 | |
Issue
34 — September 2003 |
| | | |
Dry skin often poses a problem in dermatology
and represents a dysfunction of the epidermis, in particular of the stratum corneum
as morphological equivalent of the skin barrier. Different skin diseases, e.g.
atopic dermatitis or ichthyosis, are based on a genetic disposition for dry skin.
Other genetically anchored diseases such as diabetes mellitus, hypothyreoidism,
etc. may also have pathophysiological relevance for the symptom dry skin.
In their guideline the dermocosmetic group suggests the following definition for
dry skin: The term "dry skin" (also xerosis cutis or xerodermie) describes
a skin condition characterized by reduced quantity and/or quality of moisture
and/or lipids. Ethiological factors for dry skin may be a damaged lipid barrier
or chronic inflammation leading to a higher epidermal water loss and consequently
greater desquamation. Clinical signs are rhagades and fissures. The visible symptoms
of dry skin are reduced elasticity, scaling and roughness. Patients complain about
tightness and itching.
Exogenous factors responsible for the development of xerosis cutis are the frequent
use of grease dissolving shower and bath additives, cold surroundings or job-related
frequent contact with water and detergents. In the elderly dry skin or even eczema
is seen more often.
Subject panels and test designs suitable for dry skin products have to take into
account endogenous and exogenous factors.
Selection of the subject panel
An optimal study design requires the selection of a homogeneous group of subjects
with clearly defined inclusion and exclusion criteria. The target group for later
use of the formulation should be considered when selecting the subject panel.
For example, subjects with atopic dermatitis or ichthyosis vulgaris might be included
in a study. Relevant inclusion and exclusion criteria might be:
• Disease (e.g. atopic dermatitis, diabetes)
• Skin moisture (e.g. corneometer values < 50)
• Definition of clinical findings (e.g. scaling)
• Age (e.g. > 60 years)
Objectives / variables
Following definition of the inclusion and exclusion criteria, the exact determination
of objectives is essential for a good study design. Important objectives in the
assessment of formulations against dry skin are clinical evaluation by a dermatologist
and evaluation by the subjects themselves. In addition, modern, non-invasive bioengineering
methods can be used such as determination of electrical properties, measurement
of skin topography and assessment of scaling.
Measurement of electric skin properties
Skin moisture is measured using electric skin properties. The methods are based
on the conductance, impedance and capacitance of the stratum corneum. Capacitance
is the established standard method (e.g. corneometry). The principle of measurement
is based on the dielectric constant of water which strongly differs from other
substances. The capacitor's electric field, influenced by the scatter field in
the moist stratum corneum, is altered proportionally to the moisture content.
Measurement of skin topography
Roughness or wrinkles accompany dry skin. When measuring the skin topography (surface
structure) two- or three-dimensional pictures of the skin surface are taken. The
roughness values are calculated from the profile lines of these images. These
numerical values are a measure of roughness and deeper lines. The measurements
are performed in vitro on replicas by mechanical scanning or image analysis. New
measuring principles allow in vivo measurements.
Determination of scaling
Scaling is determined by removal of corneocytes on the skin surface with an adhesive
film. The total area and the degree of agglomeration of the corneocytes are a
measure of desquamation. The samples are analyzed by image analysis or by chromametry.
For the latter the samples are attached to a dark background. The chromameter
produces a light flash and the quantity of reflected light is measured.
Study designs
Study designs have to be selected according to whether an immediate effect or
a long-term effect should be achieved.
For the investigation of an immediate effect that is based on the interaction
of the formulation with the skin surface measurements have to be made a short
time after application. Figure 1 shows the direct effect on skin moisture of two
formulations tested in a short-term kinetic. Following a steep increase of the
skin moisture curve, a decline of corneometer values is seen 10 to 20 minutes
after application.
|
Figure
1: Short-term kinetic of skin moisture
A, B = application of formulations A and B
control = untreated control field
Enlarged
version
|
In contrast, a long-term effect of a formulation following repeated applications
is measured at the earliest 12 hours after the last application. Figure 2 shows
a long-term effect after two weeks of application. Persistence of the effect is
documented by performing additional measurements at intervals following the last
application. This design is particularly interesting for measurement of treatment
effects in inflammatory diseases with an increased epidermal turnover.
Inclusion of an untreated control field or a reference product is a main factor
allowing comparability of measurements. Furthermore, it is possible to integrate
the dependence of skin moisture on climatic conditions.
An example for the dependence of skin moisture on climatic conditions can be seen
in Figure 3. This figure demonstrates skin moisture over a period of 14 days with
increasing outside temperatures (shown in the lower part of the figure). Three
different skin moisturizing formulations (A, B, C) were compared to an untreated
area. Corneometer values are shown in the upper curve. In the treated areas there
was a marked increase in skin moisture compared to a slight increase in the untreated
areas. The increase in the untreated area was dependent on the outside temperature
and has to be considered when evaluating the treatments. Figure 4 illustrates
the converse effect. Skin moisture decreased as the outside temperature decreased.
|
Figure 2: Long-term
effect on skin moisture
A, B, C = treatment
with formulations A, B, C
control = untreated control field
Enlarged
version
|
Figure
3: Dependence of skin moisture on the outside
temperature, increasing temperature
A, B, C = Treatment with formulations A, B, C
control = untreated control field
Enlarged
version
|
Safety aspects
The dermal tolerability of a formulation should always be evaluated as a secondary
variable. The occurrence of an irritant reaction should at least be recorded as
an "adverse event".
A well designed study carried out in accordance with current standards (Standard
Operating Procedures, Good Clinical Practice) and under controlled conditions
is still not more than the right tool. Neither standardization and optimal designs
nor intensive quality controls can replace the experienced investigator.
This text was presented in German at the 2001 Annual Meeting of the Society of
Dermopharmacy (GD) in Düsseldorf under the title "Wirkungen von Dermokosmetika".
The text was published in German on the homepage of the Society of Dermopharmacy
in DermoTopics, Issue 1 (2002), www.dermotopics.de.
Author
Dr. Betsy Hughes-Formella
Dr. Betsy Hughes-Formella is managing director of bioskin GmbH, a contract research
organization specialized in dermatological testing of drugs and cosmetics. Her
main responsibilities include consultation and regulatory affairs as well as the
conception of clinical development plans. Dr. Hughes-Formella holds a MS and PhD
in Physiology from the University of Georgia, Athens, Georgia. Before joining
bioskin in 1993 she was involved in basic research in the fields of melanoma and
steroid receptors at the University Medical Center, Hamburg, Germany. Currently
she is active in several scientific societies including a position in the board
of regents of the Association of Applied Human Pharmacology (AGAH) and the working
group for dermocosmetics in the Association for Dermopharmacie (GD).
