunoblotting of dermal extract, and type VII collagen ELISA were sensitive methods, with possible multiplicity of circulating autoantibodies against other basement membrane autoantigens.

Conclusion: The present study analyzed the largest cohort of EBA patients, confirming the scarcity of EBA (only 105 of the 5063 AIBD patients), and showed that the three serological tests are useful for the diagnosis of EBA.     

获得性大疱性表皮松解症基底膜自身抗体靶抗原的定位研究

目的 探讨获得性大疱性表皮松解症(EBA)基底膜带自身抗体(BMZ—Ab)的靶抗原及其定位情况。方法 用免疫印迹(IB)、盐裂皮肤间接免疫荧光(IIF)、间接免疫电镜(IIEM)等方法检测6例EBA血清中。IgG型及IgA型BMZ—Ab识别的真表皮抗原以及抗原定位情况。结果 6例EBA血清中IgG型BMZ—Ab均结合真皮提取物中290ku蛋白，3例同时伴有结合290ku蛋白的IgA型BMZ—Ab。盐裂皮肤IIF显示BMZ真皮侧IgG线状沉积，IIEM示金颗粒沉积于BMZ致密下层，即真皮锚原纤维的Ⅶ型胶原处。结论 位于BMZ致密下层的Ⅶ型胶原是EBA中BMZ-Ab的特异性靶抗原，Ⅶ型胶原上的抗原表位可被EBA血清中IgG及IgA型BMZ—Ab识别。     

Clinical and molecular features in a cohort of Middle Eastern patients with epidermolysis bullosa

Background

Epidermolysis bullosa (EB) features skin and mucosal fragility due to pathogenic variants in genes encoding components of the cutaneous basement membrane. Based on the level of separation within the dermal-epidermal junction, EB is sub-classified into four major types including EB simplex (EBS), junctional EB (JEB), dystrophic EB (DEB), and Kindler EB (KEB) with 16 EB-associated genes reported to date.

Methods

We ascertained a cohort of 151 EB patients of various Middle Eastern ethnic backgrounds.

Results

The cohort was comprised of EBS (64%, 97/151), DEB (21%, 31/151), JEB (12%, 18/151), and KEB (3%, 5/151). KRT14 and KRT5 variants were most common among EBS patients with 43% (42/97) and 46% (45/97) of EBS patients carrying mutations in either of these two genes, respectively. Truncal involvement was more common in KRT14-associated EBS as compared to EBS due to KRT5 mutations (p < .05). Mutations in COL17A1 and laminin 332-encoding genes were identified in 55% (10/18) and 45% (8/18) of JEB patients. Scarring alopecia, caries, and EB nevi were most common among JEB patients carrying COL17A1 mutations as compared to laminin 332-associated JEB (p < .05). Abnormal nails were evident in most DEB and JEB patients while poikiloderma was exclusively observed in KEB (p < .001).

Conclusions

EB patients of Middle Eastern origin were found to feature specific phenotype–genotype correlations of relevance to the diagnosis and genetic counseling of patients in this region.     

先天性皮肤缺损三例报告并文献复习

目的 探讨先天性皮肤缺损的病因、分类、治疗及预后,提高该病的诊治水平.方法 回顾性分析我院治疗的3例先天性皮肤缺损患儿发病特点、治疗过程、方法,并复习国内外文献中报道的皮肤缺损305例,总结先天性皮肤缺损的临床特点及诊治经验.结果 3例患儿缺损皮肤均由羊皮纸样瘢痕组织愈合,无组织挛缩,无活动障碍.305例患儿中死亡8例;保守治疗234例;手术治疗63例,其中因瘢痕挛缩影响肢体功能者5例.该病致死率、致残率低,预后良好.结论 先天性皮肤缺损是一种病因尚不明确的疾病,创面表浅者多可经保守治疗后痊愈,骨外露、重要脏器外露、深度缺损宜适时采用手术治疗,该疾病若能给予正确处理,预后良好,对患儿日常生活影响小.     

营养不良性大疱性表皮松解症COL7A1基因诊断及产前诊断

目的 分析2个营养不良性大疱性表皮松解症(DEB)家系致病基因COL7A1基因突变位点,并在此基础上探讨COL7A1基因分析用于产前诊断的可行性.方法 应用全基因捕获新一代测序(NGS)对2013年10月和2014年4月在郑州大学第一附属医院就诊的2个DEB家系中2例先证者COL7A1基因进行全基因突变检测,获得变异序列后,针对所检出变异序列进行PCR扩增后Sanger双向测序对2个DEB家系中2例先证者及其父母和100名健康个体的COL7A1基因序列进行突变验证分析,确定致病突变后,对其中1个家系中的高危胎儿进行孕早期产前诊断.结果 共发现4种COL7A1基因突变:c.5230G ＞T (p.E1744X)、c.5932C ＞T (p.R1978X)、c.5605-10 T＞G(IVS66-10 T＞G)、c.8305-1G＞A(IVS110-1G＞A).其中p.E1744X、IVS66-10 T＞G和IVS110-1G＞A为国际首次报道的突变.家系1中先证者携带COL7A1基因p.E1744X和p.R1978X无义突变,父母分别为杂合突变携带者;家系2中先证者携带COL7A1基因IVS66-10T＞G和IVS110-1G ＞A剪接区突变,父母分别为杂合突变携带者;100名健康个体未检测到上述突变.家系1中产前诊断胎儿携带与其先证者相同的突变为受累胎儿,胎儿父母选择治疗性引产术后,取胎儿标本行基因诊断,结果与产前诊断相同.结论 COL7A1基因突变是该2个DEB家系的致病原因,NGS结合Sanger测序方法可以快速且准确地进行该病的基因诊断和产前诊断.     

Epidermolysis bullosa naevi reveal a distinctive dermoscopic pattern

BACKGROUND: Large, asymmetrical and irregularly pigmented naevi in patients with epidermolysis bullosa (EB) have been reported often to mimic cutaneous melanoma clinically. OBJECTIVES: As the biological course of these peculiar moles is benign, we assessed EB naevi with a dermatoscope to determine whether they could be reliably differentiated from cutaneous melanoma. METHODS: We evaluated digital dermoscopic images of 23 EB naevi from 11 patients with EB and analysed these pigmented lesions according to pattern analysis, ABCD rule of dermoscopy and the seven-point checklist. RESULTS: Melanoma-associated dermoscopic criteria such as multicomponent pattern (20 of 23), atypical pigment network (17 of 23), irregular dots/globules (16 of 23), irregular pigmentation (22 of 23) and an atypical vascular pattern (seven of 23) were frequently seen in EB naevi. In contrast, other criteria frequently associated with melanoma progression, such as irregular streaks, blue-whitish veil, regression structures (blue-whitish areas) or black dots, were rarely seen. Most lesions gave false-positive results when the scores of the dermoscopic diagnostic algorithms were calculated. CONCLUSIONS: Recurring dermoscopic structures in EB naevi reveal a distinctive dermoscopic pattern of this recently defined entity. Although EB naevi represent an exception to dermoscopic diagnostic algorithms, their dermoscopic evaluation most often allows us to estimate their benign nature. Nevertheless, as an unequivocal discrimination from malignant melanoma in vivo is sometimes not possible, regular clinical follow up of EB naevi with histopathological evaluation of highly suspicious lesions is mandatory.     

CLINICAL MANAGEMENT FOR EPIDERMOLYSIS BULLOSA DYSTROPHICA

Epidermolysis bullosa (EB) consists of a group of genetic hereditary disorders in which patients frequently present fragile skin and mucosa that form blisters following minor trauma. More than 20 subtypes of EB have been recognized in the literature. Specific genetic mutations are well characterized for most the different EB subtypes and variants. The most common oral manifestations of EB are painful blisters affecting all the oral surfaces. Dental treatment for patients with EB consists of palliative therapy for its oral manifestations along with typical restorative and periodontal procedures. The aim of this article is to describe two dental clinical treatments of recessive dystrophic EB cases and their specific clinical manifestations. The psychological intervention required during the dental treatment of these patients is also presented.