Basement Mbrn Zone and Vesiculobullous Diseases

Question 1

Role of basement mbrn zone

Answer 1

Connect basal layer of epidermis to underlying dermis and anchors proteins that traverse the structure.

Question 2

Inflammation directed against components of the BMZ lead to what type of diseases, characterized by what?

Answer 2

Immunobullous, w/ vesicles, bullae, and erosions.

Question 3

Absence of key structures in the BMZ causes what kind of diseases, with what symptoms?

Answer 3

mechanobullous, w/ skin fragility.

Question 4

What are the four parts of the BMZ?

Answer 4

1. plasma mbrn and hemidesmosomal plaque of basal keratinocyte 2. lamina lucida 3. lamina densa 4. sublamina densa

Question 5

Describe the structure and function of hemidesmosomes

Answer 5

unpaired structure at inferior pole of keratinocyte that contain numerous proteins (bullous pemphigoid antigen 1, bullous pemphigoid antigen 2, and integrins) to serve an anchoring purpose.

Question 6

What is BPAG1?

Answer 6

an epidermal intracytoplasmic protein in the cytoplasm of the basal keratinocyte hemidesmosome that binds keratin for cell stability.

Question 7

What is BPAG2?

Answer 7

a transmembrane prot of type 7 collagen that binds BPAG1 and integrins in the hemidesmosome with laminin 5 in the lamina densa.

Question 8

Describe the structure and function of the lamina lucida.

Answer 8

A clear band below the basal layer of the epidermis. This layer is traversed by the BPAG 2.

Question 9

Describe the structure and function of the lamina densa.

Answer 9

Composed of laminins (three subunits that form heterotrimers to provide structure) and collagen 4.

Question 10

Main anchoring laminin in the lamina densa?

Answer 10

Laminin 5 is the main laminin, as it links to BPAG2, the lamina densa, and the anchoring fibrils of the sublamina densa.

Question 11

Describe type 4 collagen as it functions in the lamina densa.

Answer 11

heteropolymer of two identical alpha subunits and one different alpha subunit that form a triple helix for stability . Each helix associates with three other helices to form a tetrad, tetrads join to form a lattice structure for support.

Question 12

Describe the structure and function of the sublamina densa.

Answer 12

Composed of elastin and collagen 7 for tensile strength and pliability of the skin.

Question 13

Describe type 7 collagen and its function in the sublamina densa

Answer 13

made of 3 identical alpha chains forming anchoring fibrils and only found in the basement membrane of stratified squamous epithelia. Terminal ends insert into the lamina densa, forming a loop for association with types 1 and 3 collagen for further stability. (Type 3 collagen more common in fetal skin and wound healing)

Question 14

Sources of vesicles and bullae

Answer 14

friction, hydrostatic pressure, or infection.

Question 15

Immunobullous disease pathology and clinical features\?

Answer 15

inflammation directed against cells in the epidermis or BMZ resulting in loss of cell-cell adhesion and bullae formation. Characterized by antibodies directed against components of BMZ, detectable in tissue or serum.

Question 16

Congenital mechanobullous disease pathology

Answer 16

absence of structural proteins, preventing cell-cell adhesion and promotes blister formation.

Question 17

A more superficial bullae that can be easily ruptured. Can present as round erosion with collarette scale if ruptured.

Answer 17

Flaccid bullae

Question 18

Bullae deep in the epidermis, so less easily ruptured because the more superficial intercellular bonds are intact.

Answer 18

tense bullae

Question 19

Common systemic sites of immunobullous diseases

Answer 19

ocular conjunctiva, oral mucosa, and genital mucosa

Question 20

Describe how to determine a positive or negative Nikolsky sign.

Answer 20

Determines whether a bullae is flaccid or tense. Apply gentle pressure on the edge of the blister and pull laterally. Positive test will lead to the extension of the bulla (flaccid), a negative test fails to extend blister edge (tense)

Question 21

Describe the use and indications of a biopsy

Answer 21

tissue sample from the edge of a blister sent for histo analysis. Allows for localization of the level of the blister and the primary inflammatory cell type.

Question 22

Describe immunofluorescence.

Answer 22

Test for the presence of immunoreactants. Antibodies directed agaisnt human Ig or complement components (taken from mice) are tagged w/ fluorescence and facilitates detection with a fluorescent microscope.

Question 23

Describe the use and indications of direct immunofluorescence.

Answer 23

performed on a tissue from a PERILESIONAL site, greater than 1 cm from edge of blister. Sent in special medium and Ab are tagged, bind to Ig in tissue sample. Tagged AB to IgG, IgM, IgA, and C3 define diagnosis. Too close to blister edge gives false negative. Direct more sensitive than indirect.

Question 24

Describe the use and indications of indirect immunofluorescence.

Answer 24

Tests serum for circulating immunoreactants, used in conjugation with DIF. Fluorescence tagged Ab added to patient serum suspected to contain an Ab against the BMZ. Ab complex then applied to foreign substrate (ex: monkey esophagus rich in desmoglein 3 to test for pemphigus vulgaris) and tested for fluorescence.

Question 25

Describe the use and indications of serological tests

Answer 25

Antigen-specific ELISA tests to confirm suspected diagnosis. Pt serum tested against desmoglein 1 and desmoglein 3 in pemphigous vulgaris and BPAG1 and BPAG2 for bullous pemphigoid. Falling levels determine when to adjust tx, esp oral immunosuppressants.

Question 26

Describe the clinical expression of Pemphigoid Vulgaris

Answer 26

An autoimmune blistering disease w/ flaccid bullae (often rupture, as they are very fragile). Oral erosions common, with significant pain (hallmark). May present w/ crusting of the scalp w/ underlying lesions. Positive Nikolsy sign.

Question 27

Pathology of Pemphigoid Vulgaris

Answer 27

Autoimmunity w/ Ab directed against desmoglein 3 that leads to loss of intercellular cohesion b/w keratinocytes in the epidermis. “Tombstoning” of BMZ in histo imaging. DIF shows staining of IgG Ab against Dsg3 in epidermis. Tx: immunosuppressants or systemic steroids.

Question 28

Describe the clinical expression of Bullous Pemphigoid

Answer 28

Typically in elderly pts (60 yrs+), tense bullae on trunk and extremities (hallmark). Also may have severe pruritus (no pain) and an urticarial or papular eruption. Negative Nikolsky sign. Oral involvement rare. Better prognosis than PV.

Question 29

Pathology of Bullous Pemphigoid

Answer 29

Ab against BPAG1 and BPAG2 result in split at level of hemidesmosomes. Intact epidermis separated from underlying BMZ in histo imaging. Inflammatory infiltration of eosinophils. Linear staining BMZ w/ IgG and C3 in DIF. Tx: high potency topical steroid or oral antibiotics. Oral steroids or immunosuppressants if severe.

Question 30

Describe the clinical expression of Cicatricial Pemphigoid

Answer 30

rare, aggressive autoimmune disease favoring mucosal surfaces. 90% w/ oral involvement, 66% with ocular involvement, 25% with skin involvement. Often, oral bleeding and pain as hallmark. Ocular burning, foreign body sensation, discharge, and pain. Cutaneous blisters and erosions on scalp, face, neck, and upper trunk. Chronic condition that leads to long-term difficulties. Tx: topical steroids (mild to moderate), oral immunosuppressants (severe). Opthalmic exams regularly for ocular issues.

Question 31

Pathology of Cicatricial Pemphigoid

Answer 31

Ab against BPAG2 and laminin 5, looks like BP in biopsy of subepidermal blister. DIF shows linear IgG at lamina lucida.

Question 32

Three main subtypes and presentation of Epidermolysis Bullosa

Answer 32

Group of diseases that present w/ bullae and mechanical fragility of skin. Subtypes: EB simplex: inherited autosomal dominant absence of epidermal keratins. Junctional EB: autosomal recessive mutations to laminin and BPAG2. Dytrophic EB: inherited autosomal dominant or recessive absence of collagen 7

Question 33

Clinical presentation of epidermolysis bullosa

Answer 33

Mild: blisters and erosions with physical activity. Moderate: chronic erosions and bullae leading to scarring and pain. Severe: scarring complications (mitten hand deformities), blindness, esophageal strictures, and joint contractures.

Question 34

Pathology of Dermatitus Herpetiformis

Answer 34

Biopsy of vesicle or erythematous patch reveals a subdermal blister with neutrophils. Perilesional biopsy for DIF shows granular deposits of IgA in dermal papillae. Serum anti-endomysial Ab to the CT covering smooth musc of the GI tract, usually IgA in 70% of DH pts and 100% of pt w/ celiac disease.

Question 35

Clinical Expression of Dermatitus Herpetiformis

Answer 35

Common in Northern European descent, mean age of onset in 40’s. Intensely pruritic (hallmark), classically affecting buttocks, extensor upper and lower extremities, and occipital scalp. Cutaneous lesions w/ papules, vesicles, and urticarial plaques, but vesicles not seen due to scratching.

Question 36

What dermatological disease is associated with celiac disease?

Answer 36

Dermatitus Herpetiformis, though celiac disease may be assymptomatic or associated with diarrhea or malabsorption. Also an association b/w DH and thyroid disease.