B. Santucci

Contact dermatitis to fragrances

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.

Levels of Enzymatic Antioxidants Activities in Mononuclear Cells and Skin Reactivity to Sodium Dodecyl Sulphate

Chemical irritants are able to produce several biological modifications of the skin, including the direct or indirect production of cytokines and reactive oxygen species leading to an inflammatory reaction. This report examines the existence of a possible correlation between the skin sensitivity to the irritant sodium dodecyl sulphate (SDS) and the activity of the enzymatic antioxidants. In twenty-three healthy subjects the evaluation of the epidermal and peripheral blood mononuclear cells (PBMCs) activities of superoxide Dismutase (SOD) and Catalase (Cat) demonstrate a significant correlation (r= 0,85 and p< 0,005 for SOD, and r= 0,87 and p< 0,0001 for Cat). Based on this result, on a further group of normal subjects (n=13) we studied the link between the threshold dose of skin reactivity to SDS and the activities of the enzymatic antioxidants in PBMCs. The degree of skin modification induced by SDS, applied at different concentrations for 24 hrs, was determined by means of Trans Epidermal Water Loss (TEWL), Erythemal Index or by Visual Score (VS). The minimal dose of the irritant capable of inducing skin modifications, was significantly correlated with SOD (r=0,77) and Cat (r=0,81) activities in PBMCs, and the modification of TEWL or EI were inversely correlated with levels of antioxidants in PBMCs (r=−0,62 for SOD and r=−0,66 for Cat). Our results indicate that the skin reactivity to irritants can be modulated by the levels of antioxidants, and suggest a possible therapeutical approach in preventing irritant contact dermatitis.

Paraphenylenediamine, a contact allergen, induces oxidative stress and ICAM-1 expression in human keratinocytes.

In an investigation of the role of keratinocytes in the pre‐immunological phase of contract allergy, we have studied the effect parphenylendiamine (PPD) on cell proliferation, membrane lipid peroxidation and the expression of the intercellular adhesion molecule 1 (ICAM‐1). Because PPD undergoes rapid autoxidation in the culture medium, the effect of PPD‐modified medium on keratinocyte proliferation and ICAM‐l expression was also examined.

Multicentre study of allergic contact cheilitis from toothpastes

The present work reports the results of a multicentre study of toothpaste allergic contact cheilitis (TACC) conducted by GIRDCA (Gruppo Italiano Ricerca Dermatiti da Contatto e Ambientali). The study examined 54 patients with eczematous lesions on the lips, the possible cause of which was suspected to be the use of toothpastes. Patch tests were conducted with a standard series, a specially‐targeted series (toothpaste cheilitis series, TCS), and with suspected toothpaste(s). A stop‐restart test (SRT) was carried out with these, together with a use test to identify possible alternative products. The TCS produced 17 positive reactions in 13 patients, the most frequent being to spearmint oil. Of the 54 patients, 5 displayed positive reactions only to the TCS. The patch tests with toothpaste produced positive reactions in 11/32 patients, the SRT a positive response in 10/12 cases. The diagnosis of TACC was confirmed in 15/54 patients. Alternative products were identified for 5 patients. In conclusion, the allergens most frequently responsible for TACC were the flavourings, and the additional series proved to be useful in many cases (together with patch tests with toothpastes and the SRT) for correct diagnosis and to initiate effective prevention.

Study on Cross-Reactivity to the Para Group

In 80 patients, positive to at least one hapten of the para group (para-phenylenediamine, diaminodiphenylmethane, benzocaine, PPD mix), patch tests were carried out with freshly prepared solutions of para-phenylenediamine (PPD) and of 3 selected aromatic compounds related structurally to PPD (para-aminophenol, ortho-aminophenol, hydroquinone). The number of positive reactions correlated with the rate of decomposition of the substances as evaluated by high-pressure liquid chromatography. PPD, which was almost decomposed after 24 h, gave the highest number of positive reactions, followed by ortho-aminophenol and by para-aminophenol, while hydroquinone, which was oxidized to the extent of 35%, did not give any reactions. To evaluate if a different rate of oxidation can modify the patch test response, in the same patients and in 10 normal volunteers, tests were carried out with PPD solutions containing the oxidizing agent silver oxide (0.1%). By this procedure a significant increase in the number of positive responses was observed. The results suggest that the rate of decomposition and therefore the amount of quinone(s) generated, might be the key to eliciting patch test responses to oxidizable aromatic haptens.

Nickel-keratinocyte interaction: a possible role in sensitization

Normal human keratinocytes and the keratinocyte‐derived cell lines NCTC 2544 and A 431, were exposed for different periods (i–5 days) to various concentrations (0·023–46.6 μg/ml) of nickel (Ni2+). A dose‐ and time‐dependent inhibition of cell growth and viability was observed. Cultures exposed to 2·3 μg Ni2+/ml showed approximately 50% cell survival at 5 days. An increase in release of interleukin I by keratinocytes was detected following culture for 24 h with a Ni2+ concentration of 2·3–11·5 μg/ml. Short periods of incubation (30 min) with these concentrations induced an activation of lipoxygenase in leucocytes from healthy subjects, without modifying cell viability. The results suggest that the percutaneous penetration of small amounts of Ni2+ can result in damage to keratinocytes and can initiate sensitization.

Nickel sensitivity: effects of prolonged oral intake of the element.

25 nickel‐sensitive females were given 10 mg NiSO4 in water in a single dose. 18 experienced daily flare‐ups 15 days later, 17 of the 25 patients were given gradually increasing daily doses of NiSO4 in water for 3 months, 14 ended the trial without flare‐up. 3 had to stop because of intense worsening of cutaneous manifestations. A relationship does exist between the daily oral intake and its clinical manifestations, but it is not uniform and depends on the changing quantities and, above all, on the manner of intake. It would seem that a 10 mg NiSO4 oral challenge represents a sudden and large intake of the element to which the majority of sensitized subjects are not able to adapt. On the other hand, a gradual intake permits a majority of subjects to adapt to the element. We hypothesize that this behaviour is more likely due to intestinal adaptivity than to immunological tolerance.

Eyelid dermatitis: an evaluation of 447 patients.

BACKGROUND Eyelids can be affected by various types of dermatitis that are often difficult to diagnose. OBJECTIVE The aim of the study was to establish some guidelines for a correct diagnosis. METHODS A total of 447 patients treated at 12 research units for eczema or other inflammatory dermatitis located on the eyelids were invited to complete a questionnaire. When necessary, patch tests with haptens of the standard series from Gruppo Italiano di Ricerca sulle Dermatiti da Contatto e Ambientali della Società Italiana di Dermatologia e Venereologia (SIDEV-GIRDCA) were performed. RESULTS Of the subjects studied, 50.2 % were diagnosed with allergic contact dermatitis (ACD); 20.9% were affected by irritant contact dermatitis (ICD), 13.5% by atopic dermatitis, 6.3% by seborrheic dermatitis, 6.5% by aspecific xerotic dermatitis, and 2.3% by psoriasis. Approximately 91% of all subjects reported an absence of familial atopy. A significant statistical association between diagnosis type and a personal history of atopy was evident (p <.000001, chi-square test). The results of gradual logistic regression models showed four-eyelid involvement as the main risk factor for ACD (odds ratio [OR] = 3.0; 95% CI, 1.1-8.1); with ICD, the main risk factor was the onset of symptoms at between 2 and 6 months (OR = 2.1; 95% CI, 1.1-4.0), whereas for atopic dermatitis, the main risk factors were the onset of symptoms later than 6 months and a personal history of atopy (OR = 4.9 and 3.6, respectively). CONCLUSION Results suggest that many characteristics of the patients examined can be used for the differential diagnosis of palpebral eczematous dermatitis.

Multiple sensitivities to transition metals: the nickel palladium reactions

Patch test data of 1000 consecutive patients sensitive to at least 1 substance of our standard series showed that transition metals gave associated reactions amongst themselves more frequently than they did with the remaining substances. The responses to transition metals were largely variable and seemed dependent not only upon the associated exposure to different metals or the concomitant responses of the T cell clones, as reported by others, but also upon the chemical properties of the metals and the consequent interactions inside the skin. Concomitant reactions to nickel sulfate and palladium chloride were the most frequently found associated positivities and occurred in a minority of nickel‐sulfate‐sensitive subjects. In 43 out of 45 of these subjects, patch tests to mixed solutions containing nickel sulfate, plus sulfates of magnesium, zinc, and manganese at higher doses, were not able to reduce the nickel sulfate reactions. This behaviour contracted with that found in the majority of subjects sensitive only to nickel sulfate. These findings seem to demonstrate that, whilst in subjects with positive reactions to nickel sulfate alone antigen formation involves biomolecules containing ions, in those with concomitant reactions to palladium chloride, other structures are involved.

Nickel dermatitis from cheap earrings

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.