Normally the cells of the spinous cell layer are kept together by the desmosomes and a series of extracellular proteins known as cadherins.

PV is an autoimmune disease where the autoantibodies, (IgG) are directed against the extracellular protein desmoglein 3 which is one of the cadherins. Desmoglein 3 is treated as an antigen and this process produces the separation of the cells of the spinous cell layer with consequent formation of vesicles and bullae. The process of destruction (lysis) of the intercellular connections (desmosomes) of the epithelial cells is known as acantholysis. The union between epithelium and connective tissue is not affected in PV.