Blistering Conditions

Question 1

How do you categorise Bullous disorders?

Answer 1

• Genetic - rare
• Acquired
  
  • Rare - Immunobullous - affecting epidermis or dermo-epidermal junction.
  • Common - non-immunobullous

Question 2

What are some non-immunobullous causing of blistering?

Answer 2

• Herpes Simplex
• Herpes Zoster
• Bullous impetigo
• Insect Bites
• Burns - friction, cold, hot.
• Pompholyx
• Acute contact dermatitis
• Drugs Reactions
  
  • Erythema Multiforme
  • Steven Johnson Syndrome
  • Toxic Epidermal Necrolysis.

Question 3

How do you know if you are dealing with a immunobullous disorder that is attacking below the epidermis?

Answer 3

• Milia or scarring can occur.
• The epidermis forms a “roof” or “blanket” over the blister causing it to be tense.

Question 4

What Immunoglobulins are form against the skin to form autoimmune bullous conditions?

Answer 4

IgG is the most common

And then IgA

Question 5

What is the extra test (Apart from H&E histology) that is used to differentiate between autoimmune bulous disorders?

Answer 5

Immunolfuoresence

It is a method of detecting autoantibodies.

Question 6

What is the workup for blistering conditions?

Answer 6

1. Biopsy of skin
2. H&E histology
3. Send some perilesional skin for Direct IMF.
4. Consider sending some serum for indirect IMF.

Question 7

Tell me the difference between direct and indirect immunofluorescence (DIMF vs IIMF) and how immunofluorescenec applies to autoimmune bullous conditions?

Answer 7

• Direct Immunofluorescence needs a biopsy
  
  • Fluoresces green.
• Indirect Immunofluorescence needs a plasma sample.
  
  • Useful if disease activity or response to therapy needs to be evaulated or if biopsy can’t be taken.
• Immunofluorescence allows us to see if autoantibodies are being produced and thus see if the condition is an autoimmune bullous condition or not.
  *

Question 8

What do the autoantibodies target in Pemphigus?

Answer 8

Desmosome - the glue that sticks the epidermal cells together.

They specifically target Desmolein 1 & Desmoglein 3 of the Desmosome.

Question 9

What is the name for the crumbling of the epidermal cells in Pemphigus?

Answer 9

ACANTHOLYSIS

Question 10

Describe Nikolsky’s sign

Answer 10

It is when a finger is placed over or next to the bullous

Then dragged gently along the skin and part of the epidermis comes off.

It is seen in conditions with epidermal fragility like PEMPHIGUS VULAGARIS

Question 11

Why are oral ulcers seen in Pemphigus Vulgaris and not Pemphigoid?

Answer 11

Because Desmoglein 3 is found in the oral mucosa and PV targets Desmoglein 1 and 3.

Question 12

What is this on H&E Histology?

Answer 12

Pemphigus Vulgaris-

split occurs within the epidermis just above the Basement Membrane Zone (suprabasal)

Question 13

What condition is this on Direct Immunofluorescence?

What is the name of the appearance called?

Answer 13

Pemphigus Vulgaris

You can see the IgG in the intercellular glue attacking desmogleins 1 & 3

Chicken-Wiring

Question 14

What are the 4 types of Pemphigus?

Answer 14

• Pemphigus VULAGARIS(most common)-autoantibodies to Desmogelins 1 & 3.
• Pemphigus FOLIACEUS- autoantibodies to Demoglein 1 - oral & mucosal involvement doesn’t occur
• Pemphigus VEGETANS- autoantibodies just to Desmogleins 3
  
  • Flaccid blisters heal to leave warty plaques in the fissures.
• PARANEOPLASTIC Pemphigus - persistent oral ulceration on the vermillion border with stomatitis.

Question 15

How do you treat Pemphigus Vulgaris?

Answer 15

• Initially high dose Prednisolone 60-80mg OD.
• Then replace with azathioprine, Mycophenate Mofetil, cyclophosphamides or plasmapheresis.
• Rituximab (B-Cell Depleter) - soon to be the first line agent.
• Referral to dermatologist is mandatory.

Question 16

How can you remember which layers of the skin are affected by Pemphigus and Pemphigoid?

Answer 16

PemphiguS = Superficial

PemphigoiD = Deep

Question 17

What is the pathophysiology of Bullous Pemphigoid?

Answer 17

IgG autoantibodies target antigens in the Basement Membrane Zone(BMZ) at the Dermo-Epidermal Junction.

C3 is then deposited at the BMZ.

(Direct IMF shows this on immunofluorescence)

Question 18

In Bullous Pemphigoid, what % of cases are positive for IgG using indirect IMF?

Answer 18

70%

Question 19

What drugs cause Bullous Pemphigoid?

Answer 19

• ACE Inhibitors
• Diuretics
• Antibiotics

Question 20

Does drug induced bullous pemphigoid more likely occur in younger or older people?

Answer 20

Younger people

Question 21

How do you manage Bullous Pemphigoid?

Answer 21

• Biopsy for H&E & Direct IMF.
• Indirect IMF can also be sent.
• Treat secondary infection.
• Superpotent topical steroids if localised.
• Usually admitted to hospital and put on oral sterids.
• Oral steroids are tapered and replaced with steroid sparing agents.
• Minocycline or Nicotinamide can be helpful.

Question 22

What is the typical presentation in Bullous Pemphigoid?

Answer 22

• Elderly patients
• Either:
  
  • Pre-Bullous Phase: Urticated lesions & Pruritus.
  • Bullous Phase: Typical tense Bullae on an erythematous urticated base.

Question 23

If you see Bullous Pemphigoid with oral involvement, what should you consider?

Answer 23

If there is an underlying cancer.

Question 24

What are 2 other types of Pemphigoid to be aware of?

Answer 24

• Cicatricial Pemphigoid (aka mucous membrane pemphigoid).
  
  • Multiple aggresive oral ulcers in middle age.
  • Associated with HLAB12.
• Pemphigoid or Gestationis - Bullous Pemphigoid in Pregnancy.
  
  • Usually in the 2nd or 3rd trimester but can be post-partum.
  • Usually start around and involve the umbilicus.
  • Neonate will blister for a few weeks.
  • Managed by Dermatologists and Obstetricians
  • Oral steroids are usually required.
  • Pt’s are to avoid the COCP in the future as this can trigger Pemphigoid.

Question 25

What condition is this?

Answer 25

**Epidermolysis Bullosa Acquisita (EBA)** **IgG Autoantibodies** attack **Type 7 Collagen**. Skin bilstering and milia form usually **in the hands** and **extensor surfaces**.

Question 26

What is Epidermolysis Bullosa Acquisita (EBA) associated with?

Answer 26

* Inflammatory Bowel Disease * Haemtological Malignancies * Myeloma * Lymphoma

Question 27

In Epidermolysis Bullosa Acquisita (EBA), what does the histology show?

Answer 27

* **Subepidermal blister** * **IMF** shows linear **IgG** at the **BMZ**.

Question 28

What other test can be used to differentiate between **Epidermolysis Bullosa Acquisita (EBA)** and **Cicatricial Pemphigoid**?

Answer 28

**Salt-Split Skin Test** * The Fluorescent-labelled skin biopsy is **immersed in** **saline**. * This causes the **lamina lucida to split**. * If **EBA** - the split occurs on the **dermal** side of the split. * If **Cicatrical Pemphigoid** - the split is on the **epidermal** side of the split.

Question 29

**Porphyria Cutanea Tarda** can look like **Epidermolysis Bullosa Acquisita** (EBA). How can you tell the **difference** betweeen the two conditions?

Answer 29

**Histology** will be **negative** in **Porphyria** **Cutanea Tarda**.

Question 30

How does Linear IgA disease manifest clinically?

Answer 30

It presents as a group of **blisters** around the **genitalia**, **umbilicus** and on the **face**.

Question 31

This is IgA disease, what is this feature called?

Answer 31

String of Pearls Sign A group of blisters around the edge of an annular configuration.

Question 32

What is seen in immunofluorescence in Linear IgA Disease?

Answer 32

Immunofluorescence shows IgA deposition at the dermo-epidermal junction

Question 33

How is Linear IgA disease similar but different to Bullous Pemphigoid in its clinical manifestation?

Answer 33

**Similar** = **thick** bullae at the **subepidermal** level **Different** = **IgA** **disease** **affects** the **mucous** **membranes** whereas Bullous Pemphigoid dosesn't.

Question 34

What drugs can cause Linear IgA Disease?

Answer 34

* Vancomycin * Penicillin Antibiotics * Antihypertensives (e.g. captopril) * Anticonvulsants (Linear IgA disease settles once the drugs are stopped)

Question 35

How is Linear IgA Disease treated?

Answer 35

**Dapsone** **Colchicine** may occasionally be needed. It improves spontaneously after **3-4 years** without medication

Question 36

What areas of the body are usually affected by **dermatitis** **herpetiformis**?

Answer 36

Skin around the buttocks, elbows and scalp.

Question 37

What disease is dermatitis herpetiformis associated with?

Answer 37

Coeliac Disease

Question 38

What are the histological findings in dermatitis herpatitis?

Answer 38

IgA is deposited in the skin

Question 39

People with dermatitis herpetiformis have an increased risk of what condition?

Answer 39

Lymphoma

Question 40

Who usually gets dermatitis herpetiformis?

Answer 40

Middle aged men | (but women can get it too)

Question 41

What condition is this?

Answer 41

Dermatitis Herpetiformis

Question 42

What is the treatment for dermatitis herpetiformis?

Answer 42

Gluten Free Diet Dapsone is also useful

Question 43

If someone has dermatitis herpetiformis, what antibodies should be tested for to help confirm the condition?

Answer 43

* Anti-Gliadin antibodies * Anti-Endomysial Antibodies

Question 44

Summarise the Diagnosis of Blistering Disorders

Answer 44

1. Is the patient an infant or child? * **Infant** - think genetic causes of blistering. Consider Epidermolysis Bullosa Acquisita (**EBA**) * **Child** - Consider **Bullous** **Impetigo if crusted and rupture easily**. If they are grouped vesicles in rings, consider **chronic** **bullous** **disease** **of** **childhood** - take a biopsy for histology and Direct-IMF. 2. In **adults** * **Tense** **Bullae** * Pregnant - consider Pemphigoid Gestationis. * Elderly - Bullous Pemphigoid * **Flaccid** **Bullae** that rupture easily - Pemphigus Vulgaris * **Grouped** **Itchy** **vesicles** on elbows, buttocks or knees. = consider Dermatitis Herpetiformis.