Vesiculobullous and Immune Disease Flashcards
What are some local immunological oral diseases?
- Apthous ulcers
- Lichen planus
- OFG
What are some systemic diseases with local effects?
- Erythema multiforme
- Pemphigus
- Pemphigoid
- Lupus erythematosis
- Systemic sclerosis
- Sjogrens syndrome
What type of hypersensitivity reaction is Erythema multiforme?
- Type 3 hypersensivity
What are some cell mediated immunity disease?
- Aphthous ulcers
- LP
-OFG
What are some antibody mediated immunity disease?
- Pemphigus
- Pemphigoid
What is the difference between epitopes and antigens?
- Antigens are the big immunological site in which antibody bind to it
- Epitope is the specific part of the antigen to which the antibody binds
Immunologically what happens during skin disease?
- Auto-antibody attack on skin components causing loss of cell-cell adhesion
- Causes loss of desmosomes to hemidesmosome by desmoglein attachment allowing cell layers to split
- Split forms in the skin
- Fills with inflammatory exudate
- Forms vesicle/blister
What is the difference between vesicle and blister?
- Vesicles 1-2mm
- Blister largers
What test is the most useful when suspected immuno bolus condition?
- Direct immunoflurorescnce
- Antibody mediated tissue disease
- Antibody causing disease targeted as it is bound to tissue, antigen containing fluorescein that binds to antibody
- If present then fluorescien shows up
What is indirect immunofluorescence ?
- Circulating antibody not yet bound to tissue
- Detected by immunofluorescnce from plasma sample
- Not always useful for diagnosis but good for monitoring disease activity
What is erythema multiforme?
- Spectrum disorder of immunogenic related skin and mucosa ulceration with variable orofacial involvement
What is the onset for erythema multiforme? What response does it create?
- Acute onset due to antigens being presented have been met before therefore antibodies rapidly produced from memory B cells
- Antigens and antibodies bind forming a complex in circulation and now unable to pass through capillaries
- When the large Complex gets to the tissues it becomes wedged and activates complements within the blood vessels causing a perivascular response
- Blistering or ulceration of the tissues
Where on the body can lesions of erythema multiforme be shown?
- Skin
- Genital
- Oral
- Oropharyngeal
- Combo of these
- Called a spectrum disorder
What is the term given to the most extreme form of erythema multiform? Where does it present on the body?
- Stevens-Johnsons syndrome
- Severe multisystem involvement
- Skin, conjunctivae, nose, pharynx, mouth, genital
In oral erythema multiforme what mucosa can be involved?
- All types of mucosa including keratinsed due to the lesion affecting capillaries
What are the lesions of oral erythema multiforme similar to?
- Primary herpetic gingivostomatitis
What is the aetiology of oral erythema multiform?
- Reactivation of herpes simplex virus triggers the immune reaction leading to this type 3 hypersensitivty (can give aciclovir prophylactically)
-Mycoplasma
What age group is most commonly affected by erythema multiforme?
- Young males in early 20s
- Have periods of ulceration for 2-3weeks which are very painful
What is the urgent txt for erythema multiforme?
- High dose prednisolone (up to 60mg/day) to suppress the antibody-antigen reaction and the complement activation within the tissue
- Systemic aciclovir can be given but only 2nd to systemic steroid as above
- Keep hydration high (sometimes mouth and pharynx so painful to let fluids into, end up in hospital due to dehydration)
- encourage Analgesia as required
What lesion do these images show?
- Erythema multiform
- Target lesions on the skin with central wheel and perilesional area of pale the erythematous tissues
- Crusting of the lips due to ulceration and healing of lesions on oral mucosa
- in the mouth shown Coalescent areas of ulceration more prominent towards front of mouth but can present further back and on pharynx
What is the txt for recurrent problems of erythema mulitforme?
- Consider prophylactic aciclovir daily
- Can perform allergy test to test for a wide variety of environmental triggers - particularly mycoplasma
What is Angina Bullosa Haemorrhagica?
Meaning tight blister bloodfilled
- Commonest oral blistering condition
- Blood blisters in the mouth
What are the most common sites for Angina Bullosa Haemorrhagica (ABH)? What is the onset? Is it painful?
- Buccal mucosa and soft palate common sites
- Can present on hard palate and these can be uncomfortable as feels swallowing is impacted
- Rapid onset of a few mins, last about 1 hr and then burst
- Relatively painless and heal with no scarring within days
- Poss due to minor trauma
What is the cause of ABH? Does it have specific aetiology?
- No aetiology
- Has non specific ulceration
- DIF and IIF negative
- No platelet/coagulation defect
- Unsure of cause
What is the txt of ABH?
- As we do not know what causes it or why it appears the way it does
- txt symptomatic relief
- Chlorhexidine mouthwash or diflam spray until blister subsides
- May recur
- Reasure pt it is benign
- Triggers might be eating or steroidal inhalers, do not stop eating or using the inhaler
What are these lesions called?
- Angina bullosa Haemorrhagica
What is Pemphigoid? What are the characteristics of a lesion?
- Relatively common immunobullous disease that is SUBEPITHELIAL antibody attack
- Antibodies cause seperation of the epithelium at the basement membrane from connective tissue
- Full thickness of epithelium is released therefore they are thick walled blisters
- Usually persist
- Can appear clear or blood filled blisters
What are the 3 different forms and presentations of Pemphigoid?
Bullous Pemphigoid when affecting Skin (can develop oral lesions)
Mucous Membrane Pemphigoid when affects all mucous membranes including eye, genital, oral
Cicatricial Pemphigoid is a subset of Mucous membrane pemphigoid when affects mucosal but has scarring
What type of biopsy sample would you take for a suspected Pemphigoid lesion?
- When taking a biopsy take from perilesional region not just the area of blister itself as this may lead to no epithelium being found so diagnosis difficult
What is the histopathology of Pemphigoid lesions? (Role of hemidesmosome)
- Hemi desmosomes attach to the epithelium through basement membrane to connective tissue
- Attack of circulating antibodies attack these hemi desmosomes therefore allowing the loss of attachment of epithelium to connective tissue (termed a sub epithelial split at epithelial/connective tissue junction)
What lesion is this showing? Describe what you see in both images
- Pemphigoid lesion
Left image
- Sub epithelial split at epithelial/connective tissue junction due to hemi desmosomes attachment
- Can see lots of inflammatory exudate (fluid) below the split which is present in the blister
Right image
- Can see the subepithelial split which is stops around halfway across the epithelium
- Can’t see any inflammatory exudate
- Different stages of blister formation
What is the disease creating these lesions? Describe the lesions and the issues they may provide for the pt
- Bullous Pemphigoid
Right - Blood stained filled intact bullous lesions
Left
- Intact clear fluid filled bulla
- Ruptured bulla showing loss of epithelial barrier
- Can allow infection into the skin
- Can also lead to dehydration due to the weeping ruptured blisters
What is the most useful test for a pt with Pemphigoid?
- Direct Immunofluorescence
- Look at image on right hand side , this shows perilesional biopsy of pemphigoid (epithelial and connective tissue junction is in contact)
- Can see linear immunofluorescent staining along the epithelial basement membrane
- Fluorescein tag is attached to antibody which binds to circulating antibody bound to the pemphigoid antigen in basement membrane
- Where we see the linear staining is where we have pemphigoid pre blister formation
What antibody is found in pemphigoid lesions?
Most common in standard pemphigoid
- C3 (always seen)
- IgG
Less common
- IgM
-IgA
If IgA is found in pemphigoid lesions what are the two disease it may be?
- If linear staining with C3 = Linear IgA disease
If granular IgA and C3 deposits = Dermatitis Herpetiformis
Describe this image. What can this cause? What disease is being shown?
- Adhesion of the bulbar and palpebral conjunctiva known as Symblepharon
- Restrict eye movement causing diplopia
- Can occur in Mucous membrane Pemphigoid
What is the management of Pemphigoid lesions?
- Steroids
- Immune modulating drugs such as azathioprine and mycophenolate, dapsone
What is Pemphigus? What desmosomes are involved and their role?
- Immune mediated antibody directed disease
- Intraepithelial bullae form due to circulating antibody being formed against the desmosomes joining the epithelial cells to each other, causing the epithelial cells to lose adhesion to each other
- Very rare to see intact fluid filled blisters due to thinning of the epithelium
- Present with erosive areas , mucosal surface loss as cell are gradually lost from surface of epithelium due to disease
Who is most likely affected in pemphigus and what sites are commonly affected?
- Uncommon before age 50
- Females > Males
- Ashkenazi jews genetic predisposition
- Oral mucosa present first then skin later develops (can be up to 3 years later)
Describe the histopathology of Pemphigus
- Loss of epithelium and Shedding of epithelium layer supra basally
- Tzank cells seen with pemphigus
Describe the immunoflurescence of this Pemphigus lesion
- Important to take perilesional tissue
- Pemphigus antibody is attacking desmosomes present on many of the surface of epithelial cells
- Shows basket weave pattern of antibody binding around each of the epithelial cells
What antibodies are common in Pemphigus Vulgaris?
- C3
- IgG
What disease are these images showing?
- Pemphigus
- Loss of epithelial covering showing redness
