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Prepared
by: Dr. Charlene DeHaven, Clinical Director
乾燥肌膚 ©
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.
References
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