Skin barrier function in patients with completely healed atopic dermatitis

Although it has been well established that the dry skin often seen in patients with atopic dermatitis shows a deranged barrier function, there is no unanimity of opinion as to whether the barrier in normal-appearing skin of patients with the disease is deranged or not. Hence, it remains unclear whether individuals with atopic dermatitis constitution have an intrinsic derangement of skin barrier function or not. To settle this problem, in the present study we examined transepidermal water loss and stratum corneum water content in normal appearing skin of the upper back of 16 patients with completely healed atopic dermatitis who had been free from skin symptoms for 5 years or more, 30 patients with active atopic dermatitis, and 39 healthy subjects. The transepidermal water loss values and the stratum corneum water content values in normal-appearing skin of the completely healed patients were not different from the values in normal controls. These findings indicate that skin barrier function is not disturbed in patients with completely healed atopic dermatitis.     

The water content of the stratum corneum in patients with atopic dermatitis. Measurement with the Corneometer CM 420

The dry looking skin seen in many patients with atopic dermatitis reflects a defect in the epidermal barrier, the stratum corneum, as demonstrated by an increased transepidermal water loss (TEWL) and a decreased ability of the stratum corneum to bind water. The absolute amount of water within the stratum corneum is of importance both for barrier properties and for the clinical appearance of the skin. This water content was measured with a new instrument, the Corneometer CM 420, which takes advantage of the high dielectric constant of water. Forty patients with atopic dermatitis were studied--20 with dry skin and 20 with clinically normal skin on non-eczematous areas. The stratum corneum in dry skin was found to have a lower content of water than that in the clinically normal skin (p less than 0.01). Clinically normal skin in patients with atopic dermatitis did not differ significantly from normal control skin. An experiment was performed in vitro in an attempt to correlate the values obtained with the Corneometer to the absolute amount of water within the corneum.     

Safety and tolerability of a body wash and moisturizer when applied to infants and toddlers with a history of atopic dermatitis: results from an open-label study

Abstract: Improving skin barrier function and moisturizing without irritation are important components of managing patients with atopic dermatitis. This study evaluated the safety and tolerability of a body wash and moisturizer regimen for infants and toddlers with atopic dermatitis. This was an open‐label study involving 56 children (3–36 months old) with a history of atopic dermatitis. The skin care regimen (Cetaphil Restoraderm Skin Restoring Body Wash and Cetaphil Restoraderm Skin Restoring Moisturizer; Galderma Laboratories, L.P.) was used at least once daily, but no more than twice daily, for 4 weeks. The primary variable of interest was the worst postbaseline scores for local tolerability (expressed as success or failure) using a 4‐point scale for each component (erythema, edema, scaling and dryness, rash, and signs of discomfort upon application). Assessments of moisture content of the stratum corneum and transepidermal water loss were also performed. Fifty‐three children completed the study. The percentage of subjects with no erythema increased from 33.9% to 50.0% by Week 4. The percentage of subjects with no scaling or dryness increased from 58.9% to 85.2% at Week 4. A statistically significant increase in corneometry from baseline (p < 0.001) and a statistically significant decrease in transepidermal water loss (p = .009) were observed. The body wash and moisturizer regimen was safe and well tolerated and improved hydration and skin barrier function in infants and toddlers as young as 3 months of age with a history of atopic dermatitis.     

Moisturizing effects of topical nicotinamide on atopic dry skin

BACKGROUND: Certain moisturizers can improve skin barrier function in atopic dermatitis. The effect of topical nicotinamide on atopic dry skin is unknown. We examined the effect of topical nicotinamide on atopic dry skin and compared the results with the effect of white petrolatum in a left-right comparison study. METHODS: Twenty-eight patients with atopic dermatitis, with symmetrical lesions of dry skin on both forearms, were enrolled, and were instructed to apply nicotinamide cream containing 2% nicotinamide on the left forearm and white petrolatum on the right forearm, twice daily over a 4- or 8-week treatment period. Transepidermal water loss and stratum corneum hydration were measured by instrumental devices. The amount of the stratum corneum exfoliated by tape stripping (desquamation index) was determined by an image analyzer. RESULTS: Nicotinamide significantly decreased transepidermal water loss, but white petrolatum did not show any significant effect. Both nicotinamide and white petrolatum increased stratum corneum hydration, but nicotinamide was significantly more effective than white petrolatum. The desquamation index was positively correlated with stratum corneum hydration at baseline and gradually increased in the nicotinamide group, but not in the white petrolatum group. CONCLUSIONS: Nicotinamide cream is a more effective moisturizer than white petrolatum on atopic dry skin, and may be used as a treatment adjunct in atopic dermatitis.     

Stratum corneum and nail lipids in patients with atopic dermatitis. Decrease in ceramides--a pathogenetic factor in atopic xerosis?

Dry skin is seen in many patients with atopic dermatitis and correlates with a disturbed epidermal barrier function demonstrated by such features as increased transepidermal water loss and diminished stratum corneum hydration. With regard to the importance of stratum corneum lipids for the permeability barrier, we have analysed plantar (n = 8) and lumbar (n = 20) stratum corneum and nail lipids (n = 15) of atopic subjects by high-performance thin-layer chromatography (HPTLC). Compared with controls our investigations show a decrease in the ceramide fraction as a percentage of total lipid and a diminished ratio of ceramides and free sterols in atopic subjects. This implies that impaired ceramide synthesis may be a factor in the pathogenesis of atopic xerosis.     

In vivo hydration and water-retention capacity of stratum corneum in clinically uninvolved skin in atopic and psoriatic patients

Hydration and the water-retention capacity of stratum corneum have been investigated in uninvolved psoriatic and atopic skin and compared with that of healthy controls. Thirty-three subjects of either sex and matched for age entered the study. The subjects were free from all signs of skin disease and skin dryness. Hydration was evaluated by means of transepidermal water loss and skin capacitance measurements. Water-retention capacity was investigated using the plastic occlusion stress test. Atopic skin differed significantly from uninvolved psoriatic and control skin which had a reduced water content and an increased transepidermal water loss. Furthermore, the skin surface water loss profile representing the stratum corneum water-retention capacity was significantly lower in normal atopic skin. The data suggest that clinically normal skin may be functionally abnormal, resulting in a defective barrier that could lead to higher risk of irritant or contact dermatitis.     

Aberrant lipid organization in stratum corneum of patients with atopic dermatitis and lamellar ichthyosis

There are several skin diseases in which the lipid composition in the intercellular matrix of the stratum corneum is different from that of healthy human skin. It has been shown that patients suffering from atopic dermatitis have a reduced ceramide content in the stratum corneum, whereas in the stratum corneum of lamellar ichthyosis patients, the amount of free fatty acids is decreased and the ceramide profile is altered. Both patient groups also show elevated levels of transepidermal water loss indicative of an impaired barrier function. As ceramides and free fatty acids are essential for a proper barrier function, we hypothesized that changes in the composition of these lipids would be reflected in the lipid organization in stratum corneum of atopic dermatitis and lamellar ichthyosis patients. We investigated the lateral lipid packing using electron diffraction and the lamellar organization using freeze fracture electron microscopy. In atopic dermatitis stratum corneum, we found that, in comparison with healthy stratum corneum, the presence of the hexagonal lattice (gel phase) is increased with respect to the orthorhombic packing (crystalline phase). In lamellar ichthyosis stratum corneum, the hexagonal packing was predominantly present, whereas the orthorhombic packing was observed only occasionally. This is in good agreement with studies on stratum corneum lipid models that show that the presence of long-chain free fatty acids is involved in the formation of the orthorhombic packing. The results of this study also suggest that the ceramide composition is important for the lateral lipid packing. Finally, using freeze fracture electron microscopy, changes in the lamellar organization in stratum corneum of both patient groups could be observed.     

Transepidermal water loss in dry and clinically normal skin in patients with atopic dermatitis

To obtain data on the function of the epidermal barrier in patients with atopic dermatitis (AD) the transepidermal water loss (TEWL) was studied. Measurements were made on three body locations in two clinically well defined groups of patients with AD and in a control group. The TEWL was found to be increased both in dry non-eczematous skin and in clinically normal skin in patients with AD. The TEWL was highest in patients with dry skin. The result of the study may indicate a primary defect in the epidermal barrier: the stratum corneum.     

Sodium lauryl sulfate (SLS) induced irritant contact dermatitis: a correlation study between ceramides and in vivo parameters of irritation

Sodium lauryl sulfate (SLS), a surfactant frequently used in the induction of experimental irritant contact dermatitis in animals and in humans, characterstically induces a dose-related increase in TEWL (transepidermal water loss). Ceramides are considered to be important in the regulation of the skin barrier. We therefore examined the relationship between initial ceramide content of stratum corneum and induced changes in skin color (erythema) and barrier function, after SLS application under occlusion (1% and 3% in water) to the forearm of 14 volunteers. Stratum corneum sheets were removed, stratum corneum lipids extracted, and ceramide composition determined from chromatograms (TLC) using densitometry. After determining baseline skin color and TEWL at each area. 2 samples of stratum corneum were obtained from each volunteer. Clinical and instrumental controls of the SLS-induced irritation were performed at 24, 48, 72 and 96 h. Erythema was evaluated by colorimetry; barrier impairment by changes in TEWL. We found inverse correlations between baseline ceramide 61 (weight) and the 24 h erythema score for SLS: between ceramide I and 24 h TEWL, and between ceramide 611 and 72 h TEWL for SLS 3%. Our findings suggest that low levels of these ceramides may determine a proclivity to SLS-induced irritant contact dermatitis.     

Reevaluation of the non-lesional dry skin in atopic dermatitis by acute barrier disruption: an abnormal permeability barrier homeostasis with defective processing to generate ceramide

Atopic dermatitis is characterized by disruption of the cutaneous barrier due to reduced ceramide levels even in non-lesional dry skin. Following further acute barrier disruption by repeated tape strippings, we re-characterized the non-lesional dry skin of subjects with atopic dermatitis, which shows significantly reduced levels of barrier function and ceramide but not of beta-glucocerebrosidase activity. For the first time, we report an abnormal trans-epidermal water loss homeostasis in which delayed recovery kinetics of trans-epidermal water loss occurred on the first day during the 4 days after acute barrier disruption compared with healthy control skin. Interestingly, whereas the higher ceramide level in the stratum corneum of healthy control skin was further significantly up-regulated at 4 days post-tape stripping, the lower ceramide level in the stratum corneum of subjects with atopic dermatitis was not significantly changed. In a parallel study, whereas beta-glucocerebrosidase activity at 4 days post-tape stripping was significantly up-regulated in healthy control skin compared with before tape stripping, the level of that activity remained substantially unchanged in atopic dermatitis. These findings indicate that subjects with atopic dermatitis have a defect in sphingolipid-metabolic processing that generates ceramide in the interface between the stratum corneum and the epidermis. The results also support the notion that the continued disruption of barrier function in atopic dermatitis non-lesional skin is associated with the impaired homeostasis of a ceramide-generating process, which underscores an atopy-specific inflammation-triggered ceramide deficiency that is distinct from other types of dermatitis.     

Effect of Standardized Skin Care Regimens on Neonatal Skin Barrier Function in Different Body Areas

Abstract:  The effect of topical skin care products on neonatal skin barrier during first 8 weeks of life has not been scientifically evaluated. In a prospective, randomized clinical study, we compared the influence of three skin care regimens to bathing with water on skin barrier function in newborns at four anatomic sites. A total of 64 healthy, full-term neonates (32 boys and 32 girls) aged <48 hours were randomly assigned to four groups receiving twice-weekly: WG, bathing with wash gel (n = 16); C, bathing and cream (n = 16); WG + C, bathing with wash gel plus cream (n = 16); and B, bathing with water (n = 16). Transepidermal water loss, stratum corneum hydration, skin pH, sebum were measured on day 2, week 2, 4, 8 of life on front, abdomen, upper leg, and buttock. Skin condition was scored and microbiologic colonization was documented. After 8 weeks, group WG + C showed significantly lower transepidermal water loss on front, abdomen, and upper leg as well as higher stratum corneum hydration on front and abdomen compared with group B. Similarly, group C showed lower transepidermal water loss and higher stratum corneum hydration on these body regions. Group WG revealed significantly lower pH on all sites compared with group B at week 8. No differences in sebum level, microbiologic colonization and skin condition score were found. Skin care regimens did not harm physiologic neonatal skin barrier adaptation within the first 8 weeks of life. However, significant influence of skin care on barrier function was found in a regional specific fashion.     

Functional analyses of the superficial stratum corneum in atopic xerosis

Dermatologists universally recognize that the unaffected skin of patients with atopic dermatitis tends to be dry and slightly scaly. To characterize the functional properties of the superficial stratum corneum in atopic xerosis, we studied the forearms of 28 patients with atopic dermatitis, aged 14 to 30 years, and 18 age-matched controls, with the use of mainly noninvasive methods. Patients with atopic xerosis showed markedly higher transepidermal water loss and markedly lower skin surface hydration levels than did the controls. The corneocytes in atopic xerosis tended to desquamate in clumps of cell aggregates instead of as individual cells. They contained a substantially lower amount of water-soluble amino acids, which play a role in the water-retaining capacity of stratum corneum, than did those of controls. Although the number of stratum corneum cell layers in atopic xerosis (21 +/- 4) was substantially larger than that in controls (15 +/- 1), its turnover time (7 +/- 2 days) was appreciably shorter than that for controls (14 +/- 2 days). Like those noted in the skin with increased epidermal proliferation, the size of superficial corneocytes in patients with atopic xerosis was substantially smaller than in controls. Histopathologic examination revealed acanthotic epidermis, mild perivascular mononuclear cell infiltrate, and pigment incontinence. Atopic xerosis, the dry skin of patients with atopic dermatitis, shows various stratum corneum functional impairments, probably reflecting increased epidermal proliferation due to a low-level ongoing dermatitis.     

Susceptibility to irritants: role of barrier function, skin dryness and history of atopic dermatitis

The susceptibility of the skin to various irritants was investigated with the aim of determining the role of the barrier function of the stratum corneum, skin dryness and whether a history of atopic dermatitis (AD) was a factor. The transepidermal water loss (TEWL) was measured using an evaporimeter and skin hydration using a Corneometer and by visual scoring. The group with a history of AD (n = 20) had a lower pre-exposure barrier function and a higher TEWL value following irritant exposure than the group with a history of allergic contact dermatitis (n = 18) and a control group (n = 18). Clinically dry skin was more susceptible than normal skin, though no difference was noted in the pre-exposure barrier function. The increased susceptibility to irritants in those with a past history of AD was probably due to impaired barrier function and/or the presence of a dry skin.     

Topisch appliziertes Argininhydrochlorid

Background and objective

Currently, there are no data on how the topical application of amino acids influences the complex moisture retaining system of the skin in vivo.

Patients/methods

An open study was performed to investigate the effects of topical application of arginine hydrochloride on epidermal stratum corneum urea content, transepidermal water loss, skin hydration, and clinical status of patients with atopic dermatitis and dry elderly skin.

Results

Treatment of patients with atopic dermatitis with 2.5% arginine hydrochloride ointment over 4 weeks showed a significant increase in urea in the stratum corneum as well as a continuous increase in skin moisture.

Conclusions

The urea deficit in the stratum corneum in atopic dermatitis and elderly skin was corrected not by applying the moisturizer urea itself but instead by using arginine ? its precursor in the Krebs-Henseleit urea cycle. This topical treatment also improved the clinical symptoms of dry skin.     

Normal recovery of the stratum corneum barrier function following damage induced by tape stripping in patients with atopic dermatitis

Patients with atopic dermatitis (AD) constantly inflict mechanical damage to their skin by scratching induced by pruritus. On excoriated lesions of the cheek we found exceedingly high levels of transepidermal water loss (TEWL) as compared to those in the normal skin of healthy subjects. However, it is not clear whether the skin of patients with AD also shows an abnormally slow recovery after mechanical damage. We compared the recovery of the barrier function of the stratum corneum (SC). after its complete removal by tape stripping, in patients with AD and age-matched healthy control subjects. On the normal-looking skin of the flexor forearm, we found no difference in the recovery process of the water barrier function of the SC between the two groups. This suggests that ability to reconstruct SC barrier function after mechanical damage is not impaired in AD patients.     

特应性皮炎动物模型表皮脂合成的研究

目的:探讨特应性皮炎(AD)皮肤生理改变(包括表皮水分丢失量和角质层水分含量)是否与表皮脂的代谢有关。方法:在小鼠的背部和躯干外涂2,4-二硝基氟苯(DNFB),建立小鼠特应性皮炎模型,利用14[C]乙酸对AD模型表皮脂的代谢进行研究,并用电子显微镜对AD皮肤的超微结构进行观察。结果:AD表皮的胆固醇和脂肪酸的合成速度明显低于对照组,正常对照组的角质细胞间均为正常的复层板层膜结构。而皮炎组的深层角质细胞间虽可见正常的复层板层结构,但有许多没有加工完全的膜结构存在。结论:推测AD皮肤生理的异常改变可能是由于表皮脂的合成减少和角质细胞间膜异常所致。     

Effect of moisturizers on epidermal barrier function

A daily moisturizing routine is a vital part of the management of patients with atopic dermatitis and other dry skin conditions. The composition of the moisturizer determines whether the treatment strengthens or deteriorates the skin barrier function, which may have consequences for the outcome of the dermatitis. One might expect that a patient's impaired skin barrier function should improve in association with a reduction in the clinical signs of dryness. Despite visible relief of the dryness symptoms, however, the abnormal transepidermal water loss has been reported to remain high, or even to increase under certain regimens, whereas other moisturizers improve skin barrier function. Differing outcomes have also been reported in healthy skin: some moisturizers produce deterioration in skin barrier function and others improve the skin. Possible targets for barrier-influencing moisturizing creams include the intercellular lipid bilayers, where the fraction of lipids forming a fluid phase might be changed due to compositional or organizational changes. Other targets are the projected size of the corneocytes or the thickness of the stratum corneum. Moisturizers with barrier-improving properties may delay relapse of dermatitis in patients with atopic dermatitis. In a worst-case scenario, treatment with moisturizing creams could increase the risks of dermatitis and asthma.     

Permeability barrier function of skin exposed to ionizing radiation

OBJECTIVE: To characterize the epidermal permeability barrier function of skin during exposure to ionizing radiation. DESIGN: A prospective cohort study. SETTING: University hospital medical center. PATIENTS: Fifteen women receiving local radiation therapy (5000-6000 rad [50-60 Gy]) following breast-conserving surgery for breast cancer. MAIN OUTCOME MEASURES: Clinical symptoms and transepidermal water loss (TEWL). RESULTS: Epidermal permeability barrier function is impaired in patients who exhibit clinical signs of radiation dermatitis. The functional damage to the stratum corneum induced by ionizing radiation occurs with a delayed course, starting within a mean period of 11 days and reaching maximal values after a mean period of 27 days (range, 13-75 days). The onset of TEWL increase precedes the onset of radiation dermatitis and the maximal TEWL measurements precede the peak of skin changes. Patients with an early onset of TEWL increase show a longer duration of skin symptoms. CONCLUSIONS: Skin changes caused by radiation dermatitis are associated with an increase in TEWL. The barrier impairment is comparable to the changes observed with UV radiation exposure but exhibits an even more delayed course. Our results suggest that preservation of the epidermal permeability barrier function by topical treatment may ameliorate radiation dermatitis.     

Factors predisposing to cutaneous irritation

In experimental skin toxicology, as well as in clinical practice, considerable interindividual variation in the susceptibility to irritant dermatitis is noted when irritant doses are low. Cutaneous sensitivity and hypersensitivity are not determined by a single known feature but are multifactorial. Previous atopic dermatitis may predispose to irritant dermatitis. Susceptibility to irritation seems to be influenced by age, race, and genetic background, whereas sex-related differences do not seem to exist. Of biophysical skin baseline features, skin-surface pH was correlated with the severity of experimentally induced irritant dermatitis, but baseline transepidermal water loss, water-holding capacity, stratum corneum turnover time, and sebum content were not.     

Evaluation of out–in skin transparency using a colorimeter and food dye in patients with atopic dermatitis

Background  Atopic dermatitis is a disease of skin barrier dysfunction and outside stimuli can cross the skin barrier.
Objectives  To examine a new method for evaluating the outside to inside skin transparency with a colorimeter and yellow dyes.
Methods  In study 1, a total of 28 volunteer subjects (24 normal and four with atopic dermatitis) participated. After provocation with yellow dye, the skin colour of all the subjects was measured using a colorimeter. The skin transparency index was calculated by the changes of the skin colour to yellow. Other variables of skin function, including transepidermal water loss (TEWL) and stratum corneum hydration, were also measured. In study 2, the skin transparency index was evaluated for a cohort of 38 patients with atopic dermatitis, 27 subjects with dry skin and 29 healthy controls.
Results  In study 1, the measurement of skin colour (b*) using tartrazine showed good results. There was a significant relationship between the skin transparency index with tartrazine and the atopic dermatitis score ( P  =   0·014). No other measurements of skin function, including the TEWL, were correlated. In study 2, the skin transparency index score obtained with tartrazine in the patients with atopic dermatitis was significantly higher than that of the controls and those with dry skin ( P  <   0·001 and P  =   0·022, respectively). However, the TEWL in patients with atopic dermatitis was not significantly higher than that of patients with dry skin and the TEWL in subjects with dry skin was not higher than that of the controls.
Conclusions  This method, which used a colorimeter and food dye, is noninvasive, safe and reliable for the evaluation of out–in skin transparency and can demonstrate the characteristic dysfunction in the skin barrier in patients with atopic dermatitis.