Vesiculobullous Disease Flashcards
5 types of hypersensitivity
Type 1 – allergy (immediate anaphylaxis)
Type 2 - antibody-mediated immune reaction in which IgG or IgM are directed against cellular/extracellular matrix antigens, resulting in cellular destruction, functional loss, or damage to tissues. CYTOTOXIC antigen on antibody
Type 3 - an abnormal immune response is mediated by the formation of antigen-antibody aggregates called “immune complexes.”
Type 4 – delayed cell-mediated reaction (T lymphocytes)
Type 5 - antibodies are produced with the property of stimulating specific cell targets
2 types of immunogenic responses
Cell mediated immunity
Antibody mediated immunity
2 local oral immunogenic diseases
Aphthous ulcers
Lichen Planus
Orofacial Granulomatosis
systemic immunogenic diseases with local effects on oral mucosa
6
Erythema Multiforme
Pemphigus
Pemphigoid
Lupus erythematosis
Systemic Sclerosis
Sjogren’s Syndrome
erythema multiforme is result of which hypersensitivty type
3
immune complex (antigen-antibody aggregates)
cell mediated immunogenic diseases which effect oral cavity
3
Aphthous ulcers
Lichen Planus
Orofacial Granulomatosis
antibody mediated immunogenic diseases which effect the oral cavity
2
Pemphigus
Pemphigoid
skin, oral, genital mucosa share
many common antigens and epitopes
epitopes
large immunogenic site within the protein site
antibody binding to epitopes on mucosa
Antibody will only bind to small parts of it (e.g. different epitopes sequences within the antibody)
Antigen antibody binding will affect the shape/conformation of the protein antigen and the change in shape will dictate the changes which are seen clinically
what causes loss of cell-cell adhesion in blistering diseases
Auto-antibody attack on skin components causing loss of cell-cell adhesion
* ‘Split’ forms in skin
* Fills with inflammatory exudate
Forms vesicle/blister (size of lesion (1-2mm vesicle, blister larger)
TARGET for antibodies - Desmoglein (DSG1 and 3)
what causes loss of cell-cell adhesion in blistering diseases
Auto-antibody attack on skin components causing loss of cell-cell adhesion
* ‘Split’ forms in skin
* Fills with inflammatory exudate
Forms vesicle/blister (size of lesion (1-2mm vesicle, blister larger)
TARGET for antibodies - Desmoglein (DSG1 and 3)
target for many autoantibodies in immunobullous/blistering conditions
Desmoglein (DSG1 and 3)
types of immunofluorescence
direct
indirect
direct immunofluoresence
antibody mediated tissue disease, good for establishing diagnosis
Manufactured second antibody with fluorescein marker is designed to bind to the primary disease causing antibody
* so if +ve result then disease present
Cannot put sample in formalin containing medium for transport (will cause binding to the site to be lost)
* Needs to be transported fresh and the lab processed quickly
indirect immunofluorescence
CIRCULATING antibody not yet bound to the tissue
Detected by immunofluorescence from a PLASMA sample
Not always useful for dx (less reliable)– often** good for monitoring disease activity **(looking for levels of antibody, can be guide for tx need e.g. pemphigoid
5 kety vesiculobullous conditions affecting the oral cavity
Erythema Multiforme
Pemphigus
Pemphigoid
Angina Bullosa Haemorrhagica
Bullous lichen planus (lichen pemphigoides)
erythema multiforme
Spectrum disorder of Immunogenic related skin and mucosa ulceration
* Variable orofacial involvement
acute onset
* M>F
* skin - target lesions
* mucosa – ulcers
* young males – recurrent within a short period
aetiology - immune complex?
* unknown, poss triggers - drugs, herpes simplex, mycoplasma
immune complex (type 3 hypersensitivtiy) reaction occurs in
erythema multiforme
antigen presents which is targeted by an antibody,
antigen which has been met before and a prompt immune response occurs from memory B cells,
creates large antigen-antibody complexes – too large to pass through tissue capillaries,
becomes wedged and activates complement within the blood vessels causing peri-vascular inflammatory response - blistering/ulceration of tissue
type 3 hypersensitivity reaction in basic terms
antigen presents which is targeted by an antibody,
antigen which has been met before and a prompt immune response occurs from memory B cells,
creates large antigen-antibody complexes – too large to pass through tissue capillaries,
becomes wedged and activates complement within the blood vessels causing peri-vascular inflammatory response - blistering/ulceration of tissue
eyrthema multiforme
lips and anterior oral cavity lesions
crops of ulcers
crusting lips
very painful - unable to eat or drink (dehydration risk)
heal within 2 weeks
steven-johnson syndrome is
severe multisystem involvement
* not just oral eythema multiforme
Skin, conjunctivae, nose, pharynx, mouth genital
* target lesions
eythema multiforme
oral lesions management
Urgent medical therapy
* systemic steroids – up to 60 mg/day (a high dose)
* systemic aciclovir
Encourage fluid intake
* May require admission for IV fluid if unable to drink
Encourage analgesia
if recurrent problems
* Consider prophylactic aciclovir daily
* Allergy test – a wide variety of environmental triggers
* Sometimes infective agent – mycoplasma
angina bullosa haemorrhagica
Commonest oral blistering condition
“blood blisters” in the mouth blood stained fluid, not usually blood
Buccal mucosa and soft palate are the common sites
Rapid onset – appear in a few minutes
* last about 1 hour then burst
* Heal with no scarring within days
Relatively painless
Possibly initiated by minor trauma
Eating may be a trigger
angina bullosa haemorrhagica management
No treatment available at present
Reassure patient that disease is benign
* pt concerned - blood, tight feeling
* CHX mouthwash or difflam spray - help with symptoms until lesions heal
check if recur
* DIF, IIF negative
* no platelet/coagulation defect
* consider if they started as blisters or ulcers
Explain known triggers and course of the disease
pemphigoid is
SUB epithelial antibody attack (on hemidesmosomes), causes separation of epithelium from basement – full thickness of epithelium and fluid is released between the epidermis and connective tissue
Thick-walled blisters (full epidermis)
* Usually persist to be seen
* Clear or blood-filled blisters
types of pemphigoid
3
Bullous Pemphigoid
* no scar tissue
* e.g. on skin
Mucous Membrane Pemphigoid
* scar tissue
* only mucous membranes involved – eye, genital, oral*
Cicatritial Pemphigoid
* skin and/or mucosal
* scarring
histopathology test for pemphigoid
biopsy site
take perilesional
if take of blister then often no epithelium found which makes dx difficult
histopathology of pemphigoid
SUB epithelial split – epithelial/connective tissue junction
HEMI-desmosomes involved at basement membrane to attach the epithelium to the connective tissue
* Attack of circulating antibody to these hemidesmosomes, causing them to lose their attachment and epithelium separate from connective tissue
direct immunofluorescence in pemphigoid
LINEAR staining along the basement membrane
C3 and IgG detected in this area in ‘standard’ Pemphigoid
IgA occasionally found
* Linear staining with C3 is called ‘Linear IgA disease’
* Granular IgA and C3 deposits is seen in ‘Dermatitis Herpetiformis’ (patchy)
mucous membrane pemphigoid sequlae
scarring of tissue
issue in:
* swallowing if oral mucosa,
* eye as scar the conjunctiva = binds the eye surface to the eyelid (restrict eye movements, cause dipolopia) SYMBLEPHARON
mucous membrane pemphigoid scarring on eye
effect
bind the eye surface to the eyelind - restrict eye movements, cause diplopia
SYMBLEPHARON - blindness
mucous membrane pemphigoid scarring on oral mucosa
effect
swallowing and speech issues
management of pemphigoid
2 options
Steroids
Immune modulating Drugs – azathioprine, mycophenolate (prevent the antibody generation which is causing the disease
pemphigus is
another immune mediated, antibody direct diseases causing blisters
commonst form is pemphigus vulgaris
INTRAEPITHELIAL BULLAE
pemphigugs histology features
intraepithelial bullae
Affects the desmosomes joining epithelial cells to each other, lose adhesion to each and form intraepithelial bullae, cells will initially thin but eventually lose the epithelium completely (erosive loss of cell structure)
supra basal only
tzank cells - float in bullae
pemphigus vulgaris clinical presentation
uncommon before age > 50
F»M
genetic – Ashkenazi Jews
blisters - burst - spread (rarely see intact bullae as thin epithelial covering) erosions more than blisters
mucosa (often first site) and skin (both eventually involved)
desquamative gingivitis appearance with red lost epithelial attachment
* Can affect any area of oral mucosa
* Can get area of fibrinous exudate to show where tissue has been lost
fluid loss and infection risk - fatal without tx
direct immunofluoresence of pemphigus vulgaris
**‘Basket Weave’ **staining around each of the epithelial cells
Due to the antibody attacking desmosomes which are present on many surfaces of epithelial cells, can see that all around the cells there is antibody binding – v different from linear seen in Pemphigoid
C3 and IgG in Pemphigus Vulgaris
vesiculobullous conditions in primary dental care
summary
Vesiculobullous disorders are uncommon in primary care
PEMPHIGOID is the LEAST uncommon
* Always consider this if patient reports a blistering disease
* See intact bullae
These conditions CAN BE FATAL and should be referred for Specialist care (esp if suspect pemigus or pemphigoid)
PERILESIONAL TISSUE FOR BIOPSIES OF ALL BLISTERING DISEASES
