eMedicine Specialties > Pediatrics: General Medicine > Dermatology
Epidermolysis Bullosa
Updated: Jun 13, 2007
Introduction
Background
Epidermolysis bullosa (EB) is a rare group of inherited disorders that manifests as blistering or erosion of the skin and, in some cases, the epithelial lining of other organs, in response to little or no apparent trauma.
Categorizations of the types of EB were once controversial and often confusing because more than 20 types of EB have been described. However, major subtypes of EB are recognized: EB simplex (EBS), junctional EB (JEB), and dystrophic EB (DEB). These major subtypes depend on the precise ultrastructural level at which the split responsible for blistering occurs.
The 3 main types of EB were clinically and histologically delineated by the 1960s. In the 1970s, electron microscopy revealed abnormal epidermal keratin filaments in EBS, disordered dermal anchoring fibrils in DEB, and defective hemidesmosomes in JEB. Antigens identified with immunohistochemistry in the 1980s led to discovery of the major EB genes in the 1990s. The identified genes included those that encode keratins 5 and 14 in EBS, collagen VII in DEB, and laminin 5 in Herlitz JEB. Toward the end of millennium, as the complex structure of desmosomes and hemidesmosomes was unraveled, the genes responsible for the rare subtypes were found, including those that encode α6β4 integrin in EB with pyloric atresia, plectin in EB with muscular dystrophy, and plakophilin in EB with ectodermal dysplasia.
Eponyms associated with different forms of EB include the following:
- Dowling-Meara
- Köbner
- Weber-Cockayne
- Kallin
- Mendes de Costa
- Herlitz
- Ogna
- Carmi
- Cockayne-Touraine
- Pasini
- Hallopeau-Siemens
Pathophysiology
Cytolysis causes blisters in the epidermis or basement membrane zone of the skin. In EBS, cytolysis causes blisters in the basal or spinous layers of the epidermis, and keratinocytes often have abnormal density and organization of keratin filaments.
In JEB, the epidermis separates from the basal lamina, forming a blister cavity in the plane of the lamina lucida, where hemidesmosome structure and density are frequently diminished.
In DEB, the basal lamina remains attached to the epidermis, but the blister cavity forms beneath the lamina densa of dermoepidermal junction, and anchoring fibrils may appear abnormal, reduced in number, or altogether absent.
Frequency
United States
The exact prevalence of EB is unknown. Mild variants have been estimated to occur as frequently as 1 per 50,000 births. The more severe varieties are believed to occur in 1 per 500,000 births annually.
Mortality/Morbidity
Depending on the type of EB, disease severity may range from occasional mild blistering of the hands and feet to severe and widespread formation of bullae. These lesions may result in nonhealing erosions, infection, scarring, and joint contracture. Mortality is also related to the abnormalities or anomalies associated with EB.
- Healing of DEB results in dystrophic or scarring change.
- In EBS, when blisters cleave in the epidermis, healing occurs without scarring.
- In JEB, when blisters cleave below the epidermis but above the basal lamina, blistering leads to mild atrophic changes.
Race
The EBS Ogna variant was described in Norwegian individuals.
Sex
EB is an autosomal inherited disorder. The incidence does not differ by sex.
Age
- The onset of EBS occurs at birth or early infancy.
- The onset of JEB occurs at birth.
- The onset of DEB occurs at birth or early childhood.
Clinical
History
Important findings in general include the age of onset; the size, frequency, and location of blisters; and the possible inciting factors (eg, heat, trauma).
Check for a family history of blistering disease and for the patient's geographic and racial ancestry. Evaluation of any patient with suspected epidermolysis bullosa (EB) should include mapping of the family's pedigree. However, an absence of affected family members does not, by itself, establish that the mode of transmission is autosomal recessive because apparently isolated cases can be due to spontaneous mutation or incomplete penetrance of an autosomal dominant trait.
Review of systems should include a search for mucosal involvement, including oral, nasopharyngeal, ocular, genitourinary, GI, and respiratory symptoms.
Physical
Perform a complete physical examination with emphasis on inspecting all skin areas and mucosal surfaces. Evaluate the size, location, and character of the blisters and determine the level at which to slit them. Examine the patient for involvement of the nails, hair, or teeth. Areas prone to blistering due to pressure, trauma, or excessive heating include the fingers, hands, elbows, feet, legs, and diaper area (in infants) (see Images 1-5).
Congenital localized absence of skin is now known to be a phenotypic pattern that neonates with any major form of EB may demonstrate at birth (see Image 6-7).
Causes
- Genetics
- EBS is an autosomal dominant disorder.
- JEB is an autosomal recessive disorder.
- DEB is either autosomal dominant or autosomal recessive.
- Types of EB and Associated Characteristics
Open table in new window
[ CLOSE WINDOW ]Table
Type of EB Feature on Light Microscopy Feature on Electron Microscopy Protein or Antigen Gene EBS (Dowling-Meara) Epidermis Keratin filaments Keratin 5 KRT5 EBS (Weber-Cockayne) Epidermis Keratin filaments Keratin 14 KRT14 EB with ectodermal dysplasia Epidermis Desmosome, attachment plaque Plakophilin PKP1 EB with muscular dystrophy Epidermis Hemidesmosome lamina lucida, attachment plaque Plectin PLEC1 Non-Herlitz JEB Basement membrane zone Hemidesmosome lamina lucida, subbasal dense plate, anchoring filaments Collagen XVII BPAG2 JEB with pyloric atresia Basement membrane zone Hemidesmosome lamina lucida, subbasal dense plate, anchoring filaments Alpha6beta4 integrin ITGB6, ITBG4 Herlitz JEB, rarely non-Herlitz JEB Basement membrane zone Lamina densa Laminin 5 LAMA3, LAMB3, LAMC2 DEB Dermis Anchoring fibrils Collagen VII COL7A1 Type of EB Feature on Light Microscopy Feature on Electron Microscopy Protein or Antigen Gene EBS (Dowling-Meara) Epidermis Keratin filaments Keratin 5 KRT5 EBS (Weber-Cockayne) Epidermis Keratin filaments Keratin 14 KRT14 EB with ectodermal dysplasia Epidermis Desmosome, attachment plaque Plakophilin PKP1 EB with muscular dystrophy Epidermis Hemidesmosome lamina lucida, attachment plaque Plectin PLEC1 Non-Herlitz JEB Basement membrane zone Hemidesmosome lamina lucida, subbasal dense plate, anchoring filaments Collagen XVII BPAG2 JEB with pyloric atresia Basement membrane zone Hemidesmosome lamina lucida, subbasal dense plate, anchoring filaments Alpha6beta4 integrin ITGB6, ITBG4 Herlitz JEB, rarely non-Herlitz JEB Basement membrane zone Lamina densa Laminin 5 LAMA3, LAMB3, LAMC2 DEB Dermis Anchoring fibrils Collagen VII COL7A1
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| References |
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Further Reading
Keywords
epidermolysis bullosa, EB, bullous disorder, blister, blistering, skin erosion, epidermolysis bullosa simplex, EBS, junctional epidermolysis bullosa, JEB, dystrophic epidermolysis bullosa, DEB, Herlitz junctional EB, pyloric atresia, ectodermal dysplasia, Dowling-Meara, Köbner, Weber-Cockayne, Kallin, Mendes de Costa, Ogna, Carmi, Cockayne-Touraine, Pasini, Hallopeau-Siemens
