Blistering disorders Flashcards
What does direct IF show & how is it carried out?
Demonstrates bound immune complexes in mucosa or skin
Method:
1. Incisional biopsy (of lesion & normal skin)
2. Biopsy sectioned on slide
3. Incubation with FITC (fluorescent marker) for anti-human IgG, IgA, IgM & complement
Limitations of Direct IF?
May be negative
Sensitive to biopsy site
Re-biopsies may be needed
Scarring
What does indirect IF show & how is it carried out?
Detects autoantibodies in serum
Method:
1. Serum sample taken & sections of normal mucosa/skin taken & put on slide
2. Primary incubation
3. Secondary incubation with FIT labelled anti-human IgG, IgA & c3
What is the alternative ‘salt split skin’ technique of indirect IF?
Normal skin incubated in molar NaCl (high salt solution which causes epidermis to raise & target antigens to be revealed)
Limitations of indirect IF?
May be negative
Dependent on substrate used
‘Split skin’ may be more sensitive
What is pemphigus vulgaris?
Chronic, organ-specific autoimmune blistering condition
How does pemphigus vulgaris occur?
Circulating & tissue-bound IgG autoantibodies against (harm) adhesion proteins of desmosomes => disruption of cell-to-cell adhesion
Causes intra-epithelial blisters affecting skin & oral mucosa (mouth often affected so dentist in prime position to flag up disease before rapid spread)
Potentially life threatening (~6% mortality); auto-antibody titre useful to monitor disease activity & treatment success
Epidemiology of pemphigus vulgaris?
40-60 y/o
Both sexes affected
Strong genetic association
Ethnicity association - Ashkenazian Jews, Mediterranean & South Asian origins
Possible aetiology of Pemphigus Vulgaris?
Diet - garlic, onions, leak, mustard, horseradish, tea (tannins), mango & red wine
Medication - sulphydryl containing (e.g. pencillamine or ACE inhibitors or non-thiol drugs with active amine group (e.g. rifampicin & diclofenac)
Oral features of pemphigus vulgaris?
Mouth often involved, only site in 50% cases & can have cutaneous spread
Oral bullae (blisters with serous fluid)- fragile & short-lived
Nikolsky’s sign (oral blisters rapidly breakdown to form erosions - lift off from underlying epithelium to give white appearance with surrounding red erythematous mucosa)
Large, shallow, non-healing ulcers
60% present with desquamative gingivitis (also in LP & MMP)
Palate, buccal mucosa & gingiva most commonly affected
Dysphagia/odynophagia may suggest oesophageal involvement
Cutaneous features of pemphigus vulgaris?
Large, non-healing erosions & ulcers of the skin
Often appear after mouth lesions (after 3-4 months)
Rare to see frank blisters
What investigations can be carried out by pemphigus vulgaris?
Biopsy (Direct IF staining & routine histology
- Biopsy taken of affected lesions & normal tissue
- Sample kept fresh or frozen (not fixed)
Serum (Indirect IF staining)
Histology of pemphigus vulgaris?
Intra-epithelial clefting & acantholysis
Intact bullae containing clumps of acantholytic cells (‘Tzanck cells’)
Positive IF staining for keratinocytes - ‘Fish net pattern’
Autoantibodies (IgG) target Desmoglein-3 in basal & supra-basal keratinocyte desmosomes
How to treat pemphigus vulgaris?
Systemic glucocoritcosteroids (e.g. prednisolone or deflazacort) & steroid-sparing agents (e.g. azathioprine, mycophenolate mofetil or ciclosporin)
Topical potent corticosteroids
Alternatives = IV immunoglobulins or Plasmapheresis
What is MMP?
Chronic, organ-specific autoimmune blistering condition
How does MMP occur?
Circulating & tissue-bound IgG autoantibodies against basement membrane zone
Belongs to a group of related conditions
Epidemiology of MMP?
Middle aged - 6th decade onward (rare in children)
Slight female predominance
3x more common than pemphigus
Aetiology of MMP?
Unknown
Oral features of MMP?
Vesicles & blood-filled blisters - rapidly rupture => irregular pseudomembrane-covered painful erosions & ulcers
Desquamative gingivitis (blisters involving attached gingivae)
Positive Nikolsky’s sign
Chronic soreness, bleeding & dysphagia
May resemble erosive LP
Scarring & lip lesions rare
Ocular, cutaneous & genital features of MMP?
Ocular:
- Chronic conjunctivitis
- Burning, irritation, photophobia & excessive tearing
- Initially 1 eye involved & 2nd eye involved within 2 years
- Can lead to scarring (cicatricial conjunctivitis) => entropion, trichiasis & blindness
- Vesicles/ulceration in aggressive disease
Cutaneous:
- 30% pts - tends to affect scalp (=> irreversible alopecia), face, neck & trunk
Genital:
- Scarring => sexual & urinary problems
How to investigate MMP?
Biopsy
Histopathology - characteristic ‘sub-basilar split’
Direct IF (homogenous, linear IgG/C3 deposits in BMZ along dermo-epithelial junction)
Treatment of MMP?
Often resistant to tx
Topical corticosteroids (1st line) -e.g. betamethasone, fluticasone, clobetasol
Dapsone (anti-bacterial abx)
Systemic corticosteroids (e.g. prednisolone)
Anti-inflammatory antibiotics (e.g. doxycycline, micocycline)
Immunosuppressants (e.g. cyclophosphamide, azahtioprine)
Clinical features of bullous pemphigoid?
Tense, large blister formation - often involves skin of limbs, trunk & flexures
Initial urticarial eruption (itchy white or red lumps) proceeds blistering
Management of bullous pemphigoid?
Topical/systemic corticosteroids +/- steroid-sparing agents (azathioprine)
Alternative = anti-inflammatory abx (minocycline) or Dapsone
Epidemiology of dermatitis herpetiformis?
Rare - Native Irish & younger ages
Associated with Coeliac disease
Treatment of dermatitis herpetiformis?
Gluten-free diet & Dapsone
Clinical features of dermatitis herpetiformis?
Chronic pruritic (itchy) papulo-vesicular rash - small blisters on urticated base
Often affects buttocks, elbows & knees
Oral presentation (~70%) => tender ulcers
May appear similar to herpetiform due to smaller bullae & vesicles
Aetiology of angina bullosa haemorrhagica?
Genetic predisposition
LT use of inhaled corticosteroids => capillary breakdown or mucosal atrophy causes decreased elastic fibres in submucosa
Diabetes => vascular fragility
Elderly
Clinical features of angina bullosa haemorrhagica?
Sudden appearance of solitary large blood-filled blisters (2-3cm diameter)
Junction between hard & soft palate
Often follow dry/rough food & pts feel they may be choking
Cycle:
- Burst spontaneously within 24 hours
- Resolve in 7-10 days without scarring
- Recur for 5-10 episodes for a few years
Management of angina bullosa haemorrhagica?
FBC & coagulation screen
Large intact blood-blister incisal (to avoid respiratory obstruction)
Symptomatic tx (e.g. Difflam benzydamine or CHX m/w)
Oral features of epidermolysis bullosa?
General fragility - minor trauma => mucosa separation from underlying CT
Scarring may lead to deformity
Severe cases may affect OH & eating
What is epidermolysis bullosa acquisita?
Chronic, acquired autoimmune disorder => widespread blistering with scarring
Clinical features of epidermolysis bullosa acquisita?
Sub-epidermal blister formation & oral involvement
