Description

• Rare, potentially fatal autoimmune mucocutaneous blistering disease due to loss of keratinocyte to keratinocyte adhesion that involves the skin and the mucous membranes
• Flaccid, painful, nonhealing bullae, pustules, or ulcerations that appear spontaneously on the skin and mucosal surfaces, typically begin in the oropharynx, and then may spread to the skin, having a predilection for the scalp, face, chest, axillae, groin, and pressure points
• Patient often presents with erosions and no intact bullae.
• System(s) affected: skin, GI, genitourinary

Epidemiology

Incidence

• Disease of the middle-aged population, typically occurring after the age of 50 years, although some cases have been reported in younger adults and children
• Affects both sexes equally
• 0.1 to 3.2 cases per 100,000 individuals annually worldwide

Prevalence

• Uncommon, affects <200,000 people in the United States
• Seen more frequently in people of Mediterranean decent and Ashkenazi Jew

Etiology and Pathophysiology

• Autoantibodies (IgG) are directed against desmoglein (Dsg) 1 and 3 adhesion molecules. Dsgs interact with desmosomes, which hold epidermal cells together. The antibodies against Dsg molecules cause intraepidermal blister formation and acantholysis.
• Dsg 3 is predominantly expressed in oral epithelium, whereas both Dsg 1 and Dsg 3 are expressed in the skin.
• Dsg 1 is expressed more intensely in the superficial layer, whereas Dsg 3 is found more abundantly in basal and suprabasal layers.
• Additionally, autoantibodies against Dsg 4, the acetylcholine receptor, and pemphaxin have been identified in patients with PV. The exact pathogenesis of pemphigus has yet to be fully explained and is likely a “multiple hit” process. Autoimmune; stimulus is unknown.
• Inducing factors include physical trauma, such as thermal burns, UV light, and ionizing radiation; neoplasm; emotional stress; drugs; and infections. Most patients lack a recognized inducing factor.

Genetics
Strong association with certain human leukocyte antigens (HLAs), especially HLA-DR4, HLA-DR14, HLA-DRB1, HLA-DQB1, HLA-DQ1, and HLA-DQ3, although the susceptibility gene differs depending on ethnic origin. >95% of patients will test positive for HLA-DR4 and/or HLA-DR6 haplotypes.

Commonly Associated Conditions

• Thymoma
• Myasthenia gravis
• Paraneoplastic pemphigus is a type of pemphigus defined by the fact that the patient has a malignancy at the time the pemphigus is diagnosed.
• Gastric adenocarcinoma