Bullous Disorders
On this page
Direct answer
Pemphigus vulgaris is intraepidermal (suprabasal) blistering from IgG against desmoglein 3, giving flaccid blisters, mouth erosions that precede skin disease, a positive Nikolsky sign and intercellular fishnet immunofluorescence; bullous pemphigoid is subepidermal blistering from IgG against the hemidesmosomal antigens BP180 and BP230 of the basement membrane zone, giving tense bullae that do not involve the mouth, a negative Nikolsky sign and linear immunofluorescence along the basement membrane. That single pair — level of split plus immunofluorescence pattern — carries more examination marks than the rest of the vesiculobullous chapter together, and dermatitis herpetiformis completes the trio with granular IgA at the dermal papillae and its silent coeliac association.
What you must remember
- Pemphigus vulgaris: flaccid blisters that rupture easily, leaving denuded erosions; oral lesions in nearly all patients and often the first sign; acantholysis (separated rounded keratinocytes) with a suprabasal split and a tombstone row of basal cells clinging to the dermis.
- Immunofluorescence pair: pemphigus — intercellular (fishnet) IgG/C3 in the epidermis; pemphigoid — continuous linear IgG/C3 along the basement membrane zone; this is the classic spotter.
- Pemphigus foliaceus: superficial split at the granular layer from anti-desmoglein 1; skin only, no mucosal involvement — because mucosa expresses desmoglein 3 as its main adhesion molecule even without desmoglein 1.
- Bullous pemphigoid: elderly patients, tense, intact bullae on flexures; may follow drugs; self-limited over years and far more benign than pemphigus; treat with topical or systemic steroids.
- Dermatitis herpetiformis: intensely itchy grouped vesicles on elbows, knees and buttocks; neutrophil microabscesses at the tips of dermal papillae; granular IgA along the basement membrane; almost all patients have coeliac disease, and dapsone relieves itch within days.
- Linear IgA disease: subepidermal blister with linear IgA — the childhood form (chronic bullous disease of childhood) gives a jewel-like ring of vesicles.
- Epidermolysis bullosa group: inherited mechanobullous disorders — junctional forms involve laminin-332, the severe dystrophic form involves type VII collagen (anchoring fibrils), and the acquired type (epidermolysis bullosa acquisita) is autoimmune against the same antigen.
- Nikolsky sign: firm sliding pressure shears the fragile epidermis of pemphigus (and toxic epidermal necrolysis); it is negative in the tense bullae of pemphigoid.
Reading one biopsy in two planes
A 42-year-old woman has had painful mouth erosions for two months and now develops flaccid blisters on the trunk that break at the slightest touch. The biopsy is taken from the edge of a fresh blister, and the report reads: suprabasal cleft with acantholytic cells, basal layer attached to the dermis. Direct immunofluorescence on perilesional skin shows IgG outlining every keratinocyte — the fishnet. Pemphigus vulgaris; the antibodies have glued apart the desmosomal junctions just above the basal layer, and because mucosal epithelium depends on desmoglein 3 alone, the mouth suffered first. Treatment is high-dose corticosteroids with a steroid-sparing agent such as azathioprine or rituximab, and mortality, once near-universal, is now low.
Compare the 74-year-old down the ward with tense, dome-shaped bullae on the groins and inner thighs, intact roofs, no mouth involvement and normal-looking skin between blisters. Histology: subepidermal blister with eosinophils; immunofluorescence: smooth linear IgG and C3 along the basement membrane. Bullous pemphigoid — the antibodies sit below the whole epidermis, at the hemidesmosome, so the entire thickness of epidermis lifts off as a tense roof. The lesson generalises: the antigen's anatomical address determines the blister's depth, the blister's depth determines flaccid versus tense, and tense versus flaccid nearly determines the diagnosis before any immunofluorescence is ordered.
Where marks are lost
The commonest lost mark is calling pemphigus vulgaris a disease of the basement membrane — the split is suprabasal, intraepidermal, and the basement membrane stays intact on the dermal floor. The desmoglein pairs are shuffled under pressure: foliaceus is desmoglein 1 (superficial, skin-only), vulgaris is desmoglein 3 (deep, mucosa-involving) — anchor with "3 goes deeper and to the mouth". Dermatitis herpetiformis is described as an autoimmune blistering disease alone; the examiner's follow-up is the coeliac association, and the candidate who adds that these patients need gluten restriction to control the skin (dapsone only buys time) has taken the full mark.
Frequently asked questions
At which level does the blister form in pemphigus vulgaris?
Just above the basal layer (suprabasal), through acantholysis — separated, rounded keratinocytes litter the blister cavity.
What does direct immunofluorescence show in pemphigus and pemphigoid?
Pemphigus: intercellular fishnet IgG/C3 in the epidermis; pemphigoid: linear IgG/C3 along the basement membrane zone.
Why does pemphigus foliaceus spare the mucosa?
Its antigen is desmoglein 1, expressed mainly in superficial skin; oral mucosa relies on desmoglein 3, which remains intact.
Which bullous disorder is associated with coeliac disease?
Dermatitis herpetiformis — granular IgA at the dermal papillae with intensely pruritic grouped vesicles; dapsone gives rapid symptomatic relief.
What is epidermolysis bullosa acquisita?
An acquired, autoimmune subepidermal blistering disease against type VII collagen of anchoring fibrils, mimicking pemphigoid but tending to scar and resisting steroids.
What is the Nikolsky sign and in which two conditions is it positive?
Sliding pressure dislodging the epidermis — positive in pemphigus vulgaris and toxic epidermal necrolysis, negative in the tense bullae of pemphigoid.