Classically, dry skin has been described in two ways—(1) as a condition that is simply either present or not or (2) as a linear progression of sequelae, resulting in the concomitant development of clinical tools such as linear visual grading scales, etc. While not refuting the validity of these, it is proposed that the induction and propagation of dry skin conditions may be best and most intuitively expressed as a cyclical model, dependent on SC integrity and particularly upon barrier function and homeostasis.
A cyclical model implies a spiralling deterioration in outcome that, without intervention, would lead to a progressive worsening in model endpoints. Additionally, it is implicit that intervention at one, or preferably multiple, points within this cycle is necessary to arrest the progression of this continuing downward spiral. This is indeed the case with most dry skin conditions and, moreover, reflects extremely well consumer perception of dry skin—the seeming repetitive cycle of product usage, re-usage, disappointment with treatment outcome, and, often, a corresponding loss of compliance. The model described below describes several phases within this cycle and, therefore, possible targets against which treatments could be directed. Reference to the graphical depiction of the model below (Fig. 18) may facilitate complete understanding of the relationship of these phases, one with another.
As discussed the induction phase can be mediated by a variety of different factors:
-low environmental temperature and humidity
-abrupt changes in environmental conditions which includes the effect of modern indoor climate-controlled environments – surfactant dissolution of SC lipid and NMF – chronological aging and genetics
Once the skin has been provoked by one or more of these mechanisms, there is an
inevitable sequence of events that may be described conveniently as a cycle.
Initially a mini-cycle of barrier deterioration is initiated and perpetuated. Blank estimated that the SC loses its flexibility once its water content falls below approximately 10% (8), the provocation for which may constitute one or a combination of the factors noted above. Without intervention, this quickly leads to a steeper SC hydration gradient, a decrease in net recondensation on the SC surface, a corresponding increase in evaporative water loss from the SC surface, a consequent further drop in SC water concentration, and so on. The inevitable rapid consequence of this series of events is a decrease in the plastic or viscous properties of the SC (commonly interpreted as skin “softness” or “suppleness”), an increase in SC fragility/brittleness, and an impairment of SC barrier function (82-85). This surface dehydration is the first step in the development of the dry skin cycle and is further exacerbated by destruction of the normal barrier lipid lamellae in the outer layers of the SC during bathing (23). The impaired barrier in the superficial layers of the SC allows leaching of NMF from the outermost skin cells, thereby reducing SC water activity. Whiteness between the dermatoglyphics (caused by backscatter from multiple tissue-air interfaces) and minor scaling due to the dehydration of individual corneocytes are the first visible steps in the cycle. Perturbation to the barrier then leads to further development of dry skin.
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Due to the cyclical nature of these processes, therefore, it becomes virtually impossible to distinguish between dry skin conditions that are provoked initially by barrier disruption or by dehydration of the SC. However, once the barrier has been disrupted, even superficially, a new cascade of events is started primarily through the induction of a hyperproliferative state.
Figure 18 Schematic diagram showing pivotal events within the “dry skin cycle.” Source: From Ref. 2.
Acute and chronic insults to the SC barrier will lead to enhanced keratinocyte proliferation, consequent hyperkeratosis, and mild inflammatory changes, one of the hallmarks of dry skin conditions, as the skin attempts to repair itself. This response is mediated via production and secretion of cytokines and growth factors, many researchers citing the ratio between interleukin 1 receptor antagonist protein and interleukin-1 alpha (IL-1 alpha) as a key marker of this process (86-89). The degree of hyperprofileration has been shown to be dependent upon the corresponding degree of barrier perturbation (90), probably reflecting both the ingress of exogenous irritants through the impaired barrier and the growing realization that the SC barrier is itself a biosensor and that corneocytes and keratinocytes themselves participating in the release of these messengers. The hyperproliferation of the epidermis probably occurs as a result of the double paracrine signaling events between the epidermis and dermis. IL-1 acts on fibroblasts which in turn secrete KGF and GMCSF inducing hyperproliferation and dysfunctional differentiation of keratinocytes (91).
The induction of this inflammatory hyperproliferative state is absolutely key in the cycle of dry skin as it fundamentally leads to aberrant differentiation and the over-hasty production of a variety of poor quality materials and structures vital to the proper functioning of the SC barrier and normal healthy skin. These include:
1. the production of smaller and immature CEs
2. changes in epidermal lipid and particular ceramide biology
3. reduced transglutaminase activity
4. reduced filaggrin synthesis and NMF levels
Finally a loss in efficiency of desquamation, due to reduced activity of desquamatory enzymes at the surface of the SC, and ensuing scaling, thickening, and loss of hygroscopicity of the SC occurs. Marked scaling is, of course, one of the obvious consumer-noticeable expressions of “dry skin.” The formation of a thicker SC with impaired desquamation has, again, immense biophysical importance. The water gradient across the thicker SC becomes steeper, leading to further increases in evaporative water loss, reducing further water concentration in the outer SC, and propagating directly another round of the dry skin cycle.
Corneocytes that should be in a mature fully hydrophobed format are now replaced by fragile corneocytes. The resulting barrier protecting these corneocytes and their contents is now weaker due to changes in barrier lipid profiles and surface hydrophobicity. Equally, the hygroscopic (though highly water-labile) NMF present within corneocytes of normal SC, are depleted gradually through normal everyday activities such as cleansing and/or occupational duties (1,61). The corneocytes of dry SC are, therefore, subject to exaggerated insult such due to their changed biochemical and biophysical properties. The dry skin cycle, thus, is propagated further by an increased loss of NMF relative to normal skin and a corresponding loss in SC hygroscopicity.
Finally and most importantly, the development of an increasingly thick, dry SC results in a layer characterized, from a biomechanical viewpoint, by a dramatic increase in hardness and brittleness. The consumer perceives this as tightness. These properties create an SC barrier inherently susceptible to mechanical stress and fracture, another factor driving the impairment in barrier function cyclical nature of the dry skin cycle.
The clinical endpoint of “dry skin” cannot be regarded as static but rather is most fully described as a cycle that, without intervention, tends to perpetuate itself. Pivotal to every stage of this cycle and its propagation is a compromised SC barrier. Interventions that truly break the dry skin cycle, therefore, by definition need not only to treat symptomatic manifestations, but repair and augment SC barrier function. This will yield a skin that is inherently better able to cope with the constantly changing external environment of the modern world.