Professional Documents
Culture Documents
a
Department of Dermatology and Allergy, Clinical Research Center for Hair and Skin Science, Charité-Universitätsmedizin
Berlin, and Departments of b Medical Statistics and Clinical Epidemiology, c Physical Medicine and Rehabilitation and
d
Allergy Center, Department of Dermatology and Allergy, Charité-Universitätsmedizin Berlin, Berlin, Germany
Key Words atopic predisposition may improve their skin condition dur-
Skin barrier · Emollient · Transepidermal water loss · ing daily emollient application. PIPJ-based formulations
Stratum corneum hydration · Skin pH · Atopic dermatitis · may be helpful to maintain skin barrier integrity.
Children · Dry skin · TEWL · Ice plant © 2014 S. Karger AG, Basel
Abstract Introduction
Background: Dry skin reflects a skin barrier defect which can
lead to atopic dermatitis. Little is known about the distinct Dry skin has a high prevalence in children and is most
effects of emollient use in children with dry skin and atopic commonly a symptom of underlying atopic dermatitis
predisposition. Objectives: We investigated the effects of (AD) [1]. An impaired skin barrier function is typically
daily application of pressed ice plant juice (PIPJ)-based found in dry skin, which exhibits increased values of tran-
emollients and petrolatum-based emollients. Methods: sepidermal water loss (TEWL) and skin surface pH (pH)
Children aged 2–6 years with dry skin and atopic predisposi- [2–5]. In addition, this epidermal barrier insufficiency is
tion were randomized into 2 groups: group 1 received emol- reflected by a decrease in stratum corneum hydration
lients containing PIPJ and natural lipids, while group 2 re- (SCH) and decreased amounts of natural moisturizing
ceived petrolatum-based emollients. Skin condition and factor (NMF) [6–10]. Compared with adult skin, the in-
biophysical properties of the skin barrier were assessed at fantile skin barrier is going through a process of matura-
inclusion and weeks 4, 12 and 16. Results: Skin condition tion as water-handling properties of the stratum corneum
improved significantly in all children. Comparing the groups, (SC) are found to be less strongly developed [11]. Regard-
children treated with emollients containing PIPJ showed ing this continuous state of development, the skin of chil-
significantly higher stratum corneum hydration values and dren exhibits a pronounced susceptibility to various ex-
significantly lower transepidermal water loss values at week ternal and environmental factors, including inadequate
16 on the forearm and forehead. A significant decrease in skin care, water hardness or infant swimming practices
skin pH was noted in group 2 on the forearm and forehead; [12, 13]. This can lead to a perturbation of the fragile skin
group 1 showed a stable course. Conclusion: Early interven- barrier homeostasis, resulting in a dry skin condition [9,
tion with emollients in children with dry skin condition and 13–15]. Previous studies investigating infants with healthy
their effect on skin barrier properties [19, 20]. This study or ≥38.5 ° C); congenital and/or contagious skin disorders; skin
aimed at investigating the effects of emollient application irritation affecting measurements; current treatment with topical
on skin barrier integrity in children with dry skin and or systemic corticosteroids or macrolides; any topical or system-
ic therapy within 4 months prior to inclusion lasting longer than
predisposition to AD. In this study, different types of 3 days with corticosteroids, pimecrolimus or antihistamines; fur-
emollients – plant-based emollients containing pressed ther phototherapy; and participation in another study. Siblings
ice plant juice (PIPJ) and petrolatum-based emollients – were not enrolled, to avoid unblinding of the study products.
were evaluated regarding their clinical and biophysical After obtaining written informed consent from both legal
effects on skin barrier function by daily application. guardians, the eligible children (n = 47) were randomly assigned
to two different intervention groups, using concealed random al-
location [25] by a person not involved in the study. Randomization
was performed using block randomization with a block length of
Methods 4. Block randomization was generated by the trial statistician.
Use of Emollients in Children with Atopic Skin Pharmacol Physiol 2014;27:208–216 209
Predisposition DOI: 10.1159/000360546
Enrollment Screening: n = 50 Excluded: n = 3
Randomized: n = 47 molluscum contagiosum: n = 1
TCS >3 days: n = 1
examination refused: n = 1
Allocation
G1: G2:
allocated: n = 24 allocated: n = 23
Follow-up
Dropout: n = 1 Dropout: n = 1
V1: n = 23 V1: n = 22
TCS >3 days: n = 1 lost contact: n = 1
Follow-up
Dropouts: n = 2
Dropout: n = 1
V2: n = 22 V2: n = 20 withdrawn consent: n = 1
request of participant: n = 1
time difficulties: n = 1
Follow-up
Dropouts: n = 2 Dropouts: n = 2
V3: n = 20 V3: n = 18
TCS >3 days: n = 2 TCS >3 days: n = 2
Analysis
Study completed regularily G1: n = 20 Study completed regularily G2: n = 18
Fig. 1. Flow diagram. In total, there were 3 dropouts in G1 and 2 dropouts in G2; those participants had used TCS
for >3 days. TCS = Topical corticosteroids.
body surface excluding the face, followed by application of the Statistical Methods
cream to the face and to the entire forearm. No other emollients Descriptives included absolute and relative frequencies for cat-
were allowed except sunscreen; however, the parents were in- egorial measurements, and mean, standard deviation (SD), medi-
structed to use physical sun protection [5]. The parents were ad- an and range for quantitative measurements. Univariate between-
vised to retain their routine bathing procedures with the usual group comparisons were performed using the χ2 test for categorial
cleaning products. Last application of emollients was more than and the Mann-Whitney U test for quantitative variables. For be-
12 h before measurements. Additionally, no bathing, use of sun- tween-visit comparisons with regard to skin functional parameters
screen or sports was allowed within 12 h prior to data collection. and SCORAD, the Wilcoxon test was used. Correlation analyses
concerning associations between quantitative measurements were
Outcome Variables and Clinical Evaluations done using Spearman’s correlation coefficient. p < 0.05 (two-sid-
The primary outcome variable was SCH on the forearm. Sec- ed) was considered significant. No Bonferroni correction was per-
ondary outcome variables were TEWL, pH and Scoring Atopic formed. All statistical analyses were performed with the commer-
Dermatitis (SCORAD) [26–32]. TEWL, SCH and pH were as- cially available software SPSS version 20 [33].
sessed noninvasively using a Tewameter® TM 300, Corneome- Sample size calculation, which was conducted with the com-
ter® CM 825 and Skin-pH-Meter® PH 905 (Courage + Khazaka, mercially available software nQuery Advisor 6.0, was based on
Cologne, Germany) according to standardized protocols [17] un- mean differences in development of the primary endpoint SCH
der standardized ambient conditions (room temperature: 22– between V0 and V3 with n = 26 children per group. A power of
26 ° C; relative humidity: 40–60%; adaption period: at least 10 min,
80% with a difference in means of 5 (SD = 8) could be shown on a
with the investigational areas not covered by clothing). Skin func- two-sided significance level of α = 0.05.
tional parameters were assessed at each visit in 3 defined investi-
gational areas: (1) the forehead, (2) the right midvolar forearm
and (3) the right midlateral thigh. Measured skin sites were free Results
of eczematous involvement. If the right side of the body could not
be assessed at inclusion, the left side was chosen for all measure-
ments. Skin condition was evaluated at each visit by visual scoring In total, 38 children completed the study (fig. 1). The
using SCORAD. Besides the criteria erythema, edema, crust, ex- baseline characteristics of both groups were comparable
coriation and lichenification, this score also evaluates skin dry- except for age (table 2). Each body region represented an
ness and subjective symptoms like pruritus and sleep loss. So far, application area for either cream (forehead) or lotion
a validated clinical scoring for the target population is missing and
data are only available from children with AD. Therefore, (leg) or both preparations (forearm; table 1). Skin func-
SCORAD was chosen to quantify dryness intensity and to com- tional parameters showed different values and develop-
pare our results with others. ment depending on the body region investigated.
G1 G2 p
(n = 24) (n = 23) G1 vs. G2
Values denote means ± SD unless specified otherwise. Data in parentheses are percentages.
1 Information given by parents during anamnesis; represents a subjective interpretation of different reactions
Table 3. Stratum corneum hydration (AU) Table 4. Transepidermal water loss (g/m2/h)
Group Baseline Week 4 Week 12 Week 16 Group Baseline Week 4 Week 12 Week 16
Forehead G1 43.9±9.5 46.3±8.4 49.3±10.8 49.8±9.9 Forehead G1 10.6±4.3 7.9±2.3 10.2±4.1 9.2±2.4
G2 41.7±10.3 40.8±12.8 44.6±11.7* 38.4±10.9 G2 12.2±6.3 14.9±8.2 12.5±6.6 11.4±3.5
G1 vs. n.s. n.s. n.s. p = 0.004 G1 vs. n.s. p < 0.001 n.s. p = 0.024
G2 G2
Forearm G1 36.3±9.1 42.4±7.1* 43.4±8.5* 40.6±7.3 Forearm G1 9.3±2.2 10.0±6.9 8.3±1.6* 8.6±2.2
G2 32.8±7.8 36.1±10.6 35.9±11.5 33.1±7.9 G2 10.7±4.1 10.5±3.7 10.7±3.2 10.0±2.8
G1 vs. n.s. p = 0.040 p = 0.033 p = 0.006 G1 vs. n.s. n.s. p = 0.008 p = 0.039
G2 G2
Leg G1 32.3±8.4 37.2±7.1* 39.0±7.0* 35.7±9.4 Leg G1 11.5±3.7 9.8±3.8* 10.6±2.3 11.7±3.6
G2 27.5±9.3 35.1±11.3* 33.7±8.6* 29.2±7.7 G2 11.0±2.9 10.6±3.4 12.4±8.1 11.9±3.8
G1 vs. p = 0.030 n.s. p = 0.046 p = 0.038 G1 vs. n.s. n.s. n.s. n.s.
G2 G2
Values denote means ± SD unless specified otherwise. n.s. = Values denote means ± SD unless specified otherwise. * p <
Not significant. * p < 0.05: significantly different from baseline. 0.05: significantly different from baseline.
Stratum Corneum Hydration table 3). On the forehead, SCH levels remained stable in
At baseline both intervention groups showed compa- both groups when comparing week 16 with the baseline
rable values for SCH on the forehead and forearm (p > (table 3). However, when comparing G1 with G2, a sig-
0.160; table 3). Skin hydration in the entire sample showed nificantly higher SCH was found at week 16 on the fore-
anatomical variability, presenting the highest values on the head (p = 0.004) and forearm (p = 0.006; table 3).
forehead (42.8 ± 9.9 AU), followed by the forearm (34.6 ±
9.5 AU; p = 0.001) and leg (29.9 ± 9.1 AU; p = 0.001), at Transepidermal Water Loss
baseline (table 3). On the forearm, SCH significantly (p < The baseline values for TEWL in each area of investiga-
0.033) increased in G1 after 4 and 12 weeks, and remained tion were comparable (p > 0.23; table 4) between groups.
stable in G2 (table 3). On the leg, both groups showed a The entire sample showed significantly lower TEWL val-
significant increase in SCH until weeks 4 and 12 (p < 0.017; ues on the forearm (10.0 ± 3.3 g/m2/h) compared with the
Use of Emollients in Children with Atopic Skin Pharmacol Physiol 2014;27:208–216 211
Predisposition DOI: 10.1159/000360546
leg (11.3 ± 3.3 g/m2/h; p = 0.012) at baseline (table 4). On Table 5. Skin pH
the forearm, a significantly lower TEWL was found in G1
after 12 weeks compared with the baseline (p = 0.023; ta- Group Baseline Week 4 Week 12 Week 16
ble 4). On the forehead and leg, TEWL remained stable at Forehead G1 4.5±0.4 4.5±0.4 4.3±0.3* 4.4±0.3
week 16 in both groups compared with the baseline (p > G2 4.5±0.4 4.4±0.3 4.2±0.3* 4.3±0.1*
0.353; table 4). When comparing both groups, G1 showed
Forearm G1 4.9±0.4 4.9±0.5 4.8±0.4 4.8±0.3
significantly lower TEWL values than G2 at weeks 12 and G2 4.9±0.4 4.8±0.4 4.7±0.3* 4.6±0.4*
16 (p = 0.008 and p = 0.039) on the forearm, and at weeks
Leg G1 4.9±0.4 4.9±0.5 4.9±0.5 5.0±0.5
4 and 16 (p < 0.001 and p = 0.024) on the forehead (table 4).
G2 5.0±0.5 4.8±0.3 4.7±0.3* 4.8±0.4
Skin Surface pH Data are given as means ± SD. * p < 0.05: significantly different
Each body region presented similar values at baseline from baseline; there were no significant differences between the
when comparing both groups (p > 0.716; table 5). When groups.
comparing the areas of the entire sample investigated,
their pH values differed significantly at baseline. A lower
pH was found on the forehead (4.5 ± 0.4) compared with
the forearm and leg (4.9 ± 0.4 and 5.0 ± 0.5; p < 0.045). Table 6. SCORAD index and dryness intensity assessment
Children in G2 showed significantly lower pH values in
all areas investigated at week 12 compared with the base- Group Baseline Week 4 Week 12 Week 16
line (table 5). On the forehead and forearm, a decrease SCORAD G1 10.7±8.8 6.8±8.3* 4.5±3.3* 3.8±4.3*
was noted also at week 16 (p < 0.016; table 5). In G1, at index G2 9.9±7.5 5.1±5.4* 5.4±5.3* 5.3±5.6*
week 16 the pH was comparable with values at baseline
Dryness G1 1.42±0.58 1.00±0.30* 0.91±0.29* 0.85±0.49*
on the forearm (p = 0.121), forehead (p = 0.132) and leg
intensity G2 1.43±0.66 0.96±0.37* 1.05±0.2 1.0±0.34*
(p = 0.615; table 5). Only at week 12 did the pH decrease
on the forehead (p = 0.033). Data are given as means ± SD. * p < 0.05: significantly different
from baseline; there were no significant differences between the
Skin Condition groups.
The SCORAD index and the dryness intensity assess-
ment of the SCORAD were comparable at baseline be-
tween groups (p > 0.911; table 6). The SCORAD index
dropped significantly in both groups comparing baseline pH by established, noninvasive methods in three represen-
with weeks 4, 12 and 16 (p < 0.014; table 6). Dryness in- tative areas of investigation [39]. The previously reported
tensity decreased significantly in G1 after 4, 12 and 16 anatomical variability in infant skin has to be considered
weeks (p < 0.020), and in G2 after 4 and 16 weeks (p < when evaluating the effect of regular emollient application
0.031; table 6). There were no statistically significant dif- on skin barrier function [14, 16, 17, 38, 40, 41]. Skin lesions
ferences between the groups. in AD are characteristically distributed in an age-related
pattern. While in infants, primarily the skin in the face is
affected, older children show lesions primarily in flexural
Discussion areas [42, 43]. At the end of the study, the forehead, which
had PIPJ cream applied, and the forearm, which received
Dry skin is often linked to impaired skin barrier func- PIPJ cream and PIPJ lotion, showed significantly higher
tion as observed in AD skin [34, 35]. Several studies have SCH values and lower TEWL values compared with chil-
been performed to evaluate the effect of emollient therapy dren receiving petrolatum-based emollients, or compared
on children with AD. Nevertheless, current awareness of with the leg, to which only the lotion was applied.
dry skin condition and effective treatment of children with
atopic predisposition is limited [36, 37]. Regular applica- Hydration of the SC
tion of emollients is discussed to exert a positive effect on The forehead and forearm showed lower SCH values
skin barrier function in infants [17, 38]. In order to scien- at study entry compared with values reported for non-
tifically characterize the effect of the emollients applied, we atopic children of the same age [44]. This might indicate
assessed the functional skin parameters SCH, TEWL and an impaired skin barrier function even in the absence of
Use of Emollients in Children with Atopic Skin Pharmacol Physiol 2014;27:208–216 213
Predisposition DOI: 10.1159/000360546
Environmental Factors sensitizations have been reported so far [73]. However,
Additionally, environmental skin barrier break- the risk of sensitization in long-term treatment with plant
down might be influenced by chlorine in swimming extracts cannot be ruled out.
pools, which frequently is not well tolerated and is sup- Dry skin requires adequate intervention; if left un-
posed to alter skin barrier permeability [64]. A positive treated, it may lead to a flare of the underlying condition
effect of using lotion after baby swimming on skin such as atopic eczema [9]. Our study indicates that ap-
functional parameters was shown by recent findings propriate daily emollient application, even with a PIPJ
[38]. As no deterioration in skin physiological param- formulation, stabilizes the susceptible skin barrier func-
eters and clinical scoring was found in this study, it can tion of children with dry skin and atopic predisposition.
be assumed that adequate skin care may be helpful in Thus, increasing awareness of dry skin condition in chil-
protecting the skin barrier in children with dry skin dren may lower the risk of developing AD. Anatomy-spe-
and atopic predisposition following a once-weekly cific regimes, the mode of application and the type of
swimming course. emollient should be considered when investigating skin
barrier properties [17, 18]. The present results contribute
Plant Extract to an improved understanding of the effects of emollient
The number of patients and consumers asking for application on skin barrier function in children with dry
plant-based therapeutic products as a complementary skin and atopic predisposition.
dermatologic therapy is increasing [19, 20]. Traditionally,
some plants have been used for the treatment of AD for a
long time as botanical compounds display interesting Limitations
skin barrier-reinforcing properties [65, 66].
The ice plant, a vegetable found in semi-arid climate A control group of children of the same age with ab-
zones, is traditionally consumed as salad or spinach [67]. sence of dry skin would have helped to compare skin bar-
The species Mesembryanthemum crystallinum is charac- rier parameter values with those of healthy children in
terized by antioxidant and antibacterial properties and is parallel.
of pharmacological and dermocosmetic interest [68]. The
plant was widely used in traditional medicine for the re-
spiratory or urinary system and has been used as an anti- Acknowledgment
diabetic agent in Japan [13, 69–71]. The pressed juice of
the plant influences the cell physiology of human kerati- We thank the European Centre for Allergy Research Founda-
tion Institute GmbH, Berlin, for providing the logistics to conduct
nocytes and fibroblasts and improves skin hydration in this study. The study was supported by WALA Heilmittel GmbH.
atopic patients [72, 73].
Nevertheless, several botanicals hold the risk of pro-
voking allergic reactions or of sensitization [19]. How- Disclosure Statement
ever, ice plant has been a nutritional compound in sev-
eral countries for many years, and no allergic reactions or None declared.
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