Blistering disorders

Question 1

What does direct IF show & how is it carried out?

Answer 1

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

Question 2

Limitations of Direct IF?

Answer 2

May be negative

Sensitive to biopsy site

Re-biopsies may be needed

Scarring

Question 3

What does indirect IF show & how is it carried out?

Answer 3

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

Question 4

What is the alternative ‘salt split skin’ technique of indirect IF?

Answer 4

Normal skin incubated in molar NaCl (high salt solution which causes epidermis to raise & target antigens to be revealed)

Question 5

Limitations of indirect IF?

Answer 5

May be negative

Dependent on substrate used

‘Split skin’ may be more sensitive

Question 6

What is pemphigus vulgaris?

Answer 6

Chronic, organ-specific autoimmune blistering condition

Question 7

How does pemphigus vulgaris occur?

Answer 7

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

Question 8

Epidemiology of pemphigus vulgaris?

Answer 8

40-60 y/o
Both sexes affected
Strong genetic association
Ethnicity association - Ashkenazian Jews, Mediterranean & South Asian origins

Question 9

Possible aetiology of Pemphigus Vulgaris?

Answer 9

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)

Question 10

Oral features of pemphigus vulgaris?

Answer 10

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

Question 11

Cutaneous features of pemphigus vulgaris?

Answer 11

Large, non-healing erosions & ulcers of the skin

Often appear after mouth lesions (after 3-4 months)

Rare to see frank blisters

Question 12

What investigations can be carried out by pemphigus vulgaris?

Answer 12

Biopsy (Direct IF staining & routine histology
- Biopsy taken of affected lesions & normal tissue
- Sample kept fresh or frozen (not fixed)

Serum (Indirect IF staining)

Question 13

Histology of pemphigus vulgaris?

Answer 13

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

Question 14

How to treat pemphigus vulgaris?

Answer 14

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

Question 15

What is MMP?

Answer 15

Chronic, organ-specific autoimmune blistering condition

Question 16

How does MMP occur?

Answer 16

Circulating & tissue-bound IgG autoantibodies against basement membrane zone

Belongs to a group of related conditions

Question 17

Epidemiology of MMP?

Answer 17

Middle aged - 6th decade onward (rare in children)

Slight female predominance

3x more common than pemphigus

Question 18

Aetiology of MMP?

Answer 18

Unknown

Question 19

Oral features of MMP?

Answer 19

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

Question 20

Ocular, cutaneous & genital features of MMP?

Answer 20

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

Question 21

How to investigate MMP?

Answer 21

Biopsy
Histopathology - characteristic ‘sub-basilar split’

Direct IF (homogenous, linear IgG/C3 deposits in BMZ along dermo-epithelial junction)

Question 22

Treatment of MMP?

Answer 22

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)

Question 23

Clinical features of bullous pemphigoid?

Answer 23

Tense, large blister formation - often involves skin of limbs, trunk & flexures

Initial urticarial eruption (itchy white or red lumps) proceeds blistering

Question 24

Management of bullous pemphigoid?

Answer 24

Topical/systemic corticosteroids +/- steroid-sparing agents (azathioprine)

Alternative = anti-inflammatory abx (minocycline) or Dapsone

Question 25

Epidemiology of dermatitis herpetiformis?

Answer 25

Rare - Native Irish & younger ages

Associated with Coeliac disease

Question 26

Treatment of dermatitis herpetiformis?

Answer 26

Gluten-free diet & Dapsone

Question 27

Clinical features of dermatitis herpetiformis?

Answer 27

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

Question 28

Aetiology of angina bullosa haemorrhagica?

Answer 28

Genetic predisposition

LT use of inhaled corticosteroids => capillary breakdown or mucosal atrophy causes decreased elastic fibres in submucosa

Diabetes => vascular fragility

Elderly

Question 29

Clinical features of angina bullosa haemorrhagica?

Answer 29

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

Question 30

Management of angina bullosa haemorrhagica?

Answer 30

FBC & coagulation screen

Large intact blood-blister incisal (to avoid respiratory obstruction)

Symptomatic tx (e.g. Difflam benzydamine or CHX m/w)

Question 31

Oral features of epidermolysis bullosa?

Answer 31

General fragility - minor trauma => mucosa separation from underlying CT

Scarring may lead to deformity

Severe cases may affect OH & eating

Question 32

What is epidermolysis bullosa acquisita?

Answer 32

Chronic, acquired autoimmune disorder => widespread blistering with scarring

Question 33

Clinical features of epidermolysis bullosa acquisita?

Answer 33

Sub-epidermal blister formation & oral involvement