Vesiculobullous disorders of the oral cavity

Question 1

vesicle - define

Answer 1

<5mm visible accumulation of fluid within or beneath epithelium
- e.g. a small blister

Question 2

bullae - define

Answer 2

> 5mm visible accumulation of fluid within or beneath epithelium
- e.g. a bigger blister

Question 3

Give examples of vesiculobullous conditions

Answer 3

mucous membrane pemphigoid
pemphigus vulgaris
Erythema multiform
Stevens-Johnson syndorme/ toxic epidermal necrosis

Question 4

features of normal oral mucosa

Answer 4

epithelium (keratinocytes)
- stratified squamous
basement membrane
- non-cellular interface
lamina propria
- collagen, fibroblasts, nerves, blood vessels etc

Question 5

desmosomes - define

Answer 5

protein complexes that join keratinocytes to kertainocytes

Question 6

function of hemi-desmosomes

Answer 6

joins basal keratinocytes to basement membrane

Question 7

mucous membrane pemphigoid - features

Answer 7

autoimmune process
50-60 year olds
1:2 male to female ratio

Question 8

mucous membrane pemphigoid - clinical features

Answer 8

oral vesicles/blisters
- ulcers
- robust blisters, sometimes blood filled
heals with scarring
desquamative gingivitis
ocular lesions
- scarring of conjunctiva
anogenital lesions
skin lesions
- scalp
nasal mucosa affected

Question 9

mucous membrane pemphigoid aetiology

Answer 9

unknown cause
likely genetic predisposition
autoimmune

Question 10

mucous membrane pemphigoid pathogenisis

Answer 10

antibody (IgG) targeting the basement membrane zone (hemidesmosomes)
complement activation
sub epithelial splitting
= vesicles, blisters, ulcers

Question 11

mucous membrane pemphigoid diagnosis

Answer 11

clinical/histological/immunopathological

biopsy
- H & E staining from affected tissue
- direct immunofluorescence microscopy - from perilesional tissue
indirect immunofluorescence
- blood sample

Question 12

MMP direct immunofluorescence - steps

Answer 12

tissue biopsy put onto slide and processed
specific antibodies applied to tissue
examined with UV microscope
fluorescence at areas of binding

Question 13

MMP indirect immunofluorescence steps

Answer 13

blood sample taken
- containing primary disease antibody)
incubated with normal mucosa
- monkey oesophagus
addition of secondary antibody and fluorophore
- tissue examined
- will show in tissue if antibodies present in serum

less sensitive in MMP
- Will show in 50-80%

Question 14

MMP symptomatic relief

Answer 14

benzydamine mouthwash
oral hygiene instruction

Question 15

MMP systemic treatment options

Answer 15

prednisolone
doxycycline
methotrexate
azathioprine
rituximab

Question 16

MMP management

Answer 16

MDT approach
- oral med
- ophthalmology
- gynaecology
- dermatology

patient education
oral disease severity score
symptomatic relief
- benzydamine
oral hygiene

topical corticosteroid
- betamethasone mouthwash

intralesional steroid injection

systemic treatment
- prednisolone
- doxycycline
- methotrexate
- azathioprine
- Rituximab

Question 17

pemphigus vulgaris features

Answer 17

autoimmune
more common in females

Question 18

pemphigus vulgaris clinical features

Answer 18

blisters, erosions and ulcers
- oral bullae - quickly rupture to leave erosions/ulcers (thin walled blisters that rupture easily)
- heal without scarring
- desquamative gingivitis
- ocular involvement
- aeorodigestive tract
- anogenital blistering
- skin affected
pain
potentially lethal
systemically unwell
- impaired oral intake
- sepsis- secondary infection

Question 19

pemphigus vulgaris aetiology

Answer 19

autoimmune overlap

Question 20

pemphigus vulgaris pathogenesis

Answer 20

antibodies (mainly IgG) directed against desmosomes
loss of cell-cell contact in epithelium
- intra-epithelial split forms
- flaccid blisters

Question 21

pemphigus vulgaris - how does pathogenis differ from mucous membrane pemphigoid?

Answer 21

MMP hemidesmosomes attacked
- compared with desmosomes in pemphigus vulgaris
MMP sub-epithelial split
- Pemphigus-vulgaris = intra-epithelial split

Question 22

pemphigus vulgaris - diagnosis (clinical/histological/immunopathological)

Answer 22

Nikolsky’s sign
- rubbing the mucosa induces a bulla
biopsy
- H and e staining from affected tissue
- direct immunofluorescence microscopy from perilesional tissue
indirect immunofluorescence
- blood sample
- more sensitive in pemphigus vulgaris than mucous membrane pemphigoid

Question 23

Management of pemphigus vulgaris

Answer 23

MDT approach
- Iv fluid rescucitation
- feeding
- management of secondary infection
- analgesia

Question 24

PV - main phases of management

Answer 24

induction of remission
maintenance

Question 25

pemphigus vulgaris - induction of remission steps

Answer 25

prednisolone +/- bone protection, gastric protection commence second agent e.g. rituximab

Question 26

pemphigus vulgaris tx - maintenance steps

Answer 26

gradual withdrawal from oral steroids - aim >10mg prednisolone e second agent regular monitoring topical steroids benzydamine excellent oral hygiene

Question 27

paraneoplastic pemphigus features

Answer 27

rare variation of pemphigus vulgaris associated with underlying malignancy - usually haematological severe mucosal and skin involvement typically systemically unwell high mortality

Question 28

Erythema multiforme features

Answer 28

acute onset hypersensitivity reaction - can often identify trigger ulceration and blistering of oral mucosa and lips skin rash younger cohort - 10-40 years olds spectrum of severity - minor - major up to 25% recurrence

Question 29

Erythema multiforme clinical features

Answer 29

flu-like prodrome 1-2 weeks skin lesions, itch lip blisters, ulceration and crusting oral ulcers - particularly anteriorly eyes, genitals may be effected

Question 30

minor vs major erythema multiforme

Answer 30

minor = oral+/- skin targets major = oral, skin + other mucosa site

Question 31

erythema multiforme aetiology

Answer 31

hypersensitivity - infective = HSV-1 in 15-20% - drugs - allopurinol, carbamazepine, NSAID'S, phenytoin - following BCG or hep B immunisations

Question 32

erythema multiforme pathogenisis

Answer 32

release of cytokines from CD4 cells amplified immune response CD8 T cells attack keratinocytes apoptosis and necrosis of keratinocytes

Question 33

diagnosis of erythema multiforme (clinical/histological/immonopathological)

Answer 33

clinical history - triggering agent biopsy of periolesional tissue - histology = lymphocytic infiltrate, keratinocyte necrosis, intra and sub-epithelial splitting immunofluorescence - non-specific HSV serology

Question 34

Erythema multiforme management

Answer 34

MDP approach - feeding fluids - analgesia stop any obvious precipitating medication/medication linked to trigger topical steroids for oral lesions (minor EM) - systemic steroids for more severe disease adjunctive oral care - OHI, CHX, comfort measures antihistamines for itchy skin

Question 35

recurrent erythema multiforme management

Answer 35

consider immunosuppression - risk/benefit prophylactic acyclovir - due to HSV implication

Question 36

Stevens-johnson syndrome/toxic epidermal necrolysis (TEN) features

Answer 36

rare very severe - critical care admission widespread blistering of skin and oral, pharyngeal, genital, nasal and conjunctival involvement a spectrum

Question 37

SJS/Toxic epidermal necrocylis aetiology

Answer 37

most cases = hypersensitivity to medications = allopurinol, carbamazepine, NSAIDs, phenytoin, penicillins >20%) genetic predisposition 100x more common in people with HIV

Question 38

SJS/TEN pathogenesis

Answer 38

antigens (medication) presented to T lymphocytes dysregulated immune reaction CD8 cells, macrophages and neutrophils into epithelium release of granulysin apoptosis and necrosis of keratinocytes breach of skin/mucosa - 'skin failure'

Question 39

SJS/TEN diagnosis

Answer 39

usually clinical history and examination skin biopsy = epidermal necrolysis, detachment from dermis

Question 40

SJS/TEN management

Answer 40

urgent assessment in specialist acre - burns unit, intensive therapy unit A- E approach - airway - breathing - circulation - sedation/pain management - temperature management MDT approach - dermalology, ophthalmology, ENT, burns team - CHX, oral lubricants, topical steroids - skin/wound management - eye care

Question 41

Linear IgA disease features

Answer 41

rare in adults - more common in children blistering condition triggered by medications clinical features similar to MMP - blisters, ulcers, erosions of skin and mucosa

Question 42

linear IgA disease management

Answer 42

removal of any triggers MDT approach topical steroids - mouthwash, ointment second line - dapsone

Question 43

epidermolysis bullosa Acquisita features and management

Answer 43

rare middle aged patient autoimmune IgG antibodies target collagen in basement membrane - destabilises epithelial/connective tissue junction blister formation, erosions, ulceration, scarring from friction/trauma management - MDT approach - topical steroids - mouthwash, ointment - systemic immunosuppression e.g. prednisolone

Question 44

desquamative gingivitis - summarise

Answer 44

clinically descriptive term, not a diagnosis - desquamation of epithelium causing subsequent erosion of the attached and marginal gingivae discomfort treat with topical steroids

Question 45

mucous membrane pemphigoid vs pemphigus vulgaris - outline the differences

Answer 45