Oral Med - Vesiculobullous Diseases Flashcards
What type of immune mediated disease is pemphigus and pemphigoid?
immunogenic - through antibody mediated immunity
What type of immune mediated disease is erythema multiforme?
hypersensitivity type 3
Describe why immunological skin and oral diseases are linked and share some common antigens and epitopes.
Immunological skin and oral disease linked as embryologically the oral mucosa develops from the same precursor tissue as the skin
Describe briefly what occurs in immunological skin and oral mucosal diseases.
Autoantibody attacks skin components = loss of cell-cell adhesion = a split forms on the skin
- This Fills with inflammatory exudate and forces the layers of the skin apart to form a vesicle or blister
What is the difference between a vesicle and a blister?
size
- Vesicle 1-2mm
- Blister larger
What is the role of desmosomes and hemidesomes? (3)
attach the epithelial cells to each other, to the basement membrane and to the protein desmoglein.
Describe the importance of desmoglein in terms of vesiculobullous disease? (2)
Target for many antibody’s involved in immunobullous diseases.
The way in which the desmogelin and the antibody interact can lead to loss of adhesion between the desmosomes = allows cell layers to split.
How can we test for vesiculobullous diseases?
Direct Immunofluorescent:
Describe how direct Immunofluorescent works?
If you suspect that an antibody is bound to the affected tissues;
Where a secondary (manufactured) antibody with a fluorescein marker attached binds to the primary antibody (from the circulation) bound to the tissues affected by immunobullous disease.
Tissues then examined by fluorescent lighting = shows where the antibodies are bound in the affected tissues.
What type of immunofluorescence is used for diagnosis of VB disease?
direct
what is the role of indirect IF? (2)
good for monitoring disease activity and levels of the antibody
Gives guide to tx need
Describe indirect IF.
Assesses the presence of circulating antibodies not bound to the tissues yet in PLASMA samples
What is an extreme form of erythema multiforme known as?
Stevens-Johnson syndrome
What is erythema multiforme?
A spectrum disorder caused by Immunogenic related skin and mucosa ulceration
Type 3 hypersensitivity reaction related to antigen antibody complexes
Describe what occurs in erythema multiforme.
An antigen presents which is targeted by an antibody
Usually the antigen has been met before by the body therefore a prompt immune response occurs = antibodies produced from memory B cells quickly
The antibody and antigen combines in the circulation = producing a large complex which is unable to pass through the capillaries = complex wedges in tissues and activates compliment within the BV causing a perivascular inflammatory response.
Significant = blistering/ulceration of the tissues
What are the characteristics/features of erythema multiforme? (6)
- acute onset
- M>F
- young males (late teens/early 20’s) – recurrent within a short period and then months ulcer free
- skin = target lesions with a central wheel and a perilesional area of pale mucosa
- ulcers on any part of the oral mucosa (including keratinised tissues)
- Ulceration present on Lips & anterior part of mouth
- Very painful – unable to eat or drink (dehydration)
- severe multisystem involvement
- can affect skin, conjunctivae, nose, pharynx, mouth genital
What is suggested to have a role in oral mucosal erythema multiforme?
herpes simplex
what is a characteristic presentation of erythema multiforme?
Lip crusting and acute illness
How do we manage/treat EM? (4)
- prednisolone - systemic steroids – up to 60 mg/day (a high dose)
- prophylactic systemic acyclovir given to those with repeated oral lesions (suppresses viral replication of the HSV)
- Encourage fluid intake - May require admission for IV fluid if unable to drink due to pain
- Encourage analgesia
How do we treat recurrent problems with EM? (2)
- Consider prophylactic aciclovir daily
- Allergy test – a wide variety of environmental triggers
Can also Sometimes have an infective agent e.g. mycoplasma
what is the commonest blistering condition?
angina bullosa haemorrhagica.
What is ABH?
Sudden onset of intermittent, tight blood filled blisters on the oral mucosa
What are the characteristics of ABH? (9)
- “blood blisters” in the mouth
- Buccal mucosa and soft palate are the common sites
- Rapid onset – appear in a few minutes
- last about 1 hour then bursts to leave a small ulcer (mildly symptomatic)
- Relatively painless
- Heal with no scarring
- Heal within days
- May recur
- DIF, IIF (immunofluorescence) negative
- no platelet/coagulation defect
Where are common sites for ABH?
buccal mucosa
soft palate
What causes ABH?
No obvious cause
Possibly initiated by minor trauma - Eating may be a trigger
What can ABH appear similar to once the inital blood blister has burst?
Oral ulceration
How do we treat/manage ABH? (4)
- No treatment available at present
- If symptomatic provide chlorhexidine mouthwash or difflam mouth spray until healing occurs
- Reassure patient that disease is benign
- Explain known triggers and course of the disease
What is pemphigoid?
A SUB epithelial antibody attack
What occurs in pemphigoid?
Antibody cause separation of the epithelium at the basement membrane from the connective tissue
Full thickness of the epithelium is released with inflammatory fluid exudate filling the space between the epidermis and the CT
What are the characteristics of pemphigoid? (6)
- Thick walled blisters (full epidermis)
- Usually persist for some time (long enough that a clinician can see)
- Clear or blood filled blisters (Red = leakage of RBC)
- Blisters rupture = exposed CT and exudate from the area
- Oral & Skin Lesions
- Scarring a feature in some cases when healing e.g. Cicatritial Pemphigoid
What are the risks of pemphigoid once the vesicles/blisters rupture? (2)
Blister ruptured = exposed CT and exudate from the area = significant problem
- Infection can enter via the loss of the epithelial barrier
- Weaping fluid = dehydration (if enough blisters involved)
List the 3 different forms/presentations of pemphigoid.
- Bullous Pemphigoid - skin
- Mucous Membrane Pemphigoid – all mucous membranes e.g. eye, genital, oral
- Cicatritial Pemphigoid – mucosal with scarring (subset of the mucous membrane pemphigoid)
What pemphigoid is cicatritial pemphigoid a subset of?
mucosal membrane
Where should biopsies be taken from a patient with a suspected pemphigoid/pemphigus lesion and why?
perilesional tissue – not the blister (pemphigoid) /erosion (pemphigus) itself – blister/erosion = no epithelium found = difficult diagnosis
What can be found in a histopathology sample of pemphigoid?
SUB epithelial split – occurs at the epithelial/connective tissue junction
What test can be useful for the diagnosis of pemphigoid?
direct IF
Describe the characteristic appearance of pemphigoid in direct IF.
- Linear fluorescent staining along the basement membrane
What antibodies can be found in direct IF of pemphigoid? (4)
- C3 detected in this area in standard pemphigoid (always occurs)
- IgG detected in this area in standard pemphigoid
- Can also be igM or igA
Describe what occurs in Pemphigoid Symblepharon.
Scarring of the conjunctiva = binds the eye surface to the eyelid = symblepharon = restricts movement and causing diplopia
How do we treat pemphigoid?
immunosuppressants
* Steroids
* Immune modulating Drugs e.g. azathioprine, mycophenolate
What is pemphigus?
Immune mediated antibody directed disease which causes intraepithelial bullae
What occurs in pemphigus?
Circulating antibody is formed which affects the desmosome tissue (not hemidesmosomes to basement membrane) which join the epithelial cells to one another
- epithelial cells lose adhesion to each other
= intraepithelial bullae form
Since there are few cell layers above/around the lesion, as the fluid fills space between the cells, the cells lose adhesion to one another and the cells drift apart
= thinning initially
= complete loss of epithelium
what is a characteristic presentation of pemphigus?
Rare to see an intact bullous in pemphigus
- if an intact bullous seen in the oral mucosa = pemphigoid
- pemphigus presents as mucosal erosion/surface loss
What are the characteristics of pemphigus? (5)
- uncommon before age > 50
- F»M
- genetic e.g. Ashkenazi Jews
- Sites
- Skin
- Oral mucosa = often first site to present
Can affect any part e.g. tongue, gingivae, buccal mucosa or palate
(Both eventually involved) - blisters initially = burst and then widespread loss of epithelial covering
What are the risks of pemphigus once the vesicles/blisters rupture? (2)
Risk for;
- Infection can enter via the loss of the epithelial barrier
- Weaping fluid = dehydration (if enough blisters involved
Describe the characteristic appearance of pemphigus in a histopathology sample. (3)
- Loss of epithelium
- Shedding of epithelial layer
= all Supra-basal - Tzank cells = characteristically Seen in pemphigus
Describe the characteristic appearance of pemphigus in a direct IF sample.
basket weave staining around each of the epithelial cells (very different to linear basement membrane staining of pemphigoid)
What antibodies are commonly found in a direct IF sample of pemphigus? (2)
common antibodies = C3 and IgG
