Chapter 8: Subepidermal Blistering Diseases

INTRODUCTION

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.

ULTRASTRUCTURE AND MOLECULAR ANATOMY OF THE CUTANEOUS BM ZONE

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 skin^1,2,6 and are involved in signal transduction and other functions. Ultrastructurally, the cutaneous BM zone consists of 3 regions^7,8 (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

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