Release of palladium from biomechanical prostheses in body fluids can induce or support PD-specific IFNgamma T cell responses and the clinical setting of a palladium hypersensitivity.

The increased use of Palladium (Pd) for biomedical applications, which has more than doubled in the last ten years, appears to be associated with an increased frequency of adverse reactions to Pd. The aim of this study is to investigate the relationship between the implant of a biomechanical apparatus containing Pd and the setting of a hypersensitivity to Pd by determining the levels of the metal released in biological fluids, assessing the effects of Pd on peripheral blood mononuclear cell (PBMC) cytokine production and exploring the clinical setting of skin sensitization. Of a total of 3,093 subjects examined in 2006, sensitization to Pd alone or in association with nickel (Ni) was observed in 1.6% and 13.03% of the individuals, respectively. Of these, a group of six subjects positive to Pd and negative to Ni at patch testing were selected on the basis of the oral clinical symptoms in order to measure both the levels of Pd in biological fluids and the degradation of the dental prostheses. Specific Pd measurements were carried out on salivary fluid, urine and serum samples by High Resolution Inductively Coupled Plasma-Mass Spectrometry. In addition, the degradation of the dental prostheses was assessed by both a leaching test and an analysis of the micro morphology of orthodontic prostheses. The induction of IFN-gamma production by Pd was assessed in PBMC by the ELISpot assay. Skin sensitization to Pd was evaluated by patch testing and clinical examination. Ten healthy subjects were comparatively tested as controls. We found a specific induction of an IFN-gamma response by Pd in PBMC collected from all the subjects positive to Pd at patch testing. On the contrary, control subjects did not show any response to Pd as assessed by IFN-gamma ELISpot assay or by skin testing. Remarkably, the levels of Pd in all biological samples (saliva, sera, urine) were significantly higher in Pd-sensitized patients than in those collected from controls, reaching the highest concentrations in the urine. The leaching studies gave additional evidence that the dental appliances can release measurable levels of Pd in saliva. Oral clinical symptoms in patients with Pd dental prostheses were associated with measurable levels of Pd in the biological fluids, the induction of Pd-specific IFN-gamma responses in PBMC and the clinical evidence of skin sensitization to Pd. These data suggest that dental appliances may represent an active source of Pd in the body, and this, in turn, can favour the clinical setting of a hypersensitivity to this metal.

Progesterone sensitive Interferon-gamma producing cells detected by ELISpot assay in autoimmune progesterone dermatitis.

Autoimmune progesterone dermatitis (APD) is a rare cutaneous disorder, characterized by recurrent polymorphous cutaneous and mucosal manifestations. It is considered to be caused by a hypersensitive reaction to endogenous progesterone. However, in vitro T-cell activity to this hormone has been described in few patients. Here we report the case of a 30-year-old woman with recurrent pruritic erythematous, and erythema multiforme-like eruptions localized to the genital area. Positive cutaneous reaction to intradermal progesterone injection suggested the diagnosis of APD. The analysis of cellular immune response to progesterone, investigated by the ELISpot assay, showed a significantly higher level of Interferon-gamma (IFN-gamma) producing cells in this patient compared with a control group comprising five asymptomatic women in the luteal phase of the menstrual cycle. Our results suggest that the ELISpot technique, together with clinical evaluations and assessment of allergies, could be useful in the diagnosis of APD.

Occupational hypersensitivity to metal salts, including platinum, in the secondary industry.

BACKGROUND: Exposure to platinum group elements (PGEs) - platinum (Pt), palladium (Pd), rhodium (Rh) and iridium (Ir) - may cause acute toxicity or hypersensitivity with respiratory symptoms, urticaria and (less frequently) contact dermatitis. Our aim was to determine the prevalence and the clinical characteristics of hypersensitivity to platinum salts and to other elements of the platinum group. METHODS: A total of 153 subjects working in a catalyst manufacturing and recycling factory were examined. The examination consisted of a work exposure and medical questionnaire, physical examination, skin prick test for PGEs and other common aeroallergens, and patch tests for PGEs. Skin prick tests and patch tests were performed with H(2)[PtCl(6)], K(2)[PtCl(4)], Na(2)[PtCl(6)], IrCl(3), RhCl(3), PdCl(2), aqueous solutions at different concentrations. RESULTS: Positive prick test reactions to Pt-salts at various concentrations were found in 22 (14.4%) of 153 workers; eight had simultaneous reactions to all Pt-salts tested; seven had positive responses to H(2)[PtCl(6)] only; four had simultaneous positive reactions to both H(2)[PtCl(6)] and K(2)[PtCl(4)]; three had positive reactions to H(2)[PtCl(6)] and Na(2)[PtCl(6)]. Three of 22 had positive reactions to H(2)[PtCl(6)] and IrCl(3) solutions, two of these had positive reactions to H(2)[PtCl(6)], IrCl(3) and RhCl(3) solutions. Positive patch test reactions to platinum salts at day 2 were seen in two of 153 subjects. CONCLUSIONS: The results of this study demonstrate that Pt-salts are important allergens in the catalyst industry and that the clinical manifestations involve both the respiratory system and the skin. Hexachloroplatinic acid should be considered the most important salt to use for skin prick tests.

Platinum in the environment: frequency of reactions to platinum-group elements in patients with dermatitis and urticaria.

The aim of the present paper is to evaluate whether increasing environmental exposure increases the frequency of the positive prick and patch test reactions to certain chlorinated platinum salts in patients with dermatitis and urticaria. 800 consecutive subjects with contact dermatitis (n=749) and urticaria (n=51) were variously patch and prick tested with 30 haptens of a standard series, with aqueous solutions of, respectively, hexachloroplatinic acid (H2[PtCl6]), potassium tetrachloroplatinate (K2[PtCl4]), sodium hexachloroplatinate (Na2[PtCl6]), iridium chloride (IrCl3), rhodium chloride (RhCl3) and palladium chloride (PdCl2), and with 16 common inhalants. 153 workers, variably exposed in a platinum refinery, were patch and prick tested only with solutions containing platinum-group elements at various concentrations and with 16 common inhalants. Platinum-group elements did not elicit positive patch or prick test reactions in non-occupationally exposed subjects. In contrast, in exposed workers, positive patch test reactions at day 2 and at 25 min, respectively, were found in 2 subjects with hand dermatitis and in 2 with urticaria and asthma. 22 out of the 153 workers, 18 of whom had rhinitis, asthma, and urticaria, gave positive prick test reactions to 1 or more salts. Furthermore, on patch and prick testing, 4 cross-reactions between platinum, palladium, iridium and rhodium were demonstrated. In conclusion, the test results demonstrate that the present concentration in the environment does not increase the incidence of reactions to platinum salts in patients with dermatitis and/or urticaria. However, if the average level of environmental platinum exposure approaches those existing in industrial settings in the future, we are going to observe more frequent health effects.