Epidermal Skin Barrier: Implications for the Wound Care Practitioner, Part II, The

Advances in Skin & Wound Care, Nov/Dec 2004 by Fore-Pfliger, Jane

The first part of this 2-part series on the epidermal skin barrier examined the anatomy and development of the epidermis and stratum corneum, as well as homeostasis and physical Stressors that affect the epidermis.1 Part II further examines conditions that affect the epidermis, especially the stratum corneum skin barrier, and discusses treatments and methods that maintain and restore epidermal functions.

FACTORS ALTERING THE STRATUM CORNEUM BARRIER

Effects of physiologic and psychological stress

Stress affects the epidermis and the stratum corneum in a way that disrupts skin barrier function.2ThIs barrier function can be impaired by psychological, perceived, or external and internal Stressors.3 Coping ability and Stressor chronicity affect the seriousness of an individual's stress response. The stress response activates pathways that increase glucocorticoid secretion from the adrenal cortex and stimulate epinephrine and norepinephrine secretion from the adrenergic system.4-5 Certain effects of stress on the skin barrier can be blocked by prevention of glucocorticoid synthesis and pretreatment with antianxiety medications.2 Topical and systemic corticosteroids reduce the production of lipids that reduce intercellular lamellae in the epidermis. This reduces barrier strength, slows recovery of the disrupted barrier, and reduces corneocyte cohesion as a result of corneodesmosome reduction.6 The effects of stress also slow the recovery of skin barrier function, as well as reduce the water content of the skin.

Levels of the inflammatory chemicals interleukin-1β (IL1β), interleukin-10 (IL-10), and tumor necrosis factor-α (TNFa) increase with stress. This induces corticotrophin-releasing factor secretion in the hypothalamus, ultimately increasing the output of glucocorticoid secretion from the adrenal gland. The increased corticosteroid secretion associated with acute stress contributes to stratum corneum barrier dysfunction.7 Acute stress also increases mast cell degranulation.8

The increased glucocorticoids and catecholamines associated with Stressors have a regulatory effect on the function and differentiation of T cells and macrophages.5 The 2 distinct populations of T-helper cells are type 1 (THl), which predominantly mediates cell immunity, and type 2 (TH2), which predominantly mediates humoral immunity. The balance of THl and TH2 is altered by the effects of stress, favoring the TH2 cells. TH2 predominance reduces cellular immune responses and enhances humoral responses.9'10 Atopic eczema, pemphigus, and other conditions associated with autoimmunity manifested during TH2 predominance may flare during times of stress because of changes in immune cell predominance. The multiple changes associated with stress place the individual at risk for skin barrier dysfunction.

Skin infections

Alterations in any condition that affects skin barrier integrity increase susceptibility to invasion. Barrier impairment weakens the stratum corneum, making it easier for microbes to invade the deeper cellular layers. Skin infections also weaken the skin barrier. The presence of microbes may initiate a hypersensitiviry response, causing a secondary inflammatory reaction in the epidermis, such as Candida infection. The antibody response to Candida plays a part in the response to invasion, increasing the inflammatory reaction to the infection. A healthy stratum corneum and attention to stratum corneum barrier maintenance maximizes the ability to fight infection.

Diabetes mellitus

The abnormal skin conditions found in persons with diabetes are not well understood. The reduced autonomie activity with neuropathy reduces sweating; however, this is not a major factor in skin hydration. Autonomie dysfunction may lead to abnormal shunting of the capillary plexus, reducing circulation to the capillary bed that nourishes the epidermis. A recent study11 noted reduced skin hydration in mice with chemically induced type 1 diabetes despite a normal intercellular lipid complex and corneocyte protein production. The low triglyceride fraction of the stratum corneum suggested abnormal triglyceride metabolism of the sebaceous glands.11 Epidermal proliferation and differentiation were reduced, slowing epidermal turnover.

Insulin receptors and insulin-like growth factor-1 (IGF-1) receptors are expressed in keratinocytes. Stimulation of these receptors, with their target hormones, mediates the cellular response to the respective hormones. These hormones likely affect the maturation and function of the stratum corneum, although details are not clear.12 An association may exist between atrophie skin lesions, such as diabetic dermopathy, and abnormal insulin receptor signaling in the cell. Despite greater thickness, transepidermal water loss is higher in the palms of the hands and the soles of the feet than in other areas of the body, and lipid content is reduced compared with other parts of the body.13 This aggravates dryness in a susceptible area of injurynamely, the feet-in persons with diabetes.14 It is interesting to note that stimulation of peroxisome-proliferator-activated receptors (PPAR), an important subgroup of the known nuclear transcriptional (hormone) receptors, has a positive effect on epidermal differentiation and barrier development.l5-16 The thiazolidinediones (eg, rosiglitazone maleate [Avandia], pioglitazone HCl [Actos]) are PPAR-stimulating medications that are currently common in diabetes treatment. They are further discussed below.