Blistering skin disorders 4

Question 1

How does autoimmunity cause blisters?

Answer 1

Inflammation within the epidermal cells, steric hindrance, complement activation, activated eosinphils

Question 2

Steric hindrance caused by autoimmunity, causing blisters?

Answer 2

autoantibodies against desmoglein bind to it, and prevent another desmoglein from binding to it–> meaning they won’t be able to attach

Question 3

What happens to the cytoskeleton as a result of acantholysis, and why?

Answer 3

Cytoskeletal collapse due to a loss of attachment to the keratin intermediate filaments

Question 4

Treatments for autoimmune skin diseases?

Answer 4

Immunosuppression
Plasmapheresis

Question 5

Immunosuppressants for autoimmune skin diseases?

Answer 5

Steroids, azathioprine, cyclophosphamide.

Question 6

What is plasmapheresis?

Answer 6

Design a recombinant desmoglein 1 and attach it to a membrane
Pass patients blood plasma over membrane
Antibodies will be removed from the blood

Question 7

Issue with plasmapheresis?

Answer 7

Has to be done regularly

Question 8

Novel drugs to combat blistering skin diseases?

Answer 8

Rituximab, cytokine blockers

Question 9

Role of rituximab?

Answer 9

Targets Ab producing B cells

Question 10

Characteristics of epidermolysis bullosa?

Answer 10

extremely fragile skin and blister formation

Question 11

Pre-adolescent mortality rate of epidermolysis bullosa?

Answer 11

40%, due to skin infections

Question 12

Why is cSCC more prevalent in epidermolysis bullosa patients?

Answer 12

High turnover rate in the epidermis

Question 13

3 epidermolysis bullosa subtypes?

Answer 13

EB simplex, junctional EB and dystrophic EB

Question 14

Differences in the 3 subtypes of EB?

Answer 14

Where the blisters form

Question 15

Where do the blisters form in EB simplex?

Answer 15

Intra epidermal cleavage Between epidermis and dermis

Question 16

Where do the blisters form in junctional EB?

Answer 16

Within lamina lucida (separation between basal keratinocytes and lamina lucida)

Question 17

Where do the blisters form in dystrophic EB?

Answer 17

Within sublamina densa in region of anchoring fibrils (below the lamina densa, in the region of the anchoring fibrils)

Question 18

Mutated genes in EB simplex?

Answer 18

Keratin genes–> KRT5 and KRT 14

Question 19

What does EB simplex cause?

Answer 19

Keratin cytoskeleton disruption
Affects skin integrity and ability to resist mechanical stresses

Question 20

Mutated genes in junctional EB ?

Answer 20

Genes encoding laminin, integrins or collagen XVII

Question 21

What does junctional EB cause?

Answer 21

Altered hemidesmosome structure
Severe can cause early infancy death

Question 22

Mutated genes in dystrophic EB ?

Answer 22

Collagen VII gene–> COL7A1

Question 23

What does dystrophic EB cause?

Answer 23

Severe skin blistering
Damage and scarring of oesophagus
Chronic inflammation

Question 24

Autoimmune version of EB?

Answer 24

Epidermolysis bullosa acquisita

Question 25

What are the autoantibodies against in Epidermolysis bullosa acquisita?

Answer 25

Type VII collagen--> component of anchoring fibrils

Question 26

WHy is Epidermolysis bullosa acquisita not as serious as dystrophic EB?

Answer 26

Epidermolysis bullosa acquisita patients have some functional type VII collagen

Question 27

EB treatment stratergies?

Answer 27

Gene, cell, or protein therapy, bone marrow or stem cell transplant

Question 28

Gene, cell, or protein therapy to treat EB?

Answer 28

Replace missing gene, inject with cells w/ normal gene or supply the missing protein

Question 29

EB case study gene therapy treatment process?

Answer 29

Took small piece of patient’s skin Cultured keratinocytes from this Transfected the cells with normal laminin gene (using retrovirus). Grew up these keratinocytes and used them to construct a skin graft

Question 30

Cause of recessive dystrophic EB?

Answer 30

Mutation in COL7A1 encoding anchoring fibril component collagen VII

Question 31

How was recessive dystrophic EB treated?

Answer 31

HSV-1 vector containing COL7A was applied as a gel to patients--> worked