Clinics in Dermatology (2012) 30, 286–296

Effect of moisturizers on epidermal barrier function

Marie Lodén, MSc Pharm ⁎
Eviderm Institute AB, Bergshamra Allé 9, SE-170 77 Solna, Sweden

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.

Introduction these restrictions, a daily moisturizing routine with

Large differences exist in the composition and function of
moisturizing creams. The products contain substances
considered to be actives (eg, humectants, ceramides,
essential fatty acids, vitamins, and herbal extracts) and
substances considered excipients (eg, emulsifiers, antioxi-
dants, preservatives). Finding the most suitable moisturizer
for an individual is more or less a matter of trial and error.
More knowledge about the mechanisms of the effect of
different ingredients on the skin is required, because the
actives and the excipients may both have unexpected
influences on the structure and function of the skin.
Most moisturizers on the market are regulated as
cosmetics; however, according to medical regulation in
most countries, only pharmaceuticals and medical devices
can be recommended for treatment of skin diseases. Despite
The Knowledge Foundation, Sweden, financed part of this work.
⁎ Corresponding author. Tel.: +46 708 285 832.
E-mail address: marie.loden@eviderm.se.
cosmetics is recommended by professionals as a vital part
of the management of patients with atopic dermatitis and
other dry skin conditions. 1 Moisturizers, however, may
contain allergens and some formulations also deteriorate
skin barrier function, with possible negative consequences
for the dermatitis. 2-5
Not surprisingly, more rigorous data on the effectiveness
of moisturizers have been requested. 6 A defective skin
barrier function drives disease activity in inflammatory
dermatoses. 7 Mutations in the filaggrin gene have been
identified as the major predisposing factor for atopic
dermatitis. 8,9 Filaggrin forms the natural moisturizing factor
(NMF) in the stratum corneum (SC) and is essential during
formation of the cornified envelope of corneocytes. 10,11
Individuals with mutations in the filaggrin gene are more
likely to report skin dryness. 12 Defects in the filaggrin gene
are also linked to the cytokine cascade and enhanced
penetration of environmental allergens, with consequences
for the development of dermatitis and the risks for asthma. 8
Repairing the barrier or preventing barrier dysfunction is

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
therefore an effective strategy for preventing dermatitis, as
well as asthma. The mechanistic pathways through which
mutations in the filaggrin gene predispose to atopic
dermatitis are still unclear.
The current research is focused on identifying agents that
are specifically delivered into the epidermis to assist the
cellular differentiation process or act as precursors to vital SC
components, or both. New methods facilitate development of
moisturizers for different types of dryness, which will be of
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.
Compliance and surface effects
Low treatment adherence can be a problem with topical
products. Patients can receive conflicting treatment advice,
leading to frustration, noncompliance, and difficulty in
following an effective regimen 1; therefore, the presentation
of the product can enhance the amount applied. 13 For
example, jars compared to tubes, promote use of larger
quantities (1.7 vs 0.7 mg/cm 2 per application, respective-
ly). 14 The applied dose will also differ between self-
application and operator-assisted application, where self-
application results in a larger amount applied per area. 14,15
After application of moisturizers to the skin, ingredients
can stay on the surface, be absorbed into the skin, be
metabolized, or disappear from the surface by evaporation,
sloughing off, or contact with other materials. The vehicle
used may also influence distribution within the treated
area. 16 Only 50% of applied cream may remain on the
surface after 8 hours. 17 Cream and ointments seem to allow
higher transfer of the actives to surrounding surfaces
compared with lotions and tinctures. 18
Application of moisturizers changes the surface friction 19
and smooths the skin when the spaces between partially
desquamated skin flakes are filled. 20,21 The distance between
the furrows may also decrease during the first hours after
application. 22
Topical application of lipids gives an inert, epicutaneous,
occlusive membrane that simply reduces the loss of water
from the skin. 23 The degree of suppression of transepidermal
water loss (TEWL) depends on the amount applied and the
types of lipid in the formulation. Approximately 50%
reduction in TEWL is observed after application of a thick,
greasy layer of petrolatum (3 mg/cm 2) to normal skin, 24
whereas ordinary moisturizers provide a fairly limited
decrease in TEWL. 25 The physical reduction in TEWL is
likely to be more important in barrier-abrogated skin than in
normal skin with excellent barrier properties.
In addition to reducing water loss from the skin, topically
applied lipids may be absorbed into the skin. 26-31 Increased
skin hydration and reduced scaling have been observed after
287
application of structural lipids from the SC. 32,33 Vernix
caseosa, which normally covers the skin of the developing
fetus, has also been proposed as an efficient mixture to
relieve dryness and improve skin barrier function. The
structure of vernix caseosa, with hydrated corneocytes
dispersed in a lipid matrix, is very similar to that of the
SC. A synthetic version that closely mimics the unique
composition was recently shown to improve barrier function
in barrier-abrogated mouse skin. 34
Absorption of actives
The efficacy of active ingredients is related to their
diffusion through the barrier and their concentration in the
formulation. Small soluble molecules with lipophilic and
hydrophilic properties have greater ability to cross the SC than
particles, polymers, or highly lipophilic substances. Ioniza-
tion also decreases absorption and efficacy; for example,
increasing the pH of lactic acid decreases its absorption. 35
The composition of the formulation and the solubility of
the active substance in the microenvironment of the vehicle in
contact with the skin determine the fate of the active
ingredients. The penetration is also influenced by the
emulsion structure; for example, encapsulation of a stinging
substance (lactic acid) in the inner water phase of an emulsion
reduces the stinging properties of the formulation. 36 Micellar
solubilization of the drug in the aqueous phase may also give a
lower release rate from oil-in-water emulsions. 37
Simply changing the fat content of a cream is another way
to influence the delivery of the active ingredient. 38,39 Creams
typically contain 15% to 25% lipids, but some lipid-rich
creams may contain up to 70%, and ointments may contain
almost 100% lipids.
Absorption into the skin is also influenced by the degree
of dermatitis and increases in dry and scaly skin. 40-46 The
barrier function may be impaired due to cracks in the dry skin
resulting from decreased softness and flexibility of the
SC. 47,48 The projected size of the corneocytes may also be
decreased, which increases skin permeability 49,50 because
the penetration route through the intercellular pathway
becomes shorter when the size of the corneocytes is
smaller. 50,51 A changed water gradient in the skin may
influence SC differentiation and the size of the corneocytes. 7
Dryness, however, is not always linked to higher permeabil-
ity because scaling may be confined only to the outermost
layer of the SC and a competent permeability barrier may
exist in the lower part of the SC. 52,53
Hydration and dryness—water
and desquamation
Water in the applied products immediately hydrates the
SC through absorption into the skin layer. 23 This is a short-
288 M. Lodén

lived effect because the excess water quickly evaporates if it
is not retained in the skin by active ingredients in the
formulation. Treatment with humectants will therefore
increase the amount of water held by the corneum, and
moisturizers with humectants are often superior to those
without humectants in the treatment of dry skin disorders
(Table 1). 35 , 54-68
Water is important in maintaining skin suppleness and
plasticity, but the humectants may also affect the physical
properties of the SC. The NMF and α-hydroxy acids increase
the skin's elasticity. 35 , 69-72 If the NMF is removed, water
alone cannot restore elasticity. 72 In xerotic skin, there is a
decrease in the amount of NMF in relation to the severity of
xerosis, a finding suggested to reflect decreased profilaggrin
production. 73 Reduced NMF levels have also been observed
in experimentally induced scaly skin 74 and in patients with
ichthyosis vulgaris. 73
The cohesion between the corneocytes and cell turnover
are also influenced by α-hydroxy acids at low pH. 75-77 An
abrupt loss of the entire abnormal SC can be noted,
probably due to a diminished cellular cohesion between
the corneocytes at the lowermost, newly forming levels of
the SC. 75,78 The α-hydroxy acids, especially glycolic and
lactic acid, are therefore used in the treatment of
ichthyosis. 79 The concentrations of lactic acid used for
treatment of hyperkeratotic skin have ranged up to 12%. 54
A reduced number of SC layers is also found in ichthyotic
patients after treatment with 10% urea combined with 5%
lactic acid. 80 A soft and pliable skin was obtained in seven
patients with severe ichthyosis after treatment with a 10%
urea formulation. 66
Prolonged exposure of SC to excess water induces
swollen corneocytes in the thickness dimension. 81 Swelling
of centrally located corneocytes has also been noted in
excised skin 24 hours after treatment with a thick layer (30
mg/cm 2) of pure petrolatum. 82 Other humectants, such as
glycerin, also promote swelling of corneocytes 82 Glycerin,
however, has also been suggested to induce a shrinking of
superficial corneocytes, independently of its osmotic ef-
fects. 83 This contraction was suggested to give a more
compact SC and reduce the risks for irritant contact
dermatitis. 83 Glycerin has furthermore been suggested to
facilitate the digestion of the superficial desmosomes in
individuals with dry skin 84 and to prevent crystallization of
the skin lipids at low relative humidity. 85 In dry skin the
proportion of lipids in the solid state may be increased, and
ingredients in moisturizers may then help to maintain the
lipids in a liquid crystalline state at low relative humidi-
ty. 85,86 Urea has also been suggested to protect against
osmotic stress by replacing water and retaining the liquid
crystalline phase at lower humidity. 87
Absorption of glycerin 88 and urea 89 into normal SC
can be monitored by using a simple tape-stripping
technique. Glycerin is transported very slowly into the
epidermis, and consequently, its transport rate is sensitive
to the intrinsic glycerin permeability of the basal
keratinocyte layer. The mode of action of glycerin on
SC hydration and epidermal barrier function seems to be
related to the aquaporin 3 channel. The aquaporins are a
family of small, integral membrane proteins that function
as plasma membrane transporters of water and, in some
cases, small polar solutes. 90
Desquamation of SC may be influenced not only by
humectants but also by excipients in the formulation.
Divalent ions, such as calcium, and chelating agents, such
as edetic acid (ethylenediaminetetraacetic acid) are examples
of such ingredients that promote dissociation of corneocytes
ex vivo. 91

Table 1 Effect of moisturizers on clinical dry skin symptoms

First author Active substance Control Condition Effect on dryness
54
Wehr 12% ammonium lactate Petrolatum-based cream Xerosis Improved, active better
Rogers 55 12% ammonium lactate 5% lactic acid + 2.5% Xerosis on legs Improved, active better
PCA
Siskin 56 12% ammonium lactate No therapy Dry heels Active improved
Dahl 57 12% lactate 5% lactic acid/emollient Xerosis on legs All improved, equally effective,
lotion but 12% lasted longer
Wehr 58 5% lactic acid Eucerin lotion Xerosis Improved, active better
Middleton 59 5% PCA Placebo and 10% urea Xerosis Active better than placebo,
and equal to urea
Schölermann 60 10% urea Placebo Senescent dryness on Improved
forearm
Frithz 61 4% urea + 4% sodium Placebo Asteatosis, senescent Improved, active better
chloride dryness on leg
Grice 62 10% urea with lactic acid and Vehicle Ichthyosis Improved, active better
betaine
Kuster 63 10% urea Placebo Ichthyosis in children Improved, active better
Serup 64 3% and 10% urea Untreated Dry skin Improved
PCA, pyrrolidone carboxylic acid.
Effect of moisturizers on epidermal barrier function
The risks for dryness and dermatitis in
normal skin
Limited attention has been paid to the influence of
moisturizers on the skin barrier function in normal skin,
although hydration is known to change skin permeability. 92
Changes in barrier properties and changed sensitivity to
environmental stimuli may be expected after treatment with
moisturizing creams. 2,3 , 93-96
Repeated applications of moisturizers to normal skin have
been reported to increase skin hydration without changing
TEWL. 94 A lipid-rich cream without any humectants
increased susceptibility to sodium lauryl sulfate (SLS)
irritation and nickel. 3,95 Increased skin reactivity was also
found in a long-term study using benzyl nicotinate as a
marker for permeability, where the time to maximum
response was shorter for the lipid-rich cream-treated area
compared with an untreated area. 96 In addition, the time to
onset of vasodilatation was shorter for the lipid-rich cream
than for a moisturizer containing 5% urea. 96
The influence on TEWL and skin susceptibility may not
be linked to differences in the pH value of the moisturizer,
because a formulation with pH 4.0 had the same effect on
skin barrier function as the same composition buffered to pH
7.5. 97 No differences in TEWL and skin susceptibility to
SLS were noted after repeated application of the two
formulations to healthy skin. 97 The pH-buffering capacity
of skin has been reported to be good. 98
To elucidate the effect of different oils on the skin barrier
function, a simple moisturizer with 40% hydrocarbon
(mineral oil) or 40% vegetable oil (canola) was applied to
skin for 7 weeks. Both formulations deteriorated skin barrier
function by increasing TEWL and making skin more
susceptible to SLS, and they tended to induce dryness of
the skin (Figure 1). 2
After repeated applications of urea-containing moistur-
izers, TEWL and SLS-induced irritation were both reduced
(Figure 1). 64,94,99 One placebo-controlled study showed 5%
urea was responsible for barrier improvement. 100 Not all 5%
urea formulations improve skin barrier function, however;
for example, one study found inclusion of 5% urea in a
simple canola oil cream did not improve skin barrier
function. 2 After treatment with a glycerin-containing
cream, skin barrier function improved, showing reduced
susceptibility to nickel. 95 In another placebo-controlled
moisturizer study, however, 20% glycerin had no influence
on skin barrier function. 101
Mechanisms for changes in barrier function are not fully
understood. Possible targets for barrier-influencing sub-
stances are the intercellular lipid bilayers, where the fraction
of lipids forming a fluid phase might be changed due to
compositional or organizational changes. 102 The most
tightly packed lipid barrier is the orthorhombic packing,
which depends on the presence of long-chain fatty acids in
combination with ceramide and on cholesterol mixtures
289
Fig. 1 Skin susceptibility to sodium lauryl sulphate (SLS),
measured as transepidermal water loss (TEWL), after long-term
treatment with different products. 2,3,25,94,99,101 The arrows denote
significant differences compared with control skin. The suscepti-
bility is measured as TEWL in comparison with untreated control
area. Values are presented as percentage of untreated control skin,
serving as 100% (dotted line).
being formed. 103 Toward the surface, a transition to a less
tightly packed hexagonal phase occurs, which can be
induced by sebum lipids. 104 Soaps and bathing can turn
the lipids into a more amorphous state. 28
Other targets are the projected size of the corneocytes or
the thickness of the SC; however, no changes in these were
observed after treatment with two moisturizers, with opposite
effects on the skin barrier function. One of the moisturizers
contained 5% urea in a complex cream base, whereas the
other was a simple cream with 40% mineral oil emulsified
using a polymeric emulsifier. This contrasts with the
outcome in another study, where SC thickness was decreased
and TEWL increased when healthy skin was treated with
Aqueous Cream BP. 105 These observations called into
question the continued use of this emollient on the already
compromised barrier of eczematous skin. 105
To understand the effect of occlusion without allowing
any moisturizer ingredients to be absorbed into the skin, a
semipermeable silicone membrane was attached to healthy
skin for 23 hours daily for 3 weeks. Application of the
membrane gave an immediate physical reduction in TEWL
of 1 to 2 g/m 2/h from the skin. 25 Treatment with the
membrane improved barrier function compared with the
contralateral arm serving as untreated control. As well as
TEWL, skin reactivity to SLS was reduced (Figure 1). 25
Wearing the membrane for 8 hours daily did not change the
barrier function, however. 25
Skin biopsy specimens after changes in barrier function
show that improvement of the barrier function induced by a
complex moisturizer containing 5% urea is accompanied by
decreased messenger RNA (mRNA) expression of cyclin-
dependent kinase inhibitor 1A, 106 suggesting influences in
cell cycle progression. 107,108 The barrier-deteriorating 40%
mineral oil cream increased mRNA expression of involucrin,
transglutaminase, and kallikrein 5 (ie, SC tryptic enzyme)
290
Fig. 2 Long-term treatment with barrier-deteriorating hydrocarbon
cream (grey boxes), but not with a barrier-improving 5% urea-cream
(white boxes), increased messenger RNA (mRNA) expression of
enzymes involved in the keratinization and synthesis of barrier lipids.
Values are presented as percentage of untreated control skin, serving
as 100% (dashed line). The horizontal line in the middle of each box
indicates the median; the top and bottom borders of the box mark the
75th and 25th percentiles, respectively, and the whiskers are the lines
that extend from the top and bottom of the box to the lowest and
highest observations that are inside the region defined by the
following limits: lower limit: Q1 – 1·5 (Q3–Q1); upper limit: Q3þ1·5
(Q3–Q1). Outliers are points outside the lower and upper limits and
are plotted with asterisks. Boxes with a bold border indicate
significant differences from control areas (P b .05). Invol, involucrin;
TGk, transglutaminase 1, HMG-Syn, 3-Hydroxy-3-methylglutaryl-
coenzyme A synthase 1, HMG-RED, 3-Hydroxy-3-methylglutaryl-
coenzyme A reductase; b-gluco, Beta-glucocerebrosidase; SPT-2,
serine palmitoyltransferase 2; SMPD-1, sphingomyelin phosphodi-
esterase 1, acid lysosomal. 106,109
and kallikrein 7 (ie, SC chymotryptic enzyme), the enzymes
responsible for desquamation, along with several barrier
lipid enzymes, such as the gene involved in formation of
cholesterol and genes involved in the formation of ceramides
(Figure 2). 106,109 Activation of the kallikreins suggests
increased desquamation because these two proteases are
believed to be the crucial enzymes in this process. 110,111
Moisturizers in experimental models of dryness
In experimental models of dryness and lipid depletion,
moisturizers have been reported to promote normalization of
the skin barrier function. 33,99 , 112-115 The percentage of lipids
in the cream has been hypothesized to be crucial for the effect
because the rate of recovery of experimentally damaged skin
correlated with the level of lipids in the creams. 113 Studies
also suggest differences in effects between different types of
lipids and oils, such as borage oil, canola oil, petrolatum, fish
oil, and sunflower seed oil, when they are applied to
surfactant-irritated skin. 116 Canola oil and its unsaponifi-
able-enriched fraction reduced the degree of acute irritation,
but the other oils did not significantly influence the degree of
irritation. 116 Another study showed petrolatum was absorbed
into delipidized SC and accelerated barrier recovery,
measured as TEWL. 117
M. Lodén
Physiologic lipid mixtures are another group of lipids that
have been suggested to penetrate deeper into the skin and
improve skin barrier function. 118-120 Complete mixtures of
ceramide, fatty acid, and cholesterol, or pure cholesterol,
allowed normal barrier recovery in acetone-treated murine
skin, whereas two-component mixtures of fatty acid plus
ceramide, cholesterol plus fatty acid, or cholesterol plus
ceramide delayed barrier recovery. 33 Cholesterol, as the
dominant lipid, has also accelerated barrier recovery in tape-
stripped, aged human skin 116; however, in SLS-damaged
human skin, no acceleration of barrier recovery was detected
after treatment with ceramide 3B in different emulsions. 121
Neither did a moisturizer consisting of ceramide-3, choles-
terol. and fatty acids (so-called skin-identical lipids) in a
petrolatum-rich emulsion show superiority to pure petrola-
tum in human skin damaged by SLS and tape-strippings. 118
The absorption of ceramides and the superiority of certain
lipid mixtures to other lipids thus remain to be proven in
randomized and controlled studies on humans, because no
evidence of such effects in humans appears to exist. 118,121
Lipids and nonionic emulsifiers have both been found to
influence TEWL in irritated skin. 122 In addition, humectants,
such as glycerin 112 and dexpantenol, 123 enhance skin barrier
repair in chemically irritated human skin. Another substance
that has received positive scientific attention is nicotinamide
(vitamin B3). Topical application of nicotinamide has been
reported to increase the level of barrier lipids, while
decreasing TEWL. 124 An interesting finding was that that
glycerin seems to act synergistically with lipids and reduces
xerosis more rapidly than expected, based on its influence on
skin dryness. 125
Suggestions for how to tailor moisturizers for various skin
abnormalities have been proposed. It is important to support
the results of experimental studies by data from the target
patient group, where the time course for the effect also
should be considered.
The influence on skin barrier function in
diseased skin
One might expect the impaired skin barrier function in
patients to improve in association with a reduction in the
clinical signs of dryness; however, the composition of the
moisturizer determines whether the treatment strengthens or
deteriorates the skin barrier function (Figure 1). In one study,
for example, the abnormal TEWL remained high in patients
with psoriasis after the plaques were treated with an emulsion
containing glycerin, despite visible relief of the dryness
symptoms, 126 and similar results were found in cleaners and
kitchen workers after treatment with a lipid-rich cream. 127
Furthermore, no evidence of changes in the skin barrier
function was noted after long-term treatment of normal and
atopic skin with 20% glycerin. 128 Another 20% glycerin-
containing moisturizer was beneficial during the dry, cold
Effect of moisturizers on epidermal barrier function
season but was not equally effective in dry, atopic patients in
the less arid seasons. 129
In atopic children, one physiologic lipid mixture de-
creased TEWL and improved dryness. 119 One moisturizer
with 5% urea also reduced TEWL in atopic patients 130 and
made skin less susceptible to irritation to SLS. 131 Another
urea-containing moisturizer was also found to be superior to
a glycerin moisturizer in lowering TEWL in a double-blind
study of atopic patients. 128 Also in ichthyotic 62 and
psoriatic patients 132 TEWL has been reported to be reduced
by treatment with moisturizers containing urea. In addition,
15% glycolic acid, with and without occlusion, lowered
TEWL in patients with psoriasis. 133
Although lactic acid has been suggested to stimulate
ceramide synthesis and improve skin barrier function, 134,135
increased TEWL was noted in patients with lamellar
ichthyosis after treatment with 5% lactic acid combined
with 20% propylene glycol. 136 Treatment with a lotion with
15% glycolic acid also increased TEWL and the suscepti-
bility to topically applied irritants in elderly patients with
xerotic legs. 137 Treatment of atopics with ammonium lactate
did not change the elevated TEWL. 5
Prevention of dermatitis in atopics and
patients with hand dermatitis
In the treatment of atopic dermatitis, moisturizers are
considered to offer a steroid-sparing alternative to topical
corticosteroids. 138 In children with atopic dermatitis, the
addition of a moisturizer reduced the need for corticosteroids
to control the disease severity. 139 The addition of a
moisturizer and a mild cleanser to corticosteroid therapy
also enhanced the degree of clearance of the dermatitis. 140
Repairing the barrier or preventing barrier dysfunction are
important strategies for reducing the risks in dermatitis and
prolonging the time to relapse of dermatitis. 141,142 To my
knowledge, however, only one published clinical study has
investigated the delay in dermatitis relapse after treatment
with moisturizer in patients with atopic dermatitis 143 ;
furthermore, only one study appears to exist where the
relapse of hand dermatitis has been monitored during
treatment with and without moisturizers. 144
In the atopic study, a strong corticosteroid cream was used
to first cleared the dermatitis before patients were randomized
to treatment with a urea-containing cream, or no treatment for
a maximum period of 26 weeks. 143 The results showed the
medium number of dermatitis-free days was than 26 weeks in
the cream group and 4 weeks in the control group (Figure 3).
The probability of not having a relapse during the 26-week
period was 68% in the moisturizer group and 32% for those
not using the moisturizer, which resulted in a 53% relative
risk reduction and 36% absolute risk reduction.
In the hand dermatitis study, the time to dermatitis relapse
was prolonged in the patients who used the urea-containing
291
Fig. 3 The influence of moisturizers on transepidermal water
loss (TEWL) in skin barrier diseases, as reported in clinical
studies 5,62,119,126,127,130,136. The diagram shows a simplified relation-
ship between the SC water content and TEWL.
cream. 144 The median time to relapse showed a 10-fold
difference between the urea moisturizer (20 days) and no
treatment (2 days). The shorter time to relapse in the hand
dermatitis patients compared with the atopic patients was
likely due to the higher vulnerability of hands, which are
frequently exposed to external stressors.
The results from the barrier-strengthening urea cream study
could be compared with results from similar studies focusing
on long-term disease control using anti-inflammatory agents.
Although these studies have slightly different designs, the
results suggest that a barrier-strengthening moisturizer may
prevent relapse of dermatitis to a comparable extent as
intermittent treatment with anti-inflammatory medicinals on
controlled atopic dermatitis (Table 2). 143 , 145-149 The close
similarity in relapse rate between the barrier-strengthening
cream with 5% urea and the reported anti-inflammatory
treatments suggests that the use of barrier-improving
treatments is effective in the prevention of dermatitis.
Whether a similar delay in the flare-up of dermatitis would
be seen with a moisturizer without barrier-improving
properties has yet to be studied (Figure 4). Notably, the
time to dermatitis relapse in the reported vehicle groups are
compatible with the hypothesis that certain moisturizers
actually promote the development of dermatitis (Table 2). In
one of the cited studies, the relapse of dermatitis was induced
within 10 days in most of of the patients, despite the use of
bland emollients to control the dermatitis. 145 The authors also
noted that some patients appeared to have derived benefit
from treatment with certain emollients because no relapse
was noted. 145
Conclusions
Moisturizers affect the SC architecture and barrier
homeostasis, that is, topically applied ingredients are not as
inert to the skin as one might expect. A number of different
292 M. Lodén

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.

mechanisms behind the barrier-influencing effects of mois- References

turizers have been suggested, such as simple deposition of
lipid material outside the skin. Ingredients in the moisturizers
may also change the lamellar organization and the packing of
the lipid matrix and thereby change skin permeability.
Topically applied substances may penetrate deeper into the
skin and interfere with the production of barrier lipids and the
maturation of the corneocytes. Creams may influence the
desquamatory proteases and change the thickness of the SC.
Clinical consequences of potential differences in the
efficacy of moisturizers include differences in hydrating
properties, effects on visible dryness symptoms, and even
more importantly, the likelihood of reduced risks of
dermatitis outbreak in patients with atopic dermatitis
(Figure 3). Restoring skin barrier function (eg, in people
with defects in the filaggrin gene), may therefore help
Fig. 4 Time to outbreak of eczema in patients with controlled
atopic eczema being treated with a barrier-improving moisturizer,
being untreated or a being treated with a potentially barrier-
deteriorating moisturizer (suggested to promote relapse of eczema).
The figure is modified from Wiren et al. 143
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