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Dry Skin
Oxidative stress and free redical damage
Pigmentary disorders
Prepared by: Dr. Charlene DeHaven, Clinical Director


Dry skin is also termed xerosis. The complex factors contributing to dry, flaky skin are just beginning to be described. Some of these relate to the environment and some relate to the particular individual involved. There are individual and genetic factors which make some persons more susceptible than others to this problem. As the biochemistry of dry skin becomes better understood, we should learn how to better treat this problem in the next several years and then develop products that will become commonly available.

The Biochemistry of Dry Skin

The structure of the epidermis, the outermost layer of skin and, especially the stratum corneum, the outermost layer of the epidermis are of greatest importance in determining who develops dry skin and also when it develops. Remember that the epidermis is composed of 4 layers. The cells of the inner layer migrate upward from the basal layer to the granular layer, until they reach the outer layer of the stratum corneum. Through this migration, the cells change, losing their nuclei (inner portion containing DNA) and becoming keratinized, i.e. forming the outer protective keratin layer of the stratum corneum. This outer layer provides a barrier function; it keeps important substances such as cellular fluids and blood within the body and it helps keep out too much water, invading micro-organisms, and toxins that might harm the inner organism if allowed to pass through the skin. When no longer functional, cells of the outer stratum corneum are shed in a process called desquamation.

All cells, including those of the stratum corneum, are held together by junctional bridges called desmosomes. When the cells are no longer functional and are shed from the skin surface, the desmosomes break down so the cells are no longer held together and can be shed. Desmosomes that are "too tight" do not allow for proper shedding of discarded cells. Several enzymes degrade the desmosomes and allow nonfunctional cells to detach from each other and desquamate (shed). Genetic differences in the amount or efficiency of these enzymes also determines the efficiency of this process. If the desmosomes are not degraded properly and the outer nonfunctional cells are held together longer than optimal, dry flaky sheets of skin develop in which the cells are still attached to one another. In a normal process, friction causes very tiny clumps of nonfunctional cells to be shed; in an abnormal process, these clumps are larger since the cells cannot dis-attach from each other; these clumps are more visible, flaky and unattractive.

The spaces between these cells and around the bridges are filled with a substance that provides the primary barrier to water loss. The composition of this substance is very important in protecting against excessive skin dryness. This substance has a very high fat content and such is called lipid-rich. There are primarily 3 critical compounds in this substance - ceramide, cholesterol, and fatty acids.

The total amount of these 3 compounds as well as their ratio amounts to each other are all very important in healthy function of the skin barrier.

These 3 substances are further classified as to type. For example, there are 9 different chemical classes of ceramides, each doing something a little different from the others. We actually do not understand the exact roles of all of these subtypes as yet and much more research needs to be done in this area. We do know that the ceramides present as longer chains provide a better water barrier than the short-chain ceramides. People with dry skin (and also with diseased skin) have too much of the short-chain ceramides and not enough of the long-chain ceramides. Linoleic acid, an essential fatty acid that must be provided in the diet, is especially important in the synthesis of long-chain ceramides. Essential fatty acids are found in the omega-3 and the omega-6 group, found in cold water fish (salmon, herring, mackerel) and in nuts, avocados, flax seed oil.

Some shapes of fats (lipids) in the skin act as better barriers than others. The "packing" of these molecules against and around each other determine how much water is let through. The amount of water allowed through a barrier is referred to as the barrier’s permeability; high permeability means a lot of water is let through and low permeability means less water is allowed through. As the cells of the epidermis migrate upward, the substance between them composed of these lipids changes configuration so that the barrier is weaker at the outermost layers of the stratum corneum. The deeper layers contain lipids that are more tightly packed against each other and less permeable to water; the outer layers have more loosely packed lipids and are more permeable to water. The more tightly packed lipids have rhomboid shapes (looking like a slightly squashed rectangle) and the loosely packed lipids have hexagonal shapes.

These packing states also influence the ease at which discarded cells are shed from the skin surface (desquamation). Higher ceramide content tends to keep the cells together. Aged skin at all times and everyone’s skin during winter contains a lower ceramide content; this contributes to weakened barrier function. People living in the very hot environment of the Arizona desert have skin with higher ceramide content which is, therefore, stronger than skin of those living in New York. A very humid environment causes a similar increase in the amount of ceramides. Lower amounts of ceramides are seen with dry, flaky skin. Changes in the types of ceramides are also seen in persons who develop dry skin very easily, such as those with atopic dermatitis (inflamed, dry skin secondary to allergy and hypersensitivity). People with atopic dermatitis have decreased skin moisture (impaired barrier function of skin) and also have decreased skin lipids.

Itch - We all know that dry skin itches. But itch is a poorly-understood component of dry skin. We know from animal studies that itching relates to individual and genetic differences in the spinal cord and in chemicals that transmit nerve impulses. Animals with genetic defects that spontaneously itch also have a stratum corneum with a weakened barrier function.

Summary - Biological processes of the stratum corneum leading to dry skin, as described above, are - lower ceramide levels, deficient enzymes that break up desmosomes (which causes shedding skin cells to stick to each other longer than they should forming flaky sheets), lower levels of long-chain ceramides, disruption in lipid packing shapes, essential fatty acid deficiency, increased itching from a variety of mechanisms, and genetic differences which could lead to any of the above abnormalities. Discovering effective treatments for dry skin will require us to address each of these areas.

Treatment of Dry Skin - have some knowledge of treating dry skin but much more research still needs to be done to develop effective treatments. Interestingly, doctors have very inconsistent prescribing practices in treating dry skin. Patients often receive conflicting and confusing advice which causes difficulty in following a therapeutic regimen. In Great Britain, the "ABC Dry Skin and Eczema Management Programme" has been developed with a simple set of guidelines for treating dry skin. However, many substances helpful to dry skin have only fairly recently been described in the research lab and are unknown by many clinicians. Some of the agents that are known to help this problem are described below.

Glycerol - Glycerol helps with moisturization. It does so by helping desmosome bridges between stratum corneum cells to degrade so the cells can be shed appropriately. Glycerol also helps the lipid molecules between cells provide a better barrier to water. And it somehow assists in the formation of the more effective long-chain ceramides. Urea-containing creams have also been found to moisturize, although they have a higher incidence of irritation associated with them than glycerol.

Hydroxy Acids - Both alpha hydroxyacids and beta hydroxyacids assist with the proper shedding of dead skin cells. Alpha hydroxyacids encourage lipid synthesis in the intercellular areas, which improves barrier function and improves dry skin. Lactic acid, an alpha hydroxyacid, particularly improves ceramide synthesis.

Enzymes - Some topical enzymes help the desmosome connections between cells break down so the cells can come apart and be shed. The pancreatic enzyme chymotrypsin and papain, found in pineapple, both work in this way. Enzymes from a bacteria called Bacillus licheniformis are also being studied in the research lab.

Improving Lipid Synthesis - Placing the correct ratio of a substance containing the 3 major intercellular lipids (ceramides, cholesterol, fatty acids) on the skin causes an improvement in dry skin. But the ratio has to be correct and we are still working on this in the laboratory. Furthermore, aged skin seems to be more deficient in cholesterol and providing a lipid mixture with more cholesterol accelerates skin barrier recovery in older persons, but not in younger.

Niacinamide - This Vitamin B3 derivative has several beneficial effects in dry skin. It encourages synthesis of ceramides.

Linoleic acid - This is an essential fatty acid necessary for proper growth and development of the epidermis. It is also required for synthesis of the important long-chain ceramides necessary to protect against dry skin. An "essential" fatty acid refers to the fact that the substance cannot be made by the human body and must be provided in the diet. Other non-essential fatty acids, such as those found in coriander seed oil, improve dry skin by increasing ceramide synthesis.

Controlling Itch - New topical antihistamines that counteract histamine receptors in the skin will probably decrease itch in the future. Another receptor in the skin related to itching is the cannabinoid receptor (yes, the same one stimulated by marijuana) but, unlike the histamine receptor, it decreases itch. Much more research involving inhibition or stimulation of itch receptors is needed before we have substances of practical use here.

Magnesium and Calcium - Salts containing magnesium and calcium improve barrier function of the skin and help dry skin or prevent its development. As yet, though, we don’t have usable cosmetic formulations of these substances to treat dry skin.

Vitamin C - Vitamin C increases ceramide synthesis in the skin and also causes more of the long-chain beneficial ceramides to be made. Both these effects help with dry skin.

Environmental Factors - Almost everyone has noticed that dry skin is worse in the winter season. As mentioned earlier, there are differences in ceramide synthesis during winter, with a relative deficiency in the long-chain more protective ceramides. Low humidity of a dry environment, either in the winter or at other times, encourages itch by increasing mast cell number and histamine content in the skin, both of which contribute to itching. Lower humidity also changes the fatty acid content of the skin, causing dry skin. Too much exposure of the skin to water also disrupts the ability of the cells to act as an effective barrier. With aging and stress, the skin is less able to accommodate to environmental factors that may be present.

Interestingly, sick buildings have also been associated with the development of dry skin, especially dry facial skin. People with allergy were more sensitive to skin changes in the "sick buildings". The more time the person spent inside the building, the more likely he/she was to develop dry skin and itching related to it. Less frequent cleaning of the building led to more severe symptoms. High ventilation flows, passive smoking, and lack of in-room temperature controls were also associated with a higher incidence of dry skin.

Future Treatments of Dry Skin - In the future, we will increasingly begin to treat dry skin from its inner chemistry rather than being limited to slightly-effective products that we placed on top of the stratum corneum. Many of these products may still be topical (placed on the skin surface), but will act in a variety of ways to improve dry skin via biochemical manipulation. These methods will help normalize the lipid layer and cellular connections in the stratum corneum to prevent and treat dry skin. We can expect dry skin treatments to be developed based on the age of the individual, the type of climate in which they live and individual genetic differences.


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