Mucocutaneous disease

Question 1

What is a macule / macular lesion (3)

Answer 1

Circumscribed flat lesion
Not elevated
Not palpable

Question 2

What is a papule / papular lesion (3)

Answer 2

Circumscribed raised lesion
Raised
Palpable

Question 3

What is a blister? (2)

Answer 3

A fluid filled sac within or below epithelium

Question 4

What is a vesicle + example (3)

Answer 4

A small blister <5mm diameter

e.g. Herpes simpex vesicles

Question 5

What is a bulla + example (3)

Answer 5

A large blister >5mm diameter

E.g. pemphigus/ pemphgoid

Question 6

Describe erosive lesions (3)

Answer 6

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

Question 7

Describe an ulcerative lesion (3)

Answer 7

 Localised loss of entire
thickness of epithelium
 Exposes underlying
connective tissue
 Usually painful

Question 8

What are the autoimmune bullous diseases and what type of hypersensitivity are they? (4)

Answer 8

Pemphigus
Pemphigoid
Dermatitis herpetiformis
-type II hypersensitivity

Question 9

Types of mucocutaneous disease (4)

Answer 9

Autoimmune bullous disease
Epidermolysis bullosa congeita (congital anomaly)
Erythema multiforme (type III/ IV hypersensitivity)
Oral luchen planus and lichenoid reactions (type IV hypersensitivity)

Question 10

Types of autoimmune bullous disease (3)

Answer 10

Pemphigus
Pemphigoid
Dermatitis herpetiformis

Question 11

Features of autoimmune bullous disease (3)

Answer 11

Organ specific
Antibody-mediated (type II hypersensitivity)
Autoimmune diseases

Question 12

Epidemiology of pemphigus (3)

Answer 12

Incidence 0.5-3.2 per 100,000
Main age group: 40-60 years
Male to female ratio = 1:1

Question 13

What is pemphigus (1)

Answer 13

Organ specific autoimmune disease targeting skin and oral mucosa

Question 14

Oral features of pemphigus (4)

Answer 14

Mouth involved in most cases, and is the only site involved in over half of cases
Palate, buccal mucosa and gingivae are most commonly affected
Bullae are short lived in mouth and on the skin
Large shallow non-healing ulcers are typical

Question 15

Nikolsky’s sign (2)

Answer 15

Used in diagnosis of pemphigus

Top layers of skin slip away from lower layers when rubbed

Question 16

Pathogenesis of pemphigus (3)

Answer 16

Circulating autoantibodies against building proteins that keep epithelial cells together
Binding protein - part of desmosomal complex, usually desmoglein3 (sometimes desmoglein 1 as well)
Autoantibody binds to desmoglein3 leading to epithelial cells separation (acantholysis) and formation of an intra-epithelial bulla

Question 17

Cells in pemphigus (1)

Answer 17

Tzank cells

Question 18

Investigations for pemphigus (5)

Answer 18

Biopsy of para-lesional and / or normal tissue
Send tissue to lab fresh or frozen (do not fix)
Routine histology
Direct immunofluorescence staining: used to detect whether autoantibodies are present in the patient’s tissue
Also send blood sample for indirect immunofluorescence, used to detect circulating autoantibodies

Question 19

Immunofluorescence - pemphigus (2) **

Answer 19

Positive direct immunofluorescent staining of keratinocytes (fish net
pattern)
Autoantibodies (IgG) target Desmoglein 3 in the desmosomes that join keratinocytes

Question 20

Sub-types of pemphigus (3)

Answer 20

Pemphigus vulgaris
Pemphigus foliaceous
Paraneoplastic pemphigus

Question 21

What is pemphigus vulgaris (1)

Answer 21

Most common (autoantibodies mainly to DG3)

Question 22

What i pemphigus foliaceous (1)

Answer 22

Lesions more superficial (autoantibodies mainly to DG1)

Question 23

What is paraneoplastic pemphigus (3)

Answer 23

Associated with a neoplasm
Usually lymphoma or chronic lymphocytic leukaemia
Extremely serious with a high morbidity and mortality

Question 24

Management of pemphigus (4)

Answer 24

Exclude cancer
Immunosuppression
Prednisolone alone or in combination with azathioprine
Occasionally other immunosuppressants or plasmaphoresis

Question 25

Intra- vs sub-epithelial bullae (5)

Answer 25

Intra-epithelial bullae (pemphigus) -partial thickness -very fragile -on rupturing, basal epithelial cells remain -therefore no stimulus to heal -however, epithelial permeability barrier is lost, therefore infection can get in; there is loss of tissue fluids (like a burn); together these are life threatening Sub-epithelial bullae (pemphigoid etc.) -full thickness -fragile -on rupturing, exposed connective tissue -healing by secondary intention (epithelial migration from edges, wound contraction i.e. scarring)

Question 26

Types of sub-epithelial bullous disease (3)

Answer 26

``` Bullous pemphigoid (BP) Mucous membrane pemphigoid (MMP) (Cicatricial pemphigoid) Dermatitis herpetiformis (DH) ```

Question 27

Pathogenesis of pemphigoid (2)

Answer 27

Autoantibodies directed against components of the hemidesmosomes: structures gluing the epithelial cells to the basement membrane. The targeted part of hemidesmosome varies between different types of pemphigoid.

Question 28

BP/ MMP - pemphigoid: histology (1)

Answer 28

Epithelium separates from connective tissue at the level of the basement membrane

Question 29

Features of bullous pemphigoid (3)

Answer 29

Skin usually involved with bullae and large shallow ulcers or erosions Mouth and other mucous membranes frequently involved Autoantibodies directed against the BP180 (BPAG1) and BP230 (BPAG2) antigens in hemidesmosomes

Question 30

Features of mucous membrane pemphigoid (6)

Answer 30

Chronic disease of the elderly Desquamative gingivitis in >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 BP`230, laminin and α6β4 in hemidesmosomes

Question 31

Gingival and mucosa involvement in MMP (5)

Answer 31

``` Gingival involvement in >90% cases Other mucosal involvement: -82.5% other oral mucosa -48.3% conjunctiva -8.3% skin -7.5% nasal ```

Question 32

Features of MMP (5)

Answer 32

Well defined ulcers Healing in 3-4 weeks; risk of scarring if eyes, larynx, oesophagus involved Erythematous, friable, tender gingiva Nikolsky sign positive Conjunctival lesions common (up to 80%) -symblepharon, ankyloblepharon, lid inversion

Question 33

Eye lesions in MMP/ cicatricial pemphigoid

Answer 33

Blisters and ulcers (conjunctivitis) Trichiasis, fibrosis and scarring Entopion plus adhesions - symblepharon

Question 34

MMP - treatment (4)

Answer 34

Steroids: topical/ systemic (if severe) Plaque reduction: daily scrupulous home care, chlorhexidene Tetraycycline/ nictinamide Other immunosuppressive agents: azathioprine, cyclophosphamide, dapsone, mycophenolate

Question 35

MMP pemphoid referral (2)

Answer 35

Immediate - telephone | Needs ophthalmology opinion

Question 36

Investigations for BP/ MMP - pemphigoid (4)

Answer 36

Biopsy of para-lesional and / or normal tissue Send tissue to lab fresh or frozen (do not fix) Routine histology Direct immunofluorescence staining: to detect autoantibodies in the tissue

Question 37

Immunofluorescence of BP/ MMP - pemphigoid (1)

Answer 37

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

Question 38

Management of BP/ MMP - pemphigoid (4)

Answer 38

Systemic or topical steroids are the mainstay of treatment Sulphonamides or Dapsone may be an effective alternative to systemic steroids Mycophenolate mofetil, an additional systemic agent Ocular examination is essential

Question 39

Features of dermatitis herpetiformis (3)

Answer 39

Similar to BP but: -may affect a younger age group including children -smaller bullae and vesicles - hence herpetiform appearance of lesions -association with Coeliac disease (gluten enteropathy)

Question 40

Histology of dermatitis herpetiformis (1)

Answer 40

Small regions of epithelial separation at the level of the basement membrane

Question 41

Immunofluorescence: dermatitis herpetiformis (1)

Answer 41

Speckled / granular IgA immunofluorescence at the basement membrane and in the adjacent connective tissue

Question 42

Management of dermatitis herpetiformis (2)

Answer 42

Gluten free diet | May respond well to sulphonamides or dapsone

Question 43

Features of epidermolysis bullosa congenita (6)

Answer 43

Not autoimmune Inherited group of conditions Genetic defects in key proteins associated with epithelial integrity or anchoring to the CT The clinical picture differs depending on which protein is defective Mainly affects children- often present at birth Some forms are severe, mutilating or fatal

Question 44

Features of erythema multiforme (6)

Answer 44

Acute onset, short duration ~2-3 wks Mucocutaneous blistering disorder Peak age range 20-30yrs 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 45

Clinical features of erythema multiforme (4)

Answer 45

``` Oral  Haemorrhagic crusting of lips  Extensive irregular mucosal ulceration erythema and blistering Ocular  Conjunctivitis Skin  “Target” lesions Severe Cases  Stevens-Johnson syndrome ```

Question 46

Causes of erythema multiforme (5)

Answer 46

``` Single episode: -drugs -mycoplasma pneumonia -radiotherapy -idiopathic Recurrent: -recurrent Herpes simplex (cold sores) ```

Question 47

Management of erythema multiforme (7)

Answer 47

``` Remove / avoid trigger Short, reducing dose course of steroids Chlorhexidine / Benzidamine mouthwash Gengigel / Gelclair Analgesics Soft diet May require admission for parentaral nutrition and more intensive therapy ```

Question 48

Management of recurrent erythema multiforme (1)

Answer 48

Prevention with systemic acyclovir