Pemphigus family of disease

Pemphigus is a group of autoimmune blistering diseases of the skin and mucous membranes, which are mediated by IgG autoantibodies against desmogleins (Dsgs), cadherin type cellcell adhesion molecules in desmosomes. Oral and cutaneous blisters and erosions with acantholysis, which is defined as intraepidermal blisters due to the loss of cell-cell adhesion of keratinocytes, are typically observed. For the diagnosis of pemphigus, immunopathological findings of in vivo-bound and circulating IgG autoantibodies directed against the cell surface of keratinocytes are essential. Pemphigus has three major forms: pemphigus vulgaris (PV), pemphigus foliaceus (PF), and paraneoplastic pemphigus (PNP). Patients with PV and PF have IgG autoantibodies against Dsg3 and Dsg1, respectively, while patients with PNP are characterized by autoantibodies against plakin molecules in addition to Dsgs and interface dermatitis suggesting the involvement of cell-mediated cytotoxicity. The relationship between clinical features and antibody profiles in pemphigus are logically explained by the Dsg compensation theory: The intraepithelial expression pattern of Dsg1 and Dsg3 is different between the skin and mucous membranes, and Dsg1 and Dsg3 compensate for each other when they are coexpressed in the same cell. Systemic corticosteroids are the mainstay of therapy for pemphigus, and adjuvant therapies, including immunosuppressive agents, plasmapheresis, high-dose intravenous immunoglobulin, and anti-CD20 monoclonal antibody are used for severe cases.