Immunobullous Diseases Flashcards
Pemphigus Foliaceus: Target Protein
Desmoglein 1
Pemphigus Vulgaris: Target Protein
Desmoglein 3, +/-1
Bullous pemphigoid: Target Protein
HEMIDESMOSOME BPAG2 = BP180, BPAG1 = BP230
Pemphigus foliaceus: clinical presentation
Superficial crusted erosions, +/- itch Distribution: face, scalp, upper central chest/back, proximal arms/legs NEVER affects mucosa
Pemphigus foliaceus: key word
“Cornflake crust”
Pemphigus foliaceus: DDx
Psoriasis, Eczema, Seborrheic dermatitis/scalp psoriasis, bullous impetigo (S. aureus), staphylococcal scalded skin syndrome
Pemphigus vulgaris: clinical presentation
MUCOSAL EROSIONS: 1. oropharyngeal, vaginal, esophageal, nasal, conjuctiva 2. NOT oral ulcers MUCOCUTEANOUS PV: widespread deep erosions 1. mucosa, face, scalp, trunk, extremities 2. spares palms and soles 3. can be itchy or painful
Pemphigus vulgaris: DDx
Mucosal PV: 1. HSV, Lichen planus, erythema multiforme Mucocutaneous: 1. SJS, disseminated zoster, TEN, erythema multiforme, paraneoplastic pemphigus
Important sign in PV?
Nikolsky sign: blister will extend or be induced when lateral pressure is applied
Bullous pemphigoid: clinical presentation
Tense bullae (arms, leg, trunk) Less often: face/scalp, mucosal, palms/soles INTENSELY ITCHY
BP variants?
- urticarial variant 2. localized (pretibial, around stomas, post-surgical)
BP: DDx
- Acute allergic contact dermatitis 2. Urticaria / urticarial drug reaction 3. Subepidermal immunobullous 4. Subepidermal non-immunobullous
How to Dx immunobullous diseases?
- Skin biopsy for histology 2. Immunofluorescence studies 3. Enzyme-linked immunosorbent assay
PV histology
Acantholysis, cytolysis, “ROW OF TOMBSTONES” – hemidesmosomes intact, desmosomes connecting keratinocytes to each other are damaged
PF histology
Superficial acantholysis, eosinophils
Desmoglein compensation theory
Different isoforms can compensate for one another in regard to their adhesive function in the epidermis
Normal human skin: Dsg1 distribution
High in epidermis, low in dermis - normal skin High in epidermis, absent in dermis - mucous membranes
Normal human skin: Dsg3 distribution
High in dermis, low in epidermis - normal skin Constant throughout mucous membranes
PF blisters: where are they?
Superficial epidermis (no Dsg3 compensation) -never in mucous membranes
Mucosal PV blisters: where are they?
Suprabasal blisters in mucous membranes - tombstoning
Mucucutaneous PV blisters: where are they?
anti-Dsg1 and anti-Dsg3 antibodies Suprabasal blisters in mucous membranes - tombstoning Suprabasal blisters due to inactivation of Dsgs throughout the skin
Are antibodies causative?
Seems to be the case, yes
Mechanisms of acantholysis
1.Steric hindrance 2. Induction of cellular signaling pathways (e.g. pathogenic antibodies that cause endocytosis of cell surface Dsgs, regulated by p38 MAPK)
Double-edged sword for immunity?
Anti-Dsg1 antibodies are protective for Leishmania infection
