Palmoplantar epidermal differentiation disorders: a new classification toward pathogenesis-based therapy

Abstract

More than 50 palmoplantar epidermal differentiation disorders (pEDDs) have been reported in the literature. Various descriptors have been used to name these conditions, including clinical features often designated as acronyms or evocative terms, and names of clinicians and of geographical locations. Not only has this nomenclature been criticized for its lack of methodological consistency, but it has also progressively lost its clinical relevance. Indeed, the advent of a wide range of pathogenesis-targeting therapeutic solutions for these disorders has raised the need for a novel classification of pEDDs, based on their causative genetic defects, to provide clinicians with genuine therapeutic guidance. Here, we present a novel classification scheme for pEDDs and its application in the form of a practical algorithm for the rapid diagnosis of pEDDs.; More than 50 inherited skin conditions feature thickening of the skin on the palms of the hands and the soles of the feet. This is known as ‘palmoplantar thickening’. These conditions are rare, but when grouped together, they may affect more than 1 in 10,000 people. In the past, these conditions were grouped based on how they looked and their symptoms. Most of the faulty genes that cause these conditions have been discovered. This has made it possible for researchers to think about the different ways in which a gene change leads to palmoplantar thickening and develop new treatments. Our group of clinical experts from the USA, Japan and Europe have reclassified these conditions, which are now called ‘palmoplantar epidermal differentiation disorders’ (or ‘pEDDs’ for short). In our new classification, pEDDs are grouped based on the eventual function of the gene and named based on the gene. We group conditions that share a cause and could respond to similar treatments. In this new classification, we removed the previous names of the conditions, which were sometimes called after the people who identified them or where the patients were located. By recognizing the skin features and connecting them to the affected gene and functional group through genetic testing, we can improve chances of an early diagnosis. In addition, we can discuss expectations for the future, treat patients appropriately and find new treatments, based on what causes the pEDD.