Basement Membrane Zone and Vesiculobullous Diseases

Question 1

What is the basement membrane zone?

Answer 1

the delicate layer of extracellular condensation of mucopolysacchrides and proteins between epithelial and connective tissue, connects basal layer of epidermis to dermis and anchors proteins transversing this region

Question 2

What are layers included in the BMZ?

Answer 2

hemidesmosome intracellularly with the BPAG1 which is connected to the lamina densa through the laminal lucida via BPAG2

Question 3

What proteins would you find associated with the hemidesmosome as part of the BMZ?

Answer 3

BPAG1 and BPAG2 along with collagen XVII and integrins

Question 4

What proteins would you find in the lamina dense?

Answer 4

composed of laminins and collagen IV, laminin 5 is the key laminin found to link BPAG2

Question 5

What are components of the sub lamina densa?

Answer 5

collagen I, II and VII act as anchoring fibrils and elastin together afford the tensile strength and pliability that are key of BMZ

Question 6

What is the function of the BMZ?

Answer 6

epidermal basement membrane zone is a complex structure that connects the basal layer of the epidermis with the underlying dermis and anchors proteins traversing the structure

Question 7

Inflammation of against components of BMZ may lead to _______ diseases characterized by vesicles, bullae and erosions

Answer 7

immunobullous diseases

Question 8

What are words used to describe the size and quality of vesiculobullous disease.

Answer 8

vesicles and bullae (+5mm) to describe size or flaccid or tense which is reflective of a positive or negative Nikolsky sign respectively

Question 9

What are the function of BPAG1 and BPAG2?

Answer 9

BPAG1 is an intracytoplasmic protein that binds to keratin intermediate filaments to stabilize the cell and BPAG2 is a transmembrane protein, comprised of type XVII collagen which binds BPAG1 and integrins in the hemidesmosome with laminin 5 located in the lamina densa

Question 10

Contrast immunobullous disease and congenital mecahnobullous disease.

Answer 10

immunobullous disease arises from inflammation directed agains cells located in the epidermis of BMZ, congenital mechanobullous disease arise from the absence of structural proteins that prevent normal cell-cell adhesion

Question 11

Where would you biopsy for histopathology and what would this biopsy help to tell you?

Answer 11

histopathology localizes the level of split (and identifies inflammatory cell type), you would biopsy at the edge of the blister

Question 12

Where would you biopsy for DIF and what would this biopsy help to tell you?

Answer 12

biopsy from the peri-lesional skin for direct immunoflurescence which can detect the presence of absence of immunoreactants causing blisters

Question 13

What is the difference between indirect and direct immunofluorescence?

Answer 13

direct uses antibodies against tissues and indirect against serum to test for the presence of antibodies

Question 14

What are serologic tests most useful for?

Answer 14

studies like ELISA measure the levels of antigens in a way that is useful for guiding/ monitoring treatments

Question 15

What is the clinical presentation of pemphigus vulgaris?

Answer 15

flaccid bullae and erosions, painful oral erosions that affect nearly all patients; tombstoning at the level of the basal layer, DIF reveals IgG and C3 throughout entire epidermis against Dsg3

Question 16

What is the clinical presentation of bullous pemphigoid?

Answer 16

typically older adult resulting in tense bullae and severe itching, less commonly affects oral mucosa, may present with urticarial plaques or inflammatory papules, level of split on histological sample is split below the basal layer with DIF showing linear deposition of C3 and IgG at BMZ (antibodies directed agains BPAG1 and 2

Question 17

What is the clinical presentation of cicatricial pemphigoid?

Answer 17

large incidence of oral erosions (85%) moderate risk of ocular disease accompanied by burning pain of the eyes and conjunctival scarring and sub epidermal blisters causing plaques, bullae and atrophic scarring, DIF shows linear IgG and C3 antibodies against BPAG2 and laminin 5

Question 18

How are immunobulllous diseases treated?

Answer 18

while BP may resolve spontaneously over time, there is a high morbidity and mortality of PV and CP if untreated; treatment includes topical corticosteroids, oral antibiotics for BP; oral corticosteriods and oral immunosuppressants for PV and CP

Question 19

Describe general causes and clinical findings of epidermolysis bullosa (EB).

Answer 19

caused by a congenital absence of BMZ structural proteins presenting with skin fragility, painful blistering, scarring and extracutaneous manifestations

Question 20

Name the 3 types of epidermolysis bullosa and how they are distinct.

Answer 20

EB simplex (AD) due to absent epidermal keratins causing blisters over hands, feet and extremities

Junctional EB (AR) due to laminin and BPAG-2 mutations causing widespread blistering and poor healing, often associated with mouth and esophageal lesions (can be severe)

Dystrophic EB (AD and AR) due to abnormal or absent collagen VII, localized to widespread blisters that heal with scarring and often accompanied by esophageal scarring, mitten-like deformities to hands (severe)

Question 21

What is the clinical presentation and cause of dermatitis herpetiformis?

Answer 21

intensely itchy vesicles and papules that is usually a symmetric distribution on the extensor upper and lower extremities, buttock and occipital scalp

considered a cutaneous manifestation of celiac disease and associated with gastric lymphoma and thyroid disease

Question 22

What does the biopsy of dermatitis herpatiformis show?

Answer 22

histopathology shoes sub epidermal bullae with neutrophils and DIF shows IgA in dips of dermal papillae which is treated with a gluten-free diet or dapsone