Generalized atrophic benign epidermolysis bullosa in 2 siblings complicated by multiple squamous cell carcinomas.

Abstract

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.