Blistering Skin Disorders

Question 1

What causes blisters?

Answer 1

Traumas- BurnsWhat
Infections- Impetigo, HSV, VZV
Auto-antibodies
Genetic diseases

Question 2

What happens when a blister forms?

Answer 2

There is separation of the dermis and epidermis

Question 3

What is bullous pemphigoid?

Answer 3

Bullous pemphigoid is a blistering disorder of the skin

Question 4

What does the fragility of blisters depend upon?

Answer 4

The fragility of blisters depends upon their location in the skin:

• Intra-epidermal blisters (within the epidermis) are ruptured easily
• Subepidermal blisters (between the epidermis and the dermis) cause blisters to be less fragile

Question 5

If a blister if fragile where is it likely to be found?

Answer 5

Within the epidermis- intra-epidermal

Question 6

What causes bullous pemphigoid?

Answer 6

Auto-antibodies against antigens between the epidermis and the dermis which causes a sub-epidermal split in the skin. Type II hypersensitivity reaction

Question 7

How does bullous pemphigoid present?

Answer 7

Tense, Fluid Filled Blisters
Erythematous base
Lesions are often itchy (as there is mast cell degranulation)
Usually affects the trunk and limbs

Question 8

Which age group is bullous pemphigoid common in?

Answer 8

Elderly people- average age of onset is above 70

Question 9

Where do blisters form in bullous pemphigoid and pemphigus vulgaris?

Answer 9

Between the epidermis and the dermis (think D in pemphigoid is for deep)

In Pemphigus vulgaris blisters are in the epidermis, intra-epidermal blisters, which are fragile. (think S in pemphigus is for superficial)

Question 10

What are the common sites for bullous pemphigoid?

Answer 10

Lower abdomen
Inner forearms and
Anterior surface of the thighs

Doesn’t typically involve the mucosa unlike pemphigus vulgaris which commonly affects the mucosal areas and this can precede skin involvement

Question 11

How can bullous pemphigoid be differentiated from pemphigus vulgaris clinically?

Answer 11

Pemphigus vulgaris causes superficial intra-epithelial blisters which are much more fragile than the sub-epidermal blisters seen in bullous pemphigoid

Nikolsky’s Sign will likely be positive in pemphigus vulgaris, blisters will deroof with gentle rubbing of the skin. This does not happen in bullous pemphigoid.

Question 12

What causes bullous pemphigoid?

Answer 12

Not-fully understood but it is an autoimmune disease as auto-antibodies are produced against the components holding the dermis and the epidermis together.

Question 13

What are the features of bullous pemphigoid?

Answer 13

Non-specific rash before blisters develop
Urticaria like red skin (as there is mast cell degranulation)
Small blisters
Clear or cloudy, yellowish blood stained blister fluid
Post-inflammatory pigment changes
Typically trunk, inner arms, anterior thigh and areas of skin fold

Note- Bullous pemphigoid rarely affects the mucosal surfaces, unlike pemphigus vulgaris

Question 14

What other skin condition is bullous pemphigoid more likely to develop with?

Answer 14

Psoriasis- and can be precipitated by patients undergoing phototherapy for psoriasis

Question 15

What are some complications of bullous pemphigoid?

Answer 15

Secondary infection:

• Bacterial: Staph, Srep (could cause bacteremia and sepsis)
• Viral: HSV, VZV, Herpes Zoster (reactivation of VZV from latent state)

Question 16

How is bullous pemphigoid diagnosed?

Answer 16

History and examination
Skin biopsy- immunofluorescence can show to auto-antibodies, split may be visible between the dermis and the epidermis on microscopy (may also show inflammatory cell infiltrate)
Blood Test- Autoantibody: Anti BP180

Question 17

What auto-antibody causes bullous pemphigoid in the majority of cases?

Answer 17

Anti BP180 (Can be tested for in the blood)

Less commonly Anti BP230

Question 18

What is the management of bullous pemphigoid?

Answer 18

General Measures-
Wound dressing for blisters and erosions,
Monitor for signs of infection (e.g FBC, CRP, ESR, Visible signs)
Analgesia to reduce pain from blisters

Topical therapies for localised disease- Highly Potent Topical steroids (e.g. clobetasol propionate)

Oral therapies for widespread disease- Steroids, Steroid sparing agents (e.g. ciclosporin, azathioprine, methotrexate)

Antibiotics if signs of secondary bacterial infection
Sedating antihistamines if itch is very problematic

Most patients are given oral steroids, Steroids are often given in combination with steroid sparing agents and antibiotics to reduce the risk of infection and SEs from steroids

Question 19

Many patients are given oral steroids for bullous pemphigoid, what should these be combined with?

Answer 19

Steroid sparing agents- e.g. azathioprine, methotrexate, mycophenolate mofetil
Antibiotics- to reduce the risk of secondary infection

Question 20

What is pemphigus vulgaris?

Answer 20

This is an auto-immune blistering disease that causes blisters to form within the epidermis. The blisters are therefore fragile and easily broken. Blisters are found in both the skin and the mucous membranes, commonly inside the mouth.

Question 21

Where does pemphigus vulgaris affect?

Answer 21

The skin and the mucous membranes

Question 22

What age group is usually affected by pemphigus vulgaris?

Answer 22

Middle aged people- 30 to 60 years

More common in Jewish people and Indian people

Question 23

What drugs have been found to induce pemphigus vulgaris?

Answer 23

Penicillamine
ACEi
ARBs
Cephalosporins

Question 24

What antibodies have been found to cause pemphigus vulgaris?

Answer 24

Anti- DSG1 antibodies (Attack desmogleins)

Note in Bullous Pemphigoid it is Anti-BP180

Question 25

What are the features of pemphigus vulgaris?

Answer 25

Blisters are flaccid and fragile (unlike Bullous pemphigoid where they are tense and less fragile) Blisters easily rupture forming erosions and crust Itching Lesions are often painful Common locations include- upper chest, back, scalp and face Oral lesions may be the first presentation with skin blisters developing alter

Question 26

What might be the first sign of pemphigus vulgaris?

Answer 26

Oral lesions/blisters in the mouth. These are often painful, slow to heal ulcers. Cause difficulty eating and drinking. Note- spread to the larynx causes hoarseness whilst eating.

Question 27

What are some complications of pemphigus vulgaris?

Answer 27

``` Secondary infection: Fungal- esp in mouth Bacterial- Staph and Strep Viral- HSV Nutritional deficiencies due to difficulty eating Bacteremia Complications of treatment Psychological impact of a skin disorder ```

Question 28

How is pemphigus vulgaris diagnosed?

Answer 28

History and examination (look in mouth too) Skin Biopsy- Immunofluorescence, Microscopy will show lesions within the epidermis (also helps to rule out other causes of blistering). Blood test- For Anti- DSG1, DSG3

Question 29

How is pemphigus vulgaris managed? Divide answer into general measures, systemic and topical.

Answer 29

``` Generally Measures Dressings and emollients to prevent loss of moisture Protect the skin from trauma and infection (aseptic technique should be used for changing dressings) Antiseptic creams/washes Nutritional support if needed Monitor fluid status Analgesia Monitor for infection. ``` Systemic Treatments (as mucosal involvement is common these are mostly systemic) Corticosteroids Steroid sparing agents: Methotrexate, Azathioprine, Mycophenolate Mofetil, Cyclophosphamide, Rituximab (Anti-B Cell), Infliximab (Anti-TNF alpha) IVIg, Plasmapheresis Topical Treatments for Cutaneous Forms: Topical Steroids Topical Tacrolimus

Question 30

Where can mucosal involvement cause issues in pemphigus vulgaris?

Answer 30

Genitals- Painful sexual intercourse Eyes- Sore, red eye (refer to opthamologist) GI- Diarrhoea and abdominal pain Nose- Stuffiness and bleeding Oral ulcers (most common)- painful when eating

Question 31

How and why is good oral hygiene encouraged in pemphigus vulgaris?

Answer 31

5-70% of patients develop blisters in the mouth that go on to ulcerate. There is a big increased risk of secondary infection. Patients should use soft toothbrushes, steroid sprays and antiseptic mouthwashes. If oral candida develops this requires anti-fungal treatment.

Question 32

What infection caused by staph aureus may cause blistering?

Answer 32

Bullous impetigo causes the development of painless, fluid filled blisters- mostly on the arms, legs, trunk Sometimes surrounded by red and itchy skin They are not painful

Question 33

What is dermatitis herpetiformis? Which condition is it associated with?

Answer 33

It is an autoimmune condition that causes blisters to form which is linked to Coeliac Disease. There is persistent blistering skin eruption that is intensely itchy.

Question 34

What condition is dermatitis herpetiformis associated with?

Answer 34

Coeliac disease- gluten allergy

Question 35

What are the features of dermatitis herpetiformis?

Answer 35

Intensely itchy rash Small red spots Very small fluid filled blisters/vesicles Wheals- raised, oedematous, red/pink/white areas (appear due to mast cell degranulation) Symmetrical distribution Blisters are often eroded and there is crusting as they are often scratched off due to intense itch Sx of coeliac disease

Question 36

What sites are commonly involved with dermatitis herpetiformis?

Answer 36

``` Back of the elbows Fronts of the knees Scalp Bottom Back ```

Question 37

What age group does dermatitis herpetiformis commonly affect?

Answer 37

15-40 years

Question 38

How is dermatitis herpetiformis diagnosed?

Answer 38

History and Examination Skin Biopsy of a lesion- Immunofluorescence can reveal the autoantibodies Bloods- Coeliac Screen- Total IgA, Anti-Gliadin, Anti-endomysial, Anti-TTG (IgA) Check for nutritional deficiencies due to coeliac process: FBC, U+Es, LFTs, CRP, ESR, B12 (Absorbed as complex with intrinsic factor in the terminal ileum), Folate, Iron studies, Calcium, TFTs (association with auto-immune thyroid disease)

Question 39

What is the management for dermatitis herpetiformis?

Answer 39

Gluten free diet, refer to a dietician. Topical Medication- Steroid creams to settle initial skin symptoms and control mild flares Oral medications- - Dapsone: sulfonamide antibiotic that has been found to reduce the itching. Can cause drop in RBC and Hb (blood test monitoring, performed weekly inititally) - Others options include steroids

Question 40

Dapsone is a medication that may be given in the management of dermatitis herpetiformis, what does it do and what needs to be monitored?

Answer 40

Dapsone can reduce itching However, it can lower red cell count and HB so requires monitoring for this. Initially weekly blood tests are taken. Patient should report any blue fingers or lips, infections, sore throat or unexplained bruising.