Vesiculobullous Disease Flashcards by niamh ritchie

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

How well did you know this?

Not at all

Perfectly

2 types of immunogenic responses

Cell mediated immunity
Antibody mediated immunity

How well did you know this?

Not at all

Perfectly

2 local oral immunogenic diseases

Aphthous ulcers
Lichen Planus
Orofacial Granulomatosis

How well did you know this?

Not at all

Perfectly

systemic immunogenic diseases with local effects on oral mucosa

Erythema Multiforme
Pemphigus
Pemphigoid
Lupus erythematosis
Systemic Sclerosis
Sjogren’s Syndrome

How well did you know this?

Not at all

Perfectly

erythema multiforme is result of which hypersensitivty type

3
immune complex (antigen-antibody aggregates)

How well did you know this?

Not at all

Perfectly

cell mediated immunogenic diseases which effect oral cavity

Aphthous ulcers
Lichen Planus
Orofacial Granulomatosis

How well did you know this?

Not at all

Perfectly

antibody mediated immunogenic diseases which effect the oral cavity

Pemphigus
Pemphigoid

How well did you know this?

Not at all

Perfectly

skin, oral, genital mucosa share

many common antigens and epitopes

How well did you know this?

Not at all

Perfectly

epitopes

large immunogenic site within the protein site

How well did you know this?

Not at all

Perfectly

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

How well did you know this?

Not at all

Perfectly

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)

How well did you know this?

Not at all

Perfectly

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)

How well did you know this?

Not at all

Perfectly

target for many autoantibodies in immunobullous/blistering conditions

Desmoglein (DSG1 and 3)

How well did you know this?

Not at all

Perfectly

types of immunofluorescence

direct

indirect

How well did you know this?

Not at all

Perfectly

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

How well did you know this?

Not at all

Perfectly

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

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