ARTICLE
Transepidermal water loss (TEWL) and stratum corneum (SC) capacitance measurements
are relevant methods for evaluating the effect of locally applied moisturisers
on skin barrier function and repair [1]. Applied in experimentally nickel
(Ni)-induced allergic contact dermatitis (ACD), these techniques have been
used in Ni-sensitive human volunteers to quantify the efficacy of topical
corticosteroids and moisturisers [2, 3].
In a recent study, the long-term use of a moisturiser was found to increase
skin susceptibility to irritants [4]. After the induction of irritant
contact dermatitis (ICD), a significant increase in TEWL values was noted
on the moisturiser pre-treated skin compared to non-treated skin. It has
also been reported that ICD in metal workers seemed to be exacerbated
after application of a barrier cream [5]. On the contrary, however, certain
topically applied moisturisers have been shown to accelerate the recovery
of a disrupted skin barrier [6] and decrease skin susceptibility to irritant
stimuli [7]. Therefore it seems that any clinical relevance in attempting
the reduction of the recovery of contact dermatitis is related to the
composition of the moisturiser applied [8].
In this study, we performed TEWL and SC-capacitance measurements and
clinical score evaluations to analyse the effect of long-term application
of skin moisturisers on the development of skin barrier damage in Ni-induced
ACD. Before the induction of ACD, both a poorly hydrating as well as a
highly hydrating formulation moisturiser were applied preventively on
the forearms of Ni-sensitive female human volunteers.
Material and methods
Volunteers
Fifteen Ni-sensitive female volunteers (mean age: 29.5 years old; range:
23-38) were included in the study after signing informed consent. The
study was approved by the Ethical Committee of the academic hospital (AZ-VUB,
Brussels Belgium). Volunteers, suffering from ICD or atopic dermatitis,
were excluded from the study.
Topical agents
The subjects were provided with two test formulations blinded for both
investigator and volunteer. A highly hydrating moisturiser, marked as
cream A, contained: Aqua, Octyl Stearate, Glycerin, Oenothera Biennis,
Glyceryl Stearate, Dimethicone, Behenyl Alcohol, Pentaerythrityl Stearate/Caprate/Caprylate/Adipate,
Allantoin, Ceteareth-20, Cetyl Palmitate, Tocopherol, Ascorbyl Palmitate,
Ceteareth-12, Cetearyl alcohol, Perfume, PEG-8, Carbomer, Disodium EDTA,
Ascorbic Acid, Citric Acid, Tetrahydroxypropyl Ethylenediamine, Triclosan,
Dichlorobenzyl alcohol, 2-Bromo-2-Nitropane-1, 3-Diol. The second, marked
as cream B, was a poorly hydrating moisturiser and contained: Aqua, Steareth-21,
Steareth-2, Paraffinum Liquidum, Stearyl alcohol, Diazolinidyl
rea, Methylparaben, Propylparaben.
Test sites and pre-treatment protocol
The experiment was carried out on the surface area of the volar forearms
between the wrist fold and a parallel line situated at 10 cm from the
wrist. These areas were equally divided into two sites, obtaining thus
four symmetrical test sites in each volunteer. After control measurements
on all test sites at day 1, both cream A and B were applied on two symmetrically
situated sites of the forearms designated as sites A and B. The non-treated
sites were designated as sites C and D. The application sites were randomly
varied between subjects. Further treatment was done on day 1, at 12 h
and in a repetitive application protocol twice daily from day 1 till 20.
Experimental allergy
Closed patch tests (Extra Large Chambers, diameter 20 mm, Epitest, Helsinki,
SF) were symmetrically applied on both forearms. Each patch included a
filter paper disc (diameter 18 mm). Four closed patch tests were applied
symmetrically, ensuring an identical distance from forearm joints. The
patches on sites A, B and C contained nickel (0.3 ml of 5% Ni in petrolatum).
On site D the patch was saturated with 150 mul of physiological saline
(sodium chloride 0.9%, B. Braun, Diegem, B) and served as a negative control.
The patches were applied at day 21 and removed after 48 hours. The forearms
were then rinsed with physiological saline.
Evaluation
At days 24 and 26, clinical evaluation recorded the presence of erythema
and papulation using a scale from 0 to 3 (0 = absent, 1 = mild, 2 = moderate,
3 = important). Volunteers were asked to evaluate their itching following
the same scale. The clinical score is the sum of these three parameters.
TEWL and SC-capacitance measurements, using a TEWAmeter TM 210®
and a Corneometer CM 810® (Courage + Khazaka, Köln,
D.), respectively, were performed under standardised conditions as described
by Rogiers et al. [9, 10].
Clinical scoring, TEWL, and SC capacitance measurements were carried
out on day 1 before starting the application of creams A and B. Further
evaluation was done at day 21 before applying the patch tests, and at
days 24 and 26 after patch tests removal.
Statistical analysis
Values of TEWL, SC-capacitance and CS of the 3 ACD sites were globally
analysed using a Friedman test. In the event of global significance the
Wilcoxon signed-rank test was further applied to investigate values of
TEWL, SC-capacitance and CS between sites. The level of significance was
set at p < 0.05.
Results
Mean values of TEWL corresponding to the pre-treated sites, A and B,
and non-treated ones, C and D, are shown in Fig.
1. Statistically significant differences in TEWL values between sites
A and B are observed on days 21 (p = 0.046) and 24 (p = 0.002).
Mean values of SC-capacitance corresponding pre-treated sites, A and
B, and non-treated ones, C and D, are shown in Fig.
2. Statistically significant differences were observed between A and
B sites at days 21 (p = 0.004) and 26 (p = 0.025), and between A and C
sites at day 21 (p = 0.001).
No statistical difference could be observed between the TEWL and SC
capacitance values of the negative control sites of the left forearms
(Figs. 1 and 2).
The results of the clinical scores are shown in Figure
3. At day 26, the clinical score of pre-treated A site was significantly
decreased in comparison to the pre-treated B site (p = 0.045).
Discussion
In the present study, the forearm skin of 15 Ni-sensitive female volunteers
was challenged with Ni-ACD after a three week pre-treatment period with
two formulations. The first formulation was a highly hydrating skin product
with a proven efficacy on both TEWL and skin hydration [6]. The second
formulation did not contain any humectants or essential fatty acids important
for the improvement of the skin barrier [1]. In comparison to the enriched
formulation moisturiser, the poorly hydrating product was shown to induce
an increase in ACD-related skin barrier damage. The rich formulation improved
skin barrier function at the end of the pre-treatment period. After the
onset of ACD, the enriched topical cream enhanced the clinical score and
prevented post-inflammatory xerosis (increased SC-capacitance) in comparison
to the poor formulation moisturiser.
It has been suggested that the effect of a topical moisturiser is transient
and therefore may not offer clinical effectiveness in the treatment of
skin pathologies [11]. Tabata et al. recently stated that the application
of an appropriate moisturiser produces an ''unexpected and persistent
clinical effect'' referred to as corneotherapy [11]. In atopic dermatitis,
the application of an adequate moisturiser helped to restore the barrier
function of the skin [12]. Similarly, efficient moisturisers, qualified
as corneotherapeutic agents, improved the clinical efficacy of topically
applied anti-inflammatory agents [3].
The efficacy of skin moisturisers for the prevention of ICD has long
been debated and their efficacy is still regarded with great scepticism.
Held et al. demonstrated that the long-term daily use of a common
moisturiser on normal skin increased susceptibility to irritation, suggesting
that moisturisers may increase skin vulnerability to irritants [4]. On
the contrary, the effectiveness of skin protective formulations was validated
in preventing and/or inhibiting experimentally induced ICD and ACD [13].
Similarly, a barrier/repair cream improved skin condition in comparison
to a placebo control petrolatum-based cream in different dermatologic
conditions, namely: household hand ICD, occupational hand ICD, latex glove
ICD, diaper dermatitis, wounds, and ACD [14]. These observations suggest
the importance of adequately formulating moisturisers in order to reach
efficacy for the treatment and/or prevention of skin barrier dysfunction
associated disorders [1, 6]. As has been suggested by Mao-Qiang et
al., the use of stratum corneum lipid mixtures optimises barrier repair
and could lead to new forms of topical therapy for dermatoses [15].
CONCLUSION
In conclusion, our study shows that the use of a deficient, poorly formulated
moisturiser may increase skin barrier damage due to ACD. Consequently
this part of the study confirms the work of Held and co-workers [4]. On
the other hand, an enriched moisturising product, with a proven efficacy,
does not provoke such an effect and is more appropriate for daily skin
care in skin inflammatory diseases triggered by abnormal barrier function:
psoriasis, atopic dermatitis, and irritant dermatitis.
Article accepted on 20/10/01
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