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Diseases of the skin are important and often preventable conditions occurring among workers with dermal exposures to irritant and sensitizing agents.
We conducted this analysis to assess the associations between metalworking exposures and current, persistent skin symptoms among male and female participants in two population-based epidemiologic studies.
We pooled data from the European Community Respiratory Health Survey II (ECRHS II) and the Swiss Cohort Study on Air Pollution and Lung and Heart Disease in Adults 2 (SAPALDIA 2), two prospective cohort studies in Europe. Participants each completed interviewer-administered questionnaires to provide information about symptoms and exposures related to selected occupations, including metalworking, during the follow-up periods. We assessed associations between skin symptoms and the frequency of metalworking exposures among 676 ECRHS II/SAPALDIA 2 respondents.
Current skin symptoms were reported by 10% of metalworkers and were associated with frequent use, defined as 4+days/week, of oil-based metalworking fluids (prevalence ratio (PR): 1.76, 95% confidence interval (CI): 1.25, 2.49) and organic solvent degreasing agents (PR: 2.06, 95% CI: 1.21, 3.50).
Skin symptom prevalence is associated with increasing frequency of oil-based metalworking fluid and degreasing agent use. Our findings justify assessing strategies for reducing the frequency of metal-related exposures.
Diseases of the skin, including contact dermatitis, eczema and urticaria, are important and often preventable diseases occurring in workplaces with dermal exposures to irritant and sensitizing agents. Metalworking has been identified a high-risk occupation for irritant contact dermatitis [1–5], and particularly for hand or forearm dermatitis. Industry-based epidemiological research indicates that components of metalworking fluids and solvents may be the key exposures associated with skin symptoms .
We conducted this analysis to assess the associations between metalworking exposures and skin symptoms among participants in the European Community Respiratory Health Survey II (ECRHS II) and Swiss Cohort Study on Air Pollution and Lung and Heart Disease in Adults 2 (SAPALDIA 2) studies. Existing evidence for an association between metalworking exposures and occupational dermatoses is strong and thus our analyses build on previous evidence by assessing the prevalence of skin symptoms with increasing frequency of exposure among male and female participants of two international population-based epidemiologic studies
The ECRHS is a prospective population-based cohort study of respiratory health among adults living near 28 study centres in 13 countries. The study design and methods have been described previously [7–9]. Summarized briefly, the ECRHS is a longitudinal study with a fixed cohort; initial survey of the population began in 1991 (ECRHS I) and in 1998–1999 follow-up of the cohort included an occupational survey component for 22 centres located in 10 European countries (ECRHS II). Comparable baseline (SAPALDIA 1) and follow-up (SAPALDIA 2) protocols were followed in 8 centres in Switzerland for the SAPALDIA study [10,11]. Data collected from participants in the two cohort studies are easily pooled for a joint analysis (e.g., Chinn et al. 2006 ). The questionnaires completed by participants in each study contained a screening questionnaire to determine whether respondents would complete one or more of the seven occupational modules included in the follow-up surveys. The occupational modules, including one module addressing metalworking occupations, were designed to collect information about specific work-related exposures encountered in jobs held at any time during the study follow-up periods. Institutional Review Boards at the participating study centres approved the study protocol and instruments and participants provided written informed consent.
In the ECRHS II and SAPALDIA 2 populations, 753 participants reported working in jobs that involved production, processing or handling of metal or metallic objects during the follow-up period. All 753 completed the occupational module about metalworking tasks and exposures. We excluded 77 respondents with missing responses to questions about the metalworking exposures (n=61) or the outcomes (n=16) included in our analyses. These exclusions resulted in a final population of 676 metalworkers from ECRHS II (n=404) and SAPALDIA 2 (n=272).
The survey module included questions about the frequency of performing specific metalworking tasks (e.g., metal smelting, metal casting), performing manual work versus operating automated machinery, working with various metals and using selected types of products (e.g., water- and oil-based metalworking fluids, organic solvents). We categorized the frequencies of exposure as <1 day/week, 1–3 day(s)/week and 4–7 days/week. To assess the frequency of performing any metalwork, we assigned each respondent the maximum frequency category that he/she reported for any of 18 specific work tasks.
To assess the presence of skin symptoms at follow-up, we used responses to two survey questions about skin irritation: ‘have you ever had an itchy rash that was coming and going for at least six months?’ and, for those with positive responses, ‘have you had this itchy rash in the last 12 months? Respondents with positive responses to both questions were identified as having skin symptoms. We identified individuals with a history of eczema and other skin allergies using one question from the baseline survey: ‘have you ever had eczema or any kind of skin allergy?’
We estimated associations between metalworking exposures and skin symptoms using generalized estimating equations, specified with a binomial outcome distribution, a log link, a cluster-level variable indicating country of residence and an independent working correlation matrix structure for estimating the covariance of observations within each country. Measures of association are reported as prevalence ratios (PRs) with 95% confidence intervals (CIs), adjusted for age as a continuous variable and sex. For two of our final results, we assessed whether the PR estimates were confounded by a history of eczema, employment status, use of respiratory protection or ventilation equipment on the job or other metalworking exposures. We categorized employment based on responses about employment status at the time of the ECRHS II /SAPALDIA 2 surveys (employed, unemployed/not working, and other employment status). Individuals in the ‘unemployed/not working’ category were unemployed (n=13) or not working due to illness, disability or poor health (n=22). Those in the ‘other employment status’ category were full-time students (n=3), retired (n=27) or had other employment statuses (n=8). A dichotomous variable for respiratory protection or ventilation equipment was assessed as a proxy for personal protection in the workplace. All analyses were performed using SAS version 9.1 (SAS Institute Inc., Cary, North Carolina, USA).
Over 13% (90/676) of the metalworkers in our final study population reported ever having a recurrent itchy rash that lasted six months or more; 10% (n=66) reported that the itchy rash occurred in the last 12 months and are thus identified as having persistent and current itchy skin symptoms (Table 1). Across categories of increasing frequency of performing metalworking tasks, we observed little variation in the age distribution of each population and a slightly increasing percentage of men. The percentage of respondents with a history of eczema or skin allergy was higher among individuals performing metalworking <1 day/week (24%) compared to the remaining population (21%).
Table 2 shows the associations of the frequency of metalworking tasks and use of specific metals or metalworking agents with skin symptoms. The prevalence of skin symptoms was highest among respondents who reported frequent use of hard metals (19%), oil-based metalworking fluids (17%) and/or degreasing agents (17%). Across categories of increasing frequency of oil-based metalworking fluid use, adjusted PR estimates indicate higher risks of skin symptoms in the population with the highest frequency of use (4–7 days/week: PR=1.76, 95% CI=1.25, 2.49). This PR estimate was not notably affected by adjustment of the models for a history of eczema (PR=1.71), manual work (PR=1.67) or use of respiratory and/or ventilation equipment (PR=1.76). Adjusting the model for the frequency of water-based metalworking fluid use generated a PR of 2.15 (95% CI: 1.35, 3.44) and for organic solvent/degreasing agent use, a PR of 1.43 (95% CI: 1.02, 2.01).
Across categories of increasing frequency of organic solvent/degreasing agent use, the prevalence of skin symptoms increased monotonically from 7% to 17% and adjusted PR estimates indicate an increase in risk across frequency categories (1 to 3 days/week: PR=1.84, 95% CI=1.14, 2.97; 4–7 days/week: PR=2.06, 95% CI=1.21, 3.50) (Table 2). The associations generated for use of organic solvent/degreasing agents were only modestly affected by adjustment for a history of eczema (1 to 3 days/week: PR=1.76; 4–7 days/week: PR=2.10), manual work (1 to 3 days/week: PR=1.76; 4–7 days/week: PR=1.92), employment status (1 to 3 days/week: PR=1.85; 4–7 days/week: PR=2.12) or use of respiratory and/or ventilation equipment (1 to 3 days/week: PR=1.89; 4–7 days/week: PR=2.09). Adjusting the model for the frequency of water-based metalworking fluids resulted in similar estimates (1 to 3 days/week: PR=1.90; 4–7 days/week: PR=2.12), as did adjusting for oil-based metalworking fluids (1 to 3 days/week: PR=1.87; 4–7 days/week: PR=1.89).
We took advantage of data available from two large, international population-based surveys to assess the prevalence of an important occupational disease in a high-risk population. If metalworking fluids are associated with skin symptoms, then frequent or unprotected use of these agents may heighten the risk among metalworkers, hobbyists and other exposed individuals. In these analyses, we observed increasing skin symptom prevalence and adjusted PRs with increasing frequency of metalworking exposures, and particularly for use of oil-based metalworking fluids or degreasing agents four or more days per week. The adjusted associations increase with increasing frequency of use and do not appear to be confounded by a history of eczema, the frequency of performing manual metalworking tasks, employment status or use of protective respiratory or ventilation equipment, used here as a proxy for personal protection in the workplace.
In previous analysis of ECRHS II data, Harrop et al. reported on geographic variation in the prevalence of all eczema and specifically in atopic eczema, which was defined as the presence of eczema and specific IgE to any of the four allergens tested . Because Harrop et al. also assessed non-occupational risk factors, the definition used to identify individuals with eczema was further restricted to include only individuals with the skin symptoms ‘in the folds of the elbows, behind the knees, in front of the ankles, under the buttocks or around the neck, ears or eyes.’ We chose not to use this more restrictive definition because of its obvious exclusion of hand dermatitis, which would most likely be associated with irritant exposures among metalworkers. As a consequence, our results are not directly comparable to those of Harrop et al.; we are unable to identify the symptoms as atopic or non atopic eczema, and instead have opted to assess skin symptoms, more broadly defined.
In our analysis, assessment of the role of atopy was limited by the small size of our metalworking population and by the number of individuals with missing information about atopic status. For example, for 13 ECRHS II respondents and for all 272 SAPALDIA 2 respondents we did not have information with which to identify atopic status. Using the remaining population (n=391), we were able to identify respondents as atopic based upon specific serum IgE levels >0.35 kU·L−1 to at least one of four common environmental allergens (dust mite, cat, Timothy grass, Cladosporium herbarum) at the time of the baseline and follow-up surveys. Among the 148 respondents with positive tests from either survey (i.e., atopic) and among the remaining 243 respondents (i.e., non-atopic), stratifying the model in which we assessed oil-based metalworking fluid exposures resulted in distinct estimates in the highest exposure categories for the atopic (PR=2.83) and non-atopic (PR=0.80) strata (data not shown). These estimates were computed using only eight exposed and symptomatic individuals with atopy and four without, and therefore our data cannot be used to thoroughly investigate the role of atopy. However, because of this difference, the extent to which the metalworking and skin symptom associations may be modified by atopic status warrants further assessment. In addition, the percentage of respondents with a history of eczema or skin allergy was higher among individuals performing metalworking once per week or less. If this difference indicates an early selection effect in which individuals with skin allergies might avoid more frequent exposures, then the associations generated here may underestimate the potential burden of more frequent exposure.
The metalworking exposures considered here are correlated with one another. For example, 77% of those who reported using water-based metalworking fluids ≥1 day(s)/week also reported using oil-based metalworking fluids ≥1 day(s)/week. The 76% increase in relative risk observed with frequent use of oil-based metalworking fluids was attenuated to a 44% increase in risk when adjusted for frequency of degreasing agent use and, when adjusted for the frequency of water-based metalworking fluids, the PR was elevated farther away from unity (PR=2.16). The 106% increase in relative risk observed with frequent use of degreasing agents was not notably attenuated following adjustment for water-based or oil-based metalworking fluids, suggesting that the elevations observed are not largely attributable to these other, albeit closely related, exposures. More thorough investigation of the impact of combining the metals and metalworking fluid exposures on both absolute and relative risk is limited by the small number of exposed individuals with the highest risk of skin symptoms and by an even smaller number (n=70) who reported never performing any of the specific metalworking tasks in the questionnaire and thus could be considered completely unexposed. These unexposed individuals were plumbers and pipe fitters, shop attendants, medical assistants, machinery repair technicians, teaching professionals, safety and health inspectors and others who may have metalworking-related exposures, but who may not perform the specific tasks included in the questionnaire. The lack of a completely unexposed comparison population may be the reason that our estimates of the relative risk among exposed individuals are fairly low; if the groups with <1 day/week of each individual exposure are exposed to the other metals and/or solvents, then the PRs generated here may underestimate the actual risks. We initially intended to contrast the prevalence of skin symptoms among metalworkers to the prevalence among individuals in professional/administrative occupations, as defined in previous analyses of ECRHS data [14,15]. In this case, however, the high prevalence of skin symptoms in this non-metalworking comparison population (13%) as well as the suggestion that individuals who work in office settings may be at risk for itchy skin symptoms due to low humidity and other characteristics of the indoor workplace  both suggest that this population may not be an appropriate comparison group for which to assess the risk of occupational exposures and skin symptoms.
Our analyses also have several important limitations related to the identification of individuals with skin symptoms. The primary objectives of the ECRHS and SAPALDIA studies were to assess respiratory outcomes, not dermatoses, and therefore our use of two questionnaire items as a proxy for skin symptoms may not fully reflect the symptom prevalence in these populations. Indeed, our use of these two questionnaire items to identify individuals with skin symptoms, but without any specific reference to symptoms on the hands, was a practical approach to use survey-based information despite this recognized gap in the survey instrument. Using these data, we are unable to estimate how many of the individuals we identified with skin symptoms may have reported skin symptoms, but did not have these symptoms on their hands. However, the association between hand eczema and metalworking has been reported previously and recently [1,2,5]; in our study, if individuals without hand symptoms have been incorrectly classified due to the low specificity of our disease definition, then our results may be biased downward and towards unity. Reducing misclassification of dermatoses in further follow-up of the ECRHS and SAPALDIA cohorts may reveal stronger associations with increasing frequency of metalworking tasks than those generated in our analyses.
Previous research provides evidence that identification of hand dermatitis using self-reported questionnaire data may incorrectly estimate the actual prevalence of the disease [17,18]. Here, we highlight relative risks rather than absolute risks and note that using our survey-based identification of skin symptoms we are not able to draw conclusions about the prevalence of hand eczema or diagnosed skin conditions. And finally, we are unable to assess whether the self-reported symptoms are consistent in appearance with contact dermatitis, atopic eczema or urticaria. In this metalworking population, we have self-reported evidence of workplace exposures to potential skin irritants. A temporal relationship is supported by the evidence of new-onset symptoms, although analysis of the incidence of symptoms is limited by the small number of metalworkers without eczema or other skin allergy symptoms at the time of ECRHS I, but who reported skin symptoms in the ECRHS survey (n=15). Additional information about whether the distribution of the skin symptoms is consistent with dermal exposure that may correspond to the job tasks reported, about non-occupational exposures and about whether the symptoms improve away from the workplace would strengthen the evidence of the reported symptoms as being occupational in nature. In addition, occupational exposure histories and information about the timing of onset of skin symptoms would improve the ability to identify the work-relatedness of the symptoms. The effects of a reduced epidermal barrier function should also be carefully investigated.
Occupational skin diseases are largely preventable conditions for which prevention is especially important because of their poor prognoses - that is, because of the likelihood that many individuals with occupational dermatoses will continue to have exacerbations of their symptoms, medical expenses and absences from work. Secondary prevention measures such as workplace education and symptom treatments may enable individuals with existing symptoms to ease the severity or frequency of their symptoms. Education programs aimed at secondary individual prevention have been assessed in several workplace environments [19,20], and the extent to which they may be effective in the addressing occupational skin diseases among metalworkers remains unknown. If such programs prove to be effective in workplaces where metals and metalworking fluids are in use, they could be a sensible addition to other prevention and treatment programs. Our findings justify further exploration of primary prevention methods to reduce the frequency of exposures to specific metals and to metalworking fluids in this population. Possible interventions may include substitution of fluids or additives, reduced exposure through automation, improvements in the use of personal protective equipment and heightened efforts to educate potentially exposed workers about the health hazards of these agents.
Dr. Mirabelli received funding from the US National Institutes of Health (NIH) (1F32ES014142-03). The ECRHS received funding from the EU Framework programme for research (FOOD-CT-2004-506378). Co-ordination of ECRHS II was supported by the European Commission, as part of their Quality of Life programme (QLK4-CT-1999- 01237). The following agencies funded the ECRHS II study centres included in this paper: Albacete: Fondo de Investigaciones Santarias (FIS) (97/0035-01, 99/0034-01, 99/0034-02), Hospital Universitario de Albacete, Consejeria de Sanidad; Antwerp: FWO (Fund for Scientific Research)-Flanders Belgium (G.0402.00), University of Antwerp, Flemish Health Ministry; Barcelona: Spanish Society of Pulmonology and Thoracic Surgery, NIH (R01HL62633-01), FIS (97/0035-01, 99/0034-01, 99/0034-02), Comissió Interdepartamental de Recerca i Innovació Tecnolòica (1999SGR 00241), Red Respira ISCIII; Basel: Swiss National Science Foundation, Swiss Federal Office for Education & Science, Swiss National Accident Insurance Fund, NIH (5P30 ES07048); Bergen: Norwegian Research Council, Norwegian Asthma & Allergy Association, Glaxo Wellcome AS, Norway Research Fund; Erfurt: GSF-National Research Centre for Environment & Health, Deutsche Forschungsgemeinschaft (FR 1526/1-1); Galdakao: Basque Health Dept; Goteborg: Swedish Heart Lung Foundation, Swedish Foundation for Health Care Sciences & Allergy Research, Swedish Asthma & Allergy Foundation, Swedish Cancer & Allergy Foundation; Grenoble: Programme Hospitalier de Recherche Clinique-DRC de Grenoble 2000 no. 2610, Ministry of Health, Direction de la Recherche Clinique, Ministere de l'Emploi et de la Solidarite, Direction Generale de la Sante, CHU de Grenoble, Comite des Maladies Respiratoires de l’Isere; Hamburg:GSF-National Reasearch Centre for Environment & Health, Deutsche Forschungsgemeinschaft (MA 711/4-1); Ipswich and Norwich: Asthma UK (formerly known as National Asthma Campaign); Huelva and Oviedo: FIS (97/0035-01, 99/0034-01, 99/0034-02); Paris: Ministere de l'Emploi et de la Solidarite, Direction Generale de la Sante, UCB-Pharma (France), Aventis (France), Glaxo France, Programme Hospitalier de Recherche Clinique-DRC de Grenoble 2000 no. 2610, Ministry of Health, Direction de la Recherche Clinique, CHU de Grenoble; Pavia: Glaxo-SmithKline Italy, Italian Ministry of University and Scientific and Technological Research (MURST), Local University Funding for research 1998 & 1999 (Pavia, Italy); Tartu: Estonian Science Foundation; Turin: ASL 4 Regione Piemonte (Italy), AO CTO/ICORMA Regione Piemonte (Italy), MURST, Glaxo-SmithKline Italy; Umeå Swedish Heart Lung Foundation, Swedish Foundation for Health Care Sciences & Allergy Research, Swedish Asthma & Allergy Foundation, Swedish Cancer & Allergy Foundation; Uppsala: Swedish Heart Lung Foundation, Swedish Foundation for Health Care Sciences & Allergy Research, Swedish Asthma & Allergy Foundation, Swedish Cancer & Allergy Foundation; Verona: University of Verona, MURST, Glaxo-SmithKline Italy. The SAPALDIA 2 study was funded by the Swiss National Science Foundation (4026-28099, 3347CO-108796, 3247BO-104283, 3247BO-104288, 3247BO-104284, 32-65896.01, 32-59302.99, 3252720.97, 32-4253.94), the Federal Office for Forest, Environment and Landscape, the Federal Office of Public Health, the Federal Office of Roads and Transport, the cantonal governments of Aargau, Basel-Stadt, Basel-Land, Geneva, Luzern, Ticino, Zurich, the Swiss Lung League, the cantonal Lung Leagues of Basel Stadt/ Basel Landschaft, Geneva, Ticino and Zurich. The contents of this manuscript are solely the responsibility of the authors and do not necessarily represent the official views of the funding agencies.
Maria C. Mirabelli, Centre for Research in Environmental Epidemiology, Barcelona, Spain. Municipal Institute of Medical Research (IMIM-Hospital del Mar), Barcelona, Spain. CIBER Epidemiología y Salud Pública, Spain.
Jan-Paul Zock, Centre for Research in Environmental Epidemiology, Barcelona, Spain. Municipal Institute of Medical Research (IMIM-Hospital del Mar), Barcelona, Spain. CIBER Epidemiología y Salud Pública, Spain.
Andreas J. Bircher, Allergy Unit, Department of Dermatology, University Hospital, Basel, Switzerland.
Debbie Jarvis, National Heart and Lung Institute, Imperial College, London, UK.
Dirk Keidel, Institute of Social and Preventive Medicine, University of Basel, Switzerland.
Hans Kromhout, Institute for Risk Assessment Sciences, Environmental Epidemiology Division, Utrecht University, Utrecht, The Netherlands.
Dan Norbäck, Department of Medical Sciences, Occupational and Environmental Medicine, Uppsala University and University Hospital, Sweden.
Mario Olivieri, Department of Medicine and Public Health, Unit of Occupational Medicine, University of Verona, Italy.
Estel Plana, Centre for Research in Environmental Epidemiology, Barcelona, Spain. Municipal Institute of Medical Research (IMIM-Hospital del Mar), Barcelona, Spain. CIBER Epidemiología y Salud Pública, Spain.
Katja Radon, Occupational and Environmental Epidemiology & NetTeaching, Institute for Occupational, Social and Environmental Medicine, Ludwig-Maximilians-University, Munich, Germany.
Christian Schindler, Institute of Social and Preventive Medicine, University of Basel, Switzerland.
Peter Schmid-Grendelmeier, Allergy Unit, Department of Dermatology, University Hospital, Zurich, Switzerland.
Kjell Torén, Department of Allergology, Sahlgrenska University Hospital, Göteborg, Sweden. Department of Occupational and Environmental Medicine, Sahlgrenska University Hospital, Göteborg, Sweden.
Simona Villani, Section of Medical Statistics and Epidemiology, Department of Health Sciences, University of Pavia, Italy.
Manolis Kogevinas, Centre for Research in Environmental Epidemiology, Barcelona, Spain. Municipal Institute of Medical Research (IMIM-Hospital del Mar), Barcelona, Spain. CIBER Epidemiología y Salud Pública, Spain. Medical School, University of Crete, Heraklion, Greece.