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The objective of our study was to investigate the tandem irritation potential of two organic solvents with concurrent exposure to the hydrophilic detergent irritant sodium lauryl sulphate (SLS). A tandem repeated irritation test was performed with two undiluted organic solvents, cumene (C) and octane (O), with either alternating application with SLS 0.5% or twice daily application of each irritant alone in 27 volunteers on the skin of the back. The cumulative irritation induced over 4 days was quantified using visual scoring and non-invasive bioengineering measurements (skin colour reflectance, skin hydration and transepidermal water loss). Repeated application of C/SLS and O/SLS induced more decline of stratum corneum hydration and higher degrees of clinical irritation and erythema compared to each irritant alone. Our results demonstrate a further example of additive harmful skin effects induced by particular skin irritants and indicate that exposure to organic solvents together with detergents may increase the risk of acquiring occupational contact dermatitis., (© 2014 S. Karger AG, Basel.)

Manufacturers employ a stepwise approach to ensure the skin safety and compatibility of consumer products that are intended for contact with mucosal skin. The properties of the ingredients are evaluated fully, along with any available safety and skin compatibility information, to eliminate any chemicals that may be strong contact sensitizers or irritants. Contact sensitization potential is evaluated by applying a quantitative exposure assessment to each ingredient or component to determine if the extent of the expected exposure is likely to pose any risk of contact sensitization. Likely exposures are calculated using the manufacturer's unique knowledge of the intended product matrix, consumer usage patterns and measurements of particular exposure variables. If adequate safety assurance cannot be provided, further testing may be conducted. The skin compatibility and irritation potential of each ingredient is evaluated using existing test data, and experience from other products containing the same or a structurally similar ingredient. Once a finished product or formulation is developed, another round of assessments is conducted to ensure that no unexpected matrix effects negatively impact the skin compatibility profile. This may include clinical testing protocols involving single and multiple patch tests, and extended use testing, with visual and/or instrumental assessments. This approach to ensuring the skin safety of products has been used successfully for many decades, and adverse skin reactions to modern products are rare. The challenge for the future is to develop test protocols that will discriminate between products that are very similar in their favorable skin compatibility profile. Options to meet this challenge include testing protocols that will: (1) further exaggerate exposure conditions, such as the behind-the-knee protocol, (2) increase the sensitivity of scoring for irritant effects, such as with the use of instrumentation, and (3) quantitatively measuring additional endpoints, such as subjective sensory effects., (Copyright © 2011 S. Karger AG, Basel.)

We analysed the patch test results in 1,374 patients suffering from dermatoses in the anogenital area (n = 561 genital dermatoses, n = 470 anal dermatoses, n = 343 anogenital dermatoses) patch tested in 44 dermatological departments of the Information Network of Departments of Dermatology from 2004 to 2008. All other patients patch tested during this time period without anogenital dermatoses formed the control group (n = 49, 142). Of the total study group, 662 (48.2%) patients were male. 179 (13%) had a past or present atopic dermatitis. The vast majority of the patients was older than 40 years (n = 989, 72%). Suspected allergen sources were first of all topical medicaments, followed by cosmetics, cleansing agents, clothes, rubber products, systemic medicaments and disinfectants. Allergic contact dermatitis was diagnosed in 409 (29.8%) of the tested patients. Patients with anogenital dermatoses were sensitized mainly to active agents of topical medicaments, in particular bufexamac (5.3%). Sensitization pattern and sensitization rates observed in patients with genital and anal involvement differed significantly. Patients with anal disease had significantly higher sensitization rates for bufexamac (9.4 vs. 1.1%), fragrance mix I (8.7 vs. 4.2%) and II (4.5 vs. 2.6%), propolis (5.4 vs. 1.9%) and methyldibromoglutaronitrile (6.3 vs. 4.1%). Patients with chronic anal dermatoses seem to have a higher risk to develop sensitizations to topically applied products and drugs than patients with genital dermatoses. Recommended patch test series (German Contact Dermatitis Research Group) are standard series, local anaesthetics series, topical antibiotics, antimycotics, steroids, ointment bases and preservative series as well as the patients' own products., (Copyright © 2011 S. Karger AG, Basel.)

The mucosa as a nonkeratinized epithelium covering body surfaces has widely differing anatomical and physiological properties depending on the organ system involved (gastrointestinal, respiratory, urinary, genital, ocular). In general, the mucosae close to the skin are more permeable to exogenous substances, more prone to irritant reactivity, and they have a unique microbial ecology which is qualitatively and quantitatively different from that of the adjacent keratinized epithelium. Clinical presentations of exogenous dermatoses in mucosae appear different from those of the skin. These specific properties of mucosae have to be considered in the development and application of topical agents, cosmetics and consumer products., (Copyright © 2011 S. Karger AG, Basel.)

Background: The behind-the-knee (BTK) clinical test system is being used increasingly to replace in-use clinical studies in the evaluation of potential irritation effects of consumer products. The objectives of these studies were to determine if the BTK test could adequately evaluate the potential to cause irritation for feminine protection products intended for mucous membrane contact, and confirm that the BTK test would not underestimate the irritant potential that may occur when products such as tampons come into contact with mucous membranes., Materials and Methods: Two identical tampon products were tested in in-use and BTK clinical studies. In the BTK clinical test, sites were scored daily 30-60 min after sample removal (PM scores with no recovery) and prior to application of the next sample (after 18 h of recovery). In the in-use clinical study, 6 sites (labia minora, introitus, lower and middle vaginal walls, upper vagina and cervix) were graded separately for erythema using colposcopy after use of each product for an entire menstrual cycle., Results: In the in-use clinical study, the labia minora were most susceptible to irritation effects with mean erythema scores (± SE) of 0.36 (± 0.05) and 0.50 (± 0.06) for the experimental and control products, respectively. All other sites produced a mean erythema ≤0.26. In the BTK clinical test, the postbaseline averages for erythema for the experimental and control products were 0.19 (± 0.04) and 0.20 (± 0.04) for the AM scores (with recovery), and 1. 25 (± 0.05) and 1. 27 (± 0.06) for the PM scores (no recovery)., Conclusions: Preliminary results showed that the BTK clinical test may be used to evaluate potential irritation effects of products that contact mucous membranes. In a first comparison of 2 tampon products in both the in-use and BTK clinical studies, the BTK protocol produced erythema reactions at the test sites that were similar to or severer than those observed on mucosal sites in the in-use study. Overall, the BTK clinical test showed a higher sensitivity, rapid turnaround time, higher flexibility and easier implementation. Thus, making the BTK clinical test a more useful tool for both safety testing and claim support., (Copyright © 2011 S. Karger AG, Basel.)

Imatinib is a specific and potent inhibitor of the BCR-ABL tyrosine kinase. Several clinical trials have demonstrated the efficacy of imatinib in chronic myeloid leukemia. Adverse cutaneous reactions induced by imatinib are frequent and may be dose related. We report a case of an unusual pustular eruption in a patient with chronic myeloid leukemia, who received high doses imatinib for blast crisis and later voriconazole for invasive pulmonary aspergillosis. At the time of his skin eruption, elevated plasma levels of imatinib were recorded. Imatinib is primarily metabolized by the cytochrome CYP3A4. Voriconazole is a cytochrome CYP3A4 inhibitor and can lead to high plasma levels of imatinib. This case suggests that severe drug reactions to imatinib may be related not only to imatinib doses, but also to elevated plasma drug levels resulting from pharmacokinetic interactions. The monitoring of imatinib plasma levels may be of help for identifying patients at risk for severe toxicity., (Copyright 2005 S. Karger AG, Basel.)

Background: There is a basic necessity to understand the mechanisms of the protective effects of emulsions. This would promote the development of protective cosmetics and therefore improve the prevention and treatment of occupational skin diseases. However, for such studies, no reliable skin model is available., Objective: An in vitro skin model test was developed to evaluate the protective mechanism of cosmetic ingredients., Methods: The efficacy of three products was assessed by an in vivo test (Repetitive Occlusive Irritation Test) and then 3-dimensional skin model tests were carried out., Results: In vivo test results demonstrate that the best protection against sodium dodecyl sulphate is offered by a multiple emulsion. In the case of a skin model test, sodium dodecyl sulphate led to cell damage, an increase in pro-inflammatory markers and some barrier lipids. The multiple emulsion increased the content of skin lipids, without inducing irritation or cell death., Conclusion: Skin models react similarly to sodium dodecyl sulphate compared to human skin and therefore they are suitable to study barrier repair after sodium dodecyl sulphate damage. It is likely that the superior protective effect of the multiple emulsion in vivo is based on the increased amount of skin barrier lipids.

Background: Since identification of subjects with high eczema risk by screening tests is desirable, different skin bioengineering methods were studied for their validity as predictive measures for the development of hand eczema., Methods: 205 metalworker trainees were followed up over 2.5 years from the beginning of their apprenticeship to observe the occurrence of hand eczema. Within the first weeks of their training they underwent a number of noninvasive biophysical tests. Transepidermal water loss, skin moisture and skin roughness were measured, and irritation tests with dimethyl sulfoxide (DMSO), sodium hydroxide (NaOH) and sodium lauryl sulfate were conducted. Sensitivity, specificity and predictive values of the performed tests and test combinations were calculated., Results: None of the observed single biophysical methods can be considered a valid screening test., Conclusion: A combination of short irritation tests (DMSO and NaOH tests) and the measurement of skin moisture, however, allows to identify individuals at high risk for hand dermatitis with a high sensitivity, though low specificity.

Background: Perfluoropolyethers (PFPEs) are non-reactive perfluorinated (no hydrogen atoms) liquid polymers that showed promise as ingredients of protective preparations in occupational dermatology., Objective: The aim of this study was to investigate if oil-in-water (o/w) emulsions containing 0.5, 1.0, 2.0 and 4.0% PFPEs (molecular weight 6,250 D) prevent epidermal barrier disruption induced by a repetitive irritation test (RIT)., Methods: PFPE-containing o/w emulsions and the emulsion base alone were evaluated against a set of 4 irritants [10% sodium lauryl sulphate (SLS), 0.5% sodium hydroxide (NaOH), 15% lactic acid (LA), and undiluted toluene (TOL)] in the RIT. Ten subjects were tested on the paravertebral skin of the mid-back. Irritation was assessed by visual scoring, transepidermal water loss (TEWL) and colorimetry., Results: Both the emulsion base and all PFPE-containing preparations significantly suppressed irritation by SLS and NaOH. Against LA and TOL, only the 4% PFPE-containing preparation was significant as assessed by TEWL., Conclusion: A 4% PFPE-containing o/w emulsion significantly inhibits irritation due to a wide spectrum of hydrophilic and lipophilic irritants. o/w emulsions with lower concentrations of PFPE are also effective against SLS and NaOH, but this is also true for the cream base alone. Therefore, further studies are necessary to evaluate if a minimum of 4% PFPE in the base provides additional benefit.

Objective: p-Phenylenediamine (PPD) has been widely distributed as hair dye ingredient and may be responsible for contact dermatitis. Since not all the subjects exposed to PPD react to the substance, we tested a possible predisposing factor of cutaneous drug metabolism., Methods: Eighty-five patients were selected on the basis of their patch test result for PPD. The acetylator status of patients was estimated using HPLC analysis of urinary caffeine metabolites., Results: Among patients with a negative result for PPD, there were three groups, i.e. fast, intermediate and slow acetylators, just as in the healthy population. However, we could not find any rapid acetylator in the PPD-sensitive patient group, and slow acetylators were more often encountered in this group (p < 0.05)., Conclusion: The acetylator phenotype might be a good marker for the cutaneous sensitivity to PPD.

Background: Protective creams (PCs) have been studied in different models indicating a protective effect of some products. In order to compare PCs in different studies, a generic reference standard should be available., Objective: The purpose of this study was to investigate if petrolatum prevents epidermal barrier disruption induced by various irritants in a repetitive irritation test (RIT) and to assess its potential as a standard reference product., Methods: White petrolatum was evaluated against a set of 4 irritants [10% sodium lauryl sulphate (SLS), 1% sodium hydroxide (NaOH), 30% lactic acid (LA) and undiluted toluene (TOL)] in the RIT. Twenty subjects were tested on the paravertebral skin of the midback. Irritation was assessed by visual scoring, transepidermal water loss and colorimetry., Results: Petrolatum was very effective against SLS, NaOH and LA irritation, and it provided a moderate protection against TOL., Conclusion: Petrolatum can be recommended as a standard reference substance against which PCs may be compared as it is effective against water-soluble and water-insoluble irritants in a standardized test procedure.

Background: Patients often tell about reduced effectiveness of topical steroids on repeated use. Tachyphylaxis to these agents has been demonstrated in humans for vasoconstriction and histamine-induced wheal suppression in normal skin, but not in diseased skin. Relevance of these data to diseased skin is not clear. Further, the clinical impression does not appear to match tachyphylaxis shown in normal skin with regard to the time course., Objectives: To examine whether tachyphylaxis to histamine-induced wheal suppression by a topical steroid occurs in dermatitic skin and to determine its time course vis-à-vis normal skin., Methods: Pharmacodynamic response to 0.05% clobetasol propionate applied daily under occlusion was measured by histamine-induced wheal suppression assay in 10 individuals. This test was performed on a steroid-treated normal site, on a steroid-treated site where dermatitis was induced by occlusive application of 40% croton oil, and on a vehicle-treated site in each individual at different intervals up to 14 days., Results: Suppression of wheal volume started from second day in steroid-treated sites. There was significant difference in the wheal volume in steroid treated normal vs. dermatitic sites from day 2 to day 10. Maximum wheal suppression occurred earlier in dermatitic skin (day 4 vs. day 6). After this, the volume of wheal started increasing and became equal to control (complete tolerance) on 12th day in dermatitic skin and on 14th day in normal skin., Conclusions: Time courses of tachyphylaxis to the action of 0.05% clobetasol propionate were significantly different in normal skin and dermatitic skin. Complete tolerance occurred earlier in dermatitic skin compared to normal skin.

Exposure of the skin to surfactant-based products can result in irritation. To control this effect researchers are probing mechanisms of surfactant action. In vitro studies show that mixing surfactants often results in less denaturation (swelling) of stratum corneum. We have explored the in vivo human irritation response (using a 21-day cumulative irritation test) to two of these surfactants-sodium lauryl sulfate (SLS) and (C12-C14) alkyl, 7-ethoxy sulfate (AEOS-7EO). Results demonstrate that addition of AEOS-7EO to a constant dose of SLS results in a significant reduction in erythema, hence producing a milder system. The reason for the synergism is unclear, but may related to experimentally determined alterations in the micellar solution properties of the SLS upon addition of AEOS-7EO.