Effect of BN 52021, a platelet activating factor antagonist, on dithranol-induced inflammation

The effect of BN 52021, a selective platelet activating factor (PAF) antagonist was studied on dithranol-induced irritant dermatitis. Pretreatment of the skin with 0.45% BN 52021 ointment significantly suppressed the decrease in capillary resistance, rise in skin temperature and increase in skin-fold thickness produced by dithranol.     

FS02.8Patch testing with gold trichloride can give false test results

Background:  Hydrochloric acid is formed in water solutions of gold trichloride. Hydrochloric acid in contact with aluminium generates hydrogen gas which can reduce and transform trivalent gold to elemental gold.
Objective:  To investigate whether patch testing with aqueous gold trichloride can cause false positive (irritant) reactions in patients without contact allergy to gold and false negative reactions in patients with gold allergy.
Methods:  13 patients with and 13 patients without positive patch test reactions to gold sodium thiosulfate were tested with gold trichloride in 2 different vehicles, water and alkaline buffer, using 2 different test techniques, the Finn Chamber technique with aluminium chambers and van der Bend technique with polypropene chambers.
Results:  Irritant patch test reactions were obtained with aqueous gold trichloride tested in van der Bend chambers in 10 patients without gold allergy. In gold‐allergic patients no positive test reactions were obtained from aqueous gold trichloride in Finn chambers while 2 positive test reactions were obtained from gold trichloride in alkaline buffer tested in van der Bend chambers.
Conclusion:  If gold trichloride is patch tested in wrong vehicle and with wrong test technique irritant test reactions may occur which can be misinterpreted as positive allergic reactions in patients without gold allergy as well as negative reactions in patients with gold allergy.     

Individual and instrumental variations in irritant patch-test reactions—clinical evaluation and quantification by bioengineering methods

A major purpose of irritant patch testing is to differentiate between normal, delicate and less sensitive skin. To assess the usefulness of irritant patch testing, knowledge of variation in responses to identical patch tests is essential. In the present study inter- and intra-individual variation in irritant patch test reactions due to sodium lauryl sulphate and nonanoic acid is given when evaluated by traditional visual scoring as well as different non-invasive methods, i.e. measurement of transepidermal water loss, the hydration state of stratum corneum by electrical conductance, cutaneous blood flow by laser Doppler flowmetry, and measurement of skin thickness by 20-MHz ultrasound A-scan. The intra-individual 'site-to-site' variation was considerably less than the inter-individual variation, which is essential to differentiate between persons with delicate and less sensitive skin. Methods used were relevant for this purpose except for the measurement of electrical conductance.     

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.     

Nonanoic acid--an experimental irritant

Irritant contact dermatitis is defined as a non-immunological skin reaction following exposure to various chemical, mechanical and physical factors. It is known that the skin response to irritants depends on the irritant applied and differs between chemically different irritants. Sodium lauryl sulfate (SLS) is an anionic detergent and the most frequently used substance in experimental irritant contact dermatitis. In 1980, it was suggested that nonanoic acid (NNA) could be used as a positive control when patch testing. Since then, NNA has been used as an experimental irritant in several studies and has been used as a chemically different substance compared to SLS. The present article presents a review of the application of NNA in studies on skin irritancy and experimental irritant contact dermatitis.     

A comparative study of the effects on the skin of a classical bar soap and a syndet cleansing bar in normal use conditions and in the soap chamber test

Background/aims: The skin irritation potential of a body cleansing product is often compared under exaggerated test conditions, although the product is intended to be used at home with repetitive and brief contact with the skin. The aim of this study was to determine how much patch testing is predictive of the clinical, sub-clinical and subjective cutaneous effects of products used at home by consumers for their normal hygienic cleansing.
Methods: A double-blind comparative study of the normal use of an alkaline soap bar and a syndet at home during 10 consecutive weeks was performed on two identical groups of 25 healthy female subjects. The eventual skin changes observed at different anatomical skin sites were evaluated by clinical visual examination and by bioengineering measurements before the start of the study and then every 2 weeks. The objective measurements were compared with the subject's perceptions of dryness, tightness and product irritancy during the testing.
Results: The bioengineering measurements did not show any significant changes on all the anatomical skin sites, except for a small increase in skin pH with the classical soap bar. However, a trend appeared, showing that the alkaline soap bar is perceived by the subjects themselves as more of an irritant than the syndet bar. In the soap chamber test, the bar soap showed a significantly higher irritancy than the syndet bar.
Conclusion: This study showed that cutaneous irritation induced by cleansing products in patch testing is not necessarily predictive of the irritation likely to occur in normal use conditions. Finally, a clear relationship could be demonstrated between the results of the soap chamber test and the consumer perception of both cleansing bars.     

Animal model for assessment of skin irritancy

Irritant skin reactions from repeated open applications of low concentrations of sodium lauryl sulphate (SLS) have been studied macroscopically and microscopically in guinea pigs. After 3 applications daily for 3 days, 2% SLS aqueous solutions gave a naked eye assessment, increase in epidermal thickness and total dermal inflammatory cell response, which was greater than for a 1% SLS solution. The dermal inflammatory cell response was mainly mononuclear (lymphocytic) in nature. With the SLS reactions as control, various organic solvents were studied and ranked against the SLS reactions and internally. Trichlorethylene was the most irritant solvent, ranking as high as 2% SLS. Other chlorinated hydrocarbons and aromatic hydrocarbons tested caused irritant reactions. The alcohols and acetone gave no reaction. White spirit was as irritant as trichlorethylene. Thinners were less irritant, around the level of the 1% SLS control reaction. The 4-day experimental design is a convenient and suitable animal model for screening irritant potential, and provides information relevant to the pathogenesis of irritant contact reactions.     

In vivo transcutaneous penetration of nicotinates and sensitive skin

Proclivity to develop irritant reactions and transcutaneous penetration of nicotinates has been investigated in 20 subjects of both sexes, divided into reactors and nonreactors on the basis of the responses to irritant stimuli. 1% sodium lauryl sulphate (patch application for 24 h) and 5% lactic acid in aqueous solutions were used to detect chemical and sensory (subjective) irritation. The vasodilatation induced was measured using a chromameter for 1 h after topical application of the chemical. The area-under-the-curve response and the peak response was used to assess the in vivo penetration of methyl nicotinate (10 mM in aqueous solution). Significant differences were found between reactors and non-reactors. Non-reactors showed a significantly decreased area-under-the-curve response and peak response to methyl nicotinate compared to reactors. Nicotinate-induced vasodilatation has been used as a model to study transcutaneous penetration of chemicals; the correlation between increased penetration of nicotinates and skin hyperreactivity to irritant substances may suggest an increased transcutaneous penetration of water-soluble chemicals in individuals with sensitive skin.     

Irritation factors of sodium hypochlorite solutions in human skin

The recommended concentration for patch testing with sodium hypochlorite [NaOCl] (bleach) is 1%, generally obtained by diluting commercial bleach. In doing so, other active (potentially irritant) components of bleach, especially hypochlorous acid [HOCl] and sodium hydroxide [NaOH], are neglected. Magnitudes of potential irritant species other than NaOCl, such as alkalinity, are ordinarily not labeled on the product, though they may vary considerably between brands. Thus, patch testing with 1% hypochlorite obtained by diluting different brand bleaches can potentially elicit non-specific irritant responses, also depending upon the test volume applied. In this study, skin irritation induced by 24-h patch testing with 20 microliters or 100 microliters, with constant NaOCl concentration (1%) and different NaOH concentrations (0.01-1.0%), was studied in adult human volunteers, by means of visual scores and skin color reflectance measurements. No irritation was elicited by application of 20 microliters 1% OCl-, independent of the NaOH concentration. However, all solutions induced significant irritation in a volume of 100 microliters. Skin reactions did not show a straight pH dose response, a maximum reaction being seen to the solution containing 0.1% NaOH. Skin surface pH values had increased when monitored immediately after removal of the patch material. However, 24 h later, baseline values were again reached at most sites, demonstrating an efficient buffering capacity of human skin, even after challenge with alkaline solutions of pH 13.4. We suggest that a non-irritant concentration for diagnostic patch testing for allergic contact dermatitis with an aluminum chamber, using 17 microliters to 20 microliters test volume, could be as high as 1% NaOCl and 1% NaOH.     

Dendritic cells: biology of the skin

Allergic contact dermatitis results from a T-cell-mediated, delayed-type hypersensitivity immune response induced by allergens. Skin dendritic cells (DCs) play a central role in the initiation of allergic skin responses. Following encounter with an allergen, DCs become activated and undergo maturation and differentiate into immunostimulatory DCs and are able to present antigens effectively to T cells. The frequency of allergic skin disorders has increased in the past decades. Therefore, the identification of potential sensitizing chemicals is important for skin safety. Traditionally, predictive testing for allergenicity has been conducted in animal models. For regulatory reasons, animal use for sensitization testing of compounds for cosmetic purposes is shortly to be prohibited in Europe. Therefore, new non-animal-based test methods need to be developed. Several DC-based assays have been described to discriminate allergens from irritants. Unfortunately, current in vitro methods are not sufficiently resilient to identify allergens and therefore need refinement. Here, we review the immunobiology of skin DCs (Langerhans' cells and dermal dendritic cells) and their role in allergic and irritant contact dermatitis and then explore the possible use of DC-based models for discriminating between allergens and irritants.     

Ultrasound for assessment of allergic and irritant patch test reactions

The oedema formation of patch test reactions was quantified by high-frequency ultrasound measurement of skin thickness. Patch testing with nickel sulphate, nickel chloride and sodium lauryl sulphate 1, 2, 5 and 10% was performed in 12 individuals with known nickel allergy. Oedema was greater in allergic than in irritant reactions similar in strength according to the clinical reading. In allergic reactions, the oedema appeared more transcutaneous, while in irritant reactions, more superficial. For differentiation of the 2 types of reaction, application of substances for a 24-h period with measurements the following day is preferable. For rating of allergic and irritant reactions, 48 h of application is preferable with measurements performed on the day patches are removed.     

Murine auricular transepidermal water loss -- a novel approach for evaluating irritant skin reaction in mice

The standard method for evaluating contact allergy in mice is the ear swelling technique. However, in experimental irritant contact dermatitis, the epidermal barrier disruption, that represents a predominant effect of irritants, cannot be assayed by this METHOD: An appropriate method to evaluate barrier disruption is the measurement of transepidermal water loss (TEWL) but to date this has so far been possible only on the trunk of hairless or shaved mice. We therefore developed a new technique to measure the TEWL of mice ears (murine auricular TEWL: MATEWL). After patch testing with irritants and allergens, respectively, we found that the ear swelling method is most suitable for evaluating allergic skin reactions, whereas MATEWL is most appropriate for evaluating irritant skin reactions.     

Temperature dependent primary irritant dermatitis from lemon perfume

In a recent outbreak of hand eczema amongst cleaning personnel after the introduction of a new, lemon-scented detergent, it was noted that the patients complained of a burning, stinging sensation when their hands were submerged in hot detergent solutions. Since routine patch testing with the Standard Series and perfume components was of no help in pinpointing the responsible agent, testing with selected perfume components was repeated at higher temperatures. Identical tests were placed on both forearms for 20 min, one arm being exposed to 43 degrees C, the other to 23-25 degrees C. Little or no reaction was seen on the "cold" arm, whereas the lemon perfume component Citral proved to be a strong primary irritant at higher temperatures. Histological examination of the test sites showed the reaction to be of a toxic (primary irritant) nature. Surprisingly, the toxic character could still be recongized in biopsies taken as late as 48 h after exposure. It is suggested that: 1. Heat plays an important part in the outbreak of primary irritant (toxic) dermatitis and can be used as an accelerating factor when testing for primary irritants. 2. It is important to be sure that detergents and detergent perfumes do not contain substances which act as irritants at the temperatures at which they are habitually used (45-50 degrees C). 3. We probably ought to use lukewarm rather than hot water for manual dishwashing and cleaning whenever it is possible.     

Skin reactions to irritants assessed by non-invasive bioengineering methods

Pathophysiological components of irritant contact dermatitis caused by 3 chemically-different irritants were investigated. 20 healthy volunteers were patch tested with sodium lauryl sulphate, nonanoic acid and hydrochloric acid on the flexor side of the upper arm. The skin response was evaluated after 24, 48 and 96 h by visual scoring and measured by the following bioengineering methods: transepidermal water loss measurement, electrical conductance for measurement of skin hydration, laser Doppler flowmetry for measurement of cutaneous blood flow and 20 MHz ultrasound A-scan for measurement of skin thickness. In spite of homogeneous inflammatory responses, significant differences in the severity of the injury to the skin barrier function caused by the different irritants were found. Also significant differences between irritants were found in the time course of development of maximum irritant reactions. Bioengineering methods indicating inflammatory responses (measurement of blood flow and skin thickness) were helpful in quantifying the irritant response in general, while bioengineering methods indicating epidermal damage (measurement of TEWL and electrical conductance) were helpful in classifying the individual irritants.     

Comparison of human back versus arm skin region for its suitability to test weak irritants

Background/aims: Large-scale comparative screening of der-matological and cosmetic products require non-invasive bioengineering methods which give reproducible results that can be statistically analyzed. To determine the most suitable test region for testing irritating substances, the response of the skin to the weak irritant sodium lauryl sulphate (SLS) was measured on standardized locations on the forearm and back. Furthermore, using 3 bioengineering methods, we aimed to establish the most sensitive method to measure skin response to SLS.
Methods: The baseline measurements of transepidermal water loss (TEWL), cutaneous blood flow (CBF) and skin colour a*-value were performed at 6 standardized locations on the volar forearms and at 12 locations on the back on 2 consecutive days, day 1 and 2, in 9 healthy volunteers. On day 2, 9 out of the 18 sites were exposed to 0.5% SLS by occlusive 24-h patches and the skin response was evaluated on days 3 and 4.
Results: For TEWL, CBF and a*-value, no significant regional variations were found within individuals at any time on the arm locations and on the back locations. However, significant inter-individual variation was found. At the back on day 4, a slightly higher skin response to SLS was found compared to that found on the forearms as measured by TEWL and the a*-value. Of the 3 bioengineering methods used, TEWL was the most sensitive method to detect cutaneous response to the weak irritant used. TEWL measurements on days 1 and 2 performed at the 6 standardized locations on the volar forearms inside and outside a specially constructed air convection protection box, showed no relevant differences in measured TEWL values.
Conclusion: Both the forearms and the back were found to be suitable sites for irritancy testing. Since considerable differences in mean reactivity between subjects have been observed the use of large numbers of subjects in predictive irritant patch testing is required.     

Minimum eliciting patch test concentration of thimerosal

Positive patch test reactions to thimerosal 0.1% pet. (40/690 subjects: 5.8%) were more common in younger age groups, in the allergic contact dermatitis group and in subjects who had used contact lens solutions. In the 40 thimerosal-positive patients, the minimum eliciting quantity of preservative was evaluated using different test concentrations: 0.05% and 0.01% pet. (patch testing) and 1:10,000 in saline (intradermal testing). Cross-reactions between thimerosal and other mercury compounds and sensitivity to thiosalicylic acid were also examined. The results of the investigation demonstrate that many of the reactions to 0.1% thimerosal are probably irritant, because only half the subjects studied had positive patch tests when allergen concentrations 5 to 10x lower than that conventionally used for patch testing, were utilized. In these subjects, the average strength of patch test reactions was higher, intradermal testing was more often positive and cross-reactions between mercurials more frequent. These data indicate that the optimal eliciting patch test concentration for studying thimerosal sensitivity is 0.05% pet.     

Allergic contact dermatitis to topical minoxidil solution: etiology and treatment.

After more than a decade of use, topical minoxidil solution has proven to be a safe and effective treatment for androgenetic alopecia. However, some patients present with complaints of pruritus and scaling of the scalp. The most common causes of these symptoms include irritant contact dermatitis, allergic contact dermatitis, or an exacerbation of seborrheic dermatitis. Patients suffering from allergic contact dermatitis may benefit from patch testing to determine the causative allergen. Among the patients we patch tested, propylene glycol was found to be the contactant in a majority of cases, not the minoxidil itself. Many of these patients may be candidates for treatment with alternative formulations using other solvents, such as butylene glycol, polysorbate, or glycerol. Although predictive, patch testing results do not ensure that the compounded preparations will be tolerated. Unfortunately, patients found to be allergic to minoxidil are no longer candidates for topical treatment of their alopecia with any preparations of minoxidil.     

Experimentally-induced irritant contact dermatitis

Patch testing with 7 irritants has been performed on a panel of 42 healthy volunteers, with the aim of determining concentrations which would induce mild to moderate reactions in at least 75% of individuals tested. The irritants studied and their optimum concentrations were as follows: benzalkonium chloride, 0.5%; sodium lauryl sulphate, 5%; croton oil, 0.8%; dithranol, 0.02%; nonanoic acid, 80%; propylene glycol, 100%; sodium hydroxide, 2%. Responder rates lower than 75% had to be accepted for benzalkonium chloride and sodium hydroxide in order to prevent overly severe reactions, whilst propylene glycol proved to have only marginal irritant properties.     

An arm immersion model of compromised skin

Patch testing and safety evaluation processes to assess the allergic or irritant potential of substances are usually performed on normal skin. However, the reactivity of compromised skin may be different. Consequently, it is important to have a test procedure which acts as a model for compromised skin and which reproduces on the target sites the cumulative insult which results from repealed exposure, working temperatures, hydration and the action of surfactants. The procedure described uses regular immersion of forearm skin in an aqueous solution of sodium dodecyl sulphate until an identifiable alteration of skin condition is produced. in this first report. the model system has been described in detail and the influence of skin compromise on the response to 3 irritants, citral, sodium dodecyl sulphate and nonanoic acid, has been assessed. The irritation potential of the materials varied, but each irritant produced a greater degree of reaction on skin compromised to be within the normal clinical range one might expect from housework.     

Prevalence of gold contact hypersensitivity in the West of Scotland

373 patients unending for routine patch testing were tested with 0.5% gold sodium thiosulfate (GST), 8(2.1%) patients had a positive patch test, and a further 4 (1.0%) patient reactions which were interpreted as irritant. 2 out of 8 patients with a positive patch test to GST suspected gold allergy prior to testing, and both of these patients reported that their eczema resolved if they avoided gold jewellery. This is the lowest prevalence of hypersensitivity to GST reported and suggests that gold contact allergy may not he as widespread as has been recently proposed.