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In superficial blistering diseases (eg pemphigus vulgaris) these proteins can be targeted and you get superficial blistering The most clinically relevant tends to be the transmembrane proteins desmoglein 1 and 3 In deeper blistering disorders (eg pemphigoid disorders), the split involves the basement membrane zone: The inferior part of basal keratinocytes The basement membrane (lamina lucida and lamina densa) The upper dermis The hemidesmosomes are the collection of proteins involved in keeping the basal keratinocytes attached to the extracellular matrix in the dermis The clinical picture depends on the depth of blistering: High in the epidermis (pemphigus diseases): shallow blisters that often present as erosions rather than intact blisters Around the dermo-epidermal junction (pemphigoid diseases): much more tense blisters At or below the lamina densa : tense blistering that often results in scarring DIFFERENTIAL DIAGNOSIS BLISTERING RASH Blistering Disorders Differential Diagnosis Overview Pemphigus vulgaris Pemphigus foliaceus Paraneoplastic pemphigus IgA pemphigus Bullous pemphigoid Mucous membrane pemphigoid Pemphigoid gestationis Dermatitis herpetiformis Linear IgA disease Epidermolysis bullosa acquisita Epidermolysis bullosa (not acquired form) HSV Herpes zoster Hand-foot-mouth disease Bullous impetigo Staphylococcal scalded skin syndrome Severe cellulitis/necrotising fasciitis Bullous tinea Bullous scabies Contact dermatitis (e.g., severe hair dye allergy) Phyto-photo dermatitis (plant dermatitis) Vesicular hand dermatitis Bullous lupus Severe vasculitis Oedema blisters (e.g., gross oedema in legs) Trauma - burns, friction, scalds Insect bites DIAGNOSTIC APPROACH A standardised approach should include: Clinical assessment : History, examination, disease activity assessment Biopsy for H&E (lesional skin) Biopsy for direct immunofluorescence (peri-lesional skin, within 1cm) +/- Blood tests : Indirect immunofluorescence +/- ELISA SKIN BIOPSY For H&E: Take a 4mm punch biopsy from lesional area containing a bit of blister and surrounding skin Send in standard formalin pot For Direct Immunofluorescence (DIF): Take a 4mm punch from peri-lesional normal skin (within 1cm of active blister) Preferably from non-inflamed skin Send in Michel's medium HISTOLOGY (H&E) H&E by itself can’t give you a full diagnosis but it can give you some clues to the diagnosis based on: Level of split: Subcorneal Intraepidermal Subepidermal Nature of inflammatory infiltrate: Neutrophils Eosinophils Lymphocytes Cell-poor DIRECT IMMUNOFLOURESCENCE (DIF) DIF is the gold-standard diagnostic tool for immunobullous disease It allows us to visualise the immune system attacking the skin by making the autoantibodies glow under a microscope This is performed on tissue from a biopsy Principle: Sample: Performed on a biopsy of perilesional skin Mechanism: Laboratory antibodies "tagged" with fluorescent dye are added to the tissue

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