Ron A. Tupker

Prediction of susceptibility to an irritant response by transepidermal water loss

The roles of the natural permeability of the stratum corneum to water, and the changes in that permeability effected by a single patch test, were investigated as parameters to predict the susceptibility of the skin to repeated exposures of an irritant. One site on the forearm skin of 27 non‐atopic healthy subjects was exposed to a 0.5% concentration of sodium lauryl sulphate by a single occlusive 24‐h patch. Another site was exposed to a twice daily 4‐day repeated occlusive patch with the same irritant solution. The effects were evaluated by transepidermal water loss measurements made prior to the applications (baseline) on day 1 (BASE), following the single 24‐h patch on day 2 (SINGL), and following the 4‐day repeated applications on day 5 (REPET). Individuals with higher BASE had higher SINGL (R= 0.80, P < 0.001) and higher REPET (R= 0.76, P < 0.001). There was also a significant linear correlation between SINGL and REPET (R= 0.63, P < 0.001). Multiple linear regression analysis of results, however, indicated that a high baseline TEWL is a better indication of an individuals increased susceptibility (high REPET) to weak irritants than a high TEWL value following a single 24‐h patch test. Baseline TEWL may therefore be used as a reasonably accurate preliminary “predictive” screening test for susceptibility to irritants.

The influence of repeated exposure to surfactants on the human skin as determined by transepidermal water loss and visual scoring

The purpose of this study was to develop a new model for the induction of chronic irritant contact dermatitis, which would reflect well the conditions of daily practice. Various weak irritant agents were tested for irritating potency on the skin and the sensitivity of transepidermal water loss (TEWL) measurements in the detection of early skin changes was also studied. 10 widely used surfactants and 1 solubilizer were applied to the skin of the forearms of healthy volunteers in aqueous solutions of 12.5 millimoles/1 for 45 min twice daily for 3 weeks. The effect on the skin was evaluated daily by means of TEWL measurements and by a visual scoring system. Each solution caused an increase in TEWL value over time due to the cumulative irritating action on the epidermal barrier. This increase in TEWL was different for the various solutions, resulting in different mean TEWL values on the last day of the experiment. Thus, it was possible to rank the agents according to irritating potency. This ranking order was the same in almost every individual and remained constant during the 3 weeks. In comparison with the visual scoring system, the TEWL measurements were more sensitive in the detection of early changes in the skin.

Baseline transepidermal water loss (TEWL) as a prediction of susceptibility to sodium lauryl sulphate

The rôle of different factors in the susceptibility of the skin to weak irritants was studied by means of multiple linear regression models. The skin of 37 healthy subjects was exposed to a solution of sodium lauryl sulphate of low molarity 2 × daily for 4 days. The condition of the skin was evaluated by transepidermal water loss (TEWL) measurements on the 1st day (before exposure, TEWL1) and on the 5th day of exposure (TEWL5), and by a visual scoring system. The TEWL5 value was strongly related to the TEWL1 value (R = 0.71). The influence of such factors as history of mucosal atopy, history of sensitivity to soap, dry skin, skin type, sex and age on the TEWL5 value was negligible. The baseline TEWL level (TEWL1) might be a reliable indication of an individuals susceptibility to weak irritants.

COMPARABILITY AND REPRODUCIBILITY OF THE RESULTS OF WATER-LOSS MEASUREMENTS - A STUDY OF 4 EVAPORIMETERS

A study was made of the comparability and reproducibility of the results of measurements of water loss, both in vitro and in vivo, using 4 Servo Med Evaporimeters (3 single–probe and 1 double–probe instrument). The optimum time for recording transepidermal water loss (TEWL) after the initial application of the probe to the skin (in vivo), and the best technique for optimizing the accuracy of measuring TEWL were determined. An evaporation device with a constant level of water loss was constructed for in vitro studies. The volar aspect of the right forearm skin of one subject was used in vivo. Both in vitro and in vivo measurements showed that there were some differences between the results of 4 of the 5 probes. The other probe was distinctly out of range. For all probes, the reproducibility of results of successive measurements was high. Stabilization of TEWL values was reached for all probes from 30–45 s after their initial application to the skin. It is recommended that TEWL be recorded for a further 30–s period, after the initial stabilization (45 s), and that this be taken as the true value. The manufacturers recommended calibration procedure is based only on adjustments for the standard specified humidities and zero water loss. The importance of incorporating an additional calibration procedure which includes adjustments for an actual standard constant water loss is thus strongly stressed.

Measurement of transepidermal water loss

Dear Sir We would like to make a number of comments regarding the articles by Berardesca & Maibach (I, 2). The values given for the baseline TEWL for the skin of the back were 2. 7 ± 0. 7 g/h (I) and 2.7±0.7 mgfcm2h (2) for the white skinned. The former statement is most likely an error, since in that same publication (I), in other tables, the units are given as mgfcm2h: or more accurately mgfcm2h. Considering then the baseline values of 2. 7 ± 0. 7 mg/cm2h (2), when converted into g/m2h, the values become 27.0±7.0 g/m2h. This is the unit displayed on the Evaporimeter (ServoMed, Stockholm) for TEWL. The baseline values for this same skin site reported by Lamrnintausta et a!. (3) are 3.7±0.6 g/m/h. We gather it to have been g/m2h, since in their previous report (4), the values given (3.22±0.65 for males and 3.35±0.69 for females) were in gjm2/h, or more accurately, gjm2h. The values given by Berardesca & Maibach (I, 2), when converted, are then more than 7 times greater than those values reported by Lamrnintausta et a!. (3, 4). Although the latter values are normalised to corresponding values at a skin temperature of 30°C, in our experience (5, 6), this cannot account for the 7-fold increase in the reported values (1, 2). The values by Lamrnintausta et a!. (3, 4) seem possible for the skin of the back, when considering the values for that same site reported by Baker & Kligman (0.29 ± 0.04 mg/ = h) (7), but the latter investigators used electrical hygrometry (7), whereas both Berardesca & Lammintausta (I-4) used the water vapour gradient estimation by the Evaporimeter. Therefore, direct comparisons are not feasible. Regional variation in TEWL has been reported by Baker & Kligman (7). The differences between the back, forearm, and abdomen are probably not significant, when considering the diffusion constants and the mean stratum corneum thicknesses for these skin sites (7). The increased diffusivity of other regions, such as the forehead, dorsum of the hand, and the palm is, however, without question (7). The constancy of this diffusive water loss from any one area from day-to-day was reported as high (7). In view of this, the large 7-fold discrepancy between the reported water loss values (1-4) for the same skin site is questionable. We have recently reported (6) on the comparison of water loss values measured with different Evaporimeters. Although considerable inter-instrumental variation was observed, the maximum differences were only 2fold (6). It is therefore tempting to attribute the discrepancies in the reported water loss values (I, 2) both to the instrumentation and to possible differences in the methodology of these measurements. Subclinical eccrine sweating may also have contributed to these results (7). Clarification of these values (1, 2) for the skin of the back is thus required, so as to be able to identify the regional differences in baseline TEWL of the human skin, by Evaporimetric measurements. The discrepancies mentioned above emphasize the need (6) for standardisation of the methodology and instrumentation for TEWL measurements.

The intra‐ and inter‐individual variability and reliability of transepidermal water loss measurements

An analysis of variance wad conducted to estimate the intra‐ and inter‐individual variations in TEWL on the forearms, by sites (8 measurement sites) and by days (10 different days), in 30 non‐exposed healthy individuals. The estimated intra‐ and inter‐individual variations, by sites, were 15.5% and 84.5′V respectively, the sum of the 2 components always being 100%. Was the exclusion of the 2 most distal sites near the wrist, which had significantly higher baseline TEWL values and fluctuations in TEWL, an improvement in the intra‐individual variation was obtained. Thus, of the 6 sites, the estimated, intra‐ and inter‐individual variations were 8.4% and 91.6%, respectively. This finding supports the exclusion of these most distal sites for future investigations. The estimated intra‐ and inlet‐individual variations, by days, were 20.6% and 79.4%, respectively. The low site‐to‐site (8.4%) and day‐to‐day (20,6%) intra‐individual variations, as compared to the large inter‐individual variations of l he same (91.6% and 79.4%), indicate that baseline TEWL is a stable personal characteristic Thus, individuals susceptible to irritant contact dermatitis (ICD). due to occupational exposure, may be reliably characterized by utilizing their baseline TEWL values, for “prediction” of risk in epidemiological field studies.

Transepidermal water loss with and without sweat gland inactivation

The influence of eccrine sweating on transepidermal water loss (TEWL) was investigated. TEWL was simultaneously measured on both forearms, with and without topical inactivation of the eccrine sweat glands by 0.3 ml of 0.5% aqueous scopolamine hydrobromide (HBr), applied under 1 h occlusive patches. The degree of sweat inhibition, after exercise, was measured at 2, 3 and 4 h after patch removal. In 42 out of 44 subjects, complete sweat inhibition (on exercise) was achieved only at 4 h after removal. After a 15‐min rest in a room at 20°C, the pre‐exercise TEWL values (at 4 h) on the treated and untreated sites were not different (P>0.05), in 38 out of 44 subjects. By this rest period, sweating due to slight physical, thermal or even emotional stimuli may be prevented in most subjects. In the other 6 subjects, the pre‐exercise TEWL values (at 4 h) on the untreated site were 1–1.8 g/m2h higher than (P < 0.001) on the treated site, due to emotional sweating Thus, accurate baseline TEWL measurements may only be made after anticholinergic suppression of the sweat glands. In this way, accurate TEWL measurements may be made even outside favourable laboratory conditions, all industrial sites etc., where circumstances are far from ideal. The effect of this agent applied to a skin site previously irritated artificially by a 24‐h occlusive sodium lauryl sulphate (SLS, 0.3 ml, 0.5% aq.) patch, was also investigated in 17 subjects. In all subjects, 4h after removal, sweating (on exercise) was completely inhibited on the scopolamine‐treated site, pre‐irritated with SLS. Systemic side‐effects were not reported from any test subject, under any condition of exposure.

House‐dust mite hypersensitivity, eczema, and other nonpulmonary manifestations of allergy

The pathogenetic role of house‐dust mites (HDM) in atopic dermatitis (AD) remains controversial, mainly because there is no common agreement on a provocation test that mimics ordinary exposure to HDM. This is related to the lack of knowledge of the mechanism of how HDM allergens enter the body. Theoretically, there are two possible routes: directly through the epidermis, or by inhalation. In “atopy patch testing”, a concentrated HDM suspension is tested on the skin under occlusion. This method is frequently used as a model of the epidermal route. The clinical relevance of this method as a provocation test for AD is discussed. As opposed to atopy patch testing, we describe another method, namely, “allergen inhalation testing”, as a model of the respiratory route. Twenty patients with AD underwent bronchial provocations with HDM extract in a double‐blind, randomized, placebo‐controlled study. In nine out of 20 AD patients, bronchial challenge with HDM evoked skin symptoms. All patients with HDM‐induced dermatitis had a history of asthma, and as a group they had a higher mean total log‐transformed IgE level than the “negative skin responders”. Thus, the respiratory route may be relevant in the provocation of AD in a subset of AD patients and may represent an appropriate model of provocation in these patients. Furthermore, the role of HDM in urticaria and allergic rhinitis is discussed.

Anaphylaxis after consuming soy products in patients with birch pollinosis

bicycle ergometer lead to generalized urticaria and dizziness proving WDEIA in our patient. A contribution of gender or female sex hormones in allergic reactions has been discussed for a long time; however, mechanisms underlying hormone-triggered allergic reactions are still poorly understood (3). Based on medical history, menses was already assumed to be a potential triggering factor of WDEIA, but systematic provocation tests to prove an impact of menses in WDEIA were still missing (1, 4). Recently, Bito et al. demonstrated a patient in which anaphylaxis to cow milk exclusively developed following combined exposure to acetylsalicylic acid, cow milk, and physical exercise at the time of her premenstrual phase (5). Our report is the first that applied systematic provocation tests to outline the triggering potential of menstruation in a patient with WDEIA. As WDEIA in our patient exclusively occurred during her menses, medical history and diagnostic measures of anaphylactic reactions such as provocation tests need to record and include menstruation to diagnose WDEIA and other types of cofactor-induced anaphylaxis. The authors have declared that they have no conflict of interest.

Relevance of positive patch-test reactions to fragrance mix.

Background: Fragrances are an important cause of allergic contact dermatitis. We presume that the traditional fragrance mix (FM) detects 70 to 80% of fragrance‐allergic patients. FM has an irritant potential. Weak positive reactions may have a greater chance of being irrelevant than strong reactions. Objective: To improve the appraisal of FM patch‐test reactions, we studied the relevance of reactions of different strength. We also studied the predictive value of the following on the relevance of the initial FM patch‐test results: patch‐test results of a repeated FM test; results of patch tests with balsam of Peru, colophony, and ingredients of the mix; and (history of) atopic dermatitis. Methods: One hundred thirty‐eight patients who had doubtful positive (?+) or positive (+ to +++) reactions were included in the study. We determined relevance by history taking, location and course of the dermatitis, and additional patch testing. Patients were retested with FM and with each ingredient separately. Results: The relevance of reactions to FM increases with the strength of the reactions. Predictors of relevance are the results of retesting with FM, the results of tests with the ingredients, and a history and/or present symptoms of atopic dermatitis. Conclusion: Retesting with FM and its ingredients may add to the benefit of patch testing.