OP13 vesiculo-bullous lesions of oral mucosa

Question 1

What are the 2 types of vesicle lesions?

Answer 1

Intraepithelial - within epithelium
Subepithelial - between epithelium and lamina propria

Question 2

What are the types of intraepithelial vesicle?

Answer 2

Acantholytic - breakdown of intercellular attachment
Non-acantholytic - death and rupture of epithelial cells

Question 3

Give examples of acantholytic diseases

Answer 3

Pemphigus, benign familial pemphigus (Hailey-Hailey disease), Darier’s disease

Question 4

Give examples of non-acantholytic diseases

Answer 4

Herpes simplex, herpes zoster, coxsackie A infections

Question 5

Give examples of subepithelial vesicle diseases

Answer 5

Pemphigoid group, bullous lichen planus, dermatitis herpetiform, linear IgA disease, epidermolysis bullosa, angina bullosa haemorrhagica, erythema multiforme (can also have intraepithelial vesicles)

Question 6

What are the 4 main mechanisms of vesicle formation?

Answer 6

Infective - death and rupture of epithelial cells
Immunological - autoimmune, pemphigus, pemphigoid group
Traumatic - epidermolysis bullosa, angina bullosa haemorragica
Idiopathic - erythema multiforme, lichen planus

Question 7

What is pemphigus?

Answer 7

Autoimmune reaction against stratified suprabasal epithelium adhesion proteins (individual create antibodies against desmosomal proteins)

Question 8

What are the clinical variants of pemphigus?

Answer 8

• Pemphigus vulgaris (anti-desmoglein 3 Abs)
• Pemphigus vegetans (+ proliferative changes, rarely in mouth)
• Pemphigus foliaceous (less serious, rarely in mouth, anti-desmoglein 1 Abs)
• Pemphigus erythematosus
• Paraneoplastic (anti-desmoplakin 1 & 2 Abs) IgG or IgA
• IgA Pemphigus (anti-desmocollin 1, 2 & 3 Abs) IgA

Question 9

Why is pemphigus fatal if untreated?

Answer 9

Due to extensive ulceration, electrolyte loss and infection.

Question 10

Where does pemphigus usually present first?

Answer 10

Mouth which is subject to trauma from eating

Question 11

How can you tell someone’s ulcers are pemphigus?

Answer 11

Nikolsky’s sign + (dont do this - pinch of skin will cause a vesicle)
Look at rubbed surfaces
Pressing already formed vesicles will cause it to spread laterally

Question 12

What is the histology of pemphigus?

Answer 12

• Thin-roofed vesicles/bullae (intraepithelial, acantholytic lesions, suprabasal split) followed by ulceration
• Tzanck cells in the blister fluid (swollen, hyperchromatic nucleus)
• Little inflammatory infiltration (until ulceration) since disease is autoimmune
• Basal cells remain attached (tombstone appearance)

Question 13

What methods of immunofluorescence are there for pemphigus? (IgG and C3 intercellulary)

Answer 13

Direct method: fluorescein-conjugated anti-human IgG and anti-C3 sera
Indirect method: patient serum incubated with normal animal mucosa, then labelled with fluorescein-conjugated anti-human globulin.

Question 14

What is treatment for pemphigus?

Answer 14

Systemic corticosteroids + steroid sparing agents. Immunosuppressive agents if that fails.

Question 15

What is benign familial pemphigus (Hailey-Hailey disease)?

Answer 15

Rare genetic dermatologic disease (dominant)
Gene against a calcium and manganese pump.
First signs usually appear between 15 and 40 years
Nikolsky +, Red, scaly areas or small blisters at areas of friction, Oral lesions similar to those in skin

Question 16

What is the histology of benign familial pemphigus?

Answer 16

Similar to pemphigus: intraepithelial acantholytic lesions, ‘collapsing brick wall’ appearance

Question 17

What are the immunological findings for benign familial pemphigus?

Answer 17

Immunological findings are negative

Question 18

What is Darier’s disease/keratosis follicularis?

Answer 18

 Autosomal dominant (ATP2A2 gene) abnormal desmosome-keratin filament complex.
 Multiple pruritic, hyperkeratotic papules and plaques in head, neck & trunk
 Palmar / sole pits, Nail dystrophy, Oral lesions
 Peak incidence 11-15 years

Question 19

What is the histology of Darier’s disease?

Answer 19

Intraepithelial, acantholytic blisters. Corp ronds: round nuclei with a perinuclear halo, Corp grains: elongated ‘grain shaped’ nucleus

Question 20

How does erythema multiforme present clinically?

Answer 20

Symmetrical, round 1-2cm, erythmatous macules, papules (elbows, knees, extensor surfaces of extremities), blisters, ulceration
Target iris or bull’s eye lesions. Itching or burning sensation

Question 21

Epidemiology of aetiology of erythema multiforme?

Answer 21

• Predominantly young patients (20-40 yrs), male slightly more common, can be recurrent.
• 50% unknown aetiology, others associated with HSV or mycoplasma infection, drugs (sulphonamides, penicillin contraceptive pill, others).

Question 22

Does erythema multiforme affect the oral cavity?

Answer 22

About half have mucous membrane involvement in the anterior mouth and lips

Question 23

What is the pathogenesis of erythema multiform?

Answer 23

Possibly an immune complex mediated disease

Question 24

Although the histology is not diagnostic, describe the histology of erythema multiforme.

Answer 24

Inter and intracellular oedema
Keratinocyte necrosis leading to both subepithelial vesicles and intraepithelial vesicles

Question 25

What is stevens-johnson syndrome?

Answer 25

Severe form of erythema multiforme causing: - painful haemorrhagic oral erosions - severe conjunctivitis - erosive genital lesions - can be fatal

Question 26

What does pemphigoids group refer to?

Answer 26

Several immune mediated blistering diseases producing autoantibodies to the hemidesmosomes and the epithelial basement membrane, resulting in subepithelial vesicle formation

Question 27

What are the clinical subtypes of pemphigoid?

Answer 27

Bullous pemphigoid - mainly skin Mucous membrane pemphigoid - mainly mucosa

Question 28

What are the differences between desmosomes and hemidesmosomes?

Answer 28

Both cell attachment structures Desmosomes - use cadherins to attach to other cells Hemidesmosomes - use integrins to attach to the basement membrane

Question 29

What are the different components involved in different diseases?

Answer 29

BP180 - bullous pemphigoid, linear IgA disease, Cicatricial pemphigoid a6b4 - ocular cicatricial pemphigoid Collagen VII - epidermolysis bullosa acquista, dystrophic epidermolysis bullosa Laminin 5 - anti-epiligrin cicat. Pemphigoid, junctional epidermolysis.

Question 30

Where does mucous membrane pemphigoid present?

Answer 30

Mouth almost always affected, sometimes the only site 90% in the gingiva - desquamative gingivitis!!!! Also in ocular, nasal, larynx, pharynx, oesophagus, genital mucosa

Question 31

What are the bullae/ulcerations like in mucous membrane pemphigoid?

Answer 31

Occasionally haemorrhagic Bullae are 'tense' Ulcerations heal slowly, sometimes scarring (cicatricial pemphigoid)

Question 32

What is the histology of mucous membrane pemphigoid?

Answer 32

Separation of epithelium from lamina propria (bulla with 'thick roof' As vesicles develop, infiltration by neutrophils, eosinophils, perivascular infiltration (mainly lymphocytes)

Question 33

What is shown in immunofluorescence of mucous membrane pemphigoid?

Answer 33

Linear binding (IgG, IgA, C3) in the basement membrane zone. Abs against BP180.

Question 34

What is dermatitis herpetiformis?

Answer 34

Autoimmune blistering of skin, variable oral presentation: mild form erythema, severe forms extensive ulceration

Question 35

What does immunofluorescence show in dermatitis herpetiformis?

Answer 35

Granular IgA deposits in connective papilla

Question 36

What are the antibodies against in dermatitis herpetiformis?

Answer 36

Epidermal transglutaminase 3, Gliadin, endomysium, reticulin

Question 37

What do most patients with dermatitis herpetiformis also have?

Answer 37

Gluten hypersensitivity, jejunal villous atrophy and increased infiltration of intraepithelial lymphocytes Subepithelial vesicles with neutrophils and later eosinophils

Question 38

What is linear IgA disease?

Answer 38

Similar to dermatitis herpetiformis and bullous pemphigoid. Subepithelial bullae with neutrophils.

Question 39

How does linear IgA disease present in immunofluorescence?

Answer 39

Linear IgA deposits along the basement membrane Only some patients have gluten hypersensitivity No anti-endomysium antibodies

Question 40

What is epidermolysis bullosa?

Answer 40

A group of 30 diseases causing subepithelial bullae in response to minimal trauma. Abnormal keratins or basement membrane constituents.

Question 41

What is angina bullosa haemorrhagica/recurrent oral haemophlyctenosis?

Answer 41

Subepithelial haemorrhagic bullar in older patients. Usually solitary. Presents any place of oral mucosa, commonly soft palate. No immunological blood clotting abnormalities. Some association to minor trauma, hot foods, steroid inhalers, dental/periodontal treatment.

Question 42

Where is the inflammatory filtration in angina bullosa haemorrhagica?

Answer 42

Mild, nonspecific mononuclear inflammatory cell infiltration generally limited to the lamina propria.

Question 43

How does bullous lichen planus cause vesicles?

Answer 43

Due to liquefaction necrosis of the basal cell layer so fluid can accumulate there.