Irritant susceptibility and weal and flare reactions to bioactive agents in atopic dermatitis. I. Influence of disease severity

The two main pathogenetic characteristics of atopic dermatitis (AD) are: (i) antigen-dependent ‘specific’ reactivity, and (ii) altered non-immimological ‘non-specific’ reactivity. Our understanding of the role of non-specific reactivity is hampered by the fact that methods available for its quantification are limited. The aim of the present study was to assess the usefulness of two parameters as quantitative measures of non-specific skin reactivity in AD: (i) susceptibility to repeated epicutaneous exposure to an irritant (sodium lauryl sulphate, SLS), assessed by visual scoring and transepidermal water loss(TEWL) measurement, and (ii) reactivity to intracutaneously injected bioactive agents (codeine, FMLP, histamine, methacholine, substance P, trypsin), assessed by measurement of weal and flare size. These two parameters were tested in a group of AD patients, subdivided according to the severity of their dermatitis, and a control group. The visual score and TEWL after SLS exposure tended to be higher in the AD group than in the control group. Furthermore, visual score and post-exposure TEWL were positively correlated with the dermatitis severity score. Weal size following injection of codeine, histamine and substance P, and flare size following injection of all agents, except methacholine, were significantly lower in the AD group than in the control group. Negative correlations were found between weal and flare sizes and the dermatitis severity score. These findings can be explained by down-regulation of structures involved in weal and flare reactions. In conclusion, we propose that epicutaneous irritant susceptibility and reactivity to intracutaneous bioactive agents may be useful indicators of non-specific skin reactivity in AD.     

Basal electrical impedance in relation to sodium lauryl sulphate-induced skin reactions – a comparison of patients with eczema and healthy controls

Background: Identification of subjects at risk for contact dermatitis by screening tests is desirable in order to adjust the preventive measures to individual skin susceptibility. The present study aimed to examine the effects of basic physiological features, such as baseline electrical imped-ance (IMP) and transepidermal water loss (TEWL), on reactivity to sodium lauryl sulphate (SLS).
Methods: On the basis of two previous studies, we re-evaluated the experimental irritant skin reactions (50 μL of 2% SLS in large Finn Chambers for 24 h) on the volar forearms of 29 patients with eczema and 19 healthy controls.
Results: We found definite differences in the baseline values of IMP, between the patients and the controls. Moreover, patients with eczema showed higher TEWL and lower MIX values on day 3 after exposure to SLS, which may indicate differences in SLS reactivity. After the study, the biophysical parameters of the eczema patients did not return to baseline, which suggests that their skin heals more slowly than that of normal subjects.
Conclusions: Our findings indicate that the IMP technique may help to 'detect' chemically vulnerable skin. However, more studies are needed to determine the value of the basal electrical impedance parameters in assessing the risk of developing irritant contact dermatitis.     

Skin irritation thresholds in hairdressers: implications for the development of hand dermatitis

BACKGROUND: Individuals vary in their ability to react to irritants. OBJECTIVES: To observe the development of clinical hand dermatitis and sensitization prospectively in trainee hairdressers and to compare this with their irritant threshold to sodium lauryl sulphate (SLS). METHODS: Subjects were patch tested to a limited series of occupational importance and their irritant threshold to SLS was determined; patch testing was repeated 6 months later and subjects were assessed for hand dermatitis. RESULTS: The development of hand dermatitis was associated with a lower irritant threshold. A similar association was not found for sensitization. CONCLUSIONS: The development of clinical dermatitis in prospectively followed subjects with greater irritant reactivity has not previously been identified. The association of greater irritant reactivity with a proinflammatory cytokine polymorphism may partly explain this. Further development of the irritant threshold test could contribute to the identification of non-atopic subjects at risk of occupational skin disease.     

Cholinergic and adrenergic sweating in atopic dermatitis.

Sweating responses to methacholine and adrenaline were compared with an evaporimeter in normal-looking back and forearm skin from patients with atopic dermatitis (AD) and from non-atopic controls (NA). With both stimulants, the sweat rates were higher in forearm than in back skin in both groups, and between the two sites the rates showed positive correlations which were statistically significant in both groups. With methacholine the responses were slightly depressed in both areas in AD. With a low suprathreshold adrenaline concentration (5 x 10(-6) mol/l) the responses were equal in both groups but a tenfold higher adrenaline concentration elicited an increase of 55% in sweating rates in the back skin of NA and a 15% depression in the back skin of AD subjects (p less than 0.05). On arm skin there was a similar trend, but less marked. Between the cholinergic and adrenergic sweating responses a positive correlation was found on arm skin in AD, suggesting that the unknown mechanism of sweat depression in AD might be the same for both drugs.     

Skin irritant reactivity following experimental cumulative irritant contact dermatitis

Despite the frequency of irritant contact dermatitis, very little is known about the duration of barrier function impairment following cumulative irritant contact dermatitis. We studied post-irritation irritant reactivity by assessing the response to SLS irritation in previously irritated sites. Cumulative irritant contact dermatitis was induced on the forearms of 15 volunteers aged 18 to 50 years by repeated occluded application of 0.5% SLS I h per day over 3 weeks. 3, 6 and 9 weeks later, previously irritated and unirritated control sites were challenged with 2% SLS under occlusion for 23 h. Irritation was assessed by visual scoring, transepidermal water loss (TEWL) as an indicator of epidermal barrier function, and capacitance as a parameter of epidermal water content. While no difference in irritant reactivity between pre-irritated and unirritated sites was observed 3 weeks following irritant contact dermatitis, there was a significant hyporeactivity of previously irritated skin as expressed by clinical scores, TEWL and capacitance at 6 and 9 weeks. Our results indicate that epidermal barrier function remains altered even 9 weeks after cumulative irritant contact dermatitis. With regard to patch testing, post-irritation hyporeactivity might be a cause of false-negative tests on previously irritated sites.     

Acute irritant contact dermatitis: recovery time in man

Our understanding of the details of the recovery time of acute irritant contact dermatitis (ICD) is limited. We examined skin reactivity to a model surfactant, sodium lauryl sulfate (SLS). on previous acute ICD and normal sites over time with visual grading and noninvasive instruments. Acute ICD was induced on the upper arms of 18 volunteers (aged 30 to 51 years) by occluded application of 1% SLS for 24 h. Previous ICD and normal sites were provoked by occluded application of 2% or 7.5% SLS 30 min daily 4 consecutive days. Skin reactivity was assessed daily by visual erythema scoring (VES), transepidermal water loss (TEWL), skin color reflectance (SCR) and electrical capacitance (EC). Skin function of previous ICD sites assessed, by VES, TEWL. SCR, and EC did not normalize until 2 weeks later: all parameters of previous ICD returned to normal after 3 weeks. While skin reactivity to 2% und 7.5% SLS showed no differences between previous ICD and normal sites at 4 weeks, differences of irritant reactivity especially 7,5% SLS between previous ICD and normal sites were significant at 3 weeks post-provocation. Our results demonstrate that irritation evaluated with irritant provocation was long-lasting, even though skin functional parameters assessed by various bioengineering instruments returned to normal. Complete recovery of skin function including irritability after acute ICD induced by 1% SLS was achieved approximately 4 weeks later. The date were generated with a model surfactant: it remains to be determined whether similar responses will be noted with chemicals of different physicochemical properties.     

Urea-containing moisturizers influence barrier properties of normal skin

Moisturizers are used in the treatment of dry skin, both clinically and in cosmetic products. In the present study the influence of different moisturizers on the normal skin barrier properties was evaluated by measuring transepidermal water loss (TEWL) and skin capacitance. In addition, the skin reactivity to a topically applied surfactant, sodium lauryl sulphate (SLS), following the use of the moisturizers was examined. The skin reaction was assessed visually and by measuring TEWL and superficial blood flow. Treatment with two urea-containing moisturizers for 10 and 20 days decreased TEWL. The irritant reactions after exposure to SLS were also significantly decreased after prior treatment for 20 days with the urea-containing moisturizers. In a double-blind vehicle-controlled part of the study, urea was found to decrease the skin susceptibility to SLS after only three applications. However, this decrease in skin reactivity was not preceded by a reduction in TEWL. Skin capacitance increased after three applications of urea-containing moisturizers and was still increased after 10 days, but not after 20 days of this treatment. Treatment for 20 days with two moisturizers without urea did not influence either TEWL or the susceptibility to irritation from SLS, but it increased the skin capacitance significantly. The mechanism underlying these changes is not known. The lower degree of SLS-induced irritation in the skin treated previously with urea-containing moisturizers may be of clinical relevance in reducing contact dermatitis from irritant stimuli. Received: 5 January 1995     

Basal transepidermal water loss, skin thickness, skin blood flow and skin colour in relation to sodium-lauryl-sulphate- induced irritation in normal skin

The influence of basal transepidermal water loss (TEWL), skin thickness, blood flow and skin colour on susceptibility to sodium-lauryl-sulphate(SLS)-induced irritant contact dermatitis was studied in 70 healthy volunteers. SLS 0.5% was applied as a patch test. For assessment of basal values and skin response to SLS, bioengineering methods were used: TEWL was measured by an evaporimeter, skin thickness by ultrasound A-scan, blood flow by laser Doppler flowmetry, and skin colour by a colorimeter, using the L*a*b* system of the Commission Internationale de l'Eclairage (CIE). By use of multiple regression analysis, it was demonstrated that basal TEWL was substantially related to skin susceptibility to SLS, high basal TEWL predicting an increased susceptibility to SLS. Also increased light reflection from the skin, indicating a 'fair' skin, was found to be associated with increased susceptibility to SLS.     

A dose-response study of irritant reactions to sodium lauryl sulphate in patients with seborrhoeic dermatitis and atopic eczema.

The susceptibility of the skin of patients with seborrhoeic dermatitis to surfactant irritation was investigated and compared to that of a group of normal subjects and patients with a history of atopic eczema. Responses to six concentrations of sodium lauryl sulphate (SLS), applied to forearm skin, were assessed clinically and measured by laser Doppler flowmetry. Analysis of dose-response curves showed statistically significant increased susceptibility to SLS-induced irritation in patients with seborrhoeic dermatitis and atopic eczema compared with normal subjects. Increased susceptibility to chemical irritation may be important in the pathogenesis of seborrhoeic dermatitis.     

Intra-individual variation of irritant threshold and relationship to transepidermal water loss measurement of skin irritation

Irritant susceptibility studies have used either visual assessment or transepidermal water loss (TEWL) to determine subject response. We have developed a visual assessment method which determines subject irritant threshold. We examined the relationship between sodium lauryl sulfate (SLS) irritant threshold and TEWL measurements from normal skin and SLS patch tests. 19 subjects were recruited. The irritant threshold of each subject was measured and TEWL measurements made from the applied SLS patch tests. Individuals with a lower irritant threshold (easily irritated skin) had elevated TEWL levels compared to those with higher thresholds. The irritant threshold test had a low intraindividual variation. This study showed that the 2 methods grouped patients in a similar manner. The variation seen may reflect the different outcomes measured: irritant threshold visually assesses the skin inflammatory response while TEWL measures skin barrier modification.     

Human cutaneous irritation: induced hyporeactivity

The variation in human skin response to sodium lauryl sulfate (SLS) was determined with patch and open applications. Reactions in different subjects and in multiple simultaneous patch tests were compared. Skin responses were assessed with visual scoring (VS), laser Doppler velocimetry (LDV) and transepidermal water loss (TEWL). Previous open, unpatched SLS exposure decreased patch test reactivity to 1% SLS assessed with VS (p less than 0.05) or LDV (p less than 0.05). Corresponding TEWL alteration was inconstant. Variation in reactivity at different test sites in multiple simultaneous tests was considerable, though less than the variation at different test times (p less than 0.05). Inter-subject variation in test reactivity was greater than the variation between different test times or adjacent test sites. Repeated open applications and the subclinical dermatitis appear to have produced a hyporeactive state. The results suggest that non-specific skin inflammation is elicited by multiple factors, e.g., stratum corneum integrity and vascular reactivity. Their balance determines the ensuing reactions. The induced hyporeactivity may be one of many causes of false negative diagnostic patch tests.     

Skin susceptibility of atopic individuals

The relevance of the irritant skin reaction of individuals with an atopic history (atopic dermatitis, rhinoconjunctivitis or atopic asthma) to sodium lauryl sulfate (SLS), a widely used irritant, is still controversial. The aim of this study was to evaluate transepidermal water loss (TEWL) as an indicator of stratum corneum integrity, before and after SLS patch testing, in various groups of atopic individuals with and without atopic dermatitis. 95 volunteers were divided into 4 groups: (1) individuals with active atopic dermatitis; (2) individuals with a history of atopic dermatitis but without active skin lesions; (3) individuals with rhinoconjunctivitis or atopic asthma without any symptoms at the time of testing; (4) healthy individuals serving as controls. The volunteers were patch-tested at the unaffected volar side of the forearm with aqueous SLS 0.5% for 48 h. TEWL was measured before application and after removal of the patch. Individuals with active atopic dermatitis showed a significantly higher TEWL value after SLS and a tendency to a higher basal TEWL as compared to the 3 other groups. There were no significant differences in TEWL between individuals who were classified as atopic but without active dermatitis, individuals with rhinoconjunctivitis or atopic asthma and healthy controls, either at the basal or at the post-SLS measurement. Enhanced skin susceptibility is only present in individuals with active dermatitis. The skin susceptibility of atopic individuals might therefore be increased as soon as the skin becomes eczematous, suggesting a reduced epidermal integrity probably caused by the endogenous atopy and/or respiratory allergens. When interpreting the atopy score in relation to skin susceptibility, the actual condition of the skin should hence be taken into consideration.     

Patch testing with the irritant sodium lauryl sulfate (SLS) is useful in interpreting weak reactions to contact allergens as allergic or irritant

Several contact allergens are tested at concentrations which might cause irritant reactions. In this study we investigated whether the reactivity to a standard irritant is useful in identifying subjects with hyperreactive skin yielding a higher rate of doubtful or irritant reactions. Sodium lauryl sulfate (SLS) 0.5% (aqua) was tested in addition to the standard series routinely for 5 years in the Department of Dermatology, Dortmund. For data analysis, we compared reactions at D3 to the standard series, the vehicle/emulsifier and preservative series and benzoyl peroxide to the reactions obtained with SLS. Proportions were standardized for age and sex. The association between reactivity to a certain allergen and SLS reactivity as a dichotomous outcome, controlled for age and sex as potential confounders, was assessed with logistic regression analysis. Results showed that of the 1600 tested patients, 668 (41.8%) had an irritant reaction to SLS which exceeded 2 + in only 41 patients. Seasonal variation was statistically significant, showing reduced SLS reactivity in summer vs. winter. Patients with irritant reactions to SLS showed significantly more erythematous reactions to the following 10 allergens of the standard series: fragrance mix, cobalt chloride, balsam of Peru (Myroxylon pereirae), lanolin alcohol, 4-phenylenediamine base (PPD), propolis, formaldehyde, N-isopropyl-N'-phenyl-p-phenylenediamine (IPPD), benzocaine, and 4-tert-butylphenol-formaldehyde resin. No significant differences regarding strong positive allergic reactions were observed. Concerning other allergens, significantly more erythematous reactions were observed in SLS-reactive patients to benzoyl peroxide, octyl gallate, cocamidopropyl betaine, Amerchol L-101, tert-butylhydroquinone, and triethanolamine. In the SLS-reactive group of patients, the reaction index was negative for 10 allergens of the standard series compared to only 5 in the SLS non-responder group. For the first time, this study, based on a large data pool, revealed a significant association between reactivity to the irritant SLS and erythematous reactions to certain allergens. With SLS as a marker for hyperreactive skin at hand, some of these reactions can now be classified as irritant more confidently, particularly if there is no history of exposure to the allergen.     

Water, salts and skin barrier of normal skin

Background: We recently reported that open application of seawater for 20 min ameliorated experimental irritant contact dermatitis induced by sodium lauryl sulphate (SLS) cumulative irritation. The efficacy was overall contributed by 500 mm of sodium chloride (NaCI) and 10 mm of potassium chloride (KCl), which are consistent with the each concentration in seawater. Although the usefulness of mineral water with 500 mm NaCl and 10 mm KCl to treat atopic dermatitis (AD) or irritated skin was considered, seawater or its components would induce a feel of stinging in patients with AD. Furthermore, 20 min application was thought to be too long to use everyday as a treatment. Objective: We report the effects of 3 types of mineral water with NaCl and KCl to check the further efficacy with lesser stinging by 2 min application. Results: A mineral water with 250 mm NaCl and 50 mm KCl was the most effective water to prevent disruption of skin barrier and stratum corneum water content after cumulating irritation by SLS. Moreover, improvement of skin dryness and pruritus were shown 2 weeks after the application of the mineral water to a 6‐year‐old boy with atopic dermatitis. Conclusion: Our results suggested the possible usefulness of the mineral water with 250 mm NaCl and 50 mm KCl as the therapy of atopic dermatitis of other chronic dermatitis. Although the mineral water would not cure those skin diseases, it could be an adjunctive therapy. Further controlled clinical trials with evaluation by TEWL and capacitance are required to declare the efficacy of the mineral water in the treatment of patients with AD or other chronic dermatitis.     

Barrier recovery and influence of irritant stimuli in skin treated with a moisturizing cream

Moisturizers are used daily by many people to alleviate symptoms of clinically and subjectively dry skin. Recent studies suggest that certain ingredients in creams may accelerate the recovery of a disrupted barrier and decrease the skin susceptibility to irritant stimuli. In the present single-blind study, a moisturizing cream was tested for its influence both on barrier recovery in surfuctant-damaged skin and on the susceptibility of normal skin to exposure to the irritant sodium lauryl sulphate (SLS). Parameters measured were transepidermal water loss (TEWL) and skin corneometer values, indicating degree of hydration. Treatment of surfactant-damaged skin with the test cream for 14 days promoted barrier recovery, as observed as a decrease in TEWL. Skin corneometer values also normalized more rapidly during the treatment. In normal skin, use or the test cream significantly reduced TFWL after 14 days of treatment, and irritant reactions to SLS were, significantly decreased. Skin corneometer values increased after only 1 application and remained elevated after 14 days. In conclusion, the accelerated rate of recovery of surfactant-damaged skin and the lower degree of SLS-induced irritation in normal skin treated with the test cream may be of clinical relevance in attempts to reduce contact dermatitis due to irritant stimuli.     

Differential irritant skin responses to tandem application of topical retinoic acid and sodium lauryl sulphate: II. Effect of time between first and second exposure

In clinical practice, the cutaneous exposure to chemical irritants such as surfactants and topical drugs is frequent. Topical all-trans retinoic acid (RA) is often associated with irritation and induces epidermal changes similar to those produced by sodium lauryl sulphate (SLS). Using bioengineering techniques, e.g. assessing transepidermal water loss (TEWL), capacitance and chromametry, we investigated the variations of the skin response to SLS and RA and to both chemicals applied sequentially, allowing different time periods (from 1 h to 2 weeks) between applications of SLS and RA. Both chemicals caused irritation as assessed by visual scoring, but the values from the objective variables differed at different time periods. TEWL increased dramatically shortly after applying SLS but the increase was delayed after RA. After applying SLS, the capacitance generally decreased then returned to basal values; treatment with RA produced an overall increase. Only the results from chromametry were similar. After tandem application, the drugs were synergistic for all variables except capacitance, showing an antagonistic interaction for skin hydration. These results suggest that non-specific skin irritation profoundly reflects different mechanisms of action at tissue level. With sequential application, SLS injury modified the response to RA for at least 1 week after applying SLS. These late effects of detergents should be considered when studying irritant chemical interactions and in developing strategies for the management of occupational and other irritant dermatitis.     

Fluorescence confocal laser scanning microscopy for in vivo imaging of epidermal reactions to two experimental irritants

Background: Fibre‐optic fluorescence confocal laser scanning microscopy (CLSM) is a novel non‐invasive technique for in vivo imaging of skin. The cellular structure of the epidermis can be studied. A fluorophore, e.g. fluorescein sodium, is introduced by an intradermal injection or applied to the skin surface before scanning. Images are horizontal optical sections parallel to the skin surface. Fluorescence CLSM has hitherto not been applied to experimental contact dermatitis. Objective: The aim was to study the applicability of fluorescence CLSM for in situ imaging of irritant contact dermatitis reactions caused by established model irritants, e.g. sodium lauryl sulphate (SLS) and pelargonic acid (PA). Methods: Twelve healthy individuals volunteered. The flexor aspect of the right and the left forearm was exposed to SLS in water and PA in isopropanol and occluded under Finn Chambers for 24 h. The reactions were rated clinically and, following epicutaneous and intra‐dermal application of fluorescein sodium, studied by fluorescence CLSM, magnification × 1000. Results: Both irritants disturbed the epidermal intercellular borders, which became blurred, thickened and variably altered. This was interpreted as being a result of chemical damage to cellular membranes. Cell borders might show a double contour as a result of inter‐cellular oedema. PA might increase the size of individual keratinocytes interpreted as a result of intra‐cellular disturbance with oedema. SLS‐exposed sites showed clusters of keratinocytes with visible nuclei in the outer layers of the epidermis, e.g. a parakeratotic shift supposed to be due to increased cell proliferation elicited by SLS. The isopropanol vehicle and PA did not interfere with the CLSM imaging technique or the experimental procedures. SLS, being a detergent, however, modified the physico‐chemical properties of the skin surface and both disturbed epicutaneous labelling with the flurophore and immersion oil coupling between the skin surface and the optical system. Thus, SLS was technically more difficult to study by CLSM than PA. Conclusions: This preliminary study demonstrated the applicability of fluorescence CLSM for a detailed study of experimental skin irritants in vivo. Essential findings were disturbed and widened cell borders, swelling of keratinocytes by PA and induction of a parakeratotic shift by SLS with clusters of keratinocytes holding nuclei in the epidermis. Fluorescence CLSM offers a unique opportunity to study the inter‐ and intracellular water compartments directly in the epidermis in situ and an opportunity to visualize cell proliferation manifested as parakeratosis. Fibre‐optic fluorescence CLSM of irritant reactions is, however, technically more complicated than reflectance CLSM and may not be applicable to any irritant. SLS applied epicutaneously interacted with the skin surface and coupling to the microscope and was thus found to be more difficult to study technically than PA. PA dissolved in isopropanol is for technical reasons, and with SLS as alternative, considered the preferred model irritant.     

Experimental irritant contact dermatitis due to cumulative epicutaneous exposure to sodium lauryl sulphate and toluene: single and concurrent application

In clinical practice, cutaneous exposure to a variety of irritants such as surfactants and solvents is frequent. Although the induction of irritant dermatitis by single irritants has been extensively studied in recent years, our knowledge of the effects of simultaneous application of different irritants is limited. Using non-invasive techniques for measurements of transepidermal water loss (TEWL) and skin colour reflectance, we quantified the irritant effects of single and concurrent application of 0.5% sodium lauryl sulphate (SLS) and undiluted toluene (TOL) in vivo. The irritants were applied twice daily for 30 min to the volar forearms of 20 volunteers. Repeated application of SLS and TOL induced an irritant reaction, as indicated by an increase in TEWL and skin redness. In contrast to SLS alone, the application of TOL alone induced only a moderate increase in TEWL, confirming previous results. Concurrent application of SLS/TOL and TOL/SLS induced significantly stronger reactions than those caused by twice daily application of each irritant on its own. Our results demonstrate that a mixed application of an anionic detergent and an organic solvent has an additive effect on skin irritation. It is suggested that pretreatment with SLS causes an increased susceptibility to TOL irritation and vice versa. Thus, the necessity for special precautions against skin absorption of TOL when handling detergents such as SLS is emphasized.     

Irritant reactivity in males and females

Repeated, daily, open sodium lauryl sulfate (SLS) applications caused slight alterations in transepidermal water loss (TEWL) and dielectric water content (DEWC) in males and females. No erythema developed. Inter-individual variation in skin reactivity was demonstrated; sex-related patterns in reactivity to open cumulative irritant exposure did not exist. In patch testing with 0.5 and 1% SLS, reflecting acute irritation capacity, the reaction pattern, assessed by TEWL, DEWC, laser Doppler velocimetry (LDV) and visual scoring (VS), differed from that induced by open, cumulative SLS irritation. Again, inter-individual variation in the reactivity was demonstrated; significant sex-related differences did not develop. Individual reactivity showed considerable variation in acute and cumulative irritant response and was greater than the sex-related variation. We did not identify responses demonstrating that women have delicate (easily irritated) skin, nor that males have "tougher" skin than females.     

Skin susceptibility in uninvolved skin of hand eczema patients and healthy controls

Basic physiological characteristics were examined in the uninvolved skin of 39 patients with hand eczema and in 39 healthy controls. Susceptibility to sodium lauryl sulphate (SLS)-induced irritant dermatitis was evaluated by the application of a single 24-h SLS patch test to the upper arm. Transepidermal water loss (TEWL) was measured by an evaporimeter, skin thickness by ultrasound A-scan, blood flow by laser-Doppler flowmetry and skin colour by a chroma meter using the L*a*b* system of the Commission Internationale de l'Eclairage (CIE). No difference in basal TEWL values was found between patients and controls. A decreased skin thickness was found in those with hand eczema as compared to the controls. The hand eczema patients had significantly increased L* and decreased b*-values compared to controls, indicating a more 'fair' skin. Susceptibility to SLS was increased only in patients with acute eczema, indicating that the presence of an active eczema increases the reactivity to irritants of distant uninvolved skin.