Bullous and acantholytic diseases of the epidermis and the dermal–epidermal junction

Question 1

What characterises junctional epidermolysis bullosa?

Answer 1

Fragility and cleavage within the lamina lucida of the BMZ.

Question 2

Describe the 3 subcategories epidermolysis bullnose is divided into in humans?

Answer 2

1) EB Simplex/epidermolytic.
2) Junctional EB.
3) Dystrophic EB/demolytic EB.

Question 3

Why does junctional fragility arise in human junctional EB?

Answer 3

Due to defective expression of hemidesomosome/anchoring filament proteins (inclu. Collagen XVII, Bullous pemphigoid antigens BPAG2, BP180), interim alpha-6 and laminin 5.

Question 4

In non-lethal junction all epidermolysis bullosa in German Shorthaired Pointers what collagen is absent?

Answer 4

Collagen XVII. Normal secretion was found in vitro.

Question 5

What defect causes junctional EB in German Shorthaired Pointers?

Answer 5

Mutation in the gene encoding laminin 5.

Question 6

How is dystrophic EB characterised?

Answer 6

Fragility and separation between the lamina densa. Formation of clefts below the lamina densa of the BMZ has been reported in Golden Retrievers & Cats .

Question 7

What defects contribute to the development of dystrophic EB?

Answer 7

Defects in the anchoring fibrils that include diminished or absent expression of type VII collagen.

Question 8

What is the age of onset for hereditary junctional EB?

Answer 8

Early; birth-2 months of age.

Question 9

What species/breeds have published cases of junctional EB?

Answer 9

Toy Poodle, Beaucerons, German Shorthaired Pointers, mixed breed dogs and Siamsese cats. Putative junctional EB has only been reported 2x in the cat; Siamese cats & domestic long haired.

Question 10

What clinical differences can be appreciated between dystrophic and junctional EB?

Answer 10

1) Lesions more severe in dystrophic vs junction all EB. Ulcers are deeper and may be more widespread.
2) More extensive oral and oropharyngeal lesions occur.

Question 11

What is the clinical ddx for heritable EB?

Answer 11

Epidermolysis bullosa acquisita, toxic epidermal necrolysis and chemical or thermal burns.

Question 12

Where does PAS (periodic acid-Schiff) stain in 1) Junctional and 2) dystrophic inherited EB?

Answer 12

1) Junctional: lamina densa along the floor of the bulla.

2) Dystrophic form: Roof of the bullae.

Question 13

What species/breeds has dystrophic EB been reported in?

Answer 13

Akitas, Golden Retrievers and a Persian cat.

Question 14

How do primary and secondary lesions of both junctional and dystrophic EB differ?

Answer 14

In primary lesions the epidermis is cleanly separated from the underlying dermis to form a bulla or vesicle, inflammation is not present within early bullae and dermal inflammation is sparse. Earliest lesions may occur as vacuoles along the BMZ. As the bullae evolve into ulcers secondary sever fibrinosuppurative exudation and neutrophilic dermal inflammation develop. This is often accompanied by a fibrovascular reaction in the dystrophic form,

Question 15

What does inherited EB look like histopathologically?

Answer 15

It resembles:

1) Epidermolysis bullosa acquisita, 2) Bullous pemphigoid.
3) Mucous membrane pemphigoid.
4) Linear IgA disease.

Question 16

Histopathologically how does inherited EB differ from other sub-epidermal bullous dermatoses?

Answer 16

Inflammation within and beneath the intact cleft of inherited EB is generally sparse vs others (except for linear IgA disease). Autoantibodies are not present in inherited EB vs other disease.

Question 17

What is epidermolysis bullosa acquisita?

Answer 17

Autoimmune blistering disease due to antibody targeting of the basal cell layer or various levels of the BMZ.

Question 18

What forms does EBA present in and which is more common?

Answer 18

Localised and generalised. Generalised is more common with only 1 localised case reported.

Question 19

What % of subepidermal autoimmune blistering diseases associated with anti-basement membrane autoantibodies does EBA make up?

Answer 19

Up to 25%

Question 20

What autoantibodies are the target in EBA?

Answer 20

Aminoterminal, non-collagenous (NC1) and NC2 segments of type VII collagen.

Question 21

What is the role of Collagen VII?

Answer 21

It is a major component of dermal anchoring fibrils that bind to the BMZ.

Question 22

How can EBA be differentiated from bullous pemphigoid or mucous membrane pemphigoid clinically?

Answer 22

EBA is more likely to have paw pad involvement and systemic signs.

Question 23

What epidermal changes are seen histopathologically with EBA?

Answer 23

Usually large & flat sub epidermal bullae are present and may be filled with blood. Few strands of dermal collagen may cling to the roof to the bulla. Neutrophils accumulate along the base or within the cleft (can be intense). Non-inflammatory blisters can be seen. Neutrophils often line up beneath the basement membrane and may degenerate resulting in the presence of nuclear fragments in this location (Leuko