Swensson O, Christophers E
Department of Dermatology, Christian Albrechts University, Kiel, Germany.
Arch Dermatol. 1998 Feb;134(2):199-203. doi: 10.1001/archderm.134.2.199.
Generalized atrophic benign epidermolysis bullosa is a form of junctional epidermolysis bullosa characterized by skin fragility; atrophic alopecia; sparse eyebrows, eyelashes, and axillary and pubic hair; dystrophic fingernails and toenails; and enamel defects in decidual and permanent teeth. Substantial progress was recently made elucidating the genetic defects underlying this disorder. In affected persons, pathogenetic mutations were identified in the genes encoding the beta 3 chain of laminin 5 (LAMB3) or the 180-kd bullous pemphigoid antigen (BPAG2/COL17A1).
Two brothers, aged 39 and 32 years, had characteristic clinical features of generalized atrophic benign epidermolysis bullosa. By electron microscopy, dermoepidermal separation was seen at the level of the lamina lucida, establishing a diagnosis of junctional epidermolysis bullosa. Lesional and clinically unaffected skin showed basal keratinocytes with hypoplastic hemidesmosomes, possibly indicating a defect of hemidesmosomal or associated proteins. Both patients presented with multiple fungating tumors on atrophic and scarred skin on their lower legs; 2 tumors in the older sibling and 4 tumors in the younger sibling were diagnosed as well-differentiated squamous cell carcinomas. Tumor staging elicited no evidence of regional lymph node involvement or systemic disease. Treatment was by microscopically controlled surgery. All wounds were allowed to heal by secondary intention. In both patients, wound healing was markedly delayed and characterized by the formation of abundant granulation tissue and poor re-epithelialization.
In the absence of other apparent risk factors for the development of squamous cell carcinomas, chronic wounding resulting from recurrent skin blistering probably provided an important prerequisite for tumor promotion in these patients. The 2 cases presented herein provide evidence that the development of malignant skin tumors in patients with epidermolysis bullosa is not confined to the dystrophic forms but also may occur in some variants of junctional epidermolysis bullosa, such as generalized atrophic benign epidermolysis bullosa.
泛发性萎缩性良性大疱性表皮松解症是交界性大疱性表皮松解症的一种形式，其特征为皮肤脆弱、萎缩性脱发、眉毛、睫毛、腋毛和阴毛稀疏、指甲和趾甲营养不良以及乳牙和恒牙釉质缺陷。最近在阐明该疾病的遗传缺陷方面取得了重大进展。在受影响的个体中，在编码层粘连蛋白5β3链（LAMB3）或180-kd大疱性类天疱疮抗原（BPAG2/COL17A1）的基因中发现了致病突变。
两名年龄分别为39岁和32岁的兄弟具有泛发性萎缩性良性大疱性表皮松解症的典型临床特征。通过电子显微镜检查，在透明层水平可见真皮表皮分离，从而确诊为交界性大疱性表皮松解症。病变皮肤和临床未受累皮肤显示基底角质形成细胞半桥粒发育不全，这可能表明半桥粒或相关蛋白存在缺陷。两名患者小腿萎缩和瘢痕化皮肤上均出现多个蕈样肿瘤；年龄较大的患者有2个肿瘤，年龄较小的患者有4个肿瘤，均被诊断为高分化鳞状细胞癌。肿瘤分期未发现区域淋巴结受累或全身疾病的证据。治疗采用显微镜控制下的手术。所有伤口均让其二期愈合。两名患者的伤口愈合均明显延迟，其特征为形成大量肉芽组织且上皮再形成不良。
在没有其他明显的鳞状细胞癌发生风险因素的情况下，反复皮肤水疱形成导致的慢性伤口可能是这些患者肿瘤发生的重要前提条件。本文报告的2例病例提供了证据，表明大疱性表皮松解症患者发生恶性皮肤肿瘤不仅局限于营养不良型，也可能发生在交界性大疱性表皮松解症的某些变异型中，如泛发性萎缩性良性大疱性表皮松解症。
