Mucocutaneous - Vesiculo-bullous disease Flashcards
Macule (macular lesion) features?
Circumscribed flat lesion
Not elevated
Not palpable
Papule (papular lesion) features?
Circumscribed raised lesion
Raised
Palpable
Blister
Fluid filled sac within or below epithelium
Vesicle
Small blister less than 5mm
e.g. herpes simplex virus
Bulla
Large blister more than 5mm diameter
e.g. pemphigus/pemphigoid
Erosion
Marked thinning/partial loss of epithelium
But with a thin epithelial covering of the CT
Usually looks red and is v sensitive
Ulcer
Localised loss of entire thickness of epithelium
Exposes underlying CT
Usually painful
Examples of mucocutaneous disease?
Autoimmune bullous disease - Pemphigus - Pemphigoid - Dermatitis herpetiformis = Type II hypersensitivity
Epidermolysis bullosa congenita = congenital anomaly
Erythema multiforme = type III/IV
Oral lichen planus and lichenoid reactions = type IV
Autoimmune bullous diseases features?
Organ specific
Antibody mediated Type II hypersensitivity
Autoimmune disease
Pemphigus epidemiology?
Incidence 0.5-3.2 per 100,000
40-60 yrs old
1:1 M:F
Organ specific autoimmune disease targeting skin and oral mucosa
Oral features of pemphigus?
Mouth involved in most cases, only site involved in over half of cases
Palate, buccal mucosa and gingivae - most commonly affected
Bullae - short lived in mouth and on skin
Large shallow non healing ulcers are typical
Pathogenesis of pemphigus?
Circulating autoantibodies against binding proteins that keep epithelial cells together (desmosomes). Binding protein- part of the desmosomal complex, usually desmoglein3 (sometimes desmoglein 1 as well). Autoantibody binds to desmoglein3- acantholysis and formation of an intra-epithelial bulla.
Pemphigus histology?
Parakeratinised SS epi
CT under it
Bullae either side has epithelium = intraepithelial bullae
Rounded cells in vesicle fluid = sank cells
Pemphigus investigations?
Biopsy of para-lesional and/or normal tissue
Send tissue to lab fresh
Routine histology - separate biopsy or part of fresh specimen
Direct immunofluorescence staining - used to detect whether autoantibodies are present in the patient’s tissue
Pemphigus immunofluorescence
Positive direct immunofluorescent staining in epithelial cells (fish net pattern)
Autoantibodies (IgG) target desmoglein 3 in the desmosomes that join keratinocytes
Direct immunofluorescence - how does it work?
If pt has pemphigus the autoantibodies are present in the sample
Add in fluorescent labelled anti-human IgG to attach to the autoantibody
When are blood samples needed to investigate pemphigus?
Circulating desmoglein levels
For indirect immunofluorescence
Used to detect circulating autoantibodies
Not used routinely any more
Indirect immunofluorescence?
Sample of pts blood (not tissue) contains autoantibodies added to normal tissue sample and fluorescent labelld anti-human IgG added - will bind
Subtypes of pemphigus?
Pemphigus vulgaris
- Most common (antibodies mainly DSG3)
Pemphigus foliaceous
- Lesions more superficial (antibodies mainly DSG1)
Paraneoplastic pemphigus
- Associated with neoplasm
- Usually lymphoma or chronic lymphocytic leukaemia
- Extremely serious with a high morbidity and mortality
Management of pemphigus?
Exclude cancer
Immunosuppression
Prednisolone alone or in combo with azathioprine
Occasionally other immunosuppressants or plasmapheresis
How to differentiate intra-epithelial bullae (pemphigus) and sub-epithelial bullae (pemphigoid)?
Intra-epithelial bullae - pemphigus: Partial thickness Very fragile On rupturing, basal epithelial cells remain therefore: - Infec can get in - Loss of tissue fluids - = Life threatening
Sub-epithelial bullae (pemphigoid)
- Full thickness
- Less fragile
- On rupturing, exposed CT
- Healing by secondary intention: epithelial migration from edges, wound contraction e.g. scarring
Pathogenesis of pemphigoid?
Autoantibodies against components of the hemidesmosomes: structures gluing epithelial cells to the basement membrane
The targeted part of hemidesmosome varies between different types of pemphigoid
Types of sub-epithelial autoimmune bullous diseases?
Bullous pemphigoid
Mucous membrane pemphigoid
Dermatitis herpetiformis
Histology of bullous pemphigoid/mucous membrane pemphigoid?
Epithelium separates from CT at the level of the basement membrane
- Top = epithelium and under = CT
Mucous membrane pemphigoid?
Chronic disease of elderly
Desquamative gingivitis >90% of cases
Buccal mucosa and palate often involved
Eyes may be severely damaged by scarring - cicatricial pemphigoid
Skin lesions are rare in MMP
Autoantibodies directed against BP230, laminin and Alpha6Beta4 in hemidesmosomes
Gingival involvement in more than 90% of cases
82.5% other oral mucosa
48.3% conjunctiva = inversion of lower eyelid (droopy)
Skin and nasal
Mucous membrane pemphigoid signs?
Well marginated ulcers
Healing in 3-4 weeks, risk of scarring if eyes, larynx, oesophagus involved
Erythematous, friable, tender gingivae
Nikolsky sign positive (shearing away of the epidermis)
Conjunctival lesions common: lid inversion (droopy), symblepharon, ankyloblepharon
Eye lesions with MMP?
Trichiasis, fibrosis and scarring
Inversion of lower eyelid (droopy)
Entropion plus adhesions = symblepharon
Ankyloblepharon = both eyelids start to stick together
Treatment for MMP?
Steroids - Topical/systemic if severe Plaque reduction - Daily scruptulous home care - Chlorhexidine Tetracycline/nicatinamide (B3) Other immunosuppressive agents - Azathioprine, cyclophosphamide, dapsone, mycophenolate
What to do if you suspect MMP?
Phone
Needs opthalmology opinion
BP/MMP investigations?
Biopsy of para-lesional and/or normal tissue
Send tissue to lab fresh
Routine histology
Direct immunofluorescence staining: to detect autoantibodies
Linear IgG or IgM immunofluoresence at the basement membrane
Indirect immunofluoresence usually negative
BP/MMP immunofluorescence result?
Linear IgG or IgM immunofluorescence at the basement membrane
Standard indirect immunofluorescence studies usually negative
Management of MMP/BP?
Systemic or topical steroids - mainstay of tx
Sulphonamides or dapsone - may be an effective alternative to systemic steroids
Mycophenolate mofetil
Ocular examination
Dermatitis herpetiformis features?
May affect a younger age group including children
Smaller bullae and vesicles = herpetiform appearance of lesions - ask if they have any stomach, eye or skin problems
Associated with coeliac disease
Management of dermatitis herpetiformis?
GF diet
May respond well to sulphonamides or dapsone
Histology of dermatitis herpetiformis?
Small regions of epithelial separation at the level of the basement membrane
Neutrophil/eosinophil abscesses
Mixed inflammation in CT
Immunofluorescence of dermatitis herpetiformis?
Speckled/granular IgA immunofluorescence - basement membrane and adjacent CT
= Speckled texture
Epidermolysis bullosa congenita features?
Not autoimmune (inherited)
Genetic defects in key proteins involved with epithelial integrity or anchoring to the CT
Variable clinical picture depending upon which protein is defective
Mainly affects children - often present at birth
Some forms are severe, mutilating or fatal
Epidermolysis bullosa congenita types?
EB simplex
EB junctional = most severe
EB dystrophica
Epidermolysis bullosa congenita signs?
Large erosive lesions Large bullae Raw wounds Quite common on hands and feet Scarring
Erythema multiforme?
Acute onset, short duration 2-3 weeks
Mucocutaneous blistering disorder
Peak age range 20-30 yrs
Complex pathogenesis
Some cases immune complex mediated - type III hypersensitivity, immune complexes deposited in tissues
Some recurrent cases - type IV hypersensitivity to herpes antigens
Erythema mutliforme clincial features?
Oral
- Haemorrhagic crusting of lips
- Extensive irregular mucosal ulceration erythema and blistering
Ocular
- Conjunctivitis
Skin
- Target lesions
Severe cases
- Steven’s johnson syndrome
Causes of single episode and recurrent erythema multiforme?
Single episode
- Drugs
- Mycoplasma pneumonia
- Radiotherapy
- Idiopathic
Recurrent
- Recurrent herpes simples (cold sores)
Management of erythema multiforme?
Remove/avoid trigger Short, reducing dose course of steroids Chlorhexidine/benzydamine mouthwash Gelclair Analgesics Soft diet Admission for parentaral nutrition and more intensive therapy
Recurrent
- Prevention with systemic aciclovir
Bullous pemphigoid features?
Skin usually involved with bullae and large shallow ulcers or erosions
Mouth and other mucous membranes frequently involved
Autoantibodies directed against the BP180 and BP230 antigens in hemidesmosomes
