Urban legends: pemphigus vulgaris.

Pemphigus vulgaris (PV) is the most common type of pemphigus. PV pathogenesis is still debated, and treatment remains challenging. We investigated five controversial topics: (1) What are the target antigens in PV? (2) Do desmogleins adequately address PV pathophysiology? (3) How does acantholysis occur in PV? (4) Is PV still a lethal disease? (5) What is the role of rituximab (RTX) in PV treatment? Results from extensive literature searches suggested the following: (1) Target antigens of PV include a variety of molecules and receptors that are not physically compartmentalized within the epidermis. (2) PV is caused by a variety of autoantibodies to keratinocyte self-antigens, which concur to cause blistering by acting synergistically. (3) The concept of apoptolysis distinguishes the unique mechanism of autoantibody-induced keratinocyte damage in PV from other known forms of cell death. (4) PV remains potentially life-threatening largely because of treatment side effects, but it is uncertain which therapies carry the highest likelihood of lethal risk. (5) RTX is a very promising treatment option in patients with widespread recalcitrant or life-threatening PV. RTX's cost is an issue, its long-term side effects are still unknown, and randomized controlled trials are needed to establish the optimal dosing regimen.