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Bullous pemphigoid was originally classified as a unique disease with distinctive clinical and histologic features by Walter Lever in 1953.1 Its separation from pemphigus was important, because at the time pemphigus vulgaris was often fatal, whereas bullous pemphigoid had a comparatively good prognosis. The separation of bullous pemphigoid from pemphigus was confirmed and fully justified by the characteristic immunopathologic features of these diseases described approximately 12 years later.2,3
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Bullous pemphigoid typically occurs in patients over 60 years of age, with a peak incidence in the 70s.4 There are several reports of bullous pemphigoid in infants and children, although this is rare.5–8 There is no known ethnic, racial, or sexual predilection for developing bullous pemphigoid. The incidence of bullous pemphigoid is estimated to be 7 per million per year in both France and Germany, and 14 per million per year in Scotland.4,9–11 A recent large cohort study suggests that the incidence of bullous pemphigoid may be as high as 43 per million per year in the United Kingdom with incidence increasing over the last several years.12
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The hallmarks of bullous pemphigoid include the presence of subepidermal blisters, lesional and perilesional polymorphonuclear cell infiltrates in the upper dermis, and immunoglobulin (Ig) G autoantibodies and C3 bound to the dermal epidermal junction. Remarkable advances have been made in the last decades characterizing the antigens as hemidesmosomal components and developing an animal model that demonstrates the pathogenicity of bullous pemphigoid autoantibodies.
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Bullous Pemphigoid Antigens
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Immunofluorescence (IF) techniques demonstrate that patients with bullous pemphigoid exhibit circulating and tissue-bound autoantibodies directed against antigens of the cutaneous basement membrane zone (BMZ).3 Immunoelectron microscopy studies localize bullous pemphigoid antigens to the hemidesmosome, an organelle that is important in anchoring the basal cell to the underlying basement membrane.13 These autoantibodies bind to both the intracellular plaque of the hemidesmosome and the extracellular face of the hemidesmosome. Bullous pemphigoid autoantibodies recognize two distinct antigens with molecular weights of 230 kDa and 180 kDa by immunoblot analysis of human skin extracts.14 The 230-kDa molecule is termed BP230, BPAG1, or BPAG1e.14–17 BPAG1e belongs to a gene family that includes desmoplakin I, a desmosomal plaque protein that is important in anchoring keratin intermediate filaments ...