Week 2 - D - Immunobullous disorders - Pemphigoid, Pemphigus, dermatitis herpetiformis - (also impetigo and lichen disorders)

Question 1

Blistering is seen in many skin diseases - what is the difference between a vesicle and a bullae? What separates the bullous disorders from the bistering seen in the many skin diseases?

Answer 1

Vsicles are small blisters less than 0.5cm in diameter. Bullae are larger blisters greater than 0.5cm in diameter. The immunobullous disorders are autoimmune blistering disorders where damage to adhesion mechanisms in the skin result in blistering at various levels

Question 2

Vesicles and bullae occur as a secondary phenomenon in many skin diseases e.g. eczema, herpes virus infection, burns IMMUNOBULLOUS DISEASES have blisters as the primary feature What are three important autoimmune blistering diosrders?

Answer 2

* Bullous pemphigoid * Pemphigus vulgaris * Dermatitis herpetiformis

Question 3

Apart from the immunobullous disorders which cause blistering, what are other examples of aetiologies linked to blistering?

Answer 3

Physical injuries eg friction

Infection - staph arues causing bullous impetigo

Acute dermatitis

Different drugs - causing Steven Johnson’syndrome or Toxic epidermal necrolysis

Metabolic - eg blistering and fragility seen in porphyric cutanea tarda (defect in uroporphyringoen decarboxylase)

Question 4

Lets discuss the levels of blistering What skin level does the separation occur in Bullous pemphigoid Pemphigus vulgars Dermatitis herpetiformis Also, bullous impetigo? (just threw this in since i had it 1st year)

Answer 4

Bullous pemphigoiD - split is Deeper (through Dermal epidermal junction) - subepidermal blistering

Pemphigus vulgariS - split is more Superifical- intraepidermal

Dermatitis herpetiformis - also subepidermal

Bullous impetigo - sub-corneal layer

Question 5

Why is there a difference in appearance in the blisters formed in bullous pemphigoid/dermatitis herpetiformis compared to pemphigus vulgaris? What will be seen clinically from both types of blistering?

Answer 5

In bullous pemphigoid and DH- the entire epidermis will be lifted off causing a roof off the blister to be lifted off which is very strong - clinically we will see blistering from subepidermal blisteing

In contrast, if there is an insult causing split in the upper layers, eg in the epidermis in pemphigus, this roof will be very thin and fragile and will essentially pop immediately on encountering pressure - clinically we will see erosions from intrapeidermal blistering

Question 6

There are different investigations carried out to diagnose the type of blistering Initial clinical assessment will of course guide to the appropriate investigation What is the investigation carried out in the autoimmune bullous disorders?

Answer 6

In the autoimmune bullous disorders, a skin biopsy is taken and immunoflourescensce is used to detect the immunoglobulins present (biopsy with IMF)

Question 7

What is the most frequent of all the autoimmune blistering disorders? What age group is usually affected?

Answer 7

Bullous pemphigoid is the most common autoimmune blistering disorder, typically occurring in the elderly - majority of patients >60 years

Question 8

What is Nikolsy sign and is it positive in Bullous pemphigoid?

Answer 8

Nikolsky sign is when the top layer of the skin slips away from the lower layer when slightly rubbed

This indicated a plane of cleaveage within the epidermis

Bullous pemphigoid is Nikolsky sign negative - entire epidermis lifted in BP causing a strong roof

Question 9

What causes the sub-epidermal blisters to form in bullous pemphigoid? * ie which antibodies attack what

Answer 9

Circulating IgG antibodies attack antigens in the the basement membrane (bullous pemphigoid antigens 1&2) and attack the hemidesmosomes which anchor the basal cells to the basement membrane (lamina lucida layer)

This results in local complement activation an tissue damage –> subepidermal bulla

Question 10

What investigation is used to diagnose bullous pemphigoid? Why is it important that early lesions are taken?

Answer 10

Skin biopsy + immunoflourescence of early lesions are taken - important as re-epithelialisation of the floor can take place in late lesions mimicking pemphigus vulgaris

Question 11

What is seen on skin biopsy and immunoflourescene in bullous pemphigoid?

Answer 11

Skin biopsy shows that the entire epidermis is raised on lots of inflammatory cells underneath

Immunoflourescence shows linear IgG (can see fluorescent horizontal line) + complement deposited round the basement membrane

Question 12

What is the treatment for bullous pemphigoid? What is the prognosis?

Answer 12

Treatment - Very potent topical steroid if localised BP - eg clobetasol proprionate (dermovate)

Systemic oral steroids if generalised BP eg prednisolone

Prognosis is usually a chronic self-limiting course often even without treatment

Question 13

PEMPHIGUS VULGARIS -much rarer than bullous pemphigoid with worse prognosis What are the clinical features of pemphigus vulgaris? * Type of lesions? * Where are the lesions on the person?

Answer 13

In pemphigus vulgaris

Typically there are flaccid vesicles/bullae which are thin roofed and rupture to leave raw ersions on the scalp, face, axillae and groins

Mucosal erosions are very common - painful ealy oral esions in nearly all cases and other mucosal areas involved also (eyes, genitals)

Question 14

Is pemphigus vulgaris Nikolsky sign positive or negative?

Answer 14

Nikolsky sign is when the top layer of the skin slips away from the lower layer when slightly rubbed

This indicated a plane of cleaveage within the epidermis

Pemphigus vulgaris is Nikolsky sign positive as they are thin roofed blisters due to intra-epidermal separation

Question 15

What causes the intra-epidermal blisters to form in pemphigus vulgaris? ie what antibodies attack what?

Answer 15

IgG autoantibodies are directed against desmoglein 3 in pemphigus vulgaris which are important in maintaining desmosomal attachments in the epidermis (prickle cell layer) - therefore disrupting desmosomes causing cells to come apart - acantholysis

Question 16

How is pemphigus vulgaris diagnosed? What is seen on investigation? - explain what acantholysis is

Answer 16

Diagnosed with skin biopsy + IF Skin biopsy shows acantholysis - loss of intracellular connections such as desmosomes, resulting in loss of cohesion between keratinocytes - leads to intra-epidermal blister

Immunoflourescece shows intraceullar IgG - IgG outlining individual keratinocytes - aka chicken wire pattern

Question 17

Treatment of pemphigus vulgaris is much more difficult than bullous pemphigoid How is it treated? What is pognosis?

Answer 17

Treat with high dose oral steroids and immunosuppresants (eg azathioprine or cyclophosphamide)

Majority of cases remit however mortality rate still around 10-20%

Question 18

DERMATITIS HERPETIFORMIS What does dermatitis herpetiformis have a strong association with? What HLA is it associated with?

Answer 18

Dermaitits herpetiformis is assoicated with the gluten sensitivity enteropathy - Coeliac’s disease

It is associated with HLA DQ2 in the majority of cases (rest tend to be HLA DQ8)

Question 19

What is the presentation of dermatitis herpetiformis?

Answer 19

There are intensly ithcy small blisters wich upon scratching leave itchy erosions - usually symmetrically on extensor aspect of elbows, knees and forearms, buttocks and scalp

Vesciular rash which leaves erosions

Question 20

How is dermatitis herpetiformis diagnosed? What is seen on biopsy and histology?

Answer 20

Uninvolved Skin biopsy + immunofluorescence

Immunoflourescence reveals granular deposits of dermal papillary IgA against tissue transglutaminase

Hallmark of the condition seen on histology is the presence of dermal papillary microasbcesses - mainly subepidermal disease

Question 21

How is dermatitis herpetiformis treated? Which treatment can be used as a diagnostic tool?

Answer 21

Gluten free diet is essential

Dapsone (a type of antibiotic) is very effective in treating the itch and rash and can be used as a diagnostic tool as failure to respond to dapsone is very rare in this condition

Question 22

What is a recognised complication of coeliac disease / dermatitis herpetiformis? (very rare)

Answer 22

Small increased risk of small bowel lymphoma with coeliac disease and dermatitis herpetiformis

Question 23

Bullous pemphigoid, pemphigus vulgaris, dermatitis herpetiformis * intra or sub epidermal disease? * What is the difference in what is seen on immunoflourescence? * What is attacked?

Answer 23

* Bullous pemphigoid - sub-epidermal bullae with linear IgG at the basement membrane (autoimmune IgG antibodies against bullous pemphigoid antigens 1&2 in the basement membrane and attacks hemidsemosomes)

* Pemphigus vulgaris - intra-epidermal bullae with chicken wire deposition of IgG (autoimmune IgG attacks demsoglein 3 component of desmosomes - results in acanothlysis)

* Dermaittis herpetiformis - sub epidermal bullae with granular IgA in dermal pappilae (autoimmune IgA against tissue transglutaminase)

Question 24

Let’s quickly talk about impetigo - bulllous and non-bullous purely because i had the bullous variant lol What is impetigo? Which type is the most common? What are the features of both? What is the ulcerative form of impetigo known as?

Answer 24

Impetigo is a skin infection caused by staphylococcus aureus

Normally it presents as yellowish crusting on the face, arms or legs +/- vesicles- non-bulllous

Less commonly it can present as fluid filled blisters developing - bullous (>0.5cm in diameter blister)

Ulcerative form is known as ecthyma

Question 25

Impetigo is usually diagnosed based on its appearance. It generally appears as honey-colored scabs formed from dried serum, Where does non-bullous aka contagious impetigo affect? Where does bullous impetigo affect?

Answer 25

Non bullous impetigo typically affects the face

Bullous impetigo typically appears around the groin, axilla, or neck or limbs

Question 26

What is the treatment off impetigo?

Answer 26

IMPETIGO

Localised lesions use topical fusidic acid If lesions are extensive or severe:

* 1st LINE flucloxacillin 500mg qds

* 2nd LINE clarithromycin 500mg bd (5-7 days)

Question 27

LICHENOID DISORDERS The term “lichenoid” derives from a resemblance to a lichen. What is a lichenoid disorder? What are the two commonest types of lichenoid disorder?

Answer 27

A lichenoid disorder is a condition characterised by damage and infiltration between the epidermis and dermis -

The commonest type is lichen planus

Lichenoid drug eruptions are another common type (lichen sclerosus affects the genitals and is discussed in repro)

Question 28

What causes lichen planus?

Answer 28

Lichen planus is caused by T cell mediated inflammation targetting an unkown protein within the skin and mucosal keratinocytes

Question 29

What is the presentation of lichen planus? Where does it affect?

Answer 29

Lichen planus typically appears as Itchy flat topped violaecoeus papules - pruritic, planar, purple papules (also poly-angular)

Seen at any age typically affecting volar wrists/forearms, shins and ankles

Can affect scalp, mouth, genitals

Question 30

Wickham’s striae is often seen in lichen planus What is this?

Answer 30

Wicham’s striae are whitish reticular netwrok visible in the papules of lichen planus and in the buccal mucosa - it shows hypergranulosis (thickening of the granular layer)

Question 31

We now lichen planus typically affects the flexural surfaces of arms/wrists, shins and ankles. and can also affect hair, nails, scalp and genitals What is it called when it can develop in sites of trauma? What other conditions does this occur in?

Answer 31

Lesions often arise in sites of trauma - Keobner’s phenomenon - seen in psoriasis and vitiligo also

Question 32

What do lichenoid drug eruptions look like? What drugs can cause it?

Answer 32

Lichenoid dug eruptions typically resemble lichen planus

Pruritic, planus, purple papules, poly angular (itchy, flat topped, violaceous papules that are poly angular)

Can be caused by eg bblockers, thiazides

Question 33

What is the treatment of lichen planus?

Answer 33

Check if drug precipitant - if so stop drug

Emollients regardless of severity

Potent/very potent (bethametasone valerate (betnovate) / clobetasol proprionate (dermovate)) topical steroids usually given

Or oral steroids if extensive