Blistering mucocutaneous autoimmune disease affecting the skin, oral cavity and other mucosal areas.
An acquired autoimmune disorder with autoantibodies.
Rare and potentially fatal autoimmune blistering disease with an incidence of 0.1 to 0.5 per 100,000 people per year.
Characterized by suprabasal and intra-epidermal blisters and skin erosions.
PV most common variant of pemphigus disorders.
PV the most common form of pemphigus in the US and Europe.
Annual incidence 1-5 per million population per year in the US.
Rare in young.
Oral lesions initial manifestation in about 50% of cases.
Associated with intraepidermal vesicles with acantholysis and intact basal layer.
Loss of integrity of normal intercellular attachments within the epidermis and mucosa epithelium.
Occurs primarily in the fourth and sixth decades of life.
Genders equally involved, with perhaps slight female prevalence.
Of the four types of Pemphigus, vulgaris is the most common accounting for 80% of cases involving the mucosa and skin, especially the scalp, face axilla groin, trunk and pressure points.
Epithelial disruption mediated by IgG autoantibodies.
Blisters occur in epidermis and mucous membranes where IgG autoantibodies target 3different proteins of the desmosomes Dsg 1, Dsg 3, and Dsg4.
Desmogleins are calcium binding transmembrane glycoproteins that bind and stabilize keratinocytes.
Dsg3 is primarily located in the suprabasal layer associated with both the mucosal and skin layers and Dsg1 is found in the intraepidermal layer in the superficial epithelium.
Patients have antibodies to desmoglein 3.
Anti-Dsg3 auto antibodies are pathogenic in pemphigus vulgaris and corresponds to disease activity.
The phenotype depends on the presence of auto antibodies against the DSG1, Dsg3 or both.
Autoantibodies, usually IgG type, directed against desmoglein an adhesion molecules.
Autoantibodies interfere with the intercellular cement that holds epidermal cells together and results in intraepidermal blister formation.
Like other autoimmune diseases it can be associated with an increased risk of thrombosis.
Increased risk of venous thrombosis is probably due to high titer of autoantibodies against desmogleins, and treatment with high dose steroids is also associated with an increased risk of VTE.
Results in superficial blisters that rapidly rupture and results in in painful ulcerations.
Typically oral lesions precede cutaneous blisters, which develop into erosions.
Patients with limited mucosal disease primarily have autoantibodies directed against desmoglein3, while those with more extensive cutaneus disease or with paraneoplastic pemphigus may have both anti-Dsg 3 and anti-Dsg1 antibodies.
Patients with pemphigus foliaceus Lesions involving only the skin, have only anti-DSg1antibodies.
All areas of the oral cavity can be involved, but the soft palate , buccal mucosa, and gingiva are predominantly affected.
Usually oral soreness present for months before seeking care.
Increased tissue frailty with any oral trauma.
Nikolsky sign, which is a lesion formed after mechanical pressure on affected tissue, is a diagnostic tool.
Differential diagnosis includes lichen plants, mucous membrane pemphigoid, epidermolysis bullosa, IgA disease, lupus erythematosus, erythema multiforme, and graft vs host disease.
Corticosteroids reduce risk of death.
Standard treatment utilizes corticosteroids and immunosuppressive agents.
Utilization of corticosteroids and immunosuppressive agents long term associated with increased risk of death.
Long term remissions can be achieved with the use of intravenous immune gamma globulins.
Combination of intravenous immune globulin and rituximab effective in the management of patients with disease refractory corticosteroids and immunosuppressive agents.
Control of disease associated with reduction in pathogenic IgG4 antikeratinocyte antibodies.