Pemphigus / Pemphigoid (Bullous dermatosis)

Autoimmune bullous skin diseases include a group of serious diseases with blisters and erosions on skin and mucous membranes. The skin has adhesion molecules that stick the keratinocytes to each other and to the underlying basement membrane. Several of its molecules are the targets in the autoimmune skin diseases. An important factor is circulating antibodies directed against adhesion structures in the epidermis, the basement membrane or anchoring fibrils of the dermis. Pemphigus and pemphigoid are the two most common and most serious bullous diseases and the autoantibodies are considered an important part of the pathogenesis. In pemphigus the antibodies are directed against desmosomal adhesion proteins in the epidermis, whereas hemidesmosomal proteins are the targets of the antibodies in pemphigoid and similar diseases, such as IgA bullous dermatosis. In epidermolysis bullosa acquisita (EBA), anchoring fibrils (type VII collagen) are the antigen.

Indications: Suspicion of autoimmune skin disease.

Pemphigus Pemphigus is a group of life threatening autoimmune bullous skin diseases with intraepithelial blisters. The molecular background of the blistering is the interference of the adhesion between the keratinocytes (acantholysis) by the autoantibodies against intercellular adhesion structures. Various forms of pemphigus have been identified and they have the intraepidermal division on different levels of the skin. In pemphigus vulgaris (PV) the blisters are located in the deeper layers of the epidermis, whereas in pemphigus foliaceus (PF), a less serious form, they are located in the upper layers of the epidermis. In PV there are autoantibodies against the extracellular domain of the desmoglein 3, an adhesion molecule that is found on the epidermal keratinocytes. Even though desmoglein 3 is the most important antigen in PV, many patients may also have antibodies against desmoglein 1, which is the most important antigen in PF. The autoantibodies in pemphigus are polyclonal and most of them are of the IgG4 subclass in active disease, whereas in remission they are usually IgG1.

Pemphigoid Bullous pemphigoid (BP) is an autoimmune bullous skin disease that is recognised by subepidermal bullae and circulating antibodies against the basement membrane zone in epithelium. Earlier studies have shown that these autoantibodies primarily react with two components of hemidesmosomes, BP180 (type XVII collagen) and BP230. Hemidesmosomes are multiple protein complexes, which participate in the epithelial cell adhesion to the underlying basement membranes and bind the cytoskeleton to the extracellular matrix. BP230 is cytoplasmic and binds to intermediary filaments. BP180 is a transmembrane protein that can bind to receptors in the extracellular matrix. Antibodies against BP180 induce blisters if injected in mice. This shows that the autoantibodies against BP180 are pathogenic and are responsible for producing the blisters in BP. It has been shown that the NC16 domain, which is closest to the cell membranes, contains most of the epithopes of the molecule. There are several variants of BP that have antibodies against BP180 but that are clinically distinct from BP. Pemphigoid gestationis (PG) is a bullous disease that occurs in the last trimester of pregnancy and that also has antibodies against BP180. Cicatricial pemphigoid (CP) is a subepidermal autoimmune bullous disease, which, in contrast to BP, mainly affects mucous membranes in the conjunctive and oral, perianal and genital mucous membranes and leads to scarring in the affected tissue. In CP it has been shown that the antibodies react with several antigens besides B180, e.g. laminin 5. Serological investigation of pemphigus/pemphigoid. IMAGE