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Skin-nontumor / Clinical Dermatology

Blistering disorders

Epidermolysis bullosa (EB)

Reviewer: Mowafak Hamodat, MB.CH.B, MSc., FRCPC, Eastern Health, St. Johns, Canada (see Reviewers page)
Revised: 4 July 2011, last major update July 2011
Copyright: (c) 2002-2011, PathologyOutlines.com, Inc.

Definition
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● Rare genetic blistering disorder (incidence of 8-19 per million) with cleavage in dermis, lower epidermis or at dermoepidermal junction
● See also Epidermolysis bullosa acquisita

Etiology
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● Defects in Keratin K5/K14 filament network architecture cause basal keratinocytes to become fragile and account for their trauma-induced rupture

Classification
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● Classified as EB simplex, junctional EB, dystrophic EB and Kindler syndrome, based on level of tissue separation within the cutaneous basement membrane zone (Orphanet J Rare Dis 2010 May 28;5:12)
● Also classified and subclassified based on clinical, electron microscopic, immunohistochemical and genotypic features (J Am Acad Dermatol 2008;58:931, free full text, Table)

● EB Simplex: intraepidermal tissue separation; degeneration of basal cell layer causes clinical bullae; usually due to dominant mutations in keratin 14 or keratin 5 (J Clin Invest 2009;119:1784)
● Junctional: blisters within lamina lucida, skin appears normal
● Dystrophic: blisters are sub-lamina densa; dominant or recessive
● Kindler syndrome: blisters at multiple levels (intra-lamina lucida and sub-lamina densa)

Clinical features
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● Blisters form shortly after birth due to pressure, rubbing or trauma
● Blisters cause scarring or milia on dorsum of hands, elbows and knees and oromucosal lesions
● EB Simplex-Dowling Meara: associated with marked morbidity; may cause death during early infancy; exhibits intact vesicles or small blisters in a grouped or arcuate (curved) configuration
● Junctional EB: characterized by enamel hypoplasia, with pitting of some or all of the tooth surfaces
● Junctional EB-Herlitz subtype: severe symptoms; presents at birth and involves all skin surfaces with exuberant granulation tissue of skin and possibly upper airway
● Recessive dystrophic EB: subtypes are severe generalized (formerly Hallopeau-Siemens), non-Hallopeau-Siemens and inverse; each arises at birth; severe generalized is "one of the most devastating multiorgan genetically transmitted diseases of mankind"; has generalized blistering at birth, progressive and often mutilating scarring of skin, corneal blisters or scarring, profound growth retardation, multifactorial anemia, failure to thrive, esophageal strictures and debilitating hand and foot deformities
● Diagnosis: usually requires focused lab testing, such as transmission EM (“gold standard”), immunofluorescence antigen mapping or immunohistochemical staining with EB-specific monoclonal antibodies

Drawings
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Normal epidermis and components


Level of disruption in EB subtypes

Clinical images
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Typical noninflammatory blister


EB simplex-blistered foot of infant


EB simplex, generalized, with Dowling-Meara variant


Junctional EB: marked pitting of enamel


Junctional EB


Junctional EB-Herlitz subtype: exuberant granulation tissue on child's neck


Dominant dystrophic EB-milia arising within erythematous patch

Generalized dominant dystrophic EB: atrophic scarring and postinflammatory hypopigmentation on extremity


Generalized dominant dystrophic EB: hypertrophic scarring


Generalized dominant dystrophic EB: dystrophy of all 20 nails

   
Recessive dystrophic EB


Severe generalized recessive dystrophic EB: partial mitten deformity of child's hand


Severe generalized recessive dystrophic EB: complete mutilating deformities of hands of young adult


Congenital absence of skin in neonate with Bart's syndrome (not specific for any EB subtype)

Micro description
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● Subepidermal blister with variable inflammation
● Superficial dermis is fibrotic (Type IV collagen positive)

Micro images
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Various images


EB simplex: intact stratum corneum and upper epidermis, with vesicle formation in the lower epidermis at the basal layer caused by degeneration of individual epidermal cells


Dystrophic EB: pretibial lesion

Virtual slides
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Epidermolysis bullosa

Positive stains
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● Linear C3 and IgG deposits along epidermal basement membrane
● Diagnostically useful differences in antigenic staining in selected EB subtypes

Electron micrographs
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● Transmission EM findings for subclassification

EM images
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EB simplex: epidermal basal keratinocytes

End of Skin-nontumor / Clinical Dermatology > Blistering disorders > Epidermolysis bullosa (EB)

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