Novel therapies for pemphigus vulgaris: an overview

Pemphigus comprises a group of autoimmune, mucocutaneous blistering disorders. Its principal cause may be a group of antibodies directed against proteins present on the surface of keratinocytes that provide mechanical structure to the epidermis. In the case of pemphigus vulgaris, the characteristic blistering noted just above the basal layer may be triggered by autoantibodies directed against desmoglein 3 (Dsg3). The process by which the binding of these antibodies leads to acantholysis, apoptosis and eventual loss of epidermal function is not completely understood. Current therapies are primarily directed against the formation of these antibodies by suppression of the immune system, and are associated with significant adverse events. As our understanding of the pathophysiology of pemphigus increases, newer therapies have been proposed and evaluated. These novel therapies include intravenous immunoglobulin, plasmapheresis, immunoadsorption, extracorporeal photochemotherapy, biological agents, as well as experimental therapies such as cholinergic receptor agonists, Dsg3 peptides and a p38 mitogen-activated protein kinase inhibitor. Current limitations to the widespread use of these therapies include cost, a lack of consistent data regarding their benefit, limited availability, and the experimental nature of some of the treatments. This review highlights the latest case reports and studies that employ established as well as new therapeutics in a novel way to treat this rare, but serious, disorder.