G. Calapai1, A. Carnì1, C. Mannucci1, G. Loschiavo2, L. Ricciardi2. 1University of Messina, Dept. of Clinical and Experimental Medicine and Pharmacology 98125, Italy, 2University of Messina, Allergy and Clinical Immunology Unit, Azienda Ospedaliera Universitaria “Policlinico G. Martino”,, Italy

Allergic contact dermatitis (ACD) is a hypersensitivity skin reaction that occurs after direct contact with irritant compounds or chemicals with low molecular weight. It is predominantly mediated by cell-mediated immunological mechanisms. Nickel sulfate is universally recognized as the most important causative agent of ACD. In recent times researchers' attention has been focused on the district symptomatology due to direct contact as well as on systemic disorders caused by absorption into the circulation of the metal. Generalized eczema and chronic urticaria, have been reported in patients with ACD caused by nickel in dental or orthopedic metal denture wearers. Several authors have linked these symptoms to the slow absorption of the metal in the circulation. It has been also observed in some patients with a diagnosis of ACD caused by nickel, as the food-containing nickel can cause wide cutaneous reactions associated with gastrointestinal symptoms such as nausea, heartburn, bloating, abdominal pain, constipation or diarrhea. This condition has been defined as systemic nickel allergy syndrome (SNAS). Since it has been suggested the involvement of different cytokines in the genesis of the clinical manifestations of allergies to metals, we carried out a study with the aim to evaluate possible changes in cytokines potentially implicated in SNAS before and after treatment with oral hypo-sensitization therapy specific for nickel. We recruited 22 patients with SNAS attending the Operative Unit of Allergology and Clinical Immunology of the University Hospital of Messina “Policlinico G.Martino”. In order to induce tolerance to nickel, has been prescribed a therapy hyposensitizing based on capsules of Nickel sulphate content according to a scheme of treatment at increasing dosage of the total duration of two years and initially associated to nickel diet restriction. Efficacy of therapy was evaluated showing each patient a visual analogue scale (VAS) immediately before the beginning of the therapy and after the 2-year period of treatment. At the time of recruitment, after the first year and at the end of treatment (after two years), blood samples were withdrawn to measure in the serum the following cytokines: IL-2, IL-6, IL-10, IL-12, IL-17. ELISA measurement for cytokines was used. Statistical analysis of VAS scores shows a highly significant difference in all the patients between symptoms collected before and after the two-year treatment with oral nickel desensitization therapy (P < 0.001). At the end of the two-year period of oral nickel desensitizing treatment, nickel oral challenge test was negative in 18 patients. Statistically significant reduction (P < 0.01) of basal seric IL-2 level (0.13 ± 0.01 pg/ml) in the serum after the two-year period of oral desensitization was observed (0.10 ± 0.01 pg/ml). Basal seric IL-10 mean level (T0) was 2.10 ± 0.97 and 2.08 ± 0.85 pg/ml after the first year (T1); IL-10 increased after the second year of treatment (T2 = 2.52 ± 1.20 pg/ml), although this date was not statistically significant. IL-6, IL-12 and IL-17 were not modified after one or two years of treatment. Therapy was effective in inducing clinical tolerance to nickel in foods with low incidence of side effects and with the concrete result of seeing significantly improved the clinical condition of patients. Conclusions: results show that increase of seric IL-2 is associated to improvement of SNAS symptoms observed after two years oral nickel desensitizing therapy.