Histopathology of the Pilosebaceous Unit and Interstitium of Hidradenitis Suppurativa

Epidermis

Epidermal thickness (from basal layer to stratum corneum) is location dependent and is considered to be approximately the same in White and African skin. The average epidermal thickness is 100 μm, although anatomical location determines more precise dimensions. AA skin is minimally but significantly 6μm thicker, which may result from differential expression of the dermal papillae and epidermis rete ridges. The main barrier function of the skin lies in the most superficial layer of the epidermis, the stratum corneum. Not only does it protect against chemical injury and microbiologic invasion from the environment, but also maintains water and solute balance. Even though the stratum corneum is equally thick in African American and White skin, African American stratum corneum contains more cell layers (20 layers vs. 16 in Whites). Also, the number of corneocyte cell layers, resistant to tape stripping and electrical resistance, were reported to be greater in African subjects presumably as a result of better intercellular cohesion.

Four major resident populations make up the cells of the epidermis: keratinocytes, melanocytes, Langerhans cells, and Merkel cells. The major populations of epidermal cells are keratinocytes. These cells originate in the stem cell pool in the basal layer and undergo maturation as they migrate upward, ultimately forming the laminated stratum corneum. The human epidermis averages 50 microns in thickness, with a surface density of approximately 50,000 nucleated cells/mm ² . Under basal conditions, differentiated keratinocytes require approximately 2 weeks to exit the nucleated compartment and an additional 2 weeks to move through the stratum corneum. Markers that identify keratinocytes in normal healthy epidermis are keratin (K) K5 and K14 in basal keratinocytes, and K1, K2e, and K10 in suprabasal keratinocytes.

Melanocytes are pigment producing cells located in the lower epidermis, manufacturing and secreting melanin. The main function of melanin is to protect against UV radiation by absorbing and scattering the rays. Melanocytes package melanin into pigment granules called melanosomes that are transferred by excretion and phagocytosis into nearby keratinocytes. It is the greater number, larger size, increased stability and distribution of melanosomes within keratinocytes that determine differences in skin color, not the number of melanocytes. Some known markers that identify melanocytes are Melan-A, S100 (α and β subunits).

Langerhans cells are the specialized immunologic cells of the skin. They traffic out of the epidermis toward regional lymph nodes, where they play a critical role in antigen presentation during the induction and regulation of skin-directed immune responses. Example of markers that identify human Langerhans cells are CD1a, CD207, and S100 (β subunit).

Merkel cells are tactile cells containing neuroendocrine peptides within intracytoplasmic granules. They are also found in the basal layer of the epidermis. Each Merkel cell is in close contact with a basolaterally settled unmyelinated afferent nerve terminal (nerve plate) that has a high tactile sensitivity to light touching. Markers that identify Merkel cells include cytokeratin (CK) 8, 18, 19, 20, and CD56.

Dermis

The dermis is predominantly composed of connective tissue, collagen, and elastic fibers. The papillary dermis (closer to the epidermis and around adnexal structures) contains mainly collagen type I and, to a lesser extent, collagen type III. The reticular dermis located underneath the papillary dermis contains thick collagen type I. In a histological study comparing the skin of White and African origins, no differences were seen in dermal collagen and elastic fiber organization. However, African skin displayed a greater convolution of the dermo-epidermal junction (DEJ).

Cells found within healthy dermis include fibroblasts (CD90) and immune cells such as macrophages (CD68 and CD163), dendritic cells (CD11c, CD14, CD1c/BDCA-1, and CD303/BDCA-2), and occasional mast cells (CD11b, CD45, CD13, CD29, CD33, CD34, CD41, CD43, CD45, CD117, CD203c, mast cell tryptase). Resident leukocytes are also found in healthy skin, such as T cells and occasional B cells. The pan-T cell marker is CD3, with subsets CD4 helper T cells and C8 cytotoxic T cells. B cells are identified by CD19 and CD20, among others.

Other differences in protein expression have been reported in African skin compared to White skin, including increased keratinocyte growth factor (KGF) and monocyte chemotactic protein (MCP)-1, twofold higher ratio of papillary to reticular fibroblast expression, increased matrix metalloproteinase (MMP)-1, and tissue inhibitor metalloproteinase protein (TIMP)-1 protein expression. In an inflammatory environment, these observations make black skin more prone to pathologies or disorders such as keloids/acne keloids and potentially HS.

Subcutis

The subcutaneous tissue is mainly formed of fibroblasts, lobules of adipose cells separated by collagenous septa that contain the neurovascular bundles, and macrophages.