Definition: Bullous Pemphigoid (BP) is a blistering disease caused by antibodies directed against components of the basement membrane.
Description: The blisters of BP are tense, filled with clear fluid, and much more resistant to rupture than the blisters seen in Pemphigus Foliaceus and Pemphigus Vulgaris.
Antibodies directed against recombinant murine BP 180 when injected intraperitoneally or under the skin into neonatal BALB/c mice cause subepidermal blisters that mimic the clinical and histological features of human BP, thus providing direct evidence that BP is an autoimmune disease.
BP is a rare disease. The classic form has an annual incidence of 7 cases per 1 million. It occurs more frequently after the age of 60 and affects males and females equally. It is characterized by tense blisters situated on either inflamed or normal-appearing skin. Pruritus (itching) is present and usually mild. The course is chronic and characterized by periods of exacerbation and partial remission. Some patients, however, experience complete remission after 6 to 10 years of active disease.
Types: A first variant of bullous pemphigoid is the one that occurs in pregnancy (usually during the second or third trimester) and it is called pemphigoid gestationis (or gestational pemhigoid). In the past it was called herpes gestationis because lesions often appear as grouped vesicles, but we now know that this disease has no relationship to an existing or prior viral infection, and thus the name should be abandoned. The lesions are similar to the ones seen in the classic bullous pemphigoid, but are mainly distributed in the umbilical and periumbilical regions, and are almost always very pruritic. The frequency is approximately 1 case in 50,000 pregnancies. The antibodies are directed against the N terminus of the bullous pemphigoid antigen 180. The disease resolves after the puerperium (period of time from end of labor to complete ivolution of uterus), with likely recurrence in subsequent pregnancies. Some neonates develop transient blisters due to the transplacental passage of maternal IgG. As maternal IgGs are cleared from such neonates, lesions resolves. There are no long-term adverse effects on the fetus or the newborn. A recent review on pemphigoid gestationis can be read here (reference).
A second variant of bullous pemphigoid is the so-called mucous membrane pemphigoid. It is characterized by blisters on the mucous membranes, especially the oral mucosa and the conjunctiva. These blisters heal with scarring, hence the alternate designation of cicatricial pemphigoid. The scarring can compromise the function of the affected organ or tissue. In mucous membrane pemphigoid the antibodies are directed mainly against the C terminus of bullous pemphigoid antigen 180. The diagnosis is made by analyzing the skin biopsy and the patient serum. The light microscopy study of the skin biopsy shows subepidermal blisters with a dermal infiltrate composed mainly of eosinophils and neutrophils. The direct immunofluorescence exam of the skin biopsy demonstrates a typical linear, not granular, deposition of antibodies and complement along the basement membrane zone. Cutaneous lupus erythematosus has a similar pattern but granular in character. The patient serum can be used to demonstrate, by indirect immunofluorescence, the presence of antibodies that bind to the basement membrane zone of skin substrates. A commonly used skin substrate is the saline separated normal human skin, but intact human skin and monkey esophagus are also used. The serum can also be used to test for the presence of specific antibodies by ELISA, coating the plate with recombinant bullous pemphigoid antigen 180.
Treatment: The first line of therapy is still the use of systemic corticosteroids. Intravenous immunoglobulins have also been shown to be useful, especially in patients who are at risk of experiencing serious or potentially fatal side effects from conventional immunosuppressive therapy.
Pathogenesis: The main targeted antigen is a 180 kDa transmembrane protein (Bullous Pemphigoid Antigen180), although a 230 kDa intracellular protein (Bullous Pemphigoid Antigen 230), laminin 5, and beta 4 integrin are also targeted. These antibodies cause a separation of the epidermis from the dermis and thus a subepidermal blister.