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 epidermolysis bullosa (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: epidermolysis bullosa (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/electron microscopic, and biochemical evaluation (Table 6-1). Only the most important are discussed here.
Table Graphic Jump Location TABLE 6-1Classification of Epidermolysis Bullosa ||Download (.pdf) TABLE 6-1 Classification of Epidermolysis Bullosa
|Disease ||Affected Gene ||Affected Protein |
|Generalized severe ||KRT5/KRT14 ||Keratin 5/keratin 14 |
|Generalized intermediate ||RT5/KRT14 ||Keratin 5/keratin 14 |
|Localized ||RT5/KRT14 ||Keratin 5/keratin 14 |
|Mottled pigmentation ||KRT5 ||Keratin 5 |
|EB with muscular dystrophy ||PLEC1 ||Plectin |
|Superficialis ||Unknown ||Unknown |
|Acantholytic ||DSP, JUP ||Desmoplakin, plakoglobin |
|Plakophillin deficiency ||PKP1 ||Plakophillin 1 |
|Plakoglobin deficiency ||JUP ||Plakoglobin |
|Ogna ||PLEC1 ||Plectin |
|BP230 deficiency ||DST-e ||BP230/BPAG1 |
|Exophilin-5 deficiency ||EXPH5 ||Exophilin 5 |
|Acral peeling skin syndrome ||TGM5 ||Transglutaminase 5 |
|EB with pyloric atresiaa ||ITGΒ4/ITGΑ6/PLEC1 ||Integrin α6, integrin β4, plectin |
|Generalized severe ||LAMΒ3/LAMΑ3/LAMC2 ||Laminin-332 |
|Generalized intermediate ||LAMΒ3/LAMΑ3/LAMC2/COL17A1 ||Laminin-332, collagen XVII |
|Localized ||LAMΒ3/LAMΑ3/LAMC2/COL17A1 ||Laminin-332, collagen XVII |
|Inversa ||LAMΒ3/LAMΑ3/LAMC2 ||Laminin-332 |
|Laryngo–onycho–cutaneous ||LAMA3A ||Laminin α3 |
|Respiratory and Renal ||ITGA3 ||Integrin α3 |
|Generalized dominant ||COL7A1 ||Collagen VII |
|Localized dominant ||COL7A1 ||Collagen VII |
|Generalized severe recessive ||COL7A1 ||Collagen VII |
|Generalized intermediate recessive ||COL7A1 ||Collagen VII |
|Localized recessive ||COL7A1 ||Collagen VII |
|Inversa recessive ||COL7A1 ||Collagen VII |
|Bullous dermolysis of the newborn ||COL7A1 ||Collagen VII |
|Kindler syndrome ||KIND1 ||Kindlin |