Inherited epidermolysis bullosa: New diagnostic criteria and classification Lizbeth R.A. Intong, MD, Dédée F. Murrell, MA, BMBCh, MD ⁎ Department of Dermatology, St. George Hospital and The University of New South Wales, Grey St, Kogarah NSW 2217, Australia Abstract Epidermolysis bullosa (EB) is a group of inherited, mechanobullous disorders caused by mutations in various structural proteins in the skin. There have been several advances in the classification of EB since it was first introduced in the late 19th century. We now recognize four major types of EB, depending on the location of the target proteins and level of the blisters: EB simplex (epidermolytic), junctional EB (lucidolytic), dystrophic EB (dermolytic), and Kindler syndrome (mixed levels of blistering). This contribution will summarize the most recent classification and discuss the molecular basis, target genes, and proteins involved. We have also included new subtypes, such as autosomal dominant junctional EB and autosomal recessive EB due to mutations in the dystonin (DST) gene, which encodes the epithelial isoform of bullouspemphigoid antigen 1. The main laboratory diagnostic techniques—immunofluores- cence mapping, transmission electron microscopy, and mutation analysis—will also be discussed. Finally, the clinical characteristics of the different major EB types and subtypes will be reviewed. © 2012 Elsevier Inc. All rights reserved. Introduction The term epidermolysis bullosa (EB) was introduced in 1886 1 and refers to a group of mechanobullous genoderma- toses, characterized by varying degrees of skin fragility caused by mutations in various skin structural proteins. Traditionally, three major types have been identified: EB simplex (EBS; epidermolytic), junctional EB (JEB; lucido- lytic), and dystrophic EB (DEB; dermolytic); however, the EB classification has been changed several times since the first scheme proposed in 1962. 2,3 The latest changes and new definitions were agreed upon during the Third International Consensus Meeting on Diagnosis and Classification of EB held in Vienna, Austria, in May 2007 and were published in 2008. 1 The initial diagnosis relied heavily on transmission electron microscopy (EM), but this was later replaced by immunofluorescence mapping (IFM) as the preferred diagnostic test because IFM has a higher sensitivity and specificity in the diagnosis of EB, in addition to being more available and easier to use. 1,4,5 Advances in molecular genetics have enabled mutation screening and identification within known genes that encode structural proteins associated with the different EB subtypes. Today, a significant amount of literature is available on the clinical features and known mutations of the different EB subtypes. More than 1000 mutations on at least 14 structural genes have been documented. 1,5 Laboratory diagnosis of EB In addition to specific clinical features, the diagnosis of EB is confirmed by the use of three main techniques: IFM, transmission EM, and mutation analysis. The technique for ⁎ Corresponding author. Tel.: +61 2 9113 2543; fax: +61 2 9113 2906. E-mail address: d.murrell@unsw.edu.au (D.F. Murrell). 0738-081X/$ – see front matter © 2012 Elsevier Inc. All rights reserved. doi:10.1016/j.clindermatol.2011.03.012 Clinics in Dermatology (2012) 30, 70–77