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.     

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.     

Membrane-coating granules in "dry" non-eczematous skin of patients with atopic dermatitis. A quantitative electron microscopic study

In recent years much interest has been focused on the functions of the membrane-coating granules (MCGs). These granules seem to play an essential role in the formation of the barrier of the stratum corneum by extruding their lipid-rich content into the extracellular space of the corneocytes. The dry non-eczematous skin in atopic dermatitis has been reported to have defective barrier function. In the present study a quantitative electron microscopic analysis was made of the volume of MCGs in the transition zone between the stratum granulosum and stratum corneum in dry skin of patients with atopic dermatitis. The relative volume of MCGs was significantly greater than that in normal skin. This finding may indicate a disturbance of the "maturation" of the MCGs, leading to a defect in the barrier function in 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.     

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.     

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.     

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.     

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.     

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.     

上海两社区特应性皮炎患儿的皮肤屏障功能研究

【摘要】 目的 探讨上海两个社区特应性皮炎（AD）患儿及健康对照儿童皮肤屏障功能及AD皮损严重程度与皮肤屏障功能的相关性。方法 3 ~ 12岁AD患儿169例和健康对照儿童142例来自上海长宁新泾社区和嘉定菊园社区,检测前臂伸侧、屈侧及脸颊、胫前4个部位非皮损区的角质层含水量和经皮失水量（TEWL）。并用欧洲AD评分标准（SCORAD）对AD患儿临床严重程度进行评分。结果 AD患儿前臂伸侧、屈侧及脸颊、胫前四个部位的TEWL值均高于健康对照儿童（P ＜ 0.05）,角质层含水量在前臂伸侧和胫前均显著低于健康对照儿童（P ＜ 0.05）。AD患儿SCORAD与TEWL均值呈正相关,与角质层含水量均值呈负相关。结论 皮肤屏障功能可以作为评价AD临床严重程度的指标之一。     

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.     

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.     

Genetic association between an AACC insertion in the 3'UTR of the stratum corneum chymotryptic enzyme gene and atopic dermatitis

Atopic dermatitis is a disease with an impaired skin barrier that affects 15%-20% of children. In the normal epidermis, the stratum corneum chymotryptic enzyme (SCCE) thought to play a central role in desquamation by cleaving proteins of the stratum corneum (e.g., corneodesmosin and plakoglobin). Genetic variations within the SCCE gene could be associated with dysregulation of SCCE activity leading to an abnormal skin barrier. We screened the SCCE gene for variations and performed a case-control study on 103 atopic dermatitis patients and 261 matched controls. 16 synonymous single nucleotide polymorphisms (SNPs) have been identified and a 4 bp (AACC) insertion has been found in the 3'UTR. We performed an association study of the SCCE AACC insertion in the 3'UTR, and found a significant trend between the AACC allele with the two insertions and disease in the overall data set [odds ratio (OR)=2.31; p=0.0007]. The AACC insertion in the SCCE gene may result in a change to SCCE activity within the skin barrier. These findings suggest that SCCE could have an important role in the development of atopic dermatitis.     

Decreased level of ceramides in stratum corneum of atopic dermatitis: an etiologic factor in atopic dry skin?

Stratum corneum lipids are an important determinant for both water-retention function and permeability-barrier function in the stratum corneum. However, their major constituent, ceramides, have not been analyzed in detail in skin diseases such as atopic dermatitis that show defective water-retention and permeability-barrier function. In an attempt to assess the quantity of ceramides per unit mass of the stratum corneum in atopic dermatitis, stratum corneum sheet was removed from the forearm skin by stripping with cyanoacrylate resin and placed in hexane/ethanol extraction to yield stratum corneum lipids. The stratum corneum was dispersed by solubilization of cyanoacrylate resin with dimethylformamide, and after membrane filtration, the weight of the stratum corneum mass was measured. The ceramides were quantified by thin-layer chromatography and evaluated as microgram/mg stratum corneum. In the forearm skin of healthy individuals (n = 65), the total ceramide content significantly declined with increasing age. In atopic dermatitis (n = 32-35), there was a marked reduction in the amount of ceramides in the lesional forearm skin compared with those of healthy individuals of the same age. Interestingly, the non-lesional skin also exhibited a similar and significant decrease of ceramides. Among six ceramide fractions, ceramide 1 was most significantly reduced in both lesional and non-lesional skin. These findings suggest that an insufficiency of ceramides in the stratum corneum is an etiologic factor in atopic dry skin.     

The effect of washing on the thickness of the stratum corneum in normal and atopic individuals

The thickness of, and number of cell layers in, the stratum corneum and the living epidermis were determined on frozen sections of washed and unwashed skin from normal and atopic individuals of both sexes. The stratum corneum of atopic patients was thinner and had fewer layers of dead cells and intercellular lipid than normal, although the living epidermis was thicker. Regular washing with soap and water had no appreciable effect on the dimensions of the living epidermis of either group but caused a reduction in the number of cell layers and the amount of sudanophilic material in the stratum corneum of both. In atopic patients little surface lipid remained, suggesting that washing with soap and water may be detrimental to the barrier function of the stratum corneum in such patients.     

Comparison of epidermal hydration and skin surface lipids in healthy individuals and in patients with atopic dermatitis

BACKGROUND: The water content of the stratum corneum and skin surface lipids are important factors in the appearance and function of the skin. A disruption of the balance between the two may lead to the clinical manifestation of dryness of skin in patients with atopic dermatitis. OBJECTIVE: The aim of our study was to examine the so-called dry skin of patients with atopic dermatitis using objective parameters. We compared the epidermal hydration and the skin surface lipids, the so-called hydro-lipid film, of the clinically unaffected skin of patients suffering from atopic dermatitis with that of healthy subjects. METHODS: A total of 48 patients of either gender were included in this retrospective case-control study. We used the Corneometer CM 820 (Courage+Khazaka Electronic GmbH, Cologne, Germany) and the Sebumeter SM 810 (Courage+Khazaka Electronic GmbH) as noninvasive measuring methods. RESULTS: The results showed marked decreases in the atopic dermatitis group for both the Corneometer and Sebumeter measuring methods. CONCLUSION: Our results show that the dry skin of patients with atopic dermatitis, as previously shown, is due not only to a decrease in skin moisture but also to a reduction of skin lipids. This finding gives rise to a new understanding of the condition, and therefore one should always speak of a hydro-lipid film.     

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.     

Eigenwirkungen von Emulsionen auf die Hornschichtbarriere und -hydratation

The appearance of the skin depends greatly on the hydration of the stratum corneum which is regulated by water binding substances of the corneocytes and also by the quality of the stratum corneum lipids. Furthermore these lipids are responsible for the barrier function. In patients with atopic dermatitis, the water binding capacity and the barrier function of the stratum corneum are reduced even in clinically healthy skin areas. Emollients can damage the stratum corneum and lead to desiccation and a disturbance of the barrier. This effect is a result of an increased permeability of the barrier lipids and direct damage to the keratinocytes and corneocytes. The degree of damage of the barrier caused by emollients in dermatological vehicles has not been sufficiently investigated. As suggested by hypothetical considerations, such an effect is not expected and cannot be demonstrated in water-in-oil-emulsions. Oil-in-water-emulsions without glycerol as well as lipophilic and hydrophilic microemulsions do damage the barrier function. Both types of microemulsions additionally lead to a dehydration of the stratum corneum. The damaging effect of oil-in-water-emulsions can be reduced by the addition of glycerol and urea.     

Ceramide profiles of the uninvolved skin in atopic dermatitis and psoriasis are comparable to those of healthy skin

Ceramides are sphingolipids consisting of sphingoidbases, which are amide-linked to fatty acids. In the stratum corneum, they represent the major constituent of the free extractable intercellular lipids and play a significant role in maintaining and structuring the water permeability barrier of the skin. Using thin layer chromatography, which represents the method of the first choice in analyzing the stratum corneum ceramides, at least seven classes can be distinguished. Each ceramide class contains various species, which have the same head group and different chain lengths. As in many other skin disorders, atopic dermatitis and psoriasis show derangements in content and profile of the ceramides. Such derangements were reported for both the lesional involved as well as for the normal-appearing uninvolved skin. In this study, we focused on investigating the stratum corneum ceramides of the uninvolved skin in atopic dermatitis and psoriasis patients compared to healthy skin. The aim of the investigations was to explore possible significant and specific differences which can be accomplished for purposes of early diagnostics. The skin lipids were collected by means of an in vivo topical extraction procedure using an extraction mixture consisting of n-hexane and ethanol, (2:1). An automated multiple development-high performance thin layer chromatography (AMD-HPTLC) method with photodensitometric detection were applied to separate the ceramides and to estimate their contents. For studying their molecular profile within each ceramide class, a new method of normal phase HPLC with atmospheric pressure chemical ionization mass spectrometry were used. The results obtained by AMD-HPTLC exposed no significant alterations regarding the relative composition of the major stratum corneum lipids and primarily the ceramides. In addition, the mass spectrometric profiles within each ceramide class were similar in the patients and the healthy control subjects. In conclusion, this study revealed that the normal-appearing uninvolved skin of atopic dermatitis and psoriasis patients does not prove significant or specific deficiencies with respect to the free extractable major stratum corneum lipids and mainly the ceramides, when compared to healthy skin. Thus, they cannot be used for diagnostic purposes. Furthermore, our data are not consistent with the concept that impairments in the ceramide composition represent an obligate etiologic factor for both diseases.     

Impairment of skin barrier function is not inherent in atopic dermatitis patients: a prospective study conducted in newborns

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.