Mucocutaneous - Vesiculo-bullous disease

Question 1

Macule (macular lesion) features?

Answer 1

Circumscribed flat lesion
Not elevated
Not palpable

Question 2

Papule (papular lesion) features?

Answer 2

Circumscribed raised lesion
Raised
Palpable

Question 3

Blister

Answer 3

Fluid filled sac within or below epithelium

Question 4

Vesicle

Answer 4

Small blister less than 5mm

e.g. herpes simplex virus

Question 5

Bulla

Answer 5

Large blister more than 5mm diameter

e.g. pemphigus/pemphigoid

Question 6

Erosion

Answer 6

Marked thinning/partial loss of epithelium
But with a thin epithelial covering of the CT
Usually looks red and is v sensitive

Question 7

Ulcer

Answer 7

Localised loss of entire thickness of epithelium
Exposes underlying CT
Usually painful

Question 8

Examples of mucocutaneous disease?

Answer 8

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

Question 9

Autoimmune bullous diseases features?

Answer 9

Organ specific
Antibody mediated Type II hypersensitivity
Autoimmune disease

Question 10

Pemphigus epidemiology?

Answer 10

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

Question 11

Oral features of pemphigus?

Answer 11

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

Question 12

Pathogenesis of pemphigus?

Answer 12

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.

Question 13

Pemphigus histology?

Answer 13

Parakeratinised SS epi
CT under it
Bullae either side has epithelium = intraepithelial bullae
Rounded cells in vesicle fluid = sank cells

Question 14

Pemphigus investigations?

Answer 14

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

Question 15

Pemphigus immunofluorescence

Answer 15

Positive direct immunofluorescent staining in epithelial cells (fish net pattern)
Autoantibodies (IgG) target desmoglein 3 in the desmosomes that join keratinocytes

Question 16

Direct immunofluorescence - how does it work?

Answer 16

If pt has pemphigus the autoantibodies are present in the sample
Add in fluorescent labelled anti-human IgG to attach to the autoantibody

Question 17

When are blood samples needed to investigate pemphigus?

Answer 17

Circulating desmoglein levels
For indirect immunofluorescence
Used to detect circulating autoantibodies
Not used routinely any more

Question 18

Indirect immunofluorescence?

Answer 18

Sample of pts blood (not tissue) contains autoantibodies added to normal tissue sample and fluorescent labelld anti-human IgG added - will bind

Question 19

Subtypes of pemphigus?

Answer 19

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

Question 20

Management of pemphigus?

Answer 20

Exclude cancer
Immunosuppression
Prednisolone alone or in combo with azathioprine
Occasionally other immunosuppressants or plasmapheresis

Question 21

How to differentiate intra-epithelial bullae (pemphigus) and sub-epithelial bullae (pemphigoid)?

Answer 21

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

Question 22

Pathogenesis of pemphigoid?

Answer 22

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

Question 23

Types of sub-epithelial autoimmune bullous diseases?

Answer 23

Bullous pemphigoid
Mucous membrane pemphigoid
Dermatitis herpetiformis

Question 24

Histology of bullous pemphigoid/mucous membrane pemphigoid?

Answer 24

Epithelium separates from CT at the level of the basement membrane

• Top = epithelium and under = CT

Question 25

Mucous membrane pemphigoid?

Answer 25

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

Question 26

Mucous membrane pemphigoid signs?

Answer 26

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

Question 27

Eye lesions with MMP?

Answer 27

Trichiasis, fibrosis and scarring Inversion of lower eyelid (droopy) Entropion plus adhesions = symblepharon Ankyloblepharon = both eyelids start to stick together

Question 28

Treatment for MMP?

Answer 28

``` Steroids - Topical/systemic if severe Plaque reduction - Daily scruptulous home care - Chlorhexidine Tetracycline/nicatinamide (B3) Other immunosuppressive agents - Azathioprine, cyclophosphamide, dapsone, mycophenolate ```

Question 29

What to do if you suspect MMP?

Answer 29

Phone | Needs opthalmology opinion

Question 30

BP/MMP investigations?

Answer 30

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

Question 31

BP/MMP immunofluorescence result?

Answer 31

Linear IgG or IgM immunofluorescence at the basement membrane Standard indirect immunofluorescence studies usually negative

Question 32

Management of MMP/BP?

Answer 32

Systemic or topical steroids - mainstay of tx Sulphonamides or dapsone - may be an effective alternative to systemic steroids Mycophenolate mofetil Ocular examination

Question 33

Dermatitis herpetiformis features?

Answer 33

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

Question 34

Management of dermatitis herpetiformis?

Answer 34

GF diet | May respond well to sulphonamides or dapsone

Question 35

Histology of dermatitis herpetiformis?

Answer 35

Small regions of epithelial separation at the level of the basement membrane Neutrophil/eosinophil abscesses Mixed inflammation in CT

Question 36

Immunofluorescence of dermatitis herpetiformis?

Answer 36

Speckled/granular IgA immunofluorescence - basement membrane and adjacent CT = Speckled texture

Question 37

Epidermolysis bullosa congenita features?

Answer 37

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

Question 38

Epidermolysis bullosa congenita types?

Answer 38

EB simplex EB junctional = most severe EB dystrophica

Question 39

Epidermolysis bullosa congenita signs?

Answer 39

``` Large erosive lesions Large bullae Raw wounds Quite common on hands and feet Scarring ```

Question 40

Erythema multiforme?

Answer 40

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

Question 41

Erythema mutliforme clincial features?

Answer 41

Oral - Haemorrhagic crusting of lips - Extensive irregular mucosal ulceration erythema and blistering Ocular - Conjunctivitis Skin - Target lesions Severe cases - Steven's johnson syndrome

Question 42

Causes of single episode and recurrent erythema multiforme?

Answer 42

Single episode - Drugs - Mycoplasma pneumonia - Radiotherapy - Idiopathic Recurrent - Recurrent herpes simples (cold sores)

Question 43

Management of erythema multiforme?

Answer 43

``` 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

Question 44

Bullous pemphigoid features?

Answer 44

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