Identification of the glycine-to-arginine substitution G2043R in type VII collagen in a family with dominant dystrophic epidermolysis bullosa from Hungary

Abstract Epidermolysis bullosa (EB) represents a group of genodermatoses characterized by fragility and easy blistering of the skin. In the dystrophic forms of EB (DEB), blisters occur below the basement membrane, at the level of the anchoring fibrils. In the dominantly inherited forms (DDEB), the predominant type of mutation detected thus far is the substitution of a glycine residue which occurs within the collagenous domain of the molecule characterized by the repeating Gly-X-Y amino acid sequence. In this study, we searched for mutations in DDEB in a family from Hungary, by PCR amplification of segments of COL7A1, followed by heteroduplex analysis. Examination of the PCR fragment corresponding to exon 73 revealed a heteroduplex in affected individuals from the family. Sequence analysis revealed a G-to-A transition at nucleotide 6127 in the triple-helical domain of COL7A1, which converted a glycine residue at amino acid position 2043 to an arginine. This report represents the second incidence of this mutation. G2043R. described first in a family with DDEB from Italy.     

Impaired secretory immunity in dystrophic epidermolysis bullosa

Dystrophic epidermolysis bullosa is a congenital disorder characterized by blistering of the skin and oral mucosa. This study investigated the hypothesis that children with dystrophic epidermolysis bullosa have impaired oral secretory immunity. Immunoglobulin A (IgA), secretory IgA and IgG concentrations, and IgA and secretory IgA antibody levels to Candida albicans, Lactobacillus casei and Streptococcus mutans were measured in whole saliva from 22 children with dystrophic epidermolysis bullosa and 22 matched controls. Salivary total IgA and total IgG concentrations were significantly raised in dystrophic epidermolysis bullosa due to serum leakage from oral blistering, but the converse was seen with secretory IgA. This suggestion of a mucosal immune defect was supported by decreased secretory IgA antibody responses to all three microorganisms tested. This apparent defect in secretory immunity in dystrophic epidermolysis bullosa may be due to mucosal involvement and damage resulting in impaired antigen sampling in mucosal associated lymphoid tissue or to impaired transport of secretory IgA across the salivary gland mucosa.     

Epidermal factors stimulate collagenase synthesis by epidermolysis bullosa fibroblasts

The effect of epidermal factors on the collagenase activity of epidermolysis bullosa (EB) fibroblasts was examined. The epidermal extract obtained from a surgical scar strikingly stimulated the collagenase activity by fibroblasts to 2.55–3.07 U/ml (EB dystrophica recessiva, EBDR) and 1.67–2.03 U/ml (EB dystrophica dominans, EBDD), compared with 0.02–0.07 U/ml (EBDR) and 0–0.04 U/ml (EBDD) in the absence of the factor. Murine epidermal cell-conditioned medium also enhanced the enzyme activity to 1.37–1.41 U/ml (EBDR) and 0.30–0.94 U/ml (EBDD). These results indicate that the epidermal factors, possibly interleukin-1, may regulate collagenase metabolism in EB. Interleukin-1-positive cells were also observed immunohistochemically in the epidermis of EB. Therefore, the present data support the possibility that epidermis may be directly or indirectly involved in altering collagenase synthesis by EB fibroblasts.     

A CASE OF JUNCTIONAL EPIDERMOLYSIS BULLOSA (HERLITZ-PEARSON) WITH CORNEAL BULLAE

A proven case of junctional epidermolysis bullosa is presented in which there have been recurrent right and left corneal lesions. The corneal changes arose either spontaneously or after minor trauma. We have no histological findings of the cornea at present, but the clinical features are similar to those reported in epidermolysis bullosa dystrophica-recessive. We believe that this is the first detailed case report of corneal involvement in proven junctional epidermolysis bullosa. The literature is reviewed.     

白色丘疹样大疱性表皮松解症—附6例报告

报告６例白色丘疹样大疱性表皮松解症，临床上均具有典型的象牙白色丘疹，部位以小腿最多，一般无自觉症状。取水疱作组织病理显示表皮下疱或裂隙，真皮浅层轻度纤维母细胞增生；丘疹的病理表现为真皮浅层结缔组织轻度增生；取１例患者外观正常皮肤作透射电镜发现锚状纤维明显减少。我们认为本病的确诊需同时具有ＥＢ典型表现和特征性的白色丘疹，治疗以对症处理为主，预后较好。     

Expression of mutant p53 gene in squamous carcinoma arising in patients with recessive dystrophic epidermolysis bullosa

Epidermolysis bullosa, a rare genodermatosis, is characterized by increased skin fragility manifest as blistering and sometimes accompanied by scarring. The latter is particularly severe in the recessive dystrophic variant and may be complicated by the development of squamous carcinoma in up to 30% of patients. We have studied 23 such tumours in six patients with this variant, with an anti-serum to p53 protein. Twenty-six per cent of the squamous carcinomas labelled positively for mutant-type p53 protein. This low figure, however, reflects the large number of well-differentiated tumours in this series, where 14 out of 15 were negative. In the moderate to poorly differentiated examples the positivity rate was 63%. Of the three patients in the latter category, one has died from disseminated tumour and another has widespread metastases. The findings support the hypothesis that mutant p53 protein expression correlates with poorer tumour differentiation. They also suggest a possible correlation between p53 protein expression and tumour behaviour.     

Successful radiation therapy for supratentorial primitive neuroectodermal tumor and epidermolysis bullosa simplex

Epidermolysis bullosa simplex (EBS) is a heritable skin disorder characterized by skin fragility and blistering. While its most severe variant, dystrophic epidermolysis bullosa (DEB) is associated with squamous cell carcinoma (SCC), the development of extracutaneous neoplasms in EBS is extremely rare. We report a novel case of supratentorial primitive neuroectodermal tumor (sPNET) in a 7‐year male with EBS. Experience of radiation therapy and its challenges in children with EBS has rarely been reported. Pediatr Blood Cancer 2010; 54:170–172. © 2009 Wiley‐Liss, Inc.     

布洛芬致大疱性表皮松解症样反应

1例47岁女性患者,因血小板减少性紫癜症状加重入院。入院后给予氨磷汀、输注血小板。第11天T38.8℃,给予布洛芬0.05g。次日,患者双下肢皮肤呈现红色皮疹伴瘙痒。第13天T38.9℃,再次给予布洛芬0.05g,随后四肢及胸背部可见红色风团样皮疹,膝部及臀部皮疹部分融合成片,伴有足部及膝部明显疼痛。入院第17天T39.5℃,第3次给予布洛芬0.1g后,患者全身明显疼痛,颌下、双上臂、腹部及背部皮肤出现水泡。行物理降温,给予糖皮质激素及人免疫球蛋白,同时对症处理皮肤水泡,症状逐渐改善。第21天实验室检查示PLT151×10^9/L。共住院1个月,痊愈出院。     

获得性大疱性表皮松解症伴宫颈鳞状细胞癌一例

患者女,54岁,因反复眼干涩2年,躯干四肢水疱伴口腔破溃2个月入院.皮肤科检查:鼻腔黏膜破溃结痂、充血.口腔大片浅溃疡,可见有水疱,表层水肿发白,边缘充血,下唇散在小溃疡,双峡颊黏膜水肿,溃疡与舌背相似.肩部、颈部及躯干见红斑周围或红斑上散在少许水疱,疱壁稍紧张,疱壁薄,尼氏征可疑阳性.该例以黏膜为突出表现,临床表现类似于瘢痕性类天疱疮,容易误诊,且皮疹和黏膜损害随着肿瘤的病情而转变.获得性大疱性表皮松解症与Ⅶ胶原有关,可能与恶性肿瘤及鳞状细胞癌有一定的相关性.