Vesiculobullous Disease

Question 1

What immune reactions can the body produce?

Answer 1

Hypersensitivity reactions type 1-5

Immunogenic responses

• cell mediated immunity
• antibody mediated immunity

Question 2

Give some diseases that produce local responses in the oral mucosa

Answer 2

Aphthous ulcers

Lichen planus

Orofacial ganulomatosis

(All cell mediated immune responses)

Question 3

Give some systemic diseases that can present with localised oral mucosa lesions

Answer 3

Erythema multiforme (type 3 hypersensitivity)

Pemphigus (antibody mediated)

Pemphigoid (antibody mediated)

Lupus erythematosis

Systemic sclerosis

Sjogrens

Question 4

Why are common blistering skin lesions often connected to oral blistering?

Answer 4

Both oral mucosa and skin share common antigens due to having the same embryonic origin

Question 5

Difference between vesicle and blister?

Answer 5

Size

Vesicle 1-2mm

Blister is larger

Question 6

How does immunological skin disease result in a blister or vesicle?

Answer 6

Auto-antibody attack on skin components causes a loss in cell - cell adhesion

This forms a split in the thin that:
- fills with inflammatory exudate
- forms vesicle / blister

Split caused by attack on protein desmoglein which in turn causes splitting of desmosomes that hold cells together

Question 7

What does direct and indirect immunofluorescence show

Answer 7

Direct = antibodies bound to tissue

Indirect = antibodies not yet bound to tissue and is in plasma

Question 8

What is angina bullous haemorrhagica?

Describe it

Answer 8

‘Blood blisters in the mouth’
- Benign
- rapid onset
- appear in a few minutes and then burst after around an hour
- relatively painless
- significant lesions can appear around vibrating line that can give pt feeling of occlusion of airway

Most common oral blistering condition

Question 9

How treat angina bullish haemorrhagica?

Answer 9

Symptomatic relief

Chlorhexadine mouthwash or difflam spray

Reassure it is benign

Question 10

What is pemphigoid? What causes it?

Answer 10

Thick walled blisters of the full epidermis
- clear or blood filled
- on skin or mucosa

Caused by sub epithelial antibody attack.
- antibodies cause separation of the epithelium at the basement membrane from the connective tissue by attacking hemidesmosomes
- achieves this as IgG and IgA antibodies bind to BP180 protein to form an immune complex. These immune complexes activate the complement system.
- triggers an influx of inflammatory cells and formation of a blister in the area.

Question 11

What is the best test for pemphigoid?

Answer 11

Direct immunofluorescence

• pemphigoid antibodies bound to the antigen of the basement membrane
• causing fluorescence
• C3 and IgG detected

Question 12

How manage pemphigoid?

Answer 12

Steroids

Immune modulating drugs - azathioprine

Question 13

What is pemphigus?

Answer 13

Circulating antibodies IgG attack desmoglein 1 and desmoglein 3 leading to destruction of the desmosomal complex that holds keratinocytes together.

Intra epithelial blisters form
- blisters burst and spread
- variable number of cells above so easily bursts
- results in epithelial / mucosal erosions

Oral lesions precursor to skin lesions by up to 3 years

Question 14

How tell difference between pemphigoid and pemphigus?

Answer 14

Rare to see intact bulla in pemphigus

Intact bulla on ora mucosa = pemphigoid

Question 15

Test for pemphigus?

Answer 15

Immunofluorescence

• basket weave pattern

Vs linear pattern in pemphigoi

C3 and IgG found again

Question 16

Tx for pemphigus?

Prognosis?

Answer 16

High dose steroids

Fatal without treatment

Now, often complications of treatment are the major cause of death

Question 17

Intra oral manifestations of pemphigoid?

Answer 17

Bullae formation - these quickly rupture to leave erosions of the mucosa

Erythema - open sores or shallow wounds

Stricture - scarring - restricted movement or narrowing of oral cavity / airway

Question 18

Extra oral manifestations of MMP?

Answer 18

Ocular involvement - inflammation of the eyes - visual impairment

Skin lesions - blistering and erosions of the skin - skin discomfort

Bullae and erosion of other mucous membranes

All can lead to psychosocial effects

Question 19

What is nikolskys sign?

Answer 19

Lateral pressure placed on a bullae

Positive sign = the exfoliation of the outermost layer by slight rubbing of the skin

Question 20

How can indirect immunofluorescence / Elisa testing be used to test for MMP?

Answer 20

IIF - detects circulating IgG autoantibodies

Elisa testing - tests for BP180 and BP230

Question 21

Histological signs of pemphigus vulgaris?

Answer 21

Perilesional biopsy

Acantholysis - loss of cell-cell adhesion in the epithelium

Tzanck cells - individual large round keratinocytes with hypertrophic nucleus

Inflammatory exudate within epithelial layers

Question 22

What is ELISA testing?

Answer 22

Enzyme linked immunosorbent assay

Question 23

Epidemiology of MMP and PV?

Answer 23

50/60 years old

Slightly more common in females

PV more common in Jewish-American population

Question 24

Basically - What is EM?

Answer 24

Spectrum disorder with skin and mucosal ulceration with varying oral involvement

Question 25

Epidemiology of EM?

Answer 25

Young adults between 20 and 40 with predominance in males

Question 26

Causes of EM?

Answer 26

Type 3 hypersensitivity reaction
- herpes virus immune complexes depositing in tissues leading to an immune reaction

Type 4 hypersensitivity to drug reaction
- T cell mediated inflammatory reaction to a drug such as:

antibiotics,
NSAIDS,
TNF-A inhibitors,
Anticonvulsants

Question 27

Types of EM?

Answer 27

Minor - only one site - often oral mucosa

Major - more than 2 mucosal sites

Steven Johnson syndrome - <10% of body affected with widespread skin blistering and scarring

Toxic epidermal necrolysis - >30% of body

Question 28

Mucosal features of EM?

Answer 28

Blisters and shallow erosions

White overlying pseudomembrane

Question 29

Cutaneous features of EM?

Answer 29

Round Target like lesions that are erythematous with concentric rings

Question 30

Histological presentation of EM?

Answer 30

Keratinocyte necrosis

Acanthosis

Elongated rete pegs

Question 31

Tx of EM?

Answer 31

Often not necessary if very mild

Identify the aetiology is crucial

If drug reaction:
- stop drug and clear infection before systemic tx
- topical steroids and anaesthetics for oral cavity

If herpes / recurrent
- antiviral therapy with aciclovir
- systemic corticosteroids and topical corticosteroids