Autoimmune bullous skin diseases

Nikhil Yawalkar

Department of Dermatology

Inselspital Bern

• 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

Pathogenesis

Pemphigus foliaceus

Dsg1

Pemphigus vulgaris

Dsg1, Dsg3

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 autoantibodies against hemidesmosomes

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

T cell

T cell

proteases

B cell

C3b,C5a

Pathogenesis

T cell

MC

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

Diagnostics

• autoantibody screening by

- immunoblot analysis

- ELISA

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)