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Skin Research and Technology 2001; 7: 209–213
Copyright CMunksgaard 2001
Printed in Denmark. All rights reserved Skin Research and Technology
ISSN 0909-752X
Instrumental and dermatologist evaluation of the effect of
glycerine and urea on dry skin in atopic dermatitis
M. Lode
´n
1
, A.-C. Andersson
2
, C. Andersson
3
, T. Frödin
3
, H. Öman
3
and M. Lindberg
4
1
ACO Hud AB, Stockholm,
2
Department of Dermatology, University Hospital, Uppsala,
3
Department of Dermatology,
Linköping University Hospital, Linköping,
4
Department of Medicin, Occupational Dermatology, Karolinska Institute, Stockholm, Sweden
Background/aims: Moisturising creams are useful treatment
adjuncts in inflammatory dermatoses and have beneficial effects
in the treatment of dry, scaly skin. The effects on dryness and
skin permeability of a new moisturising cream with 20% glycerine
was compared with its placebo and with a medicinally authorised
cream with 4% urea (combined with 4% sodium chloride) in the
treatment of dry skin.
Methods: Patients (
n
Ω109) with atopic dermatitis were treated
for 30 days with a moisturiser in a randomised, parallel and
double-blind fashion. Transepidermal water loss (TEWL) and
skin capacitance were assessed instrumentally, and changes in
the dryness of the skin were assessed by the dermatologist.
Results: No difference in TEWL was found between glycerine
treatment and its placebo, whereas a lower value was found in
A
TOPIC DERMATITIS
is a common, chronically relaps-
ing skin disorder, usually beginning in child-
hood. Moisturising creams are useful treatment ad-
juncts in such inflammatory dermatoses and have
beneficial effects in the treatment of dry, scaly skin
(1). However, although clinical experience suggests an
important role for moisturisers, more scientific studies
are considered essential to demonstrate possible dif-
ferences in mechanism and effect (2).
Moisturising creams occlude the skin and contain
humectants to increase its water content. Widely used
humectants are urea, lactic acid, PCA and glycerine.
Glycerine and urea diffuse into the stratum corneum
(3–5) and increase the water-holding capacity of nor-
mal stratum corneum and of scales from psoriatic and
ichthyotic patients (6–9). The humectants relieve clin-
ical signs of dryness, such as scaling (10–12), and
glycerine has also been shown to increase the rate of
corneocyte loss from the superficial surface of human
skin, probably due to an enhanced desmosome degra-
dation (13). Glycerine has also been proposed to in-
fluence the crystalline arrangement of the intercellular
bilayer lipids (14). The bulk of the bilamellar sheets of
the lipids has been suggested to be in crystalline/gel
209
the urea-treated area compared to the glycerine-treated area. No
difference in skin capacitance was found. The clinical assess-
ment of dryness showed urea to be superior to glycerine in treat-
ing the condition.
Conclusions: Moisturising creams are different, not only with
respect to composition but also with respect to their influence on
skin as a barrier to water in patients with atopic dermatitis.
Key words: moisturiser – dry skin – cream – emollient – per-
meability barrier – transepidermal water loss
c
Munksgaard, 2001
Accepted for publication 28 January 2001
domains bordered by lipids in a fluid crystalline state
(15). In dry skin, the proportion of lipids in the solid
state is suggested to be elevated, and glycerine may
then help to maintain the lipids in a liquid crystalline
state at low relative humidity (14).
The influence of glycerine on the intercellular lipids
may have consequences for the permeability of the
skin. Studies on normal skin show that a single appli-
cation of an aqueous solution of glycerine reduces
transepidermal water loss (TEWL) for some hours (6),
whereas repeated application of 20% glycerine in a
cream did not change TEWL or skin susceptibility to
sodium lauryl sulphate (SLS) in a placebo-controlled
study on normal skin (16). In tape-stripped and ace-
tone-treated skin, a single application has been shown
to decrease skin sensitivity to alkali, SLS and di-
methylsulfoxide, but to increase the bioavailability of
hexyl nicotinate (17). The other humectant, urea, has
been found to decrease TEWL in normal and dry skin
(8, 18–20) and to decrease skin sensitivity to SLS-in-
duced irritation (18, 19), but to be a penetration en-
hancer for some drugs (21–23).
Although moisturisers with various compositions
are used extensively on patients with atopic derma-
Lode
´n et al.
titis, controlled studies of their effects on dryness and
skin permeability are few. The aim of the present
study was to investigate the effect on dryness and
skin permeability of a 20% glycerine cream and its
placebo on patients with atopic dermatitis and to
compare the effect with an established cream contain-
ing urea (4%) and sodium chloride (4%). The effect
was judged by an expert (dermatologist) and meas-
ured as transepidermal water loss and skin capaci-
tance.
Material and Methods
Subjects
The study was randomised, double-blind and per-
formed on three parallel groups in February to April
of the same year. In total, 110 patients (93 women and
16 men) with atopic dermatitis [according to criteria
of Hanfin & Rajka (24)], but with no other significant
concurrent illness and no known allergy to ingredi-
ents in the test creams, were included. One patient
dropped out.
The mean age ∫the standard deviation (SD) was
34∫11 years in the glycerine group, 34∫13 years in
the urea group and 33∫11 years in the placebo group.
One area on the body was identified as dry by the
dermatologist and was treated twice daily for 30 days
with the cream. Among the 109 patients, the majority
(87 patients) treated one area on the upper or lower
forearm, 8 patients treated one area on the back, 8
treated the dorsal aspect of the hand and 6 treated one
area on the leg. The patients were asked to replace
their ordinary moisturiser by the test cream. The local
ethics committees approved the study, and informed
consent was obtained.
Test products
The glycerine cream contained 20% glycerine, aqua,
petrolatum, canola, mineral oil, cetearyl alcohol, gly-
ceryl stearate, dimethicone, PEG-100 stearate, glyceryl
polymethacrylate, cholesterol, propylene glycol,
methylparaben and propylparaben. Glycerine was re-
placed by water in the placebo cream. The urea cream
contained 4% urea and 4% sodium chloride as water-
binding substances in an oil-in-water emulsion, pH
about 5. Other ingredients were paraffinum liquidum,
PEG-5 glycerylstearate, cetyl alcohol, stearyl alcohol,
stearic acid, trometamol, methylparaben, propylpar-
aben, hydrochloric acid and water.
Evaluations
The expert assessment of severity of the dry skin was
done at the start of the study and after 30 days, ac-
210
cording to a newly proposed system for dry skin and
ichthyosis (25). Scaling, roughness, redness and cracks
(fissures) in the identified area were scored from 0 to
4, and the sum of the severity score was calculated
(maximum 16). The same expert evaluated the patient
at the start of and end of the study, and the evalu-
ations were performed in the same room and with the
same light conditions.
TEWL and skin capacitance were measured before
the first application of the creams (i.e., at day 0) and at
day 31. TEWL was quantified using an evaporimeter
(Servomed, Kinna, Sweden) (26). The probe is
equipped with a screen and grid to reduce air convec-
tion. The electrical capacitance, indicating degree of
skin hydration (27, 28), was measured with a Corneo-
meter CM-820 and CM-825 (Courage and Khazaka
GmbH, Cologne, Germany). During measurements,
noise and talk in the room were restricted. Measure-
ments were made in a temperature-controlled room.
Calculations and statistics
Side-by-side box-and-whisker plots are used to dis-
play the data. The box is defined by the upper and
lower quartiles and with the median marked by a sub-
division of the box. The whiskers have a maximum
length in terms of the interquartile range, and outliers
are shown (Minitab Statistical Software, Minitab Inc.,
State College, PA, USA). A Spearman rank correlation
(nonparametric) test was used to quantify the degree
of linear association between the change in TEWL and
the dryness score.
Statistical significances between the glycerine cream
and the other two treatments were tested using the
Mann-Whitney rank sum test. P⬍0.025 was con-
Fig. 1. Skin barrier function measured as TEWL at the start of the
study and after 30 days of treatment with glycerine (nΩ40), urea (nΩ
35) and placebo (nΩ34).
Evaluation of glycerine and urea in atopic dermatitis
sidered as significant for each of the two comparisons
to obtain an overall significance level of P⬍0.05.
Results
After treatment for 30 days, a significantly lower
TEWL was found in the area treated with urea com-
pared to the area treated with glycerine (PΩ0.021)
(Fig. 1). No difference was found between the glycer-
ine treatment and the placebo treatment (PΩ0.419). A
lower value of the dryness score was also found in
the area treated with urea compared to the area
treated with glycerine (PΩ0.024), while no difference
was found between the glycerine-treated area and the
placebo-treated area (PΩ0.419) (Fig. 2). One patient in
the glycerine group and four patients in the placebo
Fig. 2. Skin dryness severity score at the start of the study and after
treatment for 30 days with glycerine (nΩ40), urea (nΩ35) and placebo
(nΩ34).
Fig. 3. The mean value of the sum of the dryness severity score and
the mean value for the four parameters for dryness at the start of the
study and after treatment for 30 days with glycerine (nΩ40), urea
(nΩ35) and placebo (nΩ34).
211
Fig. 4. Skin capacitance (A.U.) measured with a Corneometer at the
start of the study and after treatment for 30 days with glycerine (nΩ
40), urea (nΩ35) and placebo (nΩ34).
Fig. 5. Multiple scatter plot displaying the relationship between the
change in TEWL and in dryness score (note: a positive change indi-
cates improved skin). Glycerine is plotted with the symbol A and urea
with the symbol B. If several points fall on the same spot, a count is
given. If the count is over 9, a πis used.
group showed more dryness after the treatment
period. No patient showed more dryness in the urea/
sodium chloride group.
The analysis of possible influences on the four
characteristics of dryness (scaling, roughness, redness
and cracks) showed no obvious difference on scaling
and roughness between the treatments (Fig. 3). How-
ever, glycerine might have had less influence on red-
ness and cracks than the other treatments. In six pa-
tients redness increased and in seven redness de-
creased during treatment with glycerine. In the pla-
cebo group, four patients showed an increased red-
ness, whereas no patients in the urea group showed
increased redness at the end of the study.
No difference in skin capacitance was detected at
day 31 between glycerine and urea, or between
Lode
´n et al.
glycerine and placebo, although the value tended to
be higher in the glycerine-treated area than in the pla-
cebo-treated area at day 31 (PΩ0.076) (Fig. 4).
The association between the change in dryness
score and the change in TEWL was significant (rΩ
0.332, PΩ0.0004). The individual data from the areas
treated with glycerine and urea can be observed in a
multiple scatter plot (Fig. 5).
Discussion
The relationship between degree of skin dryness and
TEWL is complex (29, 30). Elevated levels can be
found both in hyperhydrated (31) and in dry skin,
e.g., in atopic patients (32). The value is usually lowest
in normal appearing skin. However, a low value may
also be found in skin that appears to be dry, since
the major permeability barrier may be confined to the
lower part of the stratum corneum and the dryness to
the outermost stratum corneum (30) – i.e., the defects
can be localized at different depths of the stratum
corneum. Therefore, a change in the appearance of
dryness due to various treatments may not necess-
arily reflect a simultaneous change in TEWL.
In the present study, a significant relationship was
noted between the improvement in clinical signs of
dryness and reduction in TEWL. The clinical evalu-
ation of dryness showed the improvement from
glycerine treatment to be less pronounced compared
to the improvement from treatment with urea/so-
dium chloride. However, this was not supported by
the skin surface capacitance measurements, where no
difference between the two areas was detected. Nei-
ther could we observe a statistically significant in-
crease in capacitance in the glycerine-treated area
compared to its placebo, which is in contrast to a pre-
vious study on normal skin, where higher capacitance
levels were obtained after 10 days treatment (16).
However, in the study on normal skin, paired com-
parisons were made, which give less variability and
thus increases the possibility to detect statistically sig-
nificant differences. Moreover, data from corneometer
readings might be difficult to interpret. Corneometer
measurements are claimed to reflect the hydration sta-
tus of the skin, but can be influenced by other agents
than water – for instance, by body hair and cream
residues (33, 34). The active ingredients in the creams
tested, urea and glycerine, can also induce changes in
keratin dipole orientation and thereby affect the elec-
trical properties of the skin (28).
No evidence of deterioration of the permeability
barrier from glycerine treatment was found when
TEWL for glycerine-treated and placebo-treated skin
212
was compared, although glycerine has been proposed
to be able to influence the structure of the bilayer
lipids (14). A significantly lower TEWL was found in
the urea-treated skin, than in the glycerine-treated
skin. This is in accordance with previous findings
where TEWL was reduced by treatment with urea-
containing preparations, both in dry and in normal
skin (8, 18–20, 35), whereas several urea-free moisturi-
sers appear to cause no major changes in TEWL in dry
or in normal skin (16, 18, 36–38). Other ingredients in
topical preparations may also affect the skin barrier
function. Five of the excipients in the emulsions have
also been studied using non-invasive instruments,
and no deterioration in skin barrier function could be
detected following application of canola oil, petrol-
atum, stearic acid, glyceryl stearate or PEG-100 stear-
ate to normal and surfactant-irritated skin (39, 40). In-
stead, canola oil reduced the damage in surfactant-
irritated skin (40).
In conclusion, the chemical composition of
moisturising creams is highly variable. The differ-
ences will inevitably cause differences not only in the
hydrating power of the moisturisers but also in their
influence on the skin barrier function. The results in
the present study suggest that suitable formulations
containing urea might be superior to glycerine-con-
taining emulsions, if improvement in skin barrier
function in dry atopic skin is considered important.
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Address:
Marie Lode
´n
ACO Hud AB
Box 622
SE-194 26 Upplands Väsby
Sweden
Tel: 46 8 6223651
Fax: 46 8 6223680
e-mail: marie.loden/acohud.se
