Basement Membrane Zone and Vesiculobullous Diseases Flashcards
Basement membrane zone
connects basal layer of epidermis with underlying dermis and anchors proteins traversing this structure
- derived from ectodermal keratinocytes and mesodermally-derived fibroblasts
- divided into 4 parts:
1. plasma membrane + hemidesmosomal plaques
2. lamina lucida (clear band that BPAG2 traverses)
3. lamina densa (laminins and collagen 4)
4. sublamina densa (collagen 1,3,4,7 and elastin)
BPAG1
230kDa epidermal intracytoplasmic protein that binds to keratin and stabilizes the cell as part of hemidesmosome
BPAG2
180kDa transmembrane protein comprised of type 17 collagen that binds BPAG1 and integrins in the hemidesmosome with laminin 5 located in the lamina densa
Laminin 5
composed of three subunits that form heterotrimer
-links BPAG2 and lamina densa and anchoring fibrils of sublamina densa
Type IV collagen
heteropolymer containing two identical alpha helical subunits and one dissimilar alpha helical subunit
- polymerize into triple helix
- each molecule associates with 3 others to form tetrad
- tetrads form together to make lattice
- form anchoring fibrils that associate with type 1 and 3 collagen
Immunobullous diseases
inflammation directed against cells located in epidermis or BMC, leading to loss of cell-to-cell adhesion and subsequent bulla formation
- characterized by antibodies directed against BMZ
- may affect ocular conjunctivae, oral and genital mucosa
Congenital mechanobullous diseases
absence of structural proteins that prevents normal cell-cell adhesion and promotes blister formation
Pemphigus Vulgaris (PV)
autoimmune blistering disease w/ Ab against desmoglein3
- flaccid bullae
- oral erosions common
- significant pain
- crusting of scalp with underlying erosions
- positive Nikolsky sign
- tombstoning
- DIF shows IgG against Dsg3 throughout epidermis
- treat with steroids and immunosuppressants long term
Bullous Pemphigoid (BP)
Ab against BPAG1 and BPAG2 leads to split at hemides.
- tense bullae on trunk and extremities
- typically affects elderly (>60yrs)
- severe pruritus and urticarial or papular eruption
- no pain or oral erosions
- negative Nikolsky sign
- intact epidermis separates from BMZ
- eosinophils & DIF shows linear staining of BM w/ IgG and C3
- treat with topical steroids + oral antibiotix (oral for severe)
Cicatricial Pemphigoid (CP)
Ab against BPAG2 and laminin 5
- favors mucosal surfaces
- oral (90%), ocular (66%) and skin (25%) involvement
- oral bleeding and pain
- ocular burning, foreign body sensation, discharge, pain
- cutaneous blisters and erosions on scalp, face, neck and upper trunk
- often chronic, leaving scarring and fibrosis
- DIF reveals linear IgG at lamina lucida
- treated with topical corticosteroids and close monitoring
- oral immunosuppressant therapy crucial for severe oral and ocular disease
Epidermolysis Bullosa (EB)
group of diseases presenting with bullae and mechanical fragility of skin
- 3 major subtypes:
1. Simplex inherited AD w/ absent epidermal keratins
2. Junctional inherited AR w/ laminin and BPAG2 mutations
3. Dystrophic inherited both AD and AR w/ no collagen 7 - mild cases show blisters on feet with physical activity
- severe cases have chronic erosions and bullae leading to scarring and pain (mitten hand deformities, blindness, etc.)
- high mortality (increased squamous cell carcinoma risk)
Dermatitis Herpetiformis (DH)
Typicall affects >40 yr olds of northern european descent
- intensely pruritic disease affecting the occipital scalp, extensor upper and lower extremities and buttocks
- papules, vesicles, and urticarial plaques
- workup includes:
1. biopsy of vesicle or erythematous patch (look for subepidermal blister with neutrophils)
2. perilesional biopsy for DIF (granular deposits of IgA in dermal papillae)
3. serum anti-endomysial Ab (anti-tissue transglutaminase Ab IgA detected) - associated with celiac diseases and some thyroid disease
- follow GF diet and apply dapsone (sulfa Abx) for itch
