An increasing number of noninvasive methods have been developed to determine skin properties in an objective way.The subjective, visual or tactile evaluation of skin conditions can now be quantified and numerical values can be obtained.These techniques are particularly useful in cosmetic/topical drug products testing methods such as efficacy testing, skin compatibility, mildness assessment, and in safety/tolerability testing.
Standardization between instruments/observers is at present imperfect and measuring the same skin/hair property with different instruments/different observers can give different results.
Environment Related Variables:
Air convections is the main source of disturbance resulting in rapid fluctuations of the measurements. It is commonly produced by disturbance in the room, such as people moving around, opening and closing doors, breathing across the measurement zone, air conditioners, etc. As these disturbances are difficult to avoid, the use of a covering box is proposed to shield undesirable air turbulence as much as possible. This is particularly indicated for TEWL, capacitance, and other hydration measurements, since air flow on skin surface can change moisture content and skin temperature. On the other hand, a shielding box should have an open top, covered with a cotton cloth in order not to build up occlusive; such shield might also increase the relative humidity in this box/area should be recorded.
Ambient Air Temperature – The most important effect of the temperature of the air is that it influences the skin temperature both directly (by convection) and indirectly (by central thermoregulatory effects). A division must be made between the temperature of the measuring room and the temperature (climate) where the study participants stay. Hence, an acclimatization time of 15-20 mins is mandatory. It was found that fluctuations in the temperature of the measuring room affected stratum corneum (SC) hydration and TEWL. It is always advised to control the room temperature between 20°C to 25°C. Since ambient air temperature affects TEWL measurement, seasonal variations should be avoided. Even if one works in a temperature-controlled room, it has been observed that the TEWL baseline is not stable. No significant difference between summer and winter baseline TEWL, however, in aged people, it has been shown that SC lipid levels of different body sites were depleted in winter in comparison with spring and summer. Sweating in the summer and cold feeling in the winter seems to be obvious problems. As a consequence of this, it is evident that geographical variations also may affect measurements.
Ambient Air Humidity – The relationship of the TEWL to ambient air humidity is not linear. It is advised to work in a temperature-controlled room with additional control of the relative humidity.
Light Sources – Any light source close to the test site affecting the ambient air temperature, the probe temperature, and the temperature of the skin surface of the test persons should be avoided.
Skin Cleansing – Cleansing of the skin with surface active agents and solvents could modify surface microenvironment due to damage of skin barrier function. It is also obvious that exposure of the skin to water-containing products could result in elevated water loss from the surface and SC hydration which might interfere with several biophysical parameters ranging from microtexture, cell cohesion, stratum corneum mechanical properties, and friction coefficient. It is also important to keep in mind that agents in cleansers may deposit on the skin surface and modify its chemical composition leading to errors in reading capacitance measurement or TEWL.
Instrument Related Variables:
Commercially available instruments must be calibrated according to manufacturer’s guidelines.Differences in output data may exist, and data obtained by these devices based on the same physical principle may be not directly comparable. The calibration of the instrument, if possible should be checked frequently, recommended before use and daily calibration or as suggested by user guide. To enable successful and reliable interlaboratory comparison of results overcoming the effect of the interinstrumental variability, an additional calibration/validation procedure incorporating a calibration for an actual gold reference standard can be adopted.
Individual Related Variables:
Age, gender, and race could be important variable influencing skin function and biophysical measurements as well. Hence, all these variables should be controlled or standardized when planning a product efficacy study. In particular, studies should be designed within the same ethnic group, age range, possibly gender, unless the purpose of trial itself is to highlight these differences.
Aging skin is usually characterised by alteration in water content (uneven distribution), reduction of TEWL due to changes in corneocyte size (larger corneocytes in elderly people), increased microrelief; and loss of mechanical function. Wilhelm and Maibach suggest that there is evidence that baseline TEWL is reduced in aged individuals as compared with midadulthood values. Additionally, with increasing age, significantly decreased levels of all major barrier lipids have been observed contributing to an increased susceptibility of aged skin to perturbation of the barrier function and xerosis. Between black and white human skin some differences have been reported. This is also the case for white, Hispanic and Asian subjects. Hence, in cosmetic and topical drug products testing studies the ‘ethnic’ variability should be carefully controlled.
Different anatomical sitesdiffer widely from a physiological point of view, being characterized by different anatomical characteristics. For instance, skin thickness is lower on the volar forearm and higher on the dorsal forearm or trunk and face. Indeed, it must be emphasized that connective tissues varies tremendously according to the site of the body. In this structural organization, the dermis of the face, scalp, back, forearm, legs, palms, and soles differs greatly from site to site. There are also considerable differences in the relative proportions of each of the connective tissues components and epithelial adnexae in different regions of the body.
Physical, thermal, and emotional sweating are important variables which need to be controlled. If the ambient air temperature is below 20°C and the skin temperature is below 30°C, thermal sweat gland activity is unlikely, provided the skin is not exposed to forced convection and no excessive body heat is produced (as a result of physical exercise). Therefore, a premeasurement after a 15-20 mins rest in a temperature controlled room of 20°C – 25°C, is , in most studies, taken into consideration. Also, physical activity is to kept a minimum. It must, however, be mentioned that it is impossible to control the insensible perspiration.
Skin temperature is an important preconditioning factor of the test persons and a temperature-controlled room is required. This is of particular importance for those instruments which measure blood flow, skin color (erythema/blanching – is dependent on blood supply), and of course, thermography. Sudden changes in skin temperature such as localized heating or cooling some test areas are used as “stress test” to induce a vascular reaction to monitor some functional aspects of microcirculation.
Cosmetic testing should be avoided in subjects or sites affected by skin disease unless specifically required to the study design. Skin diseases induces tremendous changes in biophysical parameters and all these factors should be carefully standardized and monitored during the study. Skin diseases in which the barrier function is significantly altered, including burns, psoriasis, some ichthyotic disorders, contact dermatitis, and atopic dermatitis, are characterised by increased TEWL, erythema and blood flow values. Changes in barrier functions are caused by chemical contacts, surfactant damage, or diseased states (dermatitis), for example psoriasis and eczema, resulting in an increased water evaporation rate within the range of 20-60 g/m2h.
Fluctuations of some skin parameters such as TEWL, capacitance, blood flow, and pH have been described and have been recently reviewed. Fluctuations of the TEWL may be mainly temperature-dependent. TEWL has been reported to undergo a circadian rhythmand to be higher in the evening and during the night than in the morning.
Intra- and Inter Operators/ObserversVariables:
For most skin sites, important interindividual variations occur, usually also dependent on the measuring device. It should be taken into consideration that some skin sites, including some parts of the forehead, the palm of the hand, and the wrist, should be avoided because of their very high interindividual variability. The interindividual variation per site is usually smaller.
|Variables Influencing Skin Measurements||What to Do?|
Environment and Climate
Room Temperature and Relative Humidity
Outside temperature and relative humidity
Keep between 20-21°C and 40-60%
Prefer short-term studies
Make sure that study participants rest and adjust at least 15-20 mins
New Vs. Old devices
Use gold standard reference
Use gold standard reference
Area, position, surface
Standardize as much as possible
Do multiple measures in the same area
Age, gender, ethnic group, race, body site,
Carefully control and standardize
Standardize and make measures after 2 hours from last procedure.
Several factors influence skin measurements and biophysical skin testing. When testing efficacy of the cosmetics/drug products in human study participants, the following conditions must be taken into consideration: