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The epidermis binds to the dermis through the basement membrane (BM) zone, a complex network of interconnecting proteins located at the dermal-epidermal junction.1,2 Perturbing the functions of these proteins, either by mutations3 or circulating autoantibodies,4 leads to loss of tissue adhesion and causes subepidermal blistering diseases. These diseases can be classified into 3 main groups (Fig. 8-1 and Table 8-1)—namely, autoimmune subepidermal blistering diseases, subepidermal blistering diseases due to mutations of proteins of the BM zone, and miscellaneous subepidermal blistering diseases. To understand the subepidermal blistering diseases, their histopathology, and approach to diagnosis, one first requires a comprehension of the ultrastructure and the protein constituents of the basement membrane zone.

TABLE 8-1Three Main Groups of Subepidermal Blistering Diseases

Subepidermal blistering diseases algorithm.


The basement membrane zone is located between the epidermis and the dermis and is a 0.5- to 1.0-µm-thick, band like structure that is positively stained by periodic acid—Schiff (PAS).5 Ultrastructural, biochemical, and molecular studies show this zone to be a complex network of interconnecting proteins that provide integrity and mechanical stability to the skin1,2,6 and are involved in signal transduction and other functions. Ultrastructurally, the cutaneous BM zone consists of 3 regions7,8 (Fig. 8-2):

  1. Hemidesmomes into which the keratin intermediate filaments insert

  2. Lamina lucida, an electron-lucent region, which is traversed by anchoring filaments

  3. Lamina densa, an electron-dense area from which anchoring fibrils extend into the papillary dermis


Ultrastructure of the BMZ of the skin. AF = anchoring filaments, Afb = anchoring fibrils, Ap = anchoring plaque, C = collagen fibers, HD = hemidesmosome, LD = lamina densa, LL = lamina lucida, Pd = papillary dermis, Pm = plasma membrane of basal keratinocyte.

The ultrastructural location of the proteins is described in Table 8-2.

TABLE 8-2Basement Membrane Components and Their Ultrastructural Localization

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