Inherited blistering skin diseases: underlying molecular mechanisms and emerging therapies

Abstract

A key function of human skin is the formation of a structural barrier against the external environment. In part, this is achieved through the formation of a cornified cell envelope derived from a stratified squamous epithelium attached to an epithelial basement membrane. Resilient in health, the structural integrity of skin can become impaired or break down in a collection of inherited skin diseases, referred to as the blistering genodermatoses. These disorders arise from inherited gene mutations in a variety of structural and signalling proteins and manifest clinically as blisters or erosions following minor skin trauma. In some patients, blistering can be severe resulting in significant morbidity. Furthermore, a number of these conditions are associated with debilitating extra-cutaneous manifestations including gastro-intestinal, cardiac, and ocular complications. In recent years, an improved understanding of the molecular basis of the blistering genodermatoses has led to better disease classification and genetic counselling. For patients, this has also advanced translational research with the advent of new clinical trials of gene, protein, cell, drug, and small molecule therapies. Although curing inherited blistering skin diseases still remains elusive, significant improvements in patients’ quality of life are already being achieved.

Key words::

• Blister
• epidermolysis bullosa
• erosion
• mutation
• skin

Declaration of interest: The authors report no conflicts of interest.

This review has been supported by the UK National Institute for Health Research (NIHR) Biomedical Research Centre based at Guy's and St Thomas’ NHS Foundation Trust and King's College London, as well as DebRA UK, the Rosetrees Trust, and the Sohana Research Fund in conjunction with Goldman Sachs Gives. The views expressed are those of the authors and not necessarily those of the NHS, the NIHR, or the UK Department of Health.