Vesiculobullous disorders of the oral cavity Flashcards
vesicle - define
<5mm visible accumulation of fluid within or beneath epithelium
- e.g. a small blister
bullae - define
> 5mm visible accumulation of fluid within or beneath epithelium
- e.g. a bigger blister
Give examples of vesiculobullous conditions
mucous membrane pemphigoid
pemphigus vulgaris
Erythema multiform
Stevens-Johnson syndorme/ toxic epidermal necrosis
features of normal oral mucosa
epithelium (keratinocytes)
- stratified squamous
basement membrane
- non-cellular interface
lamina propria
- collagen, fibroblasts, nerves, blood vessels etc
desmosomes - define
protein complexes that join keratinocytes to kertainocytes
function of hemi-desmosomes
joins basal keratinocytes to basement membrane
mucous membrane pemphigoid - features
autoimmune process
50-60 year olds
1:2 male to female ratio
mucous membrane pemphigoid - clinical features
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
mucous membrane pemphigoid aetiology
unknown cause
likely genetic predisposition
autoimmune
mucous membrane pemphigoid pathogenisis
antibody (IgG) targeting the basement membrane zone (hemidesmosomes)
complement activation
sub epithelial splitting
= vesicles, blisters, ulcers
mucous membrane pemphigoid diagnosis
clinical/histological/immunopathological
biopsy
- H & E staining from affected tissue
- direct immunofluorescence microscopy - from perilesional tissue
indirect immunofluorescence
- blood sample
MMP direct immunofluorescence - steps
tissue biopsy put onto slide and processed
specific antibodies applied to tissue
examined with UV microscope
fluorescence at areas of binding
MMP indirect immunofluorescence steps
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%
MMP symptomatic relief
benzydamine mouthwash
oral hygiene instruction
MMP systemic treatment options
prednisolone
doxycycline
methotrexate
azathioprine
rituximab
MMP management
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
pemphigus vulgaris features
autoimmune
more common in females
pemphigus vulgaris clinical features
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
pemphigus vulgaris aetiology
autoimmune overlap
pemphigus vulgaris pathogenesis
antibodies (mainly IgG) directed against desmosomes
loss of cell-cell contact in epithelium
- intra-epithelial split forms
- flaccid blisters
pemphigus vulgaris - how does pathogenis differ from mucous membrane pemphigoid?
MMP hemidesmosomes attacked
- compared with desmosomes in pemphigus vulgaris
MMP sub-epithelial split
- Pemphigus-vulgaris = intra-epithelial split
pemphigus vulgaris - diagnosis (clinical/histological/immunopathological)
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
Management of pemphigus vulgaris
MDT approach
- Iv fluid rescucitation
- feeding
- management of secondary infection
- analgesia
PV - main phases of management
induction of remission
maintenance
pemphigus vulgaris - induction of remission steps
prednisolone +/- bone protection, gastric protection
commence second agent e.g. rituximab
pemphigus vulgaris tx - maintenance steps
gradual withdrawal from oral steroids
- aim >10mg prednisolone e
second agent
regular monitoring
topical steroids
benzydamine
excellent oral hygiene
paraneoplastic pemphigus features
rare variation of pemphigus vulgaris
associated with underlying malignancy
- usually haematological
severe mucosal and skin involvement
typically systemically unwell
high mortality
Erythema multiforme features
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
Erythema multiforme clinical features
flu-like prodrome 1-2 weeks
skin lesions, itch
lip blisters, ulceration and crusting
oral ulcers
- particularly anteriorly
eyes, genitals may be effected
minor vs major erythema multiforme
minor = oral+/- skin targets
major = oral, skin + other mucosa site
erythema multiforme aetiology
hypersensitivity
- infective = HSV-1 in 15-20%
- drugs - allopurinol, carbamazepine, NSAID’S, phenytoin
- following BCG or hep B immunisations
erythema multiforme pathogenisis
release of cytokines from CD4 cells
amplified immune response
CD8 T cells attack keratinocytes
apoptosis and necrosis of keratinocytes
diagnosis of erythema multiforme (clinical/histological/immonopathological)
clinical history
- triggering agent
biopsy of periolesional tissue
- histology = lymphocytic infiltrate, keratinocyte necrosis, intra and sub-epithelial splitting
immunofluorescence - non-specific
HSV serology
Erythema multiforme management
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
recurrent erythema multiforme management
consider immunosuppression
- risk/benefit
prophylactic acyclovir
- due to HSV implication
Stevens-johnson syndrome/toxic epidermal necrolysis (TEN) features
rare
very severe - critical care admission
widespread blistering of skin and oral, pharyngeal, genital, nasal and conjunctival involvement
a spectrum
SJS/Toxic epidermal necrocylis aetiology
most cases = hypersensitivity to medications
= allopurinol, carbamazepine, NSAIDs, phenytoin, penicillins >20%)
genetic predisposition
100x more common in people with HIV
SJS/TEN pathogenesis
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’
SJS/TEN diagnosis
usually clinical history and examination
skin biopsy = epidermal necrolysis, detachment from dermis
SJS/TEN management
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
Linear IgA disease features
rare in adults
- more common in children
blistering condition
triggered by medications
clinical features similar to MMP
- blisters, ulcers, erosions of skin and mucosa
linear IgA disease management
removal of any triggers
MDT approach
topical steroids - mouthwash, ointment
second line - dapsone
epidermolysis bullosa Acquisita features and management
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
desquamative gingivitis - summarise
clinically descriptive term, not a diagnosis
- desquamation of epithelium causing subsequent erosion of the attached and marginal gingivae
discomfort
treat with topical steroids
mucous membrane pemphigoid vs pemphigus vulgaris - outline the differences
