Transepidermal water loss and skin site: a hypothesis

The skin has a unique barrier to the ingress of hazardous materials and the egress of water. The barrier properties of the skin reside in the outer 15 microm, the stratum corneum, which has often been regarded as rather inert or even dead. The excellent barrier properties of this thin layer result from its structure which comprises of pentagonal or hexagonal corneocytes embedded in a lipid matrix. Corneocyte turnover and epidermal proliferation is controlled by desquamatory proteases and protease inhibitors in the epidermis. Disorders in barrier function and disruption of barrier homeostasis have been associated with changes in the expression patterns of epidermal serine proteases and variations in serine protease activity have also been identified at different body sites. The major route of permeation is around the corneocytes, therefore, the larger the corneocytes the longer the route for the permeation. Corneocyte size is dependent on the site on the body and this can be directly related to the permeability. For example, the face has thinner skin and the corneocyte size is smaller than the arm. This results in a shorter path for a drug to penetrate. Transepidermal water loss (TEWL) is a measure of the amount of water from within the skin to the external atmosphere. Rougier et al. showed that variations in corneocyte size at different anatomical sites were reflected in TEWL at these sites. The path length at different body sites was calculated using a simple geometric equation and a direct reciprocal relationship between the path length and TEWL was identified. A linear trend between cell size and cell layers at different sites is also evident in the data. Since higher protease activity should result in smaller corneocyte sizes and fewer cell layers, this in turn may be related to reported variations in enzyme activity at these sites.