Physiologic Lipids for Barrier Repair

Introduction

While the stratum corneum (SC) serves many defensive functions ( Table 7.1 ), none is as important as its ability to prevent excess loss of fluids and electrolytes, i.e. the permeability barrier. Permeability barrier function is mediated by the organization of the extracellular lipids of the SC into a series of parallel lamellar membranes, which mediate not only permeability barrier function, but also additional, key protective functions of the epidermis ( Fig. 7.1 ). The defensive functions of the SC further localize to the cellular (corneocyte) compartment, the extracellular matrix, or to certain features of both compartments ( Table 7.1 ).

Dynamics of barrier recovery

The skin barrier is assaulted frequently in daily life by hot water, detergents, solvents, mechanical trauma, free radicals, and occupation-related chemicals. If these insults are widespread, repeated frequently, and/or if the host's repair response is insufficient, they can threaten the organism with desiccation due to accelerated transepidermal water loss (TEWL). To avoid this outcome, the underlying epidermis mounts a coordinated metabolic response, ranging from increased lipid synthesis to accelerated lipid secretion, aimed at rapidly restoring normal function. This response is elicited by any type of barrier insult (e.g. organic solvents, detergents, tape stripping) that depletes the SC of its complement of lipids. Although the total time required for barrier recovery varies according to age, there is an initial, rapid recovery phase that leads to 50–60% recovery in young humans in about 12 hours, with full recovery requiring about 3 days ( Fig. 7.2 ). But in aged humans (>75 years), complete recovery from comparable insults is prolonged to about 1 week. Restoration of barrier function is accompanied by reaccumulation of lipids, visible with either oil red O staining or Nile red fluorescence, and by the reappearance of membrane structures within the SC interstices, as early as 2 hours after acute disruption. Because artificial restoration of the barrier with vapor-impermeable membranes inhibits barrier recovery, as well as all of the metabolic processes linked to it, this entire series of responses is aimed specifically at restoring normal permeability barrier homeostasis.

Clinical applications of the cutaneous stress test

The kinetics of barrier recovery after acute perturbations (also called the ‘cutaneous stress test’) can discern abnormal function or underlying pathology, even when basal parameters are normal ( Fig. 7.2 ), analogous to the cardiac treadmill exam. Indeed, the cutaneous stress test reveals deficient barrier function both in aged and in neonatal skin, despite deceptively normal function in both age groups under basal conditions. Further, it amplifies differences between other ‘normal’ groups:

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  Testosterone-replete versus testosterone-deficient individuals

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  Skin exposed to humid versus dry environments

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  Individuals with type IV/V versus I/II pigmentation.

Finally, individuals subjected to increased psychological stress reveal a defect in barrier recovery. These findings explain the propensity for the skin to erupt in inflammatory dermatoses, such as psoriasis and atopic dermatitis, in individuals who are subject to these stressors, perhaps by further amplifying the cytokine cascade that characterizes these disorders.