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Epidemiology, pathogenesis, classification, and clinical features of epidermolysis bullosa

Martin Laimer, MD
Johann Bauer, MD
Dedee F Murrell, MD
Section Editor
Jennifer L Hand, MD
Deputy Editor
Rosamaria Corona, MD, DSc


Epidermolysis bullosa (EB) encompasses a clinically and genetically heterogeneous group of rare inherited disorders characterized by marked mechanical fragility of epithelial tissues with blistering and erosions following minor trauma.

EB is caused by mutations involving at least 18 genes encoding structural proteins within keratin intermediate filaments, focal adhesions, desmosome cell junctions, and hemidesmosome attachment complexes, which form the intraepidermal adhesion and dermoepidermal anchoring complex within the basement membrane zone (BMZ) of the skin and mucosae (figure 1) [1-3]. The molecular aberrations interfere with the functional and structural integrity of the BMZ (which is a highly specialized interface between epithelial cells and the underlying matrix) that is crucial for cell adhesion, proliferation, and differentiation; tissue repair; and barrier function [3] and leads to cell and tissue dehiscence.

Type (homozygosity versus heterozygosity), number (monogenic, digenic inheritance), and location of mutation(s) within the gene or gene segment, as well as the spectrum of subsequent quantitative (absence, reduction) or qualitative (gradual loss of function) alteration of protein expression, results in considerable genetic heterogeneity with complex genotype-phenotype correlations. Apart from the primary structural-functional defect, secondary epigenetic factors (eg, differentially regulated expression of a host of other genes involved in the maintenance and function of this microenvironment, induction of inflammatory cascades) and environmental factors further contribute to the highly variable phenotype of EB [4,5].

The epidemiology, pathogenesis, and clinical features of EB are discussed in this topic. The diagnosis and management of EB are discussed separately. (See "Diagnosis of epidermolysis bullosa" and "Overview of the management of epidermolysis bullosa".)


The most reliable figures on prevalence and incidence of epidermolysis bullosa (EB) are derived from the National EB Registry (NEBR), which collected cross-sectional and longitudinal data on about 3300 EB patients in the United States from 1986 through 2002 [6-8]. Over a 16-year period (1986 through 2002), the prevalence of EB was estimated to be approximately 11 per million and the incidence approximately 20 per million live births [8]. Over the same period, the incidence rates of EB by subtype were approximately eight per million live births for EB simplex, three per million live births for junctional EB, two per million live births for dominant dystrophic EB, and three per million live births for recessive dystrophic EB. Data from the Dystrophic Epidermolysis Bullosa Research Association of America (DebRA) report an incidence rate of 3.6 per million per year for junctional EB over the period 2007 to 2011 [9]. Data from the Australasian EB Registry provided a prevalence estimate of 10 cases per million live births [10]. Prevalence rates ranging from 15 to 32 cases per million have been estimated in the UK [11-13].


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