Pathophysiology
Clinical meaning
Pemphigus vulgaris is caused by IgG autoantibodies directed against desmoglein-3 and desmoglein-1, transmembrane glycoproteins that form desmosomes holding keratinocytes together. When autoantibodies bind desmogleins, they disrupt desmosomal adhesion causing acantholysis (loss of cell-cell connections within the epidermis), producing intraepidermal blister formation. The blisters are characteristically flaccid (soft, easily ruptured) because they form within the thin epidermal layers. A positive Nikolsky sign (lateral pressure on normal skin causes epidermal separation) confirms epidermal fragility. Oral mucosa is typically affected first, with painful erosions preceding skin involvement by weeks to months. Without treatment, mortality exceeds 75% from secondary infection and fluid/protein losses.