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Notes: Background  The 1- and the 2-euro coins consist of nickel alloys, which release nickel. The nickel released by far exceeds the amount allowed by the European Union Nickel Directive referring to products intended to come into direct and prolonged contact with the skin. As there is only temporary contact with the skin, the clinical relevance of nickel-containing coins with regard to nickel dermatitis is a matter of debate, although there is evidence that the nickel released from the coins affects some nickel-sensitive subjects through occupational exposure.Objectives  Our aim was to study skin reactivity to euro coins, and to correlate the frequency and intensity of coin patch test responses to sensitization thresholds to nickel.Patients and methods  Sixty-four nickel-sensitized and 30 non-nickel-sensitized subjects were patch tested with serial dilutions of nickel sulfate (5, 1, 0.5, 0.1, 0.05, 0.01 and 0.005% in distilled water) and with coins. Italian coins (500, 200, 100 and 50 lira) and euro coins (2 and 1 euros, 20 and 5 euro cents) were used for patch testing and compared.Results  The application of 1- and 2-euro coins to the skin induced eczematous reactions, being more frequent and intense in comparison with those provoked by other coins. A correlation between intensity of responses to coin patch tests and sensitization threshold to nickel was observed. Patients with the strongest reactions to 1- and 2-euro coins showed positive responses to the lowest nickel concentrations.Conclusions  The nickel content in euro coins represents a possible health hazard, especially for highly nickel-sensitive subjects. We recommend that nickel sulfate patch tests should be performed at different concentrations to determine sensitization thresholds at least in individuals with occupational exposure to coins.

Notes: In 1988, 64% of our patients patch test positive to al least I allergen of the ICDRG standard series-were nickel sensitive. In 70% of 300 patients evaluated, dermatitis started on the earlobes and was related to the regular wearing of cheap earrings. At the same time, 62% of 735 young schoolgirls were found to have dermatitis of their carlobes and all regularly wore cheap earrings. 9 clasps and clips commonly used in earrings released high quantities of nickel ions (between 49 and 103 μg/12 h), having been stored in synthetic sweat. A round piece cut from a clasp was taped U the skin of nickel-sensitive patients, previously tested with 20 μl of NiSO4 5%, 2.5%, 1% aq. solutions, giving a response similar to that caused by the 5% solution. High daily absorption of Ni ions through the skin follows its repetitive exposure la cheap earring, causing, firstly, a direct inflammatory reaction, then followed, in our opinion, by sensitization.

Notes: Nickel (Ni) dermatitis is, thought to involve the formation of complexes between Ni ions and suitable proteins. 4 groups of 30 subjects who gave positive patch test responses to NiSO4 2.9% aq. were each retested to 1 of 4 different solutions containing equimolar (0.1 M) amounts of NiSO4 plus MgSO4. NiSO4 plus CuSO4, NiSO4plus ZnSO4. and NiSO4 plus Li2SO4, respectively. The results, evaluated at 2 days by visual scoring only, demonstrated that the 4 metals exerted a different influence on the nickel reactions, perhaps interfering with one or more factors affecting the formation of Ni++ complexes.

Notes: 2 groups of patients (1200 and 1500 respectively) were patch tested with different concentrations of perfume mix and fragrance raw materials. The study was to evaluate the incidence of contact dermatitis to fragrances in Roma, Italy, and the influence of limited variations in fragrance and perfume mix concentrations on patch test responses. The results showed that a decrease in the perfume mix concentration from 16% to 8% correlated with a decrease in the % of positive patients (from 5.2%j to 3.6%). Variations in the concentration of fragrance raw materials did not influence the % of positive reactions in the 2 groups. The perfume mixture at 16% or 8% gave some positive results, without a corresponding reaction to any of the constituents, that were not related to an excited skin syndrome.

Notes: The expression and the distribution of metallothioneins (MT)-I and II isoforms were evaluated in 5 healthy volunteers and in 16 subjects with positive patch test reactions to various compounds. Skin specimens taken both from the healthy skin of the back and at positive patch test sites (at 48 h), were treated using a 3-step indirect immunoperoxidase procedure with a mouse monoclonal IgG1 antibody reactive against I and II isoforms of human, rat and horse MT. MT were expressed in the basal layer of the healthy skin of both controls and sensitive subjects, without any significant difference. At positive patch test sites, there was an overexpression of MT in basal and suprabasal layers of the epidermis. Overexpression of MT, related to the degree of the inflammatory reactions elicited by the penetrating compounds was observed in the dermis. The cells expressing MT in the dermis were mostly T lymphocytes and cells with dendritic morphology which positively stained in part for CD34 and in part for XIIIa markers and negatively for KP1, S100 and HLA-DR. Taken together, these results seem to indicate that MT represent a constitutive mechanism of defence expressed by different types of cells in the skin, which is triggered by contact with both metallic and non-metallic compounds. The biological significance of MT in the skin remains to be elucidated. Our preliminary findings do not permit evaluation of whether these nearly ubiquitous proteins exert their cytoprotective effects in the skin acting simultaneously as antioxidant, metal binding or zinc suppliers, or if they display these activities mainly depending on the nature of the penetrating substances.

Notes: For a better understanding of the mechanistic details of the interactions of organomercury compounds inside the skin, 32 subjects who previously had given positive patch-test reactions to thimerosal (TH) and negative reactions to thiosalicylic acid, were divided into 2 groups. 16 subjects were repatch tested to ethylmercury chloride (EtHgCl) and to solutions containing EtHgCl mixed with L-cysteine and glutathione, respectively. The remaining 16 were repatch tested to EtHgCl and to solutions containing EtHgCl mixed with chlorides of Zn, Mg, and Mn, respectively. The results showed that whilst L-cysteine, glutathione and ZnCl2 were able to abolish or to reduce the positive reactions to EtHgCl, chlorides of Mg and Mn were unable to do so. Patch tests revealed that in causing positive reactions to TH, EtHg probably interacted with thiol groups and with Zn ions, as in biological systems when causing toxic effects. The limited number of TH reactions in the general population, the constant presence of concomitant positive reactions to EtHgCl and MeHgCl, and the lack of cross-reactivity with other organic or inorganic mercury compounds, lead us to speculate that reactions to TH are due to organomercury alkyl compounds, and that positive subjects have a constitutively reduced capability to metabolize organomercury compounds, rather than to reveal previous exposure.

Notes: Contact allergy to thimerosal (TH) has not been considered a marker for mercury allergy, since there is a low degree of cross-sensitivity to inorganic as well as to organic mercury salts. 40 subjects, who previously gave a positive patch test reaction only to thimerosal 0.1% pet. (Hermal), when simultaneously repatch-tested to solutions containing TH, mersalyl acid, p-amino-phenylmercuric acid, mercuric acetate and thiosalicylic acid, respectively, gave positive reactions only to TH. 36 out of 40 subjects were divided into 2 groups of 18 subjects and simultaneously repatch-tested to solutions containing TH, methylmercury chloride (MeHgCl), thiosalicylic acid, and, ethylmercury chloride (EtHgCl), respectively. EtHgCl was tested in the 1st group at 0.031% and in the 2nd group at 0.015%. The results showed that all subjects gave concomitant positive reactions to TH, EtHgCl and MeHgCl. EtHgCl 0.031% gave a higher number of +++ reactions than EtHgCl 0.015%, underlining the rôle of the solvent in these reactions. Patch test results in 300 consecutive patients to a standard series, to which MeHgCl was added, showed that MeHgCl and TH were never able to give isolated positive reactions, and that the concomitant positive reactions occurred in only 3.6% of subjects. In conclusion, our data seem to suggest that the positive reactions to TH found in our patients were due to EtHgCl, and that the structural similarities with MeHgCl were so close that the skin reacted against each as if they were identical.

Notes: To study the influence exerted by cutaneous ligands in nickel reactions we have evaluated the patch tests responses to 4 aqueous nickel salts (sulfate, chloride, nitrate, acetate) able to form different complexes with different geometry. Two groups of respectively 71 subjects who previously reacted only to nickel sulfate 5% petrolatum (pet) and of 30 subjects who previously reacted to nickel sulfate 5% pet and to at least 1 other transition metal, were simultaneously repatch-tested to 200 μg of Ni++ contained in nickel sulfate in pet and to 47 μg of Ni++ contained in 4 different aqueous nickel salts. Another 2 groups of 25 subjects with the same characteristics were simultaneously repatch tested to 200 μg of Ni++ in pet and to 12μg of aq Ni++ as in the first 2 groups. Visual score, total score, and mean value of the reactions were utilized in evaluating the degree of the responses. On testing to 200 μg of Ni++ in pet all the subjects were able to give positive responses. Whilst a higher percentage of the responses of 2+ degrees was found in subjects reacting to nickel sulfate 5% pet alone, a higher percentage of responses of 3+ degrees was observed in subjects reacting to more transition metals. On testing to 47 and 12 μg of aqueous Ni++ a large variability of responses to the single salts was observed in all the subjects. However, in subjects reacting to more metals there were either a greater number of multiple responses to 3 or 4 salts or responses stronger than those found in subjects reacting to nickel sulfate alone. Although patch testing cannot give us complete information about the degree of previous exposure, the results arising from the tests seem to demonstrate that the subjects allergic to nickel and other transition metals are more reactive than the subjects allergic only to nickel to the application of the same amounts of Ni++ contained in different salts. When considering the QSAR model, the difference in the sensitizing potential of the metal at the same penetration properties can depend on the possibility of combining with specific ligands. Therefore, it is likely that in subjects reacting to more metals there is a more uniform availability of cutaneous ligands which conditions the formation of complexes more immunogenic. The arising inflammatory reaction in these cases leads to a stronger but less specific response.