Characteristics of skin surface morphology and transepidermal water loss in clinically normal-appearing skin of patients with atopic dermatitis: a video-microscopy study

In patients with atopic dermatitis (AD), it is debatable whether clinically normal-appearing skin is equal to non-atopic normal skin. The aim of this study was to quantitatively evaluate the characteristics of normal-appearing skin of AD. We examined the value of skin surface morphological changes using a new, simple, computer-assisted method with a video microscope. We also investigated the physiological function as represented by transepidermal water loss (TEWL) levels in 44 patients with AD and 15 normal controls. The morphological changes were represented by a variation coefficient score that reflected the irregularity of skin ridges, named the surface irregularity index (SII). There were significant differences between the normal-appearing skin of AD and non-atopic normal skin in both SII (P<0.001) and in TEWL (P<0.01). Especially for the SII, there were significant differences between AD subgroups subdivided by peripheral blood eosinophil count (Eo), serum lactate dehydrogenase level, and clinical score. TEWL values were significantly higher in the high-Eo AD group (n=15) than in the low-Eo AD group (n=29) (P<0.05). These findings indicate that clinically normal-appearing skin of AD patients with high disease activity differs from non-atopic normal skin in both surface morphology and physiology and that these changes reflect the current disease activity.     

Transepidermal water loss in adhesive tape induced dermatitis

As an index of skin barrier function, transepidermal water loss (TEW) was investigated in subjects reactive to adhesive tapes. Tape reactive subjects showed no difference in TEW in untreated skin when compared to non-reactive subjects. Plastic tape and transparent tape produced varying degrees of dermatitis in reactive subjects; the TEW was increased up to 40-fold of the baseline values correlating with the degree of dermatitis. Paper tape and plastic film without adhesive did not produce dermatitis and increased water loss. Regeneration of skin damage was accompanied by a decrease of TEW values. The general problem of tape reactors and tape irritation is discussed.     

Friction, capacitance and transepidermal water loss (TEWL) in dry atopic and normal skin

The biophysical properties of non-eczematous skin at three locations in atopics and non-atopics were characterized using non-invasive physical methods. Skin friction was measured with a newly developed sliding friction instrument, the degree of hydration with a capacitance meter (Corneometer CM 820), and the transepidermal water loss (TEWL) was determined using an Evaporimeter EP1. The areas examined (dorsum of the hand, volar forearm and lower back) showed lower values of friction and capacitance in the atopic patients than did corresponding sites in the normal controls. In most areas a significant correlation between friction and capacitance was found. The TEWL was increased in atopic skin, but TEWL seems to correlate neither to friction nor to capacitance.     

Transepidermal water loss and absorption of hydrocortisone in widespread dermatitis

Percutaneous absorption of hydrocortisone was measured in tbree children and six adults with widespread dermatitis, after the application of 1% bydrocortisone cream. Before appiication of the cream, the transepidermal water loss (TEWL) was measured on six skin areas. A highly significant correlation was found between the post-application rise in plasma cortisol level and the mean transepidermal water loss. Thus, measurement of TEWL affords a simple, non-invasive method for assessing the systemic effect of hydrocortisone applied to widespread dermatitis.     

经表皮水分流失与皮肤屏障的遗传学研究

经表皮水分流失（Transepidermal water loss?,TEWL）测量的是水分从真皮和表皮的水合层向皮肤表面扩散的通量密度,是用于评估皮肤屏障功能的一项成熟无创的方法,最新的一项研究发现TEWL值与9号染色体9q34.3基因突变密切相关,本文总结了TEWL与皮肤屏障功能的遗传学研究进展。     

The morphologic characteristics of dry skin in atopic dermatitis

Uninvolved skin sites in 436 consecutive patients, 6 to 25 years old, with atopic dermatitis were observed during the winter months (from November to February). Ichthyosis vulgaris occurred in 133 patients. Of the 303 remaining patients, only 11 (4%) had generalized dry skin; 191 (63%) exhibited focal areas of dry skin; and 95 (33%) showed only normal-appearing skin. Microscopically, in 41 patients, dry skin associated with atopic dermatitis showed mild eczematous changes. Dry skin coexistent with ichthyosis in patients with atopic dermatitis revealed ichthyotic changes frequently superimposed on eczematous changes. We suggest that in patients with atopic dermatitis the presence of dry skin may reflect mild eczematous changes, a manifestation of concomitant ichthyosis, or a complex of both of these changes.     

Transepidermal water loss does not correlate with skin barrier function in vitro

The purpose of this study was to investigate the relationship between transepidermal water loss and skin permeability to tritiated water (3H2O) and the lipophilic penetrant sulfur mustard in vitro. No correlation was found between basal transepidermal water loss rates and the permeability of human epidermal membranes to 3H2O (p = 0.72) or sulfur mustard (p = 0.74). Similarly, there was no correlation between transepidermal water loss rates and the 3H2O permeability of full-thickness pig skin (p = 0.68). There was no correlation between transepidermal water loss rate and 3H2O permeability following up to 15 tape strips (p = 0.64) or up to four needle-stick punctures (p = 0.13). These data indicate that transepidermal water loss cannot be unconditionally ascribed to be a measure of skin barrier function. It is clear that further work should be conducted to interpret the significance of measuring transepidermal water loss by evaporimetry.     

Baseline water loss and cholinergic sweat stimulation in atopic dermatitis: a gravimetric measurement of local skin water loss

Summary The sweat gland function in atopic dermatitis (AD) and in respiratory atopy is a matter of controversy. We examined the baseline water loss and local sweating response in non-eczematous back skin of 146 young men: pure AD, AD with rhinitis/asthma, rhinitis/asthma alone, non-atopic dermatosis and non-atopic healthy. All AD subjects were further divided into the subgroups AD dry and AD normal skin. Following injections of saline and a high concentration of methacholine (5×10⁴ mol/1) into separate sites the moisture losses were collected into closed pads over a period of 40 min. The baseline water loss was significantly increased (P<0.001) and median pure sweat loss was significantly decreased (P<0.01) in AD compared with nonatopic healthy individuals. These trends were accentuated in AD dry skin. Respiratory symptoms had no appreciable influence on results. A depressed sweating response occurred in 30% of AD subjects and 9% of non-AD subjects. An elevated baseline water loss value and a depressed sweat loss value coexisted in 22% of subjects with AD dry skin compared with 3% of the non-atopics.     

Neuropeptides in the skin of patients with atopic dermatitis

There is increasing evidence that neuropeptides may be involved in the pathogenesis of atopic dermatitis (AD). This study examines whether neuropeptide distribution in the skin of patients with AD differs from normal controls. The distribution and density of several neuro-peptides were examined in lesional and non-lesional skin of AD patients (n= 5) and in normal controls (n= 4) using indirect immunofluorescence and image analysis. Cholinergic innervation was studied using cholinesterase histochemistry. Staining with the general neuronal marker protein gene product 9·5 showed a subepidermal network of nerves with fibres penetrating the epidermis, and nerves around blood vessels, sweat glands and hair follicles. Image analysis of nerves around sweat glands showed a significantly higher nerve density in non-lesional compared with both normal controls and lesional skin (P < 0·05); lesional compared with control skin showed no significant difference. In the epidermis the density of nerves was not significantly greater in non-lesional compared with lesional skin and controls. Calcitonin gene-related peptide immunoreactivity was similar in all subjects except in three of the AD patients, where more nerves appeared to penetrate the epidermis. Substance P immunoreactivity in the papillary dermis was seen in all AD patients hut no controls. Vasoactive intestinal polypeptide and neuropeptide Y staining were similar in all groups. Acetyleholinesterase-positive nerves were found around sweat glands in all subjects, the staining being greatest in non-lesional and least in lesional skin. Occasional nerves were seen in the papillary dermis in lesional skin of two out of the four patients. We have demonstrated quantitative differences in nerve growth in clinically normal skin of AD patients, and altered cutaneous neuropeptide expression in these patients which may contribute to the pathogenesis of AD.     

Transepidermal water loss, serum IgE and beta-endorphin as important and independent biological markers for development of itch intensity in atopic dermatitis

BACKGROUND: Although itch is the predominant symptom of atopic dermatitis (AD), it is poorly characterized and subjective. The objective assessment of itch intensity is important for treatment and follow-up in patients with AD. OBJECTIVES: To determine what objective clinical parameter(s) could be used as biomarker(s) for itch intensity in patients with AD. METHODS: This is a retrospective and cross-sectional study. Seventy-five patients, aged 7 months-49 years with equal sex ratio, were enrolled in 2000 according to criteria proposed by Hanifin and Rajka. Thirty-five age- and sex-matched subjects who visited the dermatological clinic but were otherwise healthy served as controls. Subjective itch intensity was divided into four grades of severity. Disease severity was measured by SCORAD index, which also includes itch intensity as part of the measurement. Transepidermal water loss (TEWL) and skin surface pH were measured by noninvasive methods in clinically normal skin on the forearm. Serum beta-endorphin and vasoactive intestinal peptide (VIP) were determined by radioimmunoassay. Ordinal logistic regression was used to assess the trend of the subjective itch intensity and SCORAD index by serum IgE, beta-endorphin, VIP, TEWL and skin pH. RESULTS: There were significant trends for itch intensity with IgE, beta-endorphin and TEWL. After adjustment for sex, age and other variables, the odds ratio (OR) for itch intensity by log IgE, beta-endorphin and TEWL was 2.103 [95% confidence interval (CI) 1.222-3.618], 1.100 (95% CI 1.005-1.203) and 1.081 (95% CI 1.009-1.158), respectively. The OR for disease severity by log IgE, beta-endorphin and TEWL was 2.250 (95% CI 1.149-4.407), 1.156 (95% CI 1.086-1.231) and 1.071 (95% CI 0.971-1.182), respectively. In contrast, there was no association between serum VIP concentration and itch intensity. CONCLUSIONS: Beta-endorphin and IgE are both useful biomarkers for itch and disease severity in patients with AD, while TEWL is a good biomarker for itch intensity. These biomarkers provide a way to assess the itch intensity in patients with AD.     

Studies of the clinically uninvolved skin in patients with dermatitis

We have studied the clinically normal skin of eighty-four patients with quiescent dermatitis of different types, and fifty normal subjects. Increased susceptibility to chemical irritation was demonstrated in patients with atopic and exogenous dermatitis. There was a reduction in mean corneocyte area and a thinner horny layer in all patients, and an increased epidermal thickness in atopic dermatitis patients only. In forced desquamation studies, patients released more corneocyte clumps from the skin surface, but there were no significant differences between patients and controls in sensitivity to UVR or electrical conductivity.     

Mast cells and atopic dermatitis. Stereological quantification of mast cells in atopic dermatitis and normal human skin

Stereological quantification of mast cell numbers was applied to sections of punch biopsies from lesional and nonlesional skin of atopic dermatitis patients and skin of healthy volunteers. We also investigated whether the method of staining and/or the fixative influenced the results of the determination of the mast cell profile numbers. The punch biopsies were taken from the same four locations in both atopic dermatitis patients and normal individuals. The locations were the scalp, neck and flexure of the elbow (lesional skin), and nates (nonlesional skin). Clinical scoring was carried out at the site of each biopsy. After fixation and plastic embedding, the biopsies were cut into 2 μm serial sections. Ten sections, 30 μm apart, from each biopsy were examined and stained alternately with either toluidine blue or Giemsa stain and mast cell profile numbers were determined. The study yielded the following results: (1) in atopic dermatitis lesional skin an increased number of mast cell profiles was found as compared with nonlesional skin, (2) comparing atopic dermatitis skin with normal skin, a significantly increased number of mast cell profiles per millimetre squared was found in specimens from the neck, (3) staining with toluidine blue yielded a lower number of mast cell profiles than Giemsa staining, (4) the use of Carnoy’s fixative resulted in a lower mast cell profile count than the use of formaldehyde, and (5) there was no statistically significant correlation between the clinical score and the number of mast cell profiles per millimetre squared. Using stereological techniques, this study indicated that mast cells might participate in the inflammatory process in skin leading to atopic dermatitis. Received: 17 April 1996