GENETIC AND ACQUIRED BULLOUS DISEASES: INTRODUCTION
Bullous diseases are defined as conditions where cavities filled with fluid form in the superficial layers of the skin clinically manifesting as vesicles or blisters. Although vesicles and blisters can arise as secondary lesions in many conditions, in the bullous diseases they are the primary pathologic event. Genetic (hereditary) and acquired (mostly autoimmune) bullous diseases exist.
HEREDITARY EPIDERMOLYSIS BULLOSA (EB) ICD-10: Q 81
A spectrum of rare genodermatoses in which a disturbed coherence of the epidermis and/or dermis leads to blister formation following trauma. Hence, the designation mechanobullous dermatoses.
Disease manifestations range from very mild to severely mutilating and even lethal forms that differ in modes of inheritance, clinical manifestations, and associated findings.
Classification based on the site of blister formation distinguishes three main groups: epidermolytic or EB simplex, junctional EB (JEB), and dermolytic or dystrophic EB (DEB).
In each of these groups, there are several distinct types of EB based on clinical, genetic, histologic, and biochemical evaluation.
Based on the level of cleavage and blister formation, there are three main types:
Epidermolytic. Cleavage occurs in keratinocytes: EB simplex (EBS).
Junctional. Cleavage occurs in basal lamina: junctional EB (JEB).
Dermolytic. Cleavage occurs in most superficial papillary dermis: dermolytic or dystrophic EB (DEB).
In each of these groups, there are several distinct types of EB based on clinical, genetic, histologic/electronmicroscopic, and biochemical evaluation (Table 6-1). Only the most important are discussed here.
TABLE 6-1Classification of Epidermolysis Bullosa |Favorite Table|Download (.pdf) TABLE 6-1 Classification of Epidermolysis Bullosa
|Level of Separation ||Disease ||Defect |
|Simplex ||Generalized/Koebner ||KRT5/KRT14 |
|Simplex ||Herpetiformis/Dowling-Meara ||KRT5/KRT14 |
|Simplex ||Localized/Weber-Cockayne ||KRT5/KRT14 |
|Simplex ||Ogna ||KRT5/KRT14/PLEC1 |
|Simplex ||Mottled pigmentation ||KRT5/KRT14 |
|Simplex ||EB with muscular dystrophy ||PLEC1 |
|Simplex ||Superficials ||KRT5/KRT14 |
|Simplex ||Ectodermal dysplasia-skin fragility ||PKP1 |
|Junctionala ||EB with pyloric atresia ||ITGB4/ITGA6/PLEC1 |
|Junctional ||Herlitz ||LAMB3/LAMA3/LAMG2 |
|Junctional ||Non-Herlitz (GABEB) ||LAMB3/LAMA3/LAMG2/COL17A1 |
|Junctional ||Localized ||COL17A1 |
|Dystrophic ||Generalized dominant ||COL7A1 |
|Dystrophic ||Localized dominant ||COL7A1 |
|Dystrophic ||Recessive ||COL7A1 |
|Dystrophic ||Hallopeau-Siemens ||COL7A1 |
|Variable ||Kindler syndrome ||KIND1 |
The overall incidence of hereditary EB is placed at 19.6 live births per 1 million births in the United States. Stratified by subtype, the incidences are 11 for EBS, 2 for JEB, and 5 for DEB. The estimated prevalence in the United States is 8.2 per million, but this figure represents only the most severe cases. ...