Epidermolysis Bullosa

EPIDERMOLYSIS BULLOSA
  • An inherited defect in the keratin formation
  • Characterised by the formation of multiple blisters on gentle rubbing or on minimal skin trauma especially over the trauma prone areas of the body 
  • There may be blisters in the pharynx, larynx, eyes and the genital mucosa.
  • There may be contractures and mitten like deformities of hands in the severe variants
  • Pyloric stenosis and squamous cell carcinoma are other complications
Molecular pathology of EB
  • Normal basement membrane is between epidermal basal layer and dermis. This basement membrane (basal lamina) is attached to basal cells hemidesmosomes with the help of keratin containing intermediate filaments and is attached to dermis (dermal papillary layer) with the help of type VII collegen containing fibrils. Any defect in this anchoring complex leads to separation of skin; the site of separation depends on the type of defect
  1. EB simplex → Mutation in gene coding for keratin 5 & 14 (major keratin of BMZ) and separation will be epidermal.
  2. EB junctional →  Mutation in Lantinin a-3 (LAM a-3), LAM [I-3, LAM 7-2 genes. As laminin is part of basement membrane the separation will be at dermo-epidermal junction (DEJ).
  3.  EB dystrophicans →  Mutation in collagen VII-Al gene. As collagen VII containing fibrils join BM to dermal papilla, separation will be in the dermis. Any of the above defect results in defective cohesiveness which leads to vulnerability to trauma and blisters formation. As the disease is inherited, Family history may be positive. Epidermolysis bullosa acquisita: 
  • EB should be distinguished from epidermolysis bullosa acquisita (EBA), which is an autoimmune blistering disease that is not inherited and often doesn't develop until adult life.
  •  Direct immunofluorescence shows, linear IgG, Ig A, Ig M at the basement-membrane zone with diagnostic U-serrated pattern. 
  • Patients’ skin split through the lamina lucida with 1 mol/L salt demonstrates the IgG antibodies to be bound to the dermal aspect of the blister. N serrated pattern is seen in bullous pemphigoid. 
Exam Question
  • Mutation in collagen -VII is present in epidermolysis bullosa .
  • In congenital dystrophic epidermolysis bullosa defect is seen in Collagen-7.
  • Etiology of Epidermolysis bullosa is Genetic.
  • The target antigen in dermolytic variant of epidermolysis bullosa is Collagen-7.
  • A 5 year old girl presented with recurrent skin lesions over the body as shown in the image following trivial trauma.The most possible diagnosis would be Epidermolysis bullosa. A 2 day old newborn girl born out of non-consanguinous marriage was evaluated for tense blister and areas of denuded skin that had been present since birth. The child develops while mother handles for bathing and feeding. The sibling of child also had h/o developing similar lesions.The most possible diagnosis would be Congenital Epidermolysis bullosa. In a 8 day old child with no history of consanguinity in the parents. The mother reports blisters and peeling off of skin at the site of handling and pressure. There was a similar history in previous child which proved to be fatal. The most possible diagnosis would be Congenital Epidermolysis bullosa.
  • U-serrated pattern in direct immunofluorescence is seen in Epidermolysis bullosa acquisita.
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