Immunobullous disease: Bullous pemphigoid, dermatitis herpetiformis, pemphigus

Question 1

What is immunobullous disease?

Answer 1

A group of heterogeneous autoimmune diseases characterised by large cutaneous blistering caused by autoantibodies targeting proteins in the epidermis, basement membrane, and dermis.

Question 2

What is Bullous pemphigoid?

Answer 2

A chronic autoimmune cutaneous blistering disease characterised by subepidermal bullae.

Question 3

What is the typical age of onset for Bullous pemphigoid?

Answer 3

70 years old and above.

Question 4

Is Bullous pemphigoid equally common in men and women?

Answer 4

True.

Question 5

Is Bullous pemphigoid rare in children?

Answer 5

True.

Question 6

What increases the likelihood of drug-induced Bullous pemphigoid?

Answer 6

Younger patients.

Question 7

What are the circulating autoantibodies in Bullous pemphigoid primarily targeting?

Answer 7

Collagen XVII (BP antigen 2 BPAG2) and BPAG1.

Question 8

Where are the antigens targeted by autoantibodies found, in bullous pemphigoid?

Answer 8

On hemidesmosomes, which provide adhesion between epidermis and dermis.

Question 9

Name a type of drug that can induce Bullous pemphigoid.

Answer 9

Sulfur-containing drugs like furosemide, sulfasalazine, and antibiotics like amoxicillin and penicillin.

Question 10

What are the two phases of Bullous pemphigoid?

Answer 10

• Nonbullous phase
• Bullous phase

Question 11

Describe the nonbullous phase of Bullous pemphigoid.

Answer 11

Urticarial and erythematous patches with pruritus.

Question 12

Describe the bullous phase of Bullous pemphigoid.

Answer 12

Multiple fluid-filled or blood-filled, tense bullae that become flaccid after rupture.

Question 13

What type of bases do bullae usually have?

Answer 13

Erythematous, urticarial bases.

Question 14

What can bullae heal without, but may leave behind?

Answer 14

Scarring but can leave postinflammatory hyperpigmentation or milia/milk spots.

Question 15

Where are bullae typically distributed in bullous pemphigoid?

Answer 15

On flexural surfaces on extremities and trunk, usually not on head and neck.

Question 16

Can Bullous pemphigoid involve mucosal membranes?

Answer 16

Yes, eg. oral mucosa with sparing of the lips.

Question 17

What is the Asboe Hansen sign?

Answer 17

Extension of a large blister to adjacent non-blistered skin occurs when pressure is applied.

Question 18

What is the Nikolsky sign?

Answer 18

Rubbing skin causes the upper epidermis to separate from the lower epidermis.

Question 19

What is the gold standard for investigating bullous pemphigoid?

Answer 19

Direct Immunofluorescence (DIF) microscopy from perilesional skin biopsy, showing linear IgG and/or linear C3 deposits along the dermoepidermal junction.

Question 20

What assay identifies anti-BPAG2 and anti-BPAG1 antibodies?

Answer 20

ELISA assay.

Question 21

What does tissue biopsy histology reveal in bullous pemphigoid?

Answer 21

Subepidermal bullae with eosinophilic infiltrate.

Question 22

What is dermatitis herpetiformis?

Answer 22

A chronic autoimmune cutaneous blistering disease strongly associated with coeliac disease.

Question 23

What is the typical epidemiology of dermatitis herpetiformis?

Answer 23

Almost all cases occur with coeliac disease or other gluten-sensitive enteropathy, but can occur without CD.

Question 24

What is the gender prevalence in dermatitis herpetiformis?

Answer 24

Overall more common in men, but more common in female children than male children.

Question 25

What is the typical age of onset for dermatitis herpetiformis?

Answer 25

In the 40s, but can occur at any age.

Question 26

Which ethnic groups are more commonly affected by dermatitis herpetiformis?

Answer 26

More common in Caucasians or North Europeans.

Question 27

What autoimmune conditions are commonly associated with dermatitis herpetiformis?

Answer 27

Common: Hashimoto's thyroiditis, insulin-dependent diabetes.

Question 28

What autoimmune conditions are less commonly associated with dermatitis herpetiformis?

Answer 28

Uncommon: Pernicious anaemia, alopecia areata, SLE, sarcoidosis.

Question 29

What genetic predisposition is involved in dermatitis herpetiformis?

Answer 29

Specific HLA genes involved in processing gliadin antigen.

Question 30

What is the pathophysiology of dermatitis herpetiformis?

Answer 30

Genetic predisposition causes IgA autoantibodies to form in response to gliadin and epidermal transglutaminase expressed by keratinocytes, as well as tissue transglutaminase associated with coeliac.

Question 31

What is the clinical presentation of dermatitis herpetiformis?

Answer 31

Bilateral and symmetrical, grouped vesicles and papules that are extremely pruritic.

Question 32

Where are the lesions of dermatitis herpetiformis typically distributed?

Answer 32

On extensor surfaces, upper back, buttocks, and scalp.

Question 33

What do patients usually present with in dermatitis herpetiformis?

Answer 33

Pinpoint erosions and excoriations due to pruritus, with rarely intact vesicles.

Question 34

What is the gold standard for investigating pemphigus?

Answer 34

Direct Immunofluorescence microscopy from perilesional skin biopsy shows discontinuous, granular deposits of IgA selectively localised in the tips of dermal papillae.

Question 35

What assay identifies epidermal transglutaminase (eTG) IgA autoantibodies?

Answer 35

ELISA assay.

Question 36

What test is used for coeliac disease?

Answer 36

TTG test.

Question 37

What does tissue biopsy histology show in dermatitis herpetiformis?

Answer 37

Subepidermal bullae with neutrophilic infiltrate.

Question 38

What characterizes pemphigus?

Answer 38

Group of chronic autoimmune blistering disorders with blisters on the skin and mucosal membranes.

Question 39

What do circulating IgG autoantibodies target in pemphigus?

Answer 39

Desmoglein 3 (Dsg 3) and desmoglein 1 (Dsg 1), which are antigens on desmosomes.

Question 40

What type of split is seen in pemphigus foliaceous?

Answer 40

Subcomeal split.

Question 41

What type of split is seen in pemphigus vulgaris?

Answer 41

Intrapidermal split.

Question 42

What type of split is seen in bullous pemphigoid?

Answer 42

Subepidermal split.

Question 43

What is the clinical presentation of pemphigus vulgaris?

Answer 43

Skin involvement as many flaccid blisters that easily rupture, leaving weeping and crusting erosions; mucous involvement, commonly oral, presents as ulcers.

Question 44

What is a positive sign associated with pemphigus vulgaris?

Answer 44

Positive Nikolsky's sign.

Question 45

What is acantholysis?

Answer 45

Loss of intercellular connections, e.g., desmosomes, causing loss of cohesion between keratinocytes.

Question 46

What are acantholytic keratinocytes?

Answer 46

Round-shaped cells with desmosomal spines, called 'prickle cells'.

Question 47

What does acantholysis cause?

Answer 47

Intrapidermal vesicles to form (clear spaces between acantholytic keratinocytes).

Question 48

What is pemphigus foliaceus?

Answer 48

A rarer form of pemphigus where only Dsg 1 is targeted, resulting in only skin involvement and no mucosal involvement.

Question 49

What are the characteristics of skin involvement in pemphigus foliaceus?

Answer 49

Involves superficial, smaller blisters that quickly rupture to form crusting erosions.

Question 50

What is paraneoplastic pemphigus?

Answer 50

A very rare malignancy-associated disorder characterized by painful oral erosions and a polymorphic inflammatory rash.

Question 51

What is paraneoplastic pemphigus usually associated with?

Answer 51

Usually associated with lymphoproliferative neoplasm.

Question 52

What is the gold standard investigation for pemphigus?

Answer 52

DIF microscopy from perilesional skin biopsy, which shows IgG autoantibodies deposited on the surface of keratinocytes in and around lesions.

Question 53

What does tissue biopsy histopathology show in pemphigus vulgaris?

Answer 53

Intraepidermal vesicles with acantholysis, characterized by a 'chicken-wire' or 'fish-net' appearance.

Question 54

What does the ELISA assay identify in pemphigus?

Answer 54

It can identify if Dsg 3 or Dsg 1 autoantibodies are present to distinguish between forms.