33 - Epidermolysis bullosa

Question 1

what are the three major types of epidermolysis bullosa?

Answer 1

• epidermolysis bullosa simplex
• junction epidermolysis bullosa
• dystrophic epidermolysis bullosa

Question 2

what mutations/genes are present in epidermolysis bullosa simplex?

Answer 2

• dominant negative mutation

- genes for keratin 5 or 14 (present in the basal layer of the epidermis).

Question 3

what are the 4 subtypes of epidermolysis bullosa simplex?

Answer 3

• Dowling- Meara (severe)
• Weber- Cockayne
• Koebner
• EB with mottled pigmentation
• most are autosomal dominant

Question 4

within regards to the form of epidermolysis bullosa simplex associated with muscular dystrophy - where is the genetic defect?

Answer 4

• plectin

Question 5

what are the major subtypes of junctional epidermolysis bullosa?

Answer 5

• Herlitz (severe)
• Non-Herlitz.
• all forms are autosomal recessive.

Question 6

What genetic defect is associated with junctional epidermolysis bullosa- Herlitz

Answer 6

• results from compound heterozygous mutations within the genes encoding laminin 332.

Question 7

What genetic defect is associated with junctional epidermolysis bullosa- NON-Herlitz

Answer 7

• laminin 332, BPAG2,

Question 8

what genetic defects are associated with junctional epidermolysis bullosa that is associated with pyloric atresia?

Answer 8

-a6b4

Question 9

what mutations are found in dystrophic epidermolysis bullosa?

Answer 9

• dominant-negative mutation wihtin type VII collagen gene.

Question 10

What are the geneodermatoses that are associated with blistering in the neonatal period?

Answer 10

• congential bullous icthyosiform erythroderma
• Kindler sydrome (Acral blistering)
• Gunther disease
• ichtyosis bullosa of Siemens
  Plakophillin 1 deficiency
• Skin fragility

Question 11

What is the level of the skin cleavage in epidermolysis bullosa simplex?

Answer 11

• basilar keratinocyte level

intrastratum granulosum layer for epidermolysis bullosa simplex superficialis

Question 12

What is the level of the skin cleavage in junctional epidermolysis bullosa ?

Answer 12

intralamina lucida in herlitz and non herlitz

Question 13

What is the level of the skin cleavage in dystrophic epidermolysis bullosa ?

Answer 13

sublamina densa

Question 14

What are the associated electron microscopy findings in junctional epidermolysis bullosa?

Answer 14

Herlitz - absence of hemidesmosmes and the sub basal dense plate

Non Herlitz- reduced number of hemidesmosomes

Question 15

What are the associated electron microscopy findings in dystrophic epidermolysis bullosa?

Answer 15

Dominant -normal or reducd anchoring fibrils
transient bullous dermolysis of the newborn - stellate shaped electron dense bodies.

recessive - Hallepeau-Siemens: absent anchoring fibrils
recessive - non Hallepeau-Siemens: reduced numbers of anchoring fibrils.

Question 16

what are the clinical manifestations of epidermolysis bullosa?

Answer 16

• mechanically fragile skin with tense, fluid filled blisters, erosions and crusts.
• scarring can occur in all forms of EB
• nail dystrophy, milia and scarring alopecia of the scalp.

Question 17

whata are the pathgnomonic findings of EBS - Dowling Meara form?

Answer 17

group blisters in an arcuate form and diffuse palmoplantar keratoderma.

Question 18

what is the pathognomonic findingsof junctional EBS Herlitz subtype?

Answer 18

• excessive granulation tissue in the perioroficial skin, axillary vaults, upper back and nape.

Question 19

what are the extracutaneous findings of epidermolysis bullosa?

Answer 19

• involvement of oesophagus –> strictures or scaring
• involvement of small bowel leading to chornic malabsorption.
• urethtral or ureterovesicular stricutres.
• Enamel hypoplasia with pitting of all primary and permanent teeth.
• pseudosyndactyly (mitten deformities of the hands and feet) –> this usually occurs in recessive dystrophic epiermolysis bullosa.
• osteoporosis is a common finding in severe generalised forms of EB.

Question 20

what deficiency occurs in generalized EBS which is associated with mild to severe muscular dystrophy?

Answer 20

Plectin deficiency.