Immunobullous Diseases Flashcards
What are immunobullous diseases and what are the two main diseases
Immunobullous diseases are autoimmune diseases where antibodies attack components of the skin or oral epithelium producing blisters
- the two main diseases are pemphigus and pemphigoid
What is pemphigus vulgaris and what is the aetiology?
Where are autoantibodies directed?
where does the process start?
what happened to epithelial cells that lose their attachment?
What happens when the bulla bursts?
- It is an autoimmune disease causing vesicles or bulla on skin and mucous membranes WITHIN epithelium
- Autoantibodies (IgG and C3) are directed against desmoglein 1 or 3 (two proteins of desmosomes that hold epithelial cells together) so the epithelium loses cohesion and disintegrates
- Process starts in the suprabasal and prickle cells forming a vesicle - enlarge to bulla - burst
- Epithelial cells that have lost their attachment become rounded and fall into the bullae
- When the bulla bursts, a layer of basal cells remains stuck to basement membrane attached by hemidesmosomes
- But these cells become abraded and forms an ulcer which becomes secondarily infected
Clinically, who is most likely to get pemphigus vulgaris and where to the blisters often first appear?
Females aged 40-60Y
- Blisters often first appear in the mouth but spread widely on the skin
- Blisters often first develop on non-keratinised lining mucosa and they rupture leaving painful erosions
How do you diagnose pemphigus vulgaris?
- Nikolsky’s sign: stroking of mucosa or skin can cause a vesicle or bulla to appear
- Biopsy: shows acantholysis (disintegration of prickle cell layer)
- Immunofluorescence: shows autoantibodies in perilesional tissue
What is the management for pemphigus vulgaris
- systemic steroids (prednisolone) and immunosuppressant (azathioprine)
- Then maintenance with lower dose depending on pt reaction
What are the pemphigus variants (resemble pemphigus clinically but have different histological features)?
- Pemphigus vegetans (benign localised form of pemphigus vulgaris)
- IgA pemphigus (have autoantibodies of IgA (not IgG class), and mucosal involvement is rare)
- Pemphigus foliaceous (has no mucosal involvement because target antigen is only desmoglein 1)
- Drug induced pemphigus
- Paraneoplastic pemphigus
- seen in pts with malignant neoplasms such as lymphomas and leukaemia
- pathogenesis is the same except there are more autoantibodies against desmoplakins and antibasement membrane antibodies
- produces a confusing clinical picture of pemphigus, pemphigoid and erythema multiforme
What is mucus membrane pemphigoid and what is the aetiology?
Where are autoantibodies directed?
What does this cause?
- Chronic autoimmune disease causing bull and painful erosions as a result of separation of epithelium from connective tissue (SUBEPIDERMAL)
- Autoantibodies (IgG class) are directed against several basement membrane components: BP180 antigen, integrins, laminin, and type VII collagen
- Antibodies bind to BM and cause complement activation, attracting neutrophils to degrade BM
- Results in epithelium falling off the CT
Clinically, who is most likely to get pemphigus vulgaris and where to the blisters often first appear?
Where are blisters often absent?
- Females 50-80Y
- Oral mucosa often first site: gingival (desquamative gingivitis), buccal mucosa, palate and tongue
- Eye involvement can cause scarring and blindness
- Skin often absent
Why do bullae and vesicles appear briefly in mucus membrane pemphigoid
- Oral bullae are subepithelial and sometimes seen intact
- Vesicles and bullae only seen for a short while as they burst soon after forming as the roof is a strong intact full thickness epithelium
- Individual erosions are painful and heal slowly
How do you diagnose mucous membrane pemphigoid?
- Nikolsky’s sign: stroking of mucosa or skin can cause a vesicle or bulla to appear
- Biopsy: can see separation of epithelium from CT at BM
- Immunofluorescence: shows IgG bound to BM
What is the management of mucous membrane pemphigoid
- mild cases: topical corticosteroids
- moderate: high potency steroids
- severe: systemic steroids with immunosuppressant
What are the pemphigoid (resemble pemphigus clinically but have different histological features)?
- Bullous pemphigoid (skin) (signs are similar to mucus membrane pemphigoid but affects mouth in only 10% of cases)
- Linear IgA (form of pemphigoid where antibodies are IgA)
- Drug induced pemphigoid
What is the pathogenesis of Epidermolysis bullae acquisita?
- Presents same as bulla pemphigoid
- Antibodies directed against collagen type VII anchoring fibrils below the BM
- Binding to the floor of BM rather than BM
What is Erythema Multiforme?
- Mucocutaneous hypersensitivity (cell-mediated) that affects the mouth in many cases
- It is one of the few causes of recurrent oral ulceration, and also produces blisters
Aetiology of Erythema Multiforme
- More common in immunosuppression: HIV, SLE, radiotherapy/chemotherapy
- Triggers for Erythema Multiforme
1. infections (90% of cases)
2. drugs
