Vesiculobullous Disorders

Question 1

What can immunogenic diseases be divided into based on their pathogenesis

Answer 1

• cell mediated
• antibody mediated (pemphigus and pemphigoid)

Question 2

Why do many immunological skin conditions also effect the oral mucosa

Answer 2

they share common antigens

Question 3

What tissues does erythema multiforme involve

Answer 3

• skin and mucous membranes

Question 4

What type of hypersensitivity reaction is erythema multiforme

Answer 4

type 3

Question 5

What is the possible aetiologies of erythema multiforme

Answer 5

• drugs
• oral herpes simplex virus
• mycoplasma

Question 6

Describe the pathogenesis of erythema multiforme

Answer 6

Large antibody antigen immune complexes get stuck in capillaries and organs and they activate complement

Question 7

Which antibody complexes get stuck in oral EM

Answer 7

IgM

Question 8

Is the onset of erythema multiforme usually acute or chronic

Answer 8

acute

Question 9

How does erythema multiforme appear on the skin

Answer 9

as target lesions

Question 10

How does erythema multiforme appear on the mucosa

Answer 10

• erythematous patches
• followed by vesiculobullous eruptions
• bullous eruptions breakdown rapidly into erosions as the bullae disintegrate
• erosions on lip accompanied by crusting
• v painful, may find it hard to eat and drink
• may resemble primary herpetic gingivostomatits

Question 11

Which age group is erythema multiforme most common in

Answer 11

young males

Question 12

What is recurrent erythema multiforme associated with

Answer 12

recurrent herpes simplex

Question 13

What are the management strategies for erythema multiforme

Answer 13

• urgent medical therapy
• encourage fluids
• encourage analgesia
• manage recurrance

Question 14

What urgent medical therapy should be provided for EM

Answer 14

• high dose systemic steroids
• systemic aciclovir

Question 15

How should we manage recurrence

Answer 15

consider daily aciclovir for prophylaxis
allergy testing
consider mycoplasma cause

Question 16

What is the presentation of angina bullosa haemorrhagia

Answer 16

• blood blister in the mouth
• rapid onset - tends to appear within a few minutes and only last an hour then burst

Question 17

What is the possible aetiology for ABH

Answer 17

trauma

Question 18

Where are the common sites for ABH

Answer 18

• buccal mucosa
• soft palate

Question 19

What does a biopsy of ABH show

Answer 19

non-specific ulceration

Question 20

What is the management of ABH

Answer 20

• CHX/difflam spray for healing
• no tx available
• reassure that disease is benign

Question 21

What type of hypersensitivity reaction is pemphigoid

Answer 21

• type 2 hypersensitivtiy

Question 22

What is pemphigoid

Answer 22

• group of immune mediated blistering diseases
• characterized by production of autoantiibodies to various components of hemidesmosomes

Question 23

What are hemidesmosomes

Answer 23

• attach epithelium to underlying connective tissue

Question 24

What type of vesicles are formed in pemphigoid

Answer 24

• sub-epithelial

Question 25

What type of antibodies develop in pemphigus/pemphigoid

Answer 25

IgG

Question 26

What are the types of pemphigoid

Answer 26

* bullous * mucous membrane * cicatritial

Question 27

What is bullous pemphigoid

Answer 27

involves skin alone

Question 28

What is mucous membrane pemphigoid

Answer 28

* involves all mucous membranes e.g eye, genitals, oral

Question 29

What is cicatritial pemphigoid

Answer 29

mucosal scarring can lead to blindness

Question 30

What does histopathology for pemphigoid show

Answer 30

subepithelial bulla can see neutrophils, eosinophils, macrophages and lymphocytes

Question 31

What is direct immunofluorescence

Answer 31

* antibody is bound to tissue * manufactured antibody has fluorescein attached * binds to bound antibody * requires biopsy (perilesional - not of lesion)

Question 32

What is indirect immunofluorescence

Answer 32

* circulating antibody not yet bound to tissue * detected using plasma sample * not always useful for diagnosis but useful for monitoring disease

Question 33

What does direct IF show for pemphigoid

Answer 33

* linear staining along BM * C3, IgG +/- IgA

Question 34

What does indirect IF show for pemphigus/pemphigoid

Answer 34

should be positive

Question 35

What happens if the pemphigoid scars

Answer 35

* can cause blindness - called ocular cicatritial pemphigoid * eventually can result in symblepharon where eyelids become attached to eye

Question 36

What is the most common pemphigus

Answer 36

* pemphigus vulgaris

Question 37

Describe the epidemiology of pemphigus vulgaris

Answer 37

* usually middle aged * f>m * genetic link? commoner in ashkenazi jews

Question 38

What sites are involved in pemphigus vulgaris

Answer 38

* skin * mucosa - often first site * eventually both

Question 39

What is the presentation of pemphigus

Answer 39

* intrapeithelial bullae * bullae are fragile and readily rupture forming crusted/weeping areas of denudation on the skin as well as irregular ragged ulcers * possible desquamative gingivitis

Question 40

What are the common oral sites for pemphigus vulgaris

Answer 40

* soft palate * buccal mucosa * lips most frequently effected

Question 41

How are the bulla produced in pemphigus vulgaris

Answer 41

* acantholysis (loss of desmosomes) * process extends laterally into surrounding epithelium for considerable distance

Question 42

What is Nikolsky's sign

Answer 42

* mostly used for pemphigus * gentle lateral pressure to mucosa * leads to formation of bulla

Question 43

What does the histology of pemphigus show

Answer 43

* splitting of epithelium * changes occur in stratum spinosum above basal cell layer * tzanck cells

Question 44

What are tzanck cells

Answer 44

* single small clumps of cells free within blister fluid

Question 45

What does direct IF show for pemphigus vulgaris

Answer 45

* basket weave appearance * C3 + IgG

Question 46

How is pemphigus managed

Answer 46

* systemic corticosteroids especially for acute phase * reduce weekly * if no response, look at mycophenolate or azathioprine

Question 47

What are the long term risks of pemphigus

Answer 47

* infection * paraneoplasm malignancy * chronic inflammation * swallowing issues

Question 48

If further testing past direct and indirect IF are required, what can be done

Answer 48

ELIZA shows us what autoantibodies are targetting

Question 49

What are the long term risks of pemphigoid

Answer 49

* blindness * no real mlaignant potential but tx can have malignant potential

Question 50

How does HSV1 result in erythema multiforme

Answer 50

* virus taken up by monocytes and macrophages * cells migrate to mucosal site/skin and deposit the virus in these skin areas resulting in antigen/antibody complexes which dont phagocytose well so the response lingers

Question 51

What is the multiorgan condition of erythema multiforme called

Answer 51

steven johnson syndrome

Question 52

What is steven johnson syndrome

Answer 52

widespread involvement of the skin, oral, genital and ocular mucosae (erythema multiforme)

Question 53

What is linear IgA disease

Answer 53

* C3 & IgA antibody subepidermal blistering disease of skin * overlaps wit bullous pemphigoid * linked to gluten intolerance

Question 54

What is dermatitis herpetiformis

Answer 54

* chronic, intensely pruritic subepidermal autoimmune blistering condition * granular IgA, C3 * oral presentation: ranges from small symptomless erythematous areas to extensive erosions

Question 55

How many biopsies do we need for pemphigus/pemphigoid

Answer 55

two one for histopathology one for direct IF