Pathogenesis: Pemphigus vulgaris is a chronic autoimmune blistering disease in which autoantibodies are directed against the desmosomal plaque. The desmosomal plaque is the most crucial element that holds adjacent keratinocytes in place and juxtaposed to one another. There are other intercellular connections between keratinocytes, including gap junctions, adherens junctions, and tight junctions. The desmosomal plaque is composed of various proteins that act to connect the intracellular actin cytoskeleton of one keratinocyte to that of another; these include various desmoglein, desmocollin, desmoplakin, plakophilin, and plakoglobin proteins. The central portion of the desmosome contains the proteins desmoglein and desmocollin. They are responsible for the tight binding of adjacent keratinocytes. There are many members in each of the desmoglein and desmocollin families.
Autoantibodies to the desmoglein family of proteins, specifically desmoglein 3, are responsible for the formation of pemphigus vulgaris. Antibodies against desmoglein 1 have also been found in patients with pemphigus vulgaris and pemphigus foliaceous.
Histology: Skin biopsies of pemphigus vulgaris shows intraepidermal blister formation. The blisters are formed by acantholysis, and keratinocytes appear to be free floating within the blister cavity. “Tombstoning” may be present. This is the designation given to the basilar keratinocytes that stay attached to the basement membrane zone by their unaffected hemidesmosomes. The basilar keratinocytes appear to be standing up in a row, mimicking tombstones. Immunofluorescence show immunoglobulin G staining in a fishnet pattern throughout the epidermis. Each intercellular connection between keratinocytes is highlighted.
Treatment: Appropriate therapy needs to be instituted as soon as the diagnosis is made. High-dose oral or intravenous corticosteroids have been the mainstay of therapy. However, patients need to be transitioned to a steroid-sparing agent. Many immunosuppressive medications have been used to treat pemphigus vulgaris. The more common ones are azathioprine, mycophenolate mofetil, cyclophosphamide, and the newer agents, intravenous immunoglobulin (IVIG) and rituximab. Morbidity and mortality have been dramatically reduced since the introduction of steroids and steroid-sparing agents.
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