immunobullous diseases

Question 1

3 main blistering diseases

Answer 1

bullous pemphigoid, pemphigus vulgaris, dermatitis herpetiformis

Question 2

2 types of blisters

Answer 2

sub epidermal; intra epidermal

Question 3

charcateristics of sub-epidermal blisters

Answer 3

thick walled and ense; hemidesmosomes (attach basal kertainocytes to BMZ); BMZ (interface betweeen dermis and epidermis);
e.g. pemphigoid

Question 4

characteristics of intra-epidermal blisters

Answer 4

thin walled and flaccid; desmosomes (keratinocyte adhesion juncitons); keratin cytoskeleton e..g pemphigus

Question 5

what is the most common autoimmune bullous disease

Answer 5

pemphigoid

Question 6

pemphigoid pathophys - come back

Answer 6

Autoimmune sub-epidermal blistering skin diseases; BPAg2 protein affects collagen VII and hemidesmosomes that anchor basal cells to the basement membrane

Question 7

urticaria vs bullus pemphigoid

Answer 7

urticaria - weals/hives that move around
penphigoid - blisters, urticariated patches that don’t more

Question 8

bullous pemphigoid investigations

Answer 8

1. biopsy (sub epidermal split - direct immunoflouresence (presence of IgG) and H&E staining)
2. bloods - indirect immunoflouresence (circulating BP can be detected)

Question 9

treatment for bullous pemphigoid

Answer 9

1. oral steroids (can give topical if localised area - very potent steroids);
2. doxycycline;
3. nicotinaminde
4. azathioprine

Question 10

bullous pemphigoid prognosis

Answer 10

relapse can occur for 5 years; morbidity/mortaility can occur due to treatment (steroids)

Question 11

what is pemphigus vulgaris

Answer 11

and acquired autoimmune disease that presents with mucocutaneous blisters

Question 12

pemphigus vulgaris pathophys

Answer 12

antibodies directed against both desmoglein 1 and desmoglein 3 (a cadherin) present in desmosomes, generally in the musoca -> desmosomes lost -> loss of cohesion between keratinocytes in the epidermis -> disruption of the barrier function served by intact skin

Question 13

typical Hx of pemphigus vulgaris

Answer 13

40-60yro presenting with oral ulcers (prior to rash) initially and then a “sore” rash (not itchy)

Question 14

presentation of pemphigus vulgaris

Answer 14

mputh ulcers; sore rash; fragile/flaccid blisters - Nikolsky sign; other mucosal membrane involvement (erosions)

Question 15

pemphigus vulgaris ddx

Answer 15

pressure uclers; SJS/TEN; burns;

Question 16

pemphigus vulgaris investigations

Answer 16

1. biopsy - ‘crazypaving’ pattern, IgG/C3 band around epidermal cells
2. bloods - indirect immunoflourescence

Question 17

pemphigus vulgaris treatment

Answer 17

1. highdose oral steroids
2. azathioprine
3. plasmapheresis
4. IV Ig

Question 18

pemphigus vulgaris prognosis

Answer 18

5-15% mortality; risk of infection; fluid and electrolyte imbalance

Question 19

what should be considered if pemphigus vulgaris presents w weightloss/fatigue

Answer 19

paraneoplastic subtype

Question 20

what is dermatitis herpetiformis

Answer 20

an autoimmune blistering disease that shows a gluten-sensitive enteropathy (coeliac); associated w other autoimmune conditions (SLE, pernicious anameia etc.)

Question 21

what is the autoimmune reaction directed against in dermatitis herpetiformis

Answer 21

transglutaminase in the skin, IgA

Question 22

dermatitis herpetiformis pathophys

Answer 22

IgA is deposited at the dermal - epidermal junction in the skin, and the release of enzymes by neutrophils to break down IgA may cause the itch and also the blisters, which are classified
as sub-epidermal

Question 23

typial dermatitis herpetiformis Hx

Answer 23

20-60yro presenting w a very itchy rash, erythematous papules and blisters on the extensor aspects of the elbow, knees etc.; no mucosal involvement

Question 24

dermatitis herpetiformis investigations

Answer 24

1. biopsy - two separate punch biopsies ->sub epidermal blister and uninvolved skin; direct immunofluoresence (in uninvolved skin, granular deposition IgA in dermal papillae);
2. distal duodenal biopsy (make sure pt carries on with normal diet prior to this test);
3. antiendomysial and tissue transglutaminase

Question 25

dermatitis herpetiformis ddx

Answer 25

psoriasis eczema, tinea corpalis

Question 26

dermatitis herpetiformis treatment

Answer 26

1. dapsone
2. gluten free diet (after investigatioms);
3. sulphonamides

Question 27

side effects of dapsones

Answer 27

1. haemolytic anaemia (sevre in G6DP deficiency);
2. headaches;
3. depression;
4. lethargy;
5. methaemoglobinaemia;
6. neuropathy

Question 28

sulphonamises side effects

Answer 28

1. bone marrow suppression
2. nausea;
3. depression;
4. rashes
5. hepatitis
6. interstitial pneumonitis

Question 29

oral steroids side effectsa

Answer 29

1. hypertension
2. peptic ulceration;
3. cataracts;
4. skin thinning;
5. osteopenia
6. weight gain
7. adrenal suppression
8. muscle wasting

Question 30

azathioprine side effects

Answer 30

1. gastrointestinal disturbances (nausea, vomiting etc.)
2. bone marrow suppression;
3. liver damage

Question 31

3 methods of blister formation

Answer 31

friction, burns (second degree) or disease

Question 32

how do burns form blisters

Answer 32

1. If the BMZ is damaged by heat it makes sense that the dermis and epidermis will
   separate somewhat, allowing plasma to leak from the blood into the space
   between the two layers;
2. It may also be the case that desomosomes connecting keratinocytes together may separate allowing fluid to accumulate there, it
   depends on the extent of the burn

Question 33

how does friction cause blisters

Answer 33

constant rubbing will cause the stratum
spinum to separate from the stratum basale, and hydrostatic forces will cause fluid to fill this gap;

Question 34

what autoantibodies are seen in bullous pemphigoid and what effect do they cause

Answer 34

autoantibodies towards the
BP180 and BP230 antigens of the
hemi-desmosome -> results in it no longer being able to anchor the stratum basale to the sublamina densa