Description

• Rare, potentially life-threatening autoimmune bullous disease characterized by a loss of cell adhesion and blister formation within the epidermis in the skin and/or the mucosal surfaces
• Flaccid bullae appear spontaneously, which 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. Bullae are tender and painful when they rupture.
• Patient often presents with erosions and no intact bullae.
• System(s) affected: Skin; Gastrointestinal; Genitourinary

Epidemiology

• Most of the patients with autoimmune pemphigus are aged 40–60 years at the onset of the disease (1), which may affect any age group (2).
• Affects both sexes similarly
• Worldwide incidence of pemphigus is 0.75–5 cases/1,000,000/, varying by country (2).

• Uncommon, affects <200,000 people in the US
• Most cases in North America, Europe, and Asia are sporadic, with a higher incidence among Ashkenazi Jews, with an estimate of 1.6/100,000 population per year in Jerusalem (2).

Risk Factors

Genetics
Strong association with certain human leukocyte antigens (HLA), especially HLA DR4, DR14, DQ1, and DQ3, although the susceptibility gene differs depending on ethnic origin.

Pathophysiology

• Autoantibodies (IgG) are directed against desmoglein (Dsg) 1 and 3 adhesion molecules. Desmogleins interact with desmosomes, which hold epidermal cells together. The antibodies against Dsg molecules cause intraepidermal blister formation and acantholysis.
• Dsg3 is expressed in deeper epidermal layers than Dsg1. Dsg3 is found in mucous membranes.
• Patients with limited mucosal disease primarily have autoantibodies directed against Dsg3, whereas those with more extensive cutaneous disease have antibodies directed against both Dsg1 and Dsg3.

Etiology

• Autoimmune; stimulus is unknown.
• Inducing factors include physical trauma, such as thermal burns, UV light, and ionizing radiation; neoplasm, emotional stress, drugs, and infections. Nevertheless, most patients lack a recognized inducing factor.

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