Pemphigus vulgaris is an autoimmune or “self-allergy” disease in which a patient’s own circulating antibodies become altered so that they attack the points of adhesion of the epithelial cells, one to another, of the skin and mucous membranes. Women are more frequently affected than men and the disease is usually diagnosed between the ages of 50-70 years, often with oral blisters as the first sign. Children are rarely affected. The typical lesion is a small or large, clear-fluid blister which breaks rapidly in the mouth to leave a flat white, somewhat tender ulcer with a thin red line around it. Skin blisters may last for hours or days, and blisters may be caused by pressure on the skin or membranes of the mouth. There is no cure, but pemphigus is treated with heavy doses of corticosteroids and azathioprine, with frequent relapses after the therapy is stopped. Secondary infection is common because of the immune system suppression from these drugs. The overall mortality is less than 6%, usually from infection or loss of body fluid from a large number of blisters.

The most serious of the bullous diseases affecting the oral mucosa is pemphigus vulgaris, a life-threatening autoimmune disorder of skin and mucous membranes. It is relatively rare but shows an increased frequency in Ashkenazi Jews. The mouth is the only site of involvement in half of all cases of pemphigus, and is the initial site of presentation in almost 3/4 of cases. An association between pemphigus vulgaris, myasthenia gravis and thymoma has been reported, and a variety of drugs have been implicated in its induction, especially penicillamine, phenylbutazone, rifampin and captopril, although most cases are idiopathic. It is also known to occur in association with a variety of internal malignancies (paraneoplastic pemphigus).

Patients with pemphigus vulgaris produce IgG autoantibodies to desmoglein 3 (the “PV antigen”), a transmembrane glycoprotein which mediates cell adhesion. Although the exact mechanism is unclear, autoantibodies theoretically produce an allosteric change in the desmoglein, impairing its adhesive abilities, and increase active plasmin in the area, producing cell degradation and acantholysis. Complement may be actively involved in this process.

Types

There are three types of pemphigus which vary in severity: pemphigus vulgaris, pemphigus foliaceus, and paraneoplastic pemphigus.

• The most common form of the disorder is pemphigus vulgaris (PV – ICD-10 L10.0). It occurs when antibodies attack Desmoglein 3. Sores often originate in the mouth, making eating difficult and uncomfortable. Although pemphigus vulgaris may occur at any age, it is most common among people between the ages of 40 and 60. It is more frequent among Ashkenazi Jews. Rarely, it is associated with myasthenia gravis. Nail disease may be the only finding and has prognostic value in management.
• Pemphigus foliaceus (PF) is the least severe of the three varieties. Desmoglein 1, the protein that is destroyed by the autoantibody, is only found in the top dry layer of the skin. PF is characterized by crusty sores that often begin on the scalp, and may move to the chest, back, and face. Mouth sores do not occur. It is not as painful as pemphigus vulgaris, and is often mis-diagnosed as dermatitis or eczema.
• The least common and most severe type of pemphigus is paraneoplastic pemphigus (PNP). This disorder is a complication of cancer, usually lymphoma and Castleman’s disease. It may precede the diagnosis of the tumor. Painful sores appear on the mouth, lips, and the esophagus. In this variety of pemphigus, the disease process often involves the lungs, causing bronchiolitis obliterans (constrictive bronchiolitis). Complete removal and/or cure of the tumor may improve the skin disease, but lung damage is generally irreversible .

Note that Hailey-Hailey disease, also called familial benign pemphigus, is an inherited (genetic) skin disease, not an autoimmune disease. It is therefore not considered part of the Pemphigus group of diseases.

Clinical Features

Pemphigus vulgaris is a disease of older individuals, usually 50 years or older, but rare examples in children and adolescents have been reported. There is no gender predilection. The oral lesion is a fragile bulla, almost always ruptured by the time of diagnosis. There is little or no erythematous inflammatory halo and a fresh lesion may retain epithelial tags at its periphery. In contradistinction to traumatic ulcers and aphthous ulcers, the base of a pemphigus ulcer is not concave or saucerized and there is considerably less associated pain. The bullae tend not to become secondarily infected but may reach more than 4 cm. in diameter and may be so numerous as to represent most of the oral mucosa. Blisters can be created by pressure or friction upon a normal-appearing area of mucosa (Nikolsky sign). With time skin blisters will usually occur and will become the major problem.