• appearance of blisters or erosions
- skin
- mucous membranes
• characterized by the presence of auto-
antibodies that target distinct adhesion
molecules in the skin
Autoimmune bullous skin diseases
Autoimmune bullous skin diseases
• Intraepidermal loss of adhesion (desmosome)
- Pemphigus group of disorders
• Subepidermal loss of adhesion (basement membrane zone)
- Pemphigoid group of disorders
- Epidermolysis bullosa acquisita
- linear IgA bullous dermatosis
Pemphigus vulgaris (PV)
- painful erosions of the oral mucosa
- flaccid, thin-walled, easily ruptured blisters
- erosions
• Clinical features:
Pemphigus foliaceus (PF)
- scaly crusted erosion because the vesicles
are fragile and rupture easily
• Clinical features:
Histology
- intraepidermal blister formation due
to a loss of cell-cell adhesion of
keratinocytes (acantholysis)
'row of tombstones'
Pemphigus foliaceus
Pemphigus vulgaris
Pathogenesis
- IgG autoantibodies against the cell surface of keratinocytes
- Desmosomes: cell-cell adhesion junctions in stratified squamous epithelia
Pathogenesis
Pemphigus vulgaris: Dsg1 160 kD IgG
Dsg3 130 kD IgG
Pemphigus foliaceus: Dsg1 160 kD IgG
Desmosome
Disease Target antigen MW Isotype
patient´s skin
direct immunfluoreszenz
antigen
antibody in situ
Diagnostics
fluorescein labelled
anti-human Ig /C3
antibody
monkey esophagus
indirect immunfluoreszenz
antigen
Diagnostics
patient´s serum
with circulating
autoantibodies
fluorescein labelled
anti-human Ig /C3
antibody
Diagnostics
• most of the autoantigens are
available as recombinant proteins
• autoantibody screening by
- ELISA
- immunoblot analysis
Autoimmune bullous skin diseases
• Intraepidermal loss of adhesion (desmosome)
- Pemphigus group of disorders
• Subepidermal loss of adhesion (basement membrane zone)
- Pemphigoid group of disorders
- Epidermolysis bullosa acquisita
- linear IgA bullous dermatosis
Bullous pemhigoid (BP)
- elderly patients
- lesions in the oral mucosa (20%)
- localized or widespread tense blisters
and erosions with an erythematous base
• Clinical features:
Histology
- subepidermal blister formation
- polymorphous inflammatory infiltrate
(eosinophils, neutrophilic, mast cells
lymphocytes)
Pathogenesis
- IgG (M,A) autoantibodies against
BP180
Laminin-5
Plectin BP230
Collagen VII
a6b4
Basal cells
- BPAg 1 (230 kD)
- BPAg 2 (180 kD)
- activation of complement
- recruitment of inflammatory cells
patient´s skin
direct immunfluoreszenz
antigen
antibody in situ
Diagnostics
fluorescein labelled
anti-human Ig /C3
antibody
human skin
indirect immunfluoreszenz
antigen
Diagnostics
patient´s serum
with circulating
autoantibodies
fluorescein labelled
anti-human Ig /C3
antibody
Summary
• Pemphigus is characterized by intraepidermal loss of adhesion
• Target antigens of pemphigus are located within the desmosome:
e.g. pemphigus vulgaris (Dsg1, Dsg3), pemphigus foliaceus (Dsg1)
• Pemphigoid is characterized by subepidermal loss of adhesion
• Target antigens of pemphigoid are located within the basement
membrane zone: BPAg 1 (230 kD), BPAg 2 (180 kD)