Jo-David Fine

Inherited epidermolysis bullosa, which encompasses at least 30 distinctive genetic diseases, may be associated with marked functional impairment, the result of the presence of severe cutaneous and extracutaneous manifestations or complications in some of its subtypes.

Introduction: Epidermolysis bullosa (EB), a rare inherited disease encompassing many distinct phenotypes and genotypes, is caused by mutations within any of several genes encoding for structural proteins normally present within the epidermis or skin basement membrane zone. In many EB subtypes the disease involves not only skin, but also extracutaneous tissues, resulting in severe morbidity and, in some, premature death. Many conventional medical and surgical interventions are currently employed to enhance wound healing and at least partially correct these extracutaneous complications. However, there are no curative interventions yet known. Several novel molecular approaches are now being studied that might potentially have substantial long-term benefit for these patients, and a few might even possibly lead to a cure. Areas covered: Current medical and surgical therapies as well as ongoing experimental ones are reviewed, based on a comprehensive literature search employing review articles, book chapters, EB monographs and Medline searches, combining keywords in EB with treatment, therapy, specific organ systems affected in EB, and known areas of active research. Expert opinion: A variety of medical and surgical interventions optimise the management of wounds and extracutaneous complications. Promising research is now underway exploring the feasibility, safety and efficacy of novel cellular, protein and molecular interventions.

This review highlights key findings, both clinical and basic, that have been published in the field of inherited epidermolysis bullosa within the past few years. New epidermolysis bullosa phenotypes, genotypes and modes of transmission have been identified, resulting in a revised classification system. Detailed evidence-based data are now available on the risk of extracutaneous complications in each of the major epidermolysis bullosa subtypes. Studies are now underway to try to better explain the biological aggressiveness of squamous cell carcinomas arising in epidermolysis bullosa skin. Cell and animal models have been refined and used to ascertain the feasibility of gene replacement therapy, stem cell transplantation, and treatment with injected allogeneic fibroblasts or recombinant type VII collagen. As a result, clinical trials are now being pursued to test each of these in humans. Epidermolysis bullosa is caused by mutations in at least 14 genes, leading to a broad spectrum of entities, each of which has its own relative risk for the development of specific extracutaneous complications and/or premature death. Intensive research, both basic and clinical, is bringing us closer to more effective treatments and possibly even a cure.

Inherited epidermolysis bullosa (EB) encompasses a number of disorders characterized by recurrent blister formation as the result of structural fragility within the skin and selected other tissues. All types and subtypes of EB are rare; the overall incidence and prevalence of the disease within the United States is approximately 19 per one million live births and 8 per one million population, respectively. Clinical manifestations range widely, from localized blistering of the hands and feet to generalized blistering of the skin and oral cavity, and injury to many internal organs. Each EB subtype is known to arise from mutations within the genes encoding for several different proteins, each of which is intimately involved in the maintenance of keratinocyte structural stability or adhesion of the keratinocyte to the underlying dermis. EB is best diagnosed and subclassified by the collective findings obtained via detailed personal and family history, in concert with the results of immunofluorescence antigenic mapping, transmission electron microscopy, and in some cases, by DNA analysis. Optimal patient management requires a multidisciplinary approach, and revolves around the protection of susceptible tissues against trauma, use of sophisticated wound care dressings, aggressive nutritional support, and early medical or surgical interventions to correct whenever possible the extracutaneous complications. Prognosis varies considerably and is based on both EB subtype and the overall health of the patient.

Inherited epidermolysis bullosa encompasses dozens of diseases characterized by mechanical fragility of the skin, blister formation, and abnormal wound healing. Most of the more severe subtypes are associated with clinically significant extracutaneous complications. Some subtypes may lead to death, even in early infancy. Over the past two decades substantial advances have been made to our understanding of the underlying molecular basis for each member of this protean group of diseases. Research has now shifted toward the identification of therapeutic interventions, to include gene therapy, recombinant protein infusions, intradermal injection of allogeneic fibroblasts, and stem cell transplantation, that might eventually lead to a definitive cure for this disease. Other developing therapies being explored are directed toward the enhancement of wound healing and the prevention of potentially life‐threatening skin cancers in these patients.