Bullous Disorders Flashcards
Skin blistering aetiology
Infection/inflammatory - viral/bacterial, acute dermatitis
Drugs/ toxins - blistering drug eruptions
Congenital - epidermolysis bullosa
Autoimmune - Bullous pemphigoid, pemphigus vulgaris, DH
Trauma - burns/friction/insect bites
Endocrine/metabolic - PCT
Blistering investigations
Infection - bacterial & viral swabs
Porphyria - porphyrin studies
Contact dermatitis - patch testing
Autoimmune - biopsy with IMF
Name the three autoimmune blistering disorders
Bullous pemphigoid
Pemphigus vulgaris
Dermatitis herpetiformis
What autoimmune blistering condition(s) cause superficially, intra epidermal blistering
pemphigus vulgaris
What autoimmune blistering condition(s) cause deep, sub-epidermal blistering
bullous pemphigoid
Dermatitis herpetiformis
how do superficial, intra epidermal blisters appear
Thin roof
Burst easily,
Flaccid vesicles/bullae & erosions
how do deep, sub-epidermal blisters appear
Thick roof
More likely to remain intact,
Itchy erythematous plaques & Fluid filled bullae
What is the pre-bullous stage in bullous pemphigoid
Itchy erythematous plaques and papules
How does bullous pemphigoid present
- Large tense bullae on normal skin or erythematous base
- Typically in flexural regions of trunk or proximal limbs
- Bullae burst to leave erosions (no scarring)
- Usually mucosal membrane is spared
What is the nikolsky sign/ test & when would it be positive vs negative
Nikolsky sign - When lateral pressure on the skin next to the blister causes the blister to extend
Is positive in pemphigus vulgaris & negative in bullous pemphigoid
Who does bullous pemphigoid vs pemphigus vulgaris tend to affect
bullous pemphigoid - elderly
pemphigus vulgaris - Mild aged (40-60)
Bullous pemphigoid pathophysiology
Anti-hemidesmosome antibodies (IgG) react with an antigen of the hemidesmosomes anchoring basal cells to basement membrane - type II hypersensitivity
This results in complement activation and tissue damage & causes interruption of the dermo-epidermal junction and the formation of tense, sub-epidermal blisters that are not readily deroofed
What type of hypersensitivity reaction is bullous pemphigoid & pemphigus vulgaris
Type II hypersensitivity
What is the antibody & antigen in bullous pemphigoid
Anti-hemidesmosome antibodies (IgG)
Hemidesmosomes antigen
Bullous pemphigoid investigations
Biopsy (histology & IMF)
- Biopsy of blistering region & nearby skin
2a. Histology of the bullae (for dermo-epidermal junction)
2b. Immunoflorescence of the nearby skin (for antibodies)
Bullous pemphigoid histology
subepidermal blisters and inflammatory infiltrates (mainly eosinophils) within the blister
Bullous pemphigoid immunoflorescence
shows liner IgG and complement deposited around the basal membrane (of DEJ)
Bullous pemphigoid management
Local disease
- High potency topical steroids at onset of symptoms
Systemic disease
- Oral steroids e.g. prednisolone
+/- tetracycline (steroid sparing agents - anti-inflammatory)
+/- antihistamine (sedating and anti-puritic properties) - If no response - immunosuppression (azathioprine/methotrexate)
Bullous pemphigoid prognosis
Chronic, self limiting
Usually remission within 3-6 months
Pemphigus vulgaris clinical features/ description & location
Flaccid vesicles/bullae affecting skin and mucosal surfaces (eyes, mouth, pharynx, larynx, oesophagus, vulva, rectum)
Pemphigus vulgaris clinical features/ description & location
Flaccid vesicles/bullae affecting skin and mucosal surfaces (eyes, mouth, pharynx, larynx, oesophagus, vulva, rectum)
Pemphigus vulgaris pathophysiology
- Type II hypersensitivity - IgG4 antibodies against desmosomal proteins lead to loss of keratinocyte adhesion in the skin and mucous membranes
- This causes superficial (intra-epidermal) blisters that are easily deroofed, erosions and mucosal ulcers
What is the name for the lysis of intracellular adhesion sites that occurs in pemphigus vulgaris
Acantholysis! - lysis of intercellular adhesion sites
Pemphigus vulgaris antibody & antigen
Antibody - Anti-desmosome IgG antibody
Antigen - Desmosome (intracellular adhesion) antigen
Pemphigus vulgaris investigations
Same as bullous pemphigoid
Pemphigus vulgaris histology
intra-epidermal blister with accumulation of inflammatory cells within the dermis
Pemphigus vulgaris immunofluorescence
chicken wire deposition of IgG within the epidermis
Pemphigus vulgaris treatment
Local disease
- Topical steroids & topical anaethetics
Systemic disease
- High dose oral steroids & immunosuppression
+/- rituximab (biologic)
Pemphigus vulgaris prognosis
Remission usually within 3-6 months
10-20% mortality rate
What autoimmune condition is associated with dermatitis herpetiformis
coeliac disease
Diabetes herpetiformis pathophysiology
- IgA antibodies target gliadin component of gluten but cross react with connective tissue matrix proteins (tissue transglutaminase - TTG)
- Immune complexes form in dermal papillae and activate complement and generate neutrophil chemotaxins → inflammation → subepidermal blisters
What type of reaction is dermatitis herpetiformis & what antibody is involved
Type III hypersensitivity - IgA anti-TTG complexes in dermal papillae
Dermatitis herpetiformis clinical features
Intensely itchy symmetrical lesions & bullae on an erythematous and swollen base
Elbows, knees and buttocks often excoriated
Dermatitis herpetiformis investigations
Anti-TTG
Biopsy with IMF
Dermatitis herpetiformis histology
sub-epidermal blisters with papillary micro-abscesses
Dermatitis herpetiformis immunoflorescence
granular deposits of IgA in dermal papillae
Dermatitis herpetiformis management
Gluten free diet +/- dapsone
Pemphigus vulgaris can be secondary to something else. Name 2 examples
Drug induced: ACEi and Penicillamine
Underlying malignancy as a paraneoplastic phenomenon
Pemphigus vs pemphigoid
Pemphigus - superficial, intra-epidermal (acantholysis)
Pemphigoid - deep, sub-epidermal
