Vesiculobullous Diseases Flashcards
Immune mediated diseases
5 types of hypersensitivity
Or
Immunogenic
- cell mediated (aphthous ulcers, lichen planus, orofacial granulomatosis)
- antibody mediated immunity ( pemphigus, pemphigoid)
It is when auto-antibody attack on skin components causing the loss of cell-cell adhesion
Causing a “splint” in the skin that fills with inflammatory exudate and forms a vesicle/blister (vesicles are smaller than blisters)
Immunological oral diseases
Local diseases:
Aphthous ulcers, lichen planus, orofacial granulomatosis
Systemic disease with local effects:
Erythema multiforme, pemphigus, pemphigoid, lupus erythematous, systemic sclerosis, Sjogrens syndrome
Immunological skin disease
Skin and oral/genital mucosa share many common antigens and epitopes (embryologically oral mucosa and skin share same precursor tissue)
Many blistering conditions also affect the mouth
Antigens vs epitopes
Antigens are a big immunogenic site within the protein but the antibody will bind to one small part of it (called epitope)
What are desmogleins?
It is a target for many of the antibodies involved in immunobullous diseases and the way in which this is bound by antibody causes loss of the adhesion between desmosomes allowing the cell layers to split
Immunofluorescence types
Direct-for antibody mediated tissue diseases; antibody bounds to the tissue that is targeted in fluorescent dye
Indirect - looking for circulating antibody not yet bound to the tissue; it is detected from plasma sample and not always useful for diagnosis but good for monitoring of disease activity
(E.g. pemphigoid disease)
Samples that will be sent to immunofluorescence mustn’t be put in formalin containing transport medium as this will cause the binding site to be lost. Sample must be fresh to laboratory and processed quickly
Erythema multiforme
Spectrum disorder of immunogenic related skin and mucosa ulceration. Usually an antigen it targeted by an antibody( usually an antigen met by body before) so this will promt the immune response and results quickly generating antibodies from the memory B cells. These antigens and antibodies combine within the circulation and this large complex is not not able to pass through the capillaries and when complex gets into the tissues, it becomes wedged and activates complement within the blood vessels causing perivascular inflammatory response. If this is significant- blisters or ulcers appear on the tissue. Location of lesions depends upon where the individual antigen-antibody complex is triggered.
Variable orofacial involvement
It is type 3 hypersensitivity reaction
Acute onset- more in male than female, target lesion on the skin, ulcers on mucosa
Aetiology - immune complex?, Drugs herpes simplex, mycoplasma
Ulcers can occur on the lips (crusty lips) and anterior part of the mouth- crops of ulcers that heal in 2 weeks, very painful (unable to eat/drink-risk of dehydration)
Two types:
Minor-all explained before
Major- Can be associated with a Stevens Johnson syndrome - involvement of severe multisystem. Including skin, conjunctiva, nose, pharynx, mouth, genital areas. When is quite extreme
High dose Prednisone is treatment
Treatment for oral lesions -
Urgent medical therapy (systemic steroids-first line treatment up to 60 mg/day) and systemic aciclovir
Encourage fluid intake (may need IV if unable to drink)
Encourage analgesics
If recurrent problems-prophylactic aciclovir, allergy testing
Angina bullosa haemorrhagoca
Commonest oral blistering condition. It is subepithelial oral mucosal blisters willed with blood.
Blood blisters in the mouth (filled with bloodstain fluid rather than blood itself)- commonly on buccal mucosa and soft palate.
Rapid onset-appear in a few minutes
Last about 1 h and then burst leaving a small ulcer
Relatively painless, can be initiated by minor trauma (such as eating).
Heal with no scars within days
No obvious aetiological cause
It is non specific ulceration
Treatment : symptomatic treatment- chlorhexidine mouthwash
As the lesion heals, small area of ulceration is left (looking like aphthous ulcers)
Management:
No direct treatment is available,.only reassurance and saying it is benign.
Should not stop using asthma inhaler or similar
Explain the disease and what triggers them. Disease won’t progress to cause any serious harm to the pt and they do not become a more widespread systemic disease affecting the skin or other parts of the body/mucosa
Pemphigoid
Relatively common
Affects the skin and the mouth and it characterised by sub epithelial antibody attack ( antibodies cause separation of epithelium at the basement membrane from the connective tissue and the full thickness of the epithelium so it is released with a fluid inflammatory exudate, filling the space between the epidermis and the CT)
So in another words- it is a disease in which auto antibodies are produced against the basement membrane zone at the junction of the epithelium and underlying dermis.
Causes think walled blisters (full thickness of epidermis)- persist for longer period of time
Filled with clear of blood stained fluid.
Can have different forms and presentations
Bullous pemphigoid affects skin
Mucus membrane pemphigoid affects all mucous membranes- eyes, genital, oral
Cicatririal pemphigoid affects mucosal tissue leaving a scar
Histopathology of pemphigoid
Subepithelial split happens- epithelial/connective tissue junction hemi-desmosomes are involved at basement membrane
Always take samples from perilesional tissue rather than blister itself as epithelium is probably not stay attached!!! IMPORTANT
if blisters rupture- there is exposed connective tissue and exudate of fluid from the area- loss of epithelial barrier allowing infection into the patient; dehydration can happen as there is weeping of that fluid from the body
Direct immunofluorescence is the most useful test for a pt with pemphigoid (often C3 and IgG or occasionally IgA). Linear staining at the basement membrane
Management of pemphigoid
Immunosuppressants:
Steroids
Immune modulating drugs
Pemphigus
Similar to pemphigoid
It is immune mediated, antibody directed disease
Difference is that desmosomes rather than hemi-desmosomes a are joining the epithelial cells to each other. Because of this- epithelial cells will lose adhesion to each other and intra- epithelial bullae forms.as not much tissue is around the blisters,.as the fluid fills the area between the cells,.the cell adhesion is completely lost and the cells gradually drift away, initially thinning and eventually losing the epithelium completely.
Rare to see intact bullae in pemphigus
(If you see intact - it is probably Pemphigoid)
Pemphigus often presents as area of mucosal erosion and mucosal surface loss as the cells are gradually lost from the surface of the mucosa by the disease.
Presents more in females, common in 50+ age group
There is genetic association in some pts and some racial groups
Sites:
Skin- usually years after oral presentation
Mucosa- oral mucosa is usually first site where it presents
Without treatment - it is fatal affects the whole of the body
Histopathology of pemphigus
Loss of epithelium and shredding of the epithelial layer but it is supra basal.
Basal cells are still attached to the basement membrane and the spit occurs above that point.
“Tzank” cells are characteristic cells seen in pemphigus.
On immunofluorescence - basket wave pattern rather than linear like in pemphigoid
C3 and IgG most often found
Clinical appearance:
Erosive areas rather than blisters
Management
High dose of steroids and immunosuppressant to prevent erosions and the loss of epithelial covering; biologics are new ways
IgG mediated response targeting cell-associated self-antigens is what type of hypersensitivity?
Type II
What is benign, mostly mildly symptomatic and self resolving?
Angina bullosa haemorrhagica
Which condition has an acute onset?
Erythema multiforme
Which condition is typically severe and rapidly progressive?
Pemphigus vulgaris
Which condition is chronic, disease severity can range from mild to very severe?
Mucus membrane pemphigoid
Which intraoral site is most commonly involved in angina bullosa haemorrhagica?
Palate
The aetiology of erythema multiforme is not fully understood however some infective agents have been associated with this condition. Which are those?
Herpes simplex
Mycoplasma
The auto-antibody response in pemphigus vulgaris is relatively well characterised. Which antigens of the basement zone membrane are the targets of the most dominant auto antigen-antibody response in pemphigus vulgaris?
Desmogleins
Which laboratory test is most useful for a definitive diagnosis of Pemphigoid or pemphigus?
Direct immunofluorescence
Which laboratory test is most useful to monitor disease activity in pemphigus? Explain why this test in not as useful to monitor disease activity in pemphigoid
Indirect immunofluorescence
Circulating antibodies are detected only in less than 50% of pemphigoid patients, while as many as 90% of pemphigus patients have circulating autoantibodies
Briefly describe the principle of direct and indirect immunofluorescence
Direct- immunoassay to detect protein deposition directly in tissue sampled from the lesion or perilesionally
Indirect - immunoassay to identify specificity of circulating autoantibodies performed topically on a suitable surrogate tissue sample (salt-split skin, monkey/rabbit oesophagus)
Disease modulating antirheumatic drugs (DMARD) are used by specialists for the management of a broad range immune- mediated disorders. In addition to system-specific toxicity, all of these drugs bear two main common risks related to their immuno- suppressive activity.
Name these two risks
Infective diseases- include reactivation of subclinical viral infection as well as opportunistic bacterial and fungal infections
Cancer- commonly skin cancers
Name all vesiculobullous diseases
Pemphigus, pemphigoid, erythema multiforme, angina bullies haemorrhagica, primary herpetic gingivostomatitis
Primary herpetic gingivostomatitis
Infection caused by herpes simplex virus
It causes multiple small round vesicles of acute onset, which ulcerate, sometimes coalesce on a background of inflamed mucosa
There may be extensive crusting of the lips and the condition is very painful and infections
Vesicles form due to the cytolytic and acantholytic effect of the virus.
The basal membrane is usually intact.
Enlarged nuclei of epithelial cells can be seen and appear like that because virus infected cells
Vesicles Vs bulla
Vesicle- a well defined, rounded swelling containing clear, serous fluid and less than 1 cm in diameter
Bulla- a well defined rounded swelling containing clear, serous fluid and greater than 1 cm in diameter
What is hyperkeratosis
An increase in the thickness of the keratin layer of the epithelium. This term also is used to describe the presence of keratin in a site it is not normally expected to be
What is ulcer
Full thickness breach of the mucosal epithelium
What are Tzanck cells
They are acantholytic cells which have a detached and rounded up as a result of contraction of the cytoplasm.
They can be present in both conditions of pemphigus vulgaris and primary herpetic gingivostomatitis
In herpes simplex virus infections, Tzanck cells may be multi-nucleated (they are multi nucleated due to incomplete cell division) and the distended degenerated nuclei of the epithelial cells may cluster together to give a typical mulberry appearance
What is Nikolsiy’s phenomenon
It is bulla formation when mild shear stress is applied to the skin or mucosa- commonly seen in pemphigus vulgaris
What is Koebner phenomenon
It is development of a skin lesion secondary to trauma or irritation. It happens often in lichen planus or psoriasis.
