Katsuko Kikuchi

Improvement of mild inflammatory changes of the facial skin induced by winter environment with daily applications of a moisturizing cream. A half-side test of biophysical skin parameters, cytokine expression pattern and the formation of cornified envelope.

Objective: Based on our previous findings that, reflecting mild inflammation, the exposed facial skin shows much poorer functional properties of the stratum corneum (SC) in the dry and cold winter than those evaluated in the same individuals in the warm and humid summer time, we conducted a half-side test on the face to determine how the facial skin changes induced by a winter environment are improved by daily applications of a moisturizing cream as assessed by non-invasive biophysical and cytological methods. Methods: One side of the face of 16 young females was treated with a moisturizing cream twice daily for 6 weeks, with the other side serving as the non-treated control. Before treatment, 3 and 6 weeks after the start of the treatment, high-frequency conductance as a parameter of the skin surface hydration, transepidermal water loss (TEWL), a parameter of the water barrier function of the skin, and the skin surface lipid level were measured on the cheeks. Obtaining the SC from the skin surface by adhesive tape, interleukin (IL) 1α and IL-1 receptor antagonist (IL-1ra) in the SC and cornified envelope (CE) maturation were determined. Results: At first, baseline measurements conducted before treatment showed rather high TEWL values suggestive of an impaired skin barrier. During the treatment with the moisturizing cream, significantly higher conductance values and lower TEWL values were found on the moisturizer-treated side, accompanied by a decreasing IL-1ra/IL-1α ratio and immature CEs. Conclusion: These results suggested that the daily application of a moisturizing cream is effective in improving mild subclinical inflammation that is induced on the facial skin by the winter environment.

The Winter Season Affects More Severely the Facial Skin than the Forearm Skin: Comparative Biophysical Studies Conducted in the Same Japanese Females in Later Summer and Winter

Skin disorders such as atopic dermatitis, psoriasis and senile xerosis show a tendency to exacerbate in winter. We investigated the seasonal influence on the functional parameters of the skin in healthy female volunteers of different age groups. Biophysical noninvasive measurements, including transepidermal water loss (TEWL) as a parameter for the barrier function of the stratum corneum (SC), high-frequency conductance as a parameter for the hydration state of the SC, temperature, color and casual surface lipid levels, were conducted during the later summer and winter months in 39 healthy adult Japanese females ranging in age from 24 to 78 years. The measurements were made on the cheek, the exposed area, and flexor forearm, the semicovered area, in the same climate-controlled chamber. The barrier function of the SC was found to be significantly impaired in winter both on the cheek and flexor forearm. This difference between summer and winter was much larger on the cheek than on the forearm. The hydration state of the SC was significantly lower in winter on the flexor forearm, whereas no such seasonal change was apparent on the cheek where sebum levels did not show any seasonal change. We measured the corneocyte size in 24 out of the 39 subjects to estimate a seasonal change of the turnover rate of the SC. It tended to be smaller only on the exposed cheek skin, suggesting an enhanced turnover of the SC in winter, whereas it was somewhat larger on the semicovered flexor forearm. The skin surface temperature and redness were also significantly higher on the cheek in winter. We think that subclinical inflammation resulted in the enhanced turnover rate of the SC associated with elevated TEWL levels observed on the face in winter. In conclusion, the obtained data suggest that the exposed facial skin becomes more irritable under the influence of the dry and cold environment of winter even in healthy individuals where the barrier function of the SC is relatively poor as compared to the skin of other areas.

Atopic xerosis: employment of noninvasive biophysical instrumentation for the functional analyses of the mildly abnormal stratum corneum and for the efficacy assessment of skin care products

The subtle dryness of the skin surrounding the lesions of atopic dermatitis (AD) is called atopic dry skin or atopic xerosis (AX). AX is more susceptible to the development of AD skin lesions under various environmental stimuli than the clinically normal skin of the people who have or have had or will have AD, which might be called normal atopic skin (NAS) that shows no functional differences as compared to the skin of normal individuals. Routine histopathologic studies of AX that involve the invasive procedures of biopsy are not so helpful in clarifying the underlying pathogenesis. Modern, noninvasive biophysical instrumentation provides rich and quantitative information about various functional aspects of skin. The stratum corneum (SC) of AX reveals not only decreased hydration but also mildly impaired barrier function demonstrable as an increase in transepidermal water loss, elevated pH values, and an increased turnover rate of the SC consisting of thick layers of smaller‐sized corneocytes. These data suggest that AX is related to mildly increased epidermal proliferation as a result of the presence of subclinical cutaneous inflammation. Although AX skin does not display any impairment in the recovery of barrier function after physical skin irritation by tape‐stripping, it produces a much more severe, long‐lasting inflammatory response together with a delay in barrier repair after chemical irritation such as that induced by sodium lauryl sulphate. The SC of AX is biochemically characterized by reduction in the amounts of ceramides, especially ceramide I, sebum lipids, and water‐soluble amino acids. None of these changes in SC functions are seen in NAS, which includes not only the normal‐looking skin of AD patients long after regression of all active lesions but also of latent atopic skin such as neonates who later develop AD. This suggests that all of the observed functional as well as biochemical abnormalities of AX are a reflection of subclinical inflammation. The presence of the underlying inflammation in AX also differentiates it from senile xerosis. The mildly impaired SC functions of AX can be improved by daily repeated applications of effective moisturizers, i.e., corneotherapy, which is effective in preventing the exacerbating progression of AX to AD resulting from inadvertent scratching of the skin that facilitates the penetration of environmental allergens into the skin. The biophysical confirmation of such efficacy of moisturizers, including cosmetic bases on the mildly impaired barrier function and decreased water‐holding capacity of the SC of AX, definitely substantiates the importance of skin care for the cosmetic skin problems that affect every individual in the cold and dry season ranging from late autumn to early spring.

The “Haptic Finger”– a new device for monitoring skin condition

Background/aims: Touching the skin is of great importance for the Clinician for assessing roughness, softness, firmness, etc. This type of clinical assessment is very subjective and therefore non‐reproducible from one Clinician to another one or even from time to time for the same Clinician. In order to objectively monitor skin texture, we developed a new sensor, placed directly on the Clinicians finger, which generate some electric signal when slid over the skin surface.

Measurement of Electrical Current Perception Threshold of Sensory Nerves for Pruritus in Atopic Dermatitis Patients and Normal Individuals with Various Degrees of Mild Damage to the Stratum corneum

Background: Patients with atopic dermatitis (AD) are well known to be sensitive to irritation from the environment due to the impaired function of the stratum corneum (SC). Electrical current perception threshold (CPT) evaluation quantifies the sensory threshold to transcutaneous electrical stimulation of the sensory nerves. Objective: To study the CPT in a noninvasive fashion using Neurometer® CPT/C, together with measurements of various functions of the SC. Methods: We measured the CPT on the flexor forearm and cheek of AD patients and normal individuals. Subsequently, we evaluated the CPT and skin sensitivity to a 30% aqueous solution of lactic acid after the infliction of various mildly disruptive measures on the SC on the flexor forearm of healthy individuals by the following three methods: (1) removal of the superficial sebum with acetone/ether, (2) scarification with a needle and (3) tape stripping of the SC. Finally, we examined the effect of topical applications of emollients such as petrolatum or a moisturizing cream to the scratched skin. Results: AD patients showed a lower barrier function and lower CPT than normal individuals. In subsequent studies conducted in normal individuals, the CPT was found to be inversely correlated with transepidermal water loss (TEWL) levels after tape stripping. However, most of all, the partial superficial scarification with a needle decreased the CPT and increased the lactic acid stinging response. Prolonged removal of lipids from the SC with acetone/ether for 30 min that increased the TEWL levels for only 1 day decreased the high-frequency conductance value for 2 days and the CPT only on the 2nd day after treatment. Topical applications of emollients were effective to prevent the increased sensitivity caused by scratching. Conclusions: AD patients showed functional abnormalities of the SC and tended to have more sensitive skin on the cheek and flexor forearm than healthy controls. Even focal SC damage caused by superficial cracking may lead to further disruption of the already damaged SC in AD patients, by eliciting scratching and facilitating the permeation of various environmental allergens and also the induction of hypersensitive skin.

Impairment of Skin Barrier Function is not Inherent in Atopic Dermatitis Patients: A Prospective Study Conducted in Newborns

Abstract:  We conducted a cohort study to determine whether the barrier dysfunction of the stratum corneum that facilitates the penetration of various exacerbating agents from the environment is inherent in atopic dermatitis patients as suggested by some dermatologists. Clinical observation and biophysical measurements of the skin were performed on the cheek and on the flexor forearm of 24 newborn infants once between 2 and 14 days postnatally and 1, 3, and 6 months later. Nineteen had atopic family histories. Most of the infants had physiologic neonatal xerosis that was observed as a reduced high‐frequency conductance without any impairment in the stratum corneum barrier function assessed by transepidermal water loss. Four of the 24 neonates developed atopic dermatitis around 2 to 3 months after birth. In all of them, barrier impairment noted as increased transepidermal water loss was observed only after the development of skin lesions. During their neonatal period, their transepidermal water loss and skin surface hydration state were indistinguishable from those of the neonates whose skin remained lesion‐free during the observation period. Therefore, we concluded that the barrier impairment found in atopic dermatitis is not inherent but represents a phenomenon secondary to dermatitic skin changes.

Sweat constitutes several natural moisturizing factors, lactate, urea, sodium, and potassium.

BACKGROUND Amino acids (AAs) play important roles in maintaining an optimal hydration state of stratum corneum (SC) as a natural moisturizing factor (NMF). Recently, however, we have reported that lactate and potassium significantly affect the hydration state of SC. OBJECTIVE To explore the source of lactate and potassium in SC, we compared the concentration of various NMFs such as AAs, pyrrolidone carbonic acid (PCA), lactate, sodium, and potassium in SC between anhidrotic and adjacent hidrotic areas of patients with acquired idiopathic generalized anhidrosis or segmental anhidrosis. METHODS We examined 13 anhidrotic areas and the adjacent hidrotic skin of 10 different patients. We first determined anhidrotic and hidrotic areas of each patient by the iodine starch method and examined the hydration state of SC by measuring the high-frequency conductance. Then we obtained SC by tape stripping and measured the content of AAs, PCA, lactate, urea, sodium, and potassium in SC obtained from the anhidrotic and hidrotic areas. We examined the effect of increased insensible perspiration on the SC hydration and the concentrations of NMFs. RESULTS The SC of anhidrotic areas showed significantly low hydration. Among NMFs, lactate, urea, sodium, and potassium were significantly decreased in the SC of anhidrotic areas, while AAs and PCA were not significantly different between hidrotic and anhidrotic areas. Increased insensible perspiration increased SC hydration as well as NMFs other than AAs and PCA. CONCLUSION Sweat constitutes lactate, urea, sodium, and potassium in NMFs and plays a crucial role in maintaining the physiological hydration state of SC.

Decreased lactate and potassium levels in natural moisturizing factor from the stratum corneum of mild atopic dermatitis patients are involved with the reduced hydration state.

BACKGROUND Atopic dermatitis (AD) shows dry skin. Water-soluble, low molecular weight components, collectively known as natural moisturizing factor (NMF), play an important role in maintaining the stratum corneum (SC) hydration. Previous studies focused on reduced levels of free amino acids (FAAs) in NMF from AD skin. It remains unknown, however, whether other NMF components are also altered in AD. OBJECTIVE To characterize the levels of various NMF components in the SC of healthy subjects and in mild AD adult patients. METHODS NMF components were extracted from three sequential tape-stripped SC samples obtained from the volar forearm. NMF components which were decreased in AD skin were topically applied to examine their contribution to SC moisturization in AD skin. RESULTS We found that although FAAs levels were not remarkably reduced, levels of pyrrolidone carboxylic acid (PCA), lactate, urea, sodium and potassium were significantly decreased in NMF from mild AD skin. Among those components, only the topical application of potassium lactate effectively increased skin surface hydration indicating that reductions of lactate and potassium influence dry skin in mild AD patients. Unlike the distribution of filaggrin-derived FAAs and PCA, lactate, urea, potassium and sodium were abundant in the surface layer of the SC compared with the inner layer of the SC. Such findings strongly suggest that those components are supplied from outside the SC, i.e. they originate from sweat. CONCLUSION The reduced levels of sweat-derived NMF components in mild AD patients suggests that impaired sweat function might in part result in the SC dryness.

Functional analyses of the eyelid skin constituting the most soft and smooth area on the face: contribution of its remarkably large superficial corneocytes to effective water-holding capacity of the stratum corneum

Background/purpose: The eyelid constitutes a unique area on the face because of its soft, smooth and thin skin distinct from that of other facial portions. Its softness facilitates their easy compliance to blinking movement, which is indispensable to protect the wet surface of the eyeball. Moreover, the skin of the eyelid does not show any prominent follicular orifices or an oily appearance even in adults. Despite such uniqueness, its biophysical characteristics have remained unclear as compared with other facial skin.

Comparison of the Effects of Daily Applications between Topical Corticosteroid and Tacrolimus Ointments on Normal Skin: Evaluation with Noninvasive Methods

Objective: To evaluate the skin changes of the neck of normal individuals after repeated applications of moderate-strength corticosteroid or tracrolimus ointment for 3 weeks by use of noninvasive biophysical measurements. Methods: A 0.12% betamethasone-17-valerate ointment or a 0.1% tacrolimus ointment was applied to the right side of the neck of 8 adult volunteers twice daily for 3 weeks together with control petrolatum applied to the left side of the neck for comparison. Biophysical skin measurements were performed on the neck skin before, 1 and 3 weeks after the start of the treatment and 1 week after the cessation of the treatment. Results: A decrease in hygroscopicity and water-holding capacity of the stratum corneum (SC) when evaluated with the in vivo water sorption-desorption test was found on the corticosteroid-ointment-treated side after 3 weeks of the treatment as compared with the petrolatum-treated side. The erythematous reaction to a topically applied 0.1% aqueous solution of methyl nicotinate, a vasodilator, appeared more slowly on the corticosteroid-ointment-treated skin than on the control skin. No such changes were observed on the skin treated with 0.1% tacrolimus ointment. Conclusion: Tacrolimus appears to cause few if any functional changes in the SC of healthy human skin because of its poor permeability into skin with an intact barrier function.