Is atopic dermatitis a predisposing factor for experimental acute irritant contact dermatitis?

Proclivity to acute irritant contact dermatitis has been reviewed by comparing the response in patients with atopic dermatitis to controls. Although several controlled studies demonstrate such a proclivity, others do not, suggesting that the mechanisms involved are complex.     

Study of cumulative irritant contact dermatitis in man utilizing open application on subclinically irritated skin

We evaluated the effect of subclinical irritation on the cutaneous reaction elicited by cumulative short-term (30-min) application of sodium lauryl sulphate (SLS), by measuring transepidermal water loss (TEWL) and assigning visual scores. 11 healthy adult volunteers, free of skin disease and with no history of atopic dermatitis, were treated with SLS solution (1%, 2%, 5%, 7.5%). On a Monday, we applied 80 μl of 1% SLS solution and deionized water (control), using large aluminum chambers with filter paper discs, for 30 min. We measured TEWL values 2x before and after patch application of control and 1% SLS solution, and then applied 80 μl of SLS solution (2%. 5%. 7.5%) using filter paper discs. From Tuesday to Friday, we applied 80 μl of each solution, using filter paper discs, and measured TEWL before and after open application of test solutions. Compared with each corresponding group, TEWL values of SLS patch groups (S-2.0, S-5.0, S-7.5) were higher than, those of water patch groups (W-2.0, W-5.0, W-7.5), respectively. TEWL values of each groups increased stepwise and the final (hour 97) TEWL values were higher than those of baseline (hour 0) TEWL. The mean visual scores of the vehicle control were lower than those of other test groups, but there were no statistically significant differences in visual scores between each test group. These findings suggested that impaired skin barrier function, elicited by subclinical irritation from short-duration contact with some irritants, might augment the cumulative irritant contact dermatitis caused by repeated open exposure to other surfactants. Relatively short-term and minimal exposure, not in great excess of many daily surfactant exposures, produced cumulative irritation. TEWL measurements were more discriminating than visual grading.     

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.     

Artificial disruption of skin barrier prior to irritant patch testing does not improve test design

BACKGROUND: Irritant patch testing is often performed as a 24- or 48-h occlusive patch test with low concentrations of sodium lauryl sulphate (SLS). OBJECTIVES: The aim of this study was to investigate potential ways to shorten this test procedure and obtain precise test results. PATIENTS AND METHODS: Thirty-six healthy volunteers underwent irritant patch testing with different pretreatments (PT) of the test fields. Occlusive test chambers were applied on the upper back with SLS 0.5%, 1%, 2% and 5% in large Finn Chambers(R). The patches were removed after 4 and 24 h, respectively, depending on the concentration used. Test fields were pretreated as follows: PT 0, field without any PT (control); PT 1, prick with lancet; PT 2, prick with test stamp; PT 3, scratch with lancet; PT 4, incision with standardized incision instrument (0.1-0.2 mm depth). Skin reactions were evaluated by transepidermal water loss (TEWL), skin erythema and skin hydration and as well by a visual score (VS) at 4, 24 and 72 h. RESULTS: Our data show an obvious distinction between PT 0-2 and PT 3-4 at all measurement methods. The average TEWL values with PT 3-4 were higher than those with PT 0-2, especially on the 4-h course. This distinction may derive from the shape and size of the skin impairment achieved by PT 3-4, leading to a mechanical barrier disruption. However, SLS may infiltrate directly into deeper skin layers supported by capillarity. Consequently, no or little penetration through the epidermis and interaction with its structures occurs, which is responsible for irritant skin reactions. The SLS dose in the upper skin layers is therefore lower at these PTs. The lower remaining dose of SLS also explains this distinction, especially for the VS. Additionally, there are presumed reactions in deeper layers of the epidermis and dermis at PT 3-4. CONCLUSIONS: In summary, all data suggest a different reaction pattern from the classical irritant response. Therefore, application without any PT seems to be best suited for irritancy skin testing, especially for visual assessment. PTs prior to irritant patch testing have been shown to be unjustifiable.     

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.     

Post-application occlusion substantially increases the irritant response of the skin to repeated short-term sodium lauryl sulfate (SLS) exposure

Occlusion often, but not always, enhances percutaneous absorption and thus may facilitate skin irritation. Quantitative data about the impact occlusivity may have on minimal irritant stimuli to which the skin is exposed in daily life, and which may lead to chronic irritant contact dermatitis, are however lacking. Irritant stimuli were administered by repeated application of sodium lauryl sulfate (SLS) in an open application procedure. After the open exposure, the skin was either left open or occluded with plastic. Skin irritancy was assessed by means of visual grading and by transepidermal water loss (TEWL) measurements. Post-exposure occlusive treatment markedly enhanced the irritant response. 5 consecutive daily applications produced more irritation, with or without occlusion, than alternate day application. Occlusion may be a relevant factor in the development of irritant contact dermatitis from certain chemicals.     

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.     

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.     

Effect of surfactant mixtures on irritant contact dermatitis potential in man: sodium lauroyl glutamate and sodium lauryl sulphate

Our purpose was to ascertain the irritant contact dermatitis potential of sodium lauroyl glutamate (SLG) and to assess its possible anti-irritating potential in a surfactant mixture on human skin, using visual scores and measurement of transepidermal water loss (TEWL). 15 healthy adult volunteers free of skin disease and with no history of atopic dermatitis were treated with sodium lauryl sulphate (SLS) solution (1%, 0.75%, 0,50%, 0.25%), 1% SLG solution, and 1% surfactant mixture solutions, Ml (75/25), M2 (50/50), M3 (25/50) (SLG/SLS). We applied 100μl of solution using a polypropylene chamber for 24 h. Application sites for each solution were randomized to minimize anatomical bias. We measured baseline TEWL before test solution application. After removal of the patches, each site was visually graded and TEWL recorded with an evaporimeter daily for 4 days. The visual scores and TEWL values of 1% SLG solutions were lower than those of the other test solutions, except the vehicle control (deionized water). 1% surfactant mixture solutions showed lower visual scores and TEWL values than 1% SLS solution. Increase of SLG concentration decreased the visual scores and TEWL values. Comparing the visual scores and TEWL values of Ml and 0.25% SLS solution, M2 and 0.50% SLS solution, and M3 and 0.75% SLS solution. Ml, M2, and M3 showed lower values, although not statistically different. These findings suggest that SLG is a mild surfactant and its utilization can decrease irritation potential in SLS and possibly other mixtures. This model may offer a facile system for screening the surfactant and other mixtures for decreased irritancy potential.     

Chronic irritant contact dermatitis: recovery time in man

Chronic irritant contact dermatitis (ICD) is a common skin disease, especially in the workplace, but determining the recovery time of chronic ICD is not easy. To measure the recovery time of chronic ICD, we examined the skin reactivity to a model surfactant, sodium lauryl sulfate (SLS), on previous chronic ICD and normal sites by visual grade and non-invasive instruments. Chronic ICD was induced on the forearms of 10 volunteers (aged 23 to 43 years) by occluded application of 1% SLS for 30 min on 5 consecutive days each week for 3 weeks. Previous ICD and normal sites were provoked by the occluded application of 7.5% SLS for 30 min daily on 4 consecutive days, 2, 5 and 10 weeks after induction. Skin reactivity was assessed daily by awarding visual erythema scores, visual scale scores and measuring transepidermal water loss, skin color reflectance, and electrical capacitance. Skin reactivity of previous chronic ICD sites to SLS showed hyperreactivity compared to normal sites even after the 10th week post-induction.     

Variation in response of human skin to irritant challenge

A major obstacle to the establishment of a protocol for in vivo irritant skin testing in humans is the apparent variability of responses between individuals. This study of the threshold response of normal human skin to a standard irritant (sodium lauryl sulfate 0.3–10%), in a group of 22 subjects, revealed a marked interindividual variation in their threshold reaction. The results demonstrate that this phenomenon does exist and that it will have to be allowed for in future human irritant test systems or assays.     

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.     

The irritant effect of different metalworking fluids

The irritant effect of different water-based cutting fluids (CFs) on the skin was investigated in healthy subjects ( n = 10) using 2 non-invasive bioengineering methods. Transepidermal water loss (TEWL) was measured by an evaporimeter EP1 (Servo Med), skin blood flow (SBF) was recorded with a laser Doppler flowmeter (MBF 3D, Moor Instruments England). Additionally all test sites were evaluated by visual scoring before measurement. 3 cutting fluids A, B and C from different manufacturers were tested at use concentrations of 4% or 5%. Single 24-h patch tests and repeated patch tests were performed on the volar side of the right forearm. Measurements were carried out before and after exposure to assess basal values and the skin response to CF. Tests with CFs A and C resulted in significant increase in TEWL after 24 h and after cumulative treatment, compared with controls ( p < 0.01). The TEWL values for CF B did not differ from the water probe. An increase in SBF was found only for CFs A and C after cumulative patch testing ( p < 0.01). In spite of their similar alkalinity, the 3 CFs showed different irritant skin reactions, due to their chemical components. This was verified particularly by measurement of TEWL.     

Acute irritant reactivity to sodium lauryl sulfate in atopics and non-atopics

Predictive testing of chemicals to assess their acute skin irritation potential is an important part of the assessment of their toxicological profile. It is possible, where safety and ethical considerations can be met, to do this work in groups of human volunteers. Previously, the relative responsiveness of atopics and non-atopics has been evaluated. The results showed that atopics (defined broadly by high IgE reactivity) were a little more susceptible to skin irritation, but not significantly so. In the present work, the relative reactivity of a skin atopic group versus a non-atopic group was examined in more detail. Sodium lauryl sulfate (SLS) was applied at a range of concentrations and exposure times, such that a fairly constant degree of skin irritation was produced. At various time points, the irritation response was measured by visual assessment, chromametry, laser Doppler flowmetry and transepidermal water loss. Using all of the methods of assessment, the reactions in atopics were similar to or a little less than those seen in non-atopics. The conclusion is that atopics and non-atopics will give similar results in a predictive human test for acute skin irritation. Furthermore, the pattern of response obtained from short duration exposure should be predictive of that following longer durations of (single) exposure.     

Effect of mineral oil and linoleic-acid-containing emulsions on the skin vapour loss of sodium-lauryl-sulphate-induced irritant skin reactions

This study evaluates the influence of mineral oil and linoleic-acid-containing emulsions on the skin vapour loss (SVL) of detergent-induced irritant skin reactions. During a period of 2 weeks, 2 x 45 min applications of a sodium lauryl sulphate solution of low molarity were performed on the forearm of 9 volunteers. In the same period, a standard amount of each emulsion was applied on the induced irritant skin reactions, 3 times each day. The effect of the emulsions on the barrier function of the skin was evaluated by means of SVL measurements. The emulsion based on mineral greases significantly reduced SVL values during both weeks, possibly because of an occlusive effect. The emulsion with 15% of linoleic acid significantly reduced SVL values during the 1st week but not during the 2nd week. The emulsion with 38% of linoleic acid did not reduce SVL values at all.     

An evaluation of the relationship between 'atopic skin' and skin irritability in metalworker trainees

Skin hyperirritability to irritants as well as atopy are considered to be predisposing factors for contact dermatitis. The aim of the study was to evaluate whether these predictive factors are independent or whether they are so closely related that one could possibly replace the oilier. 205 metalworker trainees underwent skill examination for skin atopy, including standardised questionnaire, clinical examination of the skin and a series of skin irritability tests. These tests included measurements of transepidermal water loss (TEWL) before and after irritation with 3 different irritants: sodium lauryl sulfate (SLS), dimethylsulfoxide (DMSO) and sodium hydroxide (NaOH). The results of the linear regression analysis demonstrate that skin atopy is not associated with increased skin irritability, as assessed by the irritability testing methods presented.     

Assessment of anti-inflammatory activity of Poria cocos in sodium lauryl sulphate-induced irritant contact dermatitis

OBJECTIVE: In the present study, we evaluated the anti-inflammatory activity of Poria cocos (PoCo) on experimentally induced irritant contact dermatitis (ICD) in a repeated sodium lauryl sulphate (SLS) irritation model. METHODS: The anti-irritative effect of PoCo was evaluated with a visual score and quantified by non-invasive bioengineering methods, namely chromametry and transepidermal water loss. Three concentrations of PoCo in base cream DAC (amphiphilic emollient; German pharmacopoeia) were tested in a 4-day repetitive irritation test using SLS. RESULTS: A statistically significant anti-inflammatory activity was observed for PoCo by all three methods when applied in parallel to the induction period of ICD. Application of PoCo after induction of ICD once a day for 5 days, starting just at the end of 4 days, was without any effect. CONCLUSION: An anti-inflammatory efficacy of PoCo on the elicitation phase of the ICD induced by repeated SLS test could be observed and quantified by three independent, non-invasive biophysical assessment parameters. This effect can be explained by its influence on pro-inflammatory enzymes, namely phospholipase A2.     

Profile of irritant patch testing with detergents: sodium lauryl sulfate,sodium laureth sulfate and alkyl polyglucoside

The cutaneous reaction to detergents follows distinct kinetic rules: the duration of application and the irritant concentration are of major importance. The aim of this study was to evaluate the differences in kinetics of skin reaction between the standard irritant sodium lauryl sulfate (SLS), and 2 modern detergents: sodium laureth sulfate (SLES) and alkyl polyglucoside (APG). We performed patch testing with SLS and SLES (or APG) at different concentrations (0.125, 0.25, 0.5, 1.0 and 2.0%) and with different exposure times (6, 12 and 24 h). Evaluation was conducted by measurement of transepidermal water loss (TEWL) and laser Doppler flowmetry (LD) 24 h, 7 and 10 days after patch removal. We found a pronounced reaction to SLS, and a far milder one to SLES. Even at the highest concentration the skin reaction to APG was hard to detect. During the regeneration period (day 3-10) SLS showed even at day 10 an increased TEWL at all concentrations tested. The irritation due to SLES was convincingly detectable only up to day 7, whereas the APG-tested skin areas showed no significant reaction even at day 3. These results demonstrate the improvement in reduction of skin irritation achieved by development of novel detergents.     

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.     

Baseline transepidermal water loss in patients with acute and healed irritant contact dermatitis

To examine the skin harrier function of patients with acute and healed irritant contact dermatitis ( n = 80) baseline transepidermal water loss (TEWL) was quantitatively measured using an evaporimeter. Healthy subjects served as controls ( n = 40). Test areas were the forearm and the thigh. A significant increase in TCVV'L was observed in the patients with acute and with healed irritant contact dermatitis (ICD) as compared LO healthy volunteers ( P ≤ 0.01). TEWL values in both test areas were com parable and markedly correlated ( p ≤ 0.01). with each other in every group. Thus, it is possible that basal TEWL depends more on the intrinsic skin barrier function of the subjects rather than the 2 anatomical regions examined. TEWL at the forearm with acme ICD was significantly higher ( P ≤ 0.01). than that of the group with healed ICD, but not for TCWL at the thigh suggesting that ICD may aggravate the barrier function of the adjacent involved skin. It is assumed, that increased basal TEWL in patients with ICD may relied a constitutional deviation of epidermal barrier function. This event seems to be comparable with the well-known symptom of atopic individuals. Using a detailed atopic scoring system in such a study may clarify the question of whether a proportion of patients with hand ICD may indeed be atopic individuals.