DermatologyTier 2Disease (DEADMAN)

Autoimmune bullous disease - pemphigus vulgaris

Description

Pemphigus vulgaris - an autoimmune blistering disease from IgG autoantibodies against desmoglein 3 (and often desmoglein 1), the desmosomal adhesion proteins holding keratinocytes together - causing intraepidermal blistering distinct from the subepidermal blistering of pemphigoid

Rare but more severe than bullous pemphigoid, with a peak onset in middle age; historically had very high mortality before corticosteroids/immunosuppression became available

Anti-desmoglein antibodies disrupt keratinocyte cell-cell adhesion (acantholysis) - producing fragile, flaccid blisters that rupture easily, leaving painful erosions rather than intact tense bullae
Mucosal involvement is prominent and often the presenting feature (oral erosions frequently precede skin involvement by weeks-months) - reflecting predominant desmoglein 3 expression in mucosal epithelium versus desmoglein 1's predominance in superficial skin

Flaccid, easily ruptured blisters with widespread painful erosions; positive Nikolsky sign (gentle lateral pressure on intact skin causes epidermal separation) - reflects the fragile intraepidermal split
Direct immunofluorescence of perilesional skin shows an intercellular "chicken-wire" IgG/C3 pattern; serum anti-desmoglein antibody titres (ELISA) correlate with disease activity and are used for monitoring

Systemic corticosteroids first-line for inducing remission, given the severity/mortality risk of untreated disease
Rituximab has strong trial evidence as an effective steroid-sparing agent, increasingly used earlier (including first-line in combination with corticosteroids) given superior outcomes compared with corticosteroid monotherapy in randomised trials
Additional steroid-sparing agents (azathioprine, mycophenolate) as alternatives; supportive wound care for extensive erosions

Oral mucosal erosions (often the presenting feature), other pemphigus variants (pemphigus foliaceus - more superficial, desmoglein 1 only, no mucosal involvement), thymoma/malignancy-associated paraneoplastic pemphigus (a distinct, more severe variant)

Pemphigus vulgaris was essentially universally fatal before corticosteroid treatment became available; with modern immunosuppression (particularly the shift toward earlier rituximab use) mortality has fallen substantially, though the disease still carries significant morbidity and requires prolonged treatment

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