Allergia cutanea a nichel, cobalto, cromati ed espressioni geniche in gruppi professionali

Background: the sensitization and the contact dermatitis caused by nickel, cobalt and chromate are frequent in the general population and in some occupational groups. Their prevalence is influenced by age, gender, geographical and historical factors. The patch test is the method of choice in the diagnosis of contact sensitization. Objectives: (i) to estimate the prevalence of nickel, cobalt and chromate sensitization (isolated and concurrent) in a population of consecutive patients; (ii) to investigate the possible association with individual and occupational risk factors; (iii) to study the temporal trend of nickel, cobalt and chromate cutaneous allergy between 1996 and 2010 in North-Eastern Italy and (iv) to analyze the associations between “wet workers” and health care workers and patch test sensitization. Furthermore, (v) we investigated whether the expression levels of six genes were related to nickel exposure and/or nickel sensitization, and whether they could predict allergic manifestations. Patients/methods: 19666 patients (67.3% women and 32.7% men) with suspected allergic dermatitis underwent patch tests with the European standard series between 1996 and 2010. The subjects included in the studies varied from 9971 to 19088. The associations between patch test results and occupations were studied by multivariate logistic regression analysis. The mRNA expression level of six genes involved in cell growth (PIM1 and ETS2), metabolism/synthesis (HSD11B1 and PRDX4), apoptosis (CASP8) and signal transduction (CISH) was investigated by means of quantitative real-time RT-PCR in a cohort of 110 subjects (51 healthy controls, 23 nickel exposed workers and 36 patients allergic to nickel). Results: 25.4% of the overall patients (32.5% among women and 10.8% among men) reacted positively to nickel, 9.9% to cobalt (10.8% among women and 7.9% among men) and 8.1% to chromate (7.5% among women and 9.2% among men). The prevalence of nickel sensitization in young women (≤ 26 years) decreased from 38.3% (1996-1998) to 31.9% (2002-2004), to 28.3% (2005-2007) and to 29.0% (2008-2010), whereas an increase was observed in 36–45 and 46-58 years old women. The overall prevalence of chromate allergy has decreased from 10.2% (1996-1998) to 4.6% (2008-2010) among women and from 11.3% (1996-1998) to 5.9 (2008-2010) among men. In women, the prevalence of nickel sensitization was positively associated with metal and mechanical work (OR 1.54; 95% CI 1.16-2.05). Chromate sensitization was more prevalent in building trade workers for both women (OR 1.58; 95% CI 1.00-2.49) and men (OR 2.24; 95% CI 1.55-3.22). Cobalt sensitization was associated with textile and leather work in women (OR 1.52; 95% CI 1.09-2.12) and with cleaning work in men (OR 1.86; 95% CI 1.18-2.93). Building and related trades workers showed positive reactions to chromate-nickel (OR 1.99; 95% CI 1.05-3.76) and chromate-cobalt (OR 2.61; 95% CI 1.46-4.67). Cleaning workers exhibited a high prevalence of nickel, chromate, nickel-chromate and nickel-cobalt-chromate co-sensitization (ORs 1.29, 1.66, 2.11 and 1.79, respectively). Chromate and nickel sensitization were significantly higher in “wet workers” (cleaners and bartenders). We demonstrated a significant association between healthcare working and hand/forearm dermatitis, but our results did not confirmed a particular relevance for nickel positivity in HCWs (Health Care Workers). Moreover, the investigation on expression levels of six genes in 110 subjects (healthy controls, nickel exposed workers and nickel allergic patients), showed that the expression levels of the analysed genes did not differ between allergic patients and healthy controls, while higher expression levels of ETS2 and CASP8 were detected in the nickel exposed workers. Discussion: our studies demonstrated a decreasing prevalence of nickel allergy among youngest women that could be explained by a delayed first effect of the EU nickel regulation in Italy, as reported by others Authors in Countries were the nickel regulation exists since more time. Conversely, in recent years, patch tests positive to nickel were more frequent among women aged 36-58 years (possibly because sensitized before Nickel Directive application). The chromate decreasing trend (between 1996 and 2010), is possibly due to addition of ferrous sulphate to cement (EU Directive 2003/53/EC) (causing a reduced level of exavalent chromium to trivalent state which has low degree of skin penetration) and to improved work hygiene conditions. Chromate salt in cement is an important allergen causing occupational allergic contact dermatitis among construction workers. As expected and in accord with previous findings, our data showed that chromate sensitization (isolated or in association with nickel and cobalt) was associated with building trade work in both genders. An increased risk for nickel contact allergy has been showed in metal/mechanical workers, according to previous studies that have found that nickel released from metal objects is sufficient to induce sensitization and to cause an occupational allergic dermatitis. Nickel and chromate allergy were significantly higher in wet workers (cleaners and bartenders), who have an increased risk to develop occupational contact dermatitis probably due to water and irritants exposure and to an impaired skin protective barrier causing a higher permeation of metals (present in objects commonly used in work places or in detergents). Nickel, cobalt and chromate co-sensitizations could be related to occupational exposure and is associated to severe and chronic form of dermatitis. For this reason it is important to minimize the development of multiple sensitizations especially in the workplace. In the gene expression study, the changes in ETS2 and CASP8 expression were likely to be related to nickel exposure rather than to allergy, and may be interpreted as a sign of immunological reaction to the metal. This finding may be explained as a sort of “protection” effect preventing or inhibiting nickel sensitization. Conclusion: our studies showed interesting association between some occupations and nickel, chromate and cobalt allergy and demonstrated a temporal fluctuation with a decreasing trend of nickel (only among youngest women) and chromate allergy, probably related to the introduction in Italy of the EU nickel and chromate regulations. Genes expression study revealed an increase in ETS2 and CASP8 in nickel exposed workers but not in allergic vs non allergic subjects.