Chapter 60: Inherited Epidermolysis Bullosa

AT-A-GLANCE

INTRODUCTION

Inherited epidermolysis bullosa (EB, is a family of diseases with the common feature of blistering in response to mild trauma. Patients with EB can show blistering in the form of small vesicles or larger bullae, occurring on cutaneous surfaces and, in the severe forms, on mucosal tissues as well. Although skin and mucosa fragility and trauma-induced painful blisters are hallmarks across the EB spectrum, the distribution of the involvement, the depth of blister formation, any associated extracutaneous involvement, and the severity of the blistering process vary with the different EB subtypes and depend on the underlying heritable molecular defect. EB diseases vary also in the way in which blistered areas heal. The wound repair responses are often abnormal and can eventuate into chronic erosions, hypertrophic granulation tissue, scarring, or even invasive carcinoma. Although the milder EB subtypes are associated with a normal lifespan and little or no internal involvement, the most severe recessively inherited forms are mutilating, multiorgan disorders that threaten both the quality and length of life.

A number of early studies identified the major subtypes of EB. Studies of von Hebra.^1-3 were the first to distinguish pemphigus from inherited blistering, and the term epidermolysis bullosa hereditaria was first suggested by Koebner.⁴ Hallopeau was the first to distinguish between simplex (nonscarring) and dystrophic (scarring) forms of the disease,⁵ and Weber,⁶ and Cockayne,⁷ Dowling and Meara,⁸ and Koebner⁴ each described unique forms of epidermolysis bullosa simplex. Hoffman,⁹ Cockayne,¹⁰ Touraine,¹¹, Pasini,¹² and Bart¹³ provided much of the information about subtypes of DEB. Herlitz described epidermolysis bullosas letalis,¹⁴ which was later found to be a part of the third major category of EB: the junctional form. The use of electron microscopy in EB diagnosis led to the studies of Pearson and collaborators,¹⁵ who classified the patients not only on the basis of clinical findings but also on the existence of ultrastructural changes. A comprehensive classification of EB based on a combination of ultrastructural and clinical findings was completed in an early landmark treatise by Gedde-Dahl.¹⁶ Recent major advances have led to the identification of protein and genetic abnormalities in most types of EB patients. These studies have led to an improved understanding of the biological basis of EB and culminating in the current EB classification based on genetic and protein defects,¹⁷ which provides a rational approach to specific molecular ...