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Abstract A daily moisturizing routine is a vital part of the management of patients with atopic dermatitis
and other dry skin conditions. The composition of the moisturizer determines whether the treatment
strengthens or deteriorates the skin barrier function, which may have consequences for the outcome of
the dermatitis. One might expect that a patient's impaired skin barrier function should improve in
association with a reduction in the clinical signs of dryness. Despite visible relief of the dryness
symptoms, however, the abnormal transepidermal water loss has been reported to remain high, or even
to increase under certain regimens, whereas other moisturizers improve skin barrier function. Differing
outcomes have also been reported in healthy skin: some moisturizers produce deterioration in skin
barrier function and others improve the skin. Possible targets for barrier-influencing moisturizing creams
include the intercellular lipid bilayers, where the fraction of lipids forming a fluid phase might be
changed due to compositional or organizational changes. Other targets are the projected size of the
corneocytes or the thickness of the stratum corneum. Moisturizers with barrier-improving properties
may delay relapse of dermatitis in patients with atopic dermatitis. In a worst-case scenario, treatment
with moisturizing creams could increase the risks of dermatitis and asthma.
© 2012 Elsevier Inc. All rights reserved.
0738-081X/$ – see front matter © 2012 Elsevier Inc. All rights reserved.
doi:10.1016/j.clindermatol.2011.08.015
Effect of moisturizers on epidermal barrier function 287
therefore an effective strategy for preventing dermatitis, as application of structural lipids from the SC. 32,33 Vernix
well as asthma. The mechanistic pathways through which caseosa, which normally covers the skin of the developing
mutations in the filaggrin gene predispose to atopic fetus, has also been proposed as an efficient mixture to
dermatitis are still unclear. relieve dryness and improve skin barrier function. The
The current research is focused on identifying agents that structure of vernix caseosa, with hydrated corneocytes
are specifically delivered into the epidermis to assist the dispersed in a lipid matrix, is very similar to that of the
cellular differentiation process or act as precursors to vital SC SC. A synthetic version that closely mimics the unique
components, or both. New methods facilitate development of composition was recently shown to improve barrier function
moisturizers for different types of dryness, which will be of in barrier-abrogated mouse skin. 34
benefit in the treatment and prevention of dry skin and skin
barrier disorders. In the present overview, the effects of
moisturizers on skin dryness, barrier function, and preven-
tion of dermatitis are briefly discussed.
Absorption of actives
lived effect because the excess water quickly evaporates if it excised skin 24 hours after treatment with a thick layer (30
is not retained in the skin by active ingredients in the mg/cm 2) of pure petrolatum. 82 Other humectants, such as
formulation. Treatment with humectants will therefore glycerin, also promote swelling of corneocytes 82 Glycerin,
increase the amount of water held by the corneum, and however, has also been suggested to induce a shrinking of
moisturizers with humectants are often superior to those superficial corneocytes, independently of its osmotic ef-
without humectants in the treatment of dry skin disorders fects. 83 This contraction was suggested to give a more
(Table 1). 35 , 54-68 compact SC and reduce the risks for irritant contact
Water is important in maintaining skin suppleness and dermatitis. 83 Glycerin has furthermore been suggested to
plasticity, but the humectants may also affect the physical facilitate the digestion of the superficial desmosomes in
properties of the SC. The NMF and α-hydroxy acids increase individuals with dry skin 84 and to prevent crystallization of
the skin's elasticity. 35 , 69-72 If the NMF is removed, water the skin lipids at low relative humidity. 85 In dry skin the
alone cannot restore elasticity. 72 In xerotic skin, there is a proportion of lipids in the solid state may be increased, and
decrease in the amount of NMF in relation to the severity of ingredients in moisturizers may then help to maintain the
xerosis, a finding suggested to reflect decreased profilaggrin lipids in a liquid crystalline state at low relative humidi-
production. 73 Reduced NMF levels have also been observed ty. 85,86 Urea has also been suggested to protect against
in experimentally induced scaly skin 74 and in patients with osmotic stress by replacing water and retaining the liquid
ichthyosis vulgaris. 73 crystalline phase at lower humidity. 87
The cohesion between the corneocytes and cell turnover Absorption of glycerin 88 and urea 89 into normal SC
are also influenced by α-hydroxy acids at low pH. 75-77 An can be monitored by using a simple tape-stripping
abrupt loss of the entire abnormal SC can be noted, technique. Glycerin is transported very slowly into the
probably due to a diminished cellular cohesion between epidermis, and consequently, its transport rate is sensitive
the corneocytes at the lowermost, newly forming levels of to the intrinsic glycerin permeability of the basal
the SC. 75,78 The α-hydroxy acids, especially glycolic and keratinocyte layer. The mode of action of glycerin on
lactic acid, are therefore used in the treatment of SC hydration and epidermal barrier function seems to be
ichthyosis. 79 The concentrations of lactic acid used for related to the aquaporin 3 channel. The aquaporins are a
treatment of hyperkeratotic skin have ranged up to 12%. 54 family of small, integral membrane proteins that function
A reduced number of SC layers is also found in ichthyotic as plasma membrane transporters of water and, in some
patients after treatment with 10% urea combined with 5% cases, small polar solutes. 90
lactic acid. 80 A soft and pliable skin was obtained in seven Desquamation of SC may be influenced not only by
patients with severe ichthyosis after treatment with a 10% humectants but also by excipients in the formulation.
urea formulation. 66 Divalent ions, such as calcium, and chelating agents, such
Prolonged exposure of SC to excess water induces as edetic acid (ethylenediaminetetraacetic acid) are examples
swollen corneocytes in the thickness dimension. 81 Swelling of such ingredients that promote dissociation of corneocytes
of centrally located corneocytes has also been noted in ex vivo. 91
Table 2 Effect of maintenance treatment on the time to prevent the development of atopic dermatitis and halt the
outbreak of eczema in patients with controlled atopic development and progression of allergic disease, such as
dermatitis asthma. 150 Evidence from two randomized studies showed
Treatment Days to No relapse during that a moisturizer with barrier-improving properties delayed
outbreak observation period relapse of dermatitis in patients with atopic dermatitis 143 and
hand dermatitis. 144 In a worst-case scenario, treatment with
(median) % Weeks
moisturizing creams could increase the risks for dermatitis
Barrier-strengthening N180 68 26 and asthma.
moisturizer 143 The increased understanding of the interactions between
No treatment 30 32
topically applied substances and the epidermal biochemis-
Pimecrolimus 145 N190 …
Vehicle 67 try will enhance the possibilities to tailor skin care products
Pimecrolimus 146 … 45 24 for various SC abnormalities. Whether moisturizers
Vehicle 19 strengthen or weaken the skin barrier function is easily
Tacrolimus 147 142 57 52 monitored using noninvasive bioengineering techniques.
Vehicle 15 20 Measurement of TEWL may be a proper surrogate
Pimecrolimus 148 … 60 24 parameter for the prevention or promotion of the outbreak
Vehicle 22 of flares by moisturizer treatment in dermatitis-prone
Corticosteroid N112 80 16 individuals. Treatment recommendations should be based
intermittent 149 on evidence, and the use of barrier-improving moisturizers
Vehicle 42 30 should be encouraged.
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