Recognized Occupational Diseases in Italy's Friuli-Venezia Giulia and Liguria Regions (2010-2021).

BACKGROUND: The study of recognized occupational diseases trend is important to understand the preventive approach needed in the future, however, while numbers of occupational diseases are available on web, data on incidence are missing. The aim of our study was to analyze the trend and the incidence rate ratio (IRR) of recognized occupational diseases in Italy, in Friuli-Venezia Giulia region (FVG) and Liguria region from 2010 to 2021. METHODS: Numbers of recognized occupational diseases by the Italian National Insurance for Occupational Diseases (INAIL) were analyzed and incidence were calculated considered the total number of workforces in the area. A Poisson regression model was used to estimate incidence trends. RESULTS: FVG region presented a higher incidence of all occupational diseases compared to Italy and to Liguria in the period considered. The overall incidence in 2019 was 175, 91.8 and 108 cases for 100,000 workers, for FVG, Liguria and Italy respectively. Musculoskeletal disorders (MSDs) were the majority of occupational diseases with 100, 51 and 82.8 cases per 100,000 workers, in FVG, Liguria and Italy, respectively. Incidence of occupational cancers was 16, 10 and 4.9 cases per 100,000 workers, in FVG, Liguria and Italy, respectively. The annual change of incidence from 2010 to 2019 was positive for MSDs (IRR 1.06; 95%CI 1.06 to 1.07) and decreasing for the other causes in Italy. In FVG region the trend was positive for MSDs (IRR 1.05;95%CI 1.04 to 1.06), for respiratory diseases (IRR 1.03; 95%CI 1.00 to 1.05) and pleural plaques (IRR 1.03; 95%CI 1.00 to 1.06). In Liguria the trend was positive for MSDs (IRR 1.17; 95% CI 1.15-1.19) and for pleural plaques (IRR 1.07; 95%CI 1.03-1.12). Stable trends were found for cancers. Declining trend was shown for noise induced hearing loss and skin diseases. CONCLUSIONS: FVG region presented a higher incidence of recognized occupational diseases compared to Liguria region and Italian data. Results that can be explained by a higher propensity of claiming for occupational diseases in workers, mainly for MSDs disorders. For cancers and asbestos-related diseases the higher incidence can be attributable to high exposure to asbestos in FVG and Liguria workers mainly in shipyard and dock activities.

Incidence of skin diseases in healthcare workers before and during the COVID-19 pandemic at Trieste hospitals (northeastern Italy).

BACKGROUND: Occupational skin diseases (OSDs) are common in healthcare workers (HCWs). OBJECTIVES: To investigate and compare the incidence and clinical features of OSDs among HCWs before and during the COVID-19 pandemic. MATERIALS AND METHODS: Incident cases of OSDs were investigated in the cohort of HCWs at Trieste Hospitals from 1 July 2018 (3340 workers) to 31 October 2021 (137 532 person-months). RESULTS: The monthly incidence was ranging from 0 to 11.90 cases per 10 000 person-months in pre-COVID-19 period (cumulative incidence 4.22; 95% confidence interval [CI]: 2.9-6.0) and from 0 to 13.61 cases per 10 000 person-months in COVID-19 period (cumulative incidence 5.06; 95% CI: 3.6-6.9). The incidence rate ratio (IRR) between COVID-19 and pre-COVID-19 period was 1.22 (95% CI: 0.73-1.98). The incidence of OSDs in the COVID-19 period was 6.1 (4.2-8.6) and 2.7 (95% CI: 1.1-5.6) cases × 10 000 person-months for women and men, respectively, with an IRR of 2.25 (95% CI: 0.98-5.9). Incidence in nurses in the COVID-19 period was 6.7 (95% CI: 4.2-10.2) cases × 10 000 person-months. CONCLUSIONS: Incidence of OSDs was a little bit higher during the COVID-19 pandemic compared to the previous period but fluctuation of numbers were mainly related to calendar period, with higher incidence in winter and spring. Incidence data were higher than that observed in 2004-2013 in the same cohort. Face dermatitis cases doubled after the start of COVID-19 pandemic. Overall data demonstrated a non-significant increase of OSDs in HCWs during the pandemic, probably due to the preventive strategies set up in our cohort over the years.

Low sensitivity of rapid tests detecting anti-CoV-2 IgG and IgM in health care workers' serum for COVID-19 screening.

BACKGROUND: the sensitivity and specificity of a rapid antibody test were investigated for the screening of healthcare workers. METHODS: the serum of 389 health care workers exposed to COVID-19 patients or with symptoms, were analysed. All workers underwent monthly the screening for SARS-CoV-2 with detection of viral RNA in nasopharyngeal swabs by RT-PCR. IgG antibody detection in serum was performed by Chemiluminescence Immunoassay (CLIA) and by the Rapid test (KHB diagnostic kit for SARS CoV-2 IgM/IgG antibody after a median of 7.6 weeks (25°-75° percentiles 6.6-11.5). RESULTS: the rapid test resulted positive in 31/132 (23.5%), 16/135 (11.8%) and 0/122 cases in COVID-19 positive individuals, in those with only SARS-CoV-2 IgG antibodies and in those negative for both tests, respectively. Sensitivity was 17.6% (CI95% 13.2-22.7) and 23.5% (CI95% 16.5-31.6), and specificity was 100% (CI95% 97-100) and 100% (CI95% 97-100) considering Rapid test vs CLIA IgG or Rapid test vs SARS-CoV-2 positive RNA detection, respectively. CONCLUSION: the KHB Rapid test is not suitable for the screening of workers with previous COVID-19 infection.

[Occupational allergic contact dermatitis: the role of occupational physician in the prevention.] / Dermatite allergica professionale: il ruolo del medico competente nella prevenzione.

OBJECTIVES: Occupational contact dermatitis are the second occupational diseases in industrialized countries and the preventive action and/or early diagnosis done by occupational physician (OP) is of paramount importance. METHODS: OP in the process of risk evaluation must suggest products, detergents and personal protective equipment with low irritant or sensitization potential. During work, the use of skin creams has to be promoted to prevent irritation that is the first step towards impairment of the skin barrier and sensitization. RESULTS: During periodical medical surveillance OP can control skin conditions of workers looking for signs of irritant and contact dermatitis, can give advice about preventive measures and information about products used to permit an early and correct diagnosis. CONCLUSIONS: At the retour to work workers with a diagnosis of occupational dermatitis must avoid direct contact with irritant and sensitizing products.

ESSCA results with the baseline series, 2002-2012: p-phenylenediamine.

BACKGROUND: Allergic contact dermatitis caused by p-phenylenediamine (PPD) is common among all age groups and both sexes. Monitoring of prevalence and intensity of sensitization is important. OBJECTIVE: To evaluate contact allergy to PPD in Europe, and to compare reaction intensities in different European regions. METHODS: Data collected by the European Surveillance System on Contact Allergies (ESSCA) network between 2002 and 2012 from 12 European countries were analysed regarding prevalence, grading of positive reactions to PPD, and relevance. RESULTS: A total of 99 926 PPD-positive patients from 63 departments were included for analysis. The overall (2002-2012) prevalence of PPD sensitization in Europe is ∼4%. Stratified for country, the highest overall standardized prevalence was found in Lithuania, and the lowest in Slovenia. The prevalence of PPD sensitization did not decline over the years. In the southern European countries, higher numbers of strong and extremely strong reactions were registered. The clinical relevance of PPD sensitization varied from half to three-quarters. CONCLUSION: The prevalence of PPD sensitization has not changed over time. Strong and extremely strong patch test reactions are seen more often in the South, probably because of the higher number of PPD-containing hair dye products.

Primin sensitization in north-eastern Italy: a temporal trend from 1996 to 2012.

BACKGROUND: Primin is the main contact allergen found in the ornamental plant Primula obconica Hance. OBJECTIVE: To analyse the temporal trend of sensitivity to primin in north-eastern Italy and to evaluate the associations with occupations in our geographical area. METHODOLOGY: From 1996 to 2012, 24 052 consecutive patients with suspected allergic contact dermatitis were patch tested in north-eastern Italy. Individual characteristics were collected through a standardized questionnaire in eight departments of dermatology or occupational medicine. RESULTS: The overall prevalence of primin sensitization was 1.9%; the prevalence was significantly higher in women (2.6%) than in men (0.5%). The Pordenone area had the higher prevalence of sensitization, which reached 6% in 1999-2001. We found a significant association between primin sensitization and household workers [odds ratio (OR) 2.3; 95% confidence interval (CI): 1.61-3.35], retired people (OR 1.8; 95%CI: 1.22-2.81), woodworkers (OR 2.1; 95%CI: 1.10-6.18), and chemical industry workers (OR 2.9; 95%CI: 1.05-8.29). CONCLUSION: Our study showed that contact allergy to primin is still relevant in north-eastern Italy. The frequency of sensitization is decreasing, but for retired and household workers it is still >4%. Our results suggest the need to promote the use of primin-free P. obconica in Italy.

Ten years incidence of natural rubber latex sensitization and symptoms in a prospective cohort of health care workers using non-powdered latex gloves 2000-2009.

OBJECTIVES: To assess the incidence of sensitization and gloves-related symptoms in 10-year follow-up in a group of health care workers (9,660 person-years) using non-powdered latex gloves from 2000 to 2009 and to examine related factors. MATERIALS AND METHODS: We studied 2,053 health care workers in Trieste Hospitals by means of skin prick test for latex extract, patch tests and medical examinations. We report the incidence of latex sensitization among workers using non-powdered latex gloves. RESULTS: The incidence of latex sensitization, rhinitis, asthma, urticaria, irritant and allergic contact dermatitis were 1.0; 0.12; 0.21; 0.72; 2.39 and 2.50 cases per 1,000 person-years, respectively. Respiratory symptoms and urticaria were positively related with latex sensitization (OR = 8.0; 95 % CL 1.27-48.6), with common allergic respiratory symptoms (OR = 4.19; 95 % CL 1.04-16.8) and with familial atopy (OR = 4.47; 95 % CL 1.1-17.9). CONCLUSION: The incidence of latex sensitization and latex-related symptoms were very low but subjects with allergic symptoms related to common allergens are at higher risk. The use of non-latex gloves is suggested for them.

Nickel, chromium and cobalt sensitization in a patch test population in north-eastern Italy (1996-2010).

BACKGROUND: Sensitization to nickel, cobalt and chromium is frequent in patch test populations. The prevalence is affected by geographical and socio-cultural factors. OBJECTIVES: To investigate the temporal trend of nickel, cobalt and chromium contact sensitization between 1996 and 2010 in north-eastern Italy. PATIENTS/METHODS: Nineteen thousand and eighty-eight patients (67.2% women and 32.8% men) with suspected allergic dermatitis underwent patch testing with the European baseline series. The associations between nickel, cobalt and chromium sensitization and patient age (in quintiles) and year of patch testing were investigated by means of multivariate logistic regression analysis. RESULTS: The prevalence of nickel sensitization decreased significantly among younger women (≤26 years), from 38.3% (1996-1998) to 31.9% (2002-2004), 28.3% (2005-2007) and 29.0% (2008-2010), whereas an increase was observed in the 36-45-year and 46-58-year age groups. The overall prevalence of chromium sensitization dropped 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. The prevalence of cobalt sensitization increased among younger men (≤26 years), from 2.7% (1996-1998) to 7.3% (1999-2001), 9.6% (2002-2004), and 6.6% (2005-2007). CONCLUSIONS: Our study showed a decreasing trend of nickel sensitization (only among younger women) and of chromium sensitization in both sexes.

Hand Eczema in Apprentice Nurses during the COVID-19 Pandemic after a Skin Prevention Program.

BACKGROUND: Healthcare workers, particularly nurses and apprentice nurses, are at high risk of the development of hand eczema due to daily exposure to wet work. This study aimed to assess the occurrence of hand eczema in a group of first-, second-, and third-year apprentice nurses at the University Hospitals of Trieste (northeastern Italy) during the COVID-19 pandemic. METHODS: Two hundred forty-two Nursing School students were recruited. Data were collected using a standardized questionnaire based on the Nordic Occupational Skin Questionnaire, and all patients underwent a medical examination to evaluate their skin condition based on standard scores. Transepidermal water loss was also measured. The factors associated with hand eczema were investigated using univariate and multivariate logistic regression analyses. RESULTS: The prevalence of hand eczema was low in students both before and after the traineeship (17.9 and 21.5%, respectively), but clinical signs of mild skin damage, mainly skin dryness, were present in 52.3 and 47.2%, respectively. The factor associated with hand eczema was a personal history of atopic eczema (odd ratios 2.61, 95% confidence intervals 1.18-5.80), while exposure to irritants and glove use did not reach statistical significance. CONCLUSIONS: Our findings might be explained by the preventive measures adopted for skin protection among healthcare workers in Trieste since the apprenticeship.

Multimorbidity and Serological Response to SARS-CoV-2 Nine Months after 1st Vaccine Dose: European Cohort of Healthcare Workers-Orchestra Project.

Understanding antibody persistence concerning multimorbidity is crucial for vaccination policies. Our goal is to assess the link between multimorbidity and serological response to SARS-CoV-2 nine months post-first vaccine. We analyzed Healthcare Workers (HCWs) from three cohorts from Italy, and one each from Germany, Romania, Slovakia, and Spain. Seven groups of chronic diseases were analyzed. We included 2941 HCWs (78.5% female, 73.4% ≥ 40 years old). Multimorbidity was present in 6.9% of HCWs. The prevalence of each chronic condition ranged between 1.9% (cancer) to 10.3% (allergies). Two regression models were fitted, one considering the chronic conditions groups and the other considering whether HCWs had diseases from ≥2 groups. Multimorbidity was present in 6.9% of HCWs, and higher 9-months post-vaccine anti-S levels were significantly associated with having received three doses of the vaccine (RR = 2.45, CI = 1.92-3.13) and with having a prior COVID-19 infection (RR = 2.30, CI = 2.15-2.46). Conversely, lower levels were associated with higher age (RR = 0.94, CI = 0.91-0.96), more time since the last vaccine dose (RR = 0.95, CI = 0.94-0.96), and multimorbidity (RR = 0.89, CI = 0.80-1.00). Hypertension is significantly associated with lower anti-S levels (RR = 0.87, CI = 0.80-0.95). The serological response to vaccines is more inadequate in individuals with multimorbidity.

Concurrent sensitization to metals and occupation.

BACKGROUND: Cosensitization to nickel, cobalt and chromium occurs in the general population and in some occupational groups. OBJECTIVES: To estimate the isolated and concurrent occurrence of nickel, cobalt and chromium contact sensitization and their association with individual and occupational risk factors. PATIENTS/METHODS: Twelve thousand four hundred and ninety-two patients were patch tested with the European baseline series between 1997 and 2004 in north-eastern Italy. The associations between patch test results and patient characteristics and occupations were investigated by means of multinomial logistic regression analysis. RESULTS: Of the patients, 34.7% (4334 patients) had one or more positive patch test reactions to metals. As compared with those with negative reactions to all three metals, nickel sensitization was significantly higher in females than in males, not only as monosensitization, but also as cosensitization with cobalt, with chromium, or with both metals. Building and related trades workers showed positive reactions to chromium + nickel [odds ratio (OR) 1.99; 95% confidence interval (CI) 1.05-3.76) and chromium + cobalt (OR 2.61; 95% CI 1.46-4.67]. Cleaning workers showed a high prevalence of nickel, chromium, nickel + chromium and nickel + cobalt + chromium cosensitization (ORs 1.29, 1.66, 2.11, and 1.79, respectively). An excess risk for cosensitization to all three metals was found in textile and leather workers (OR 2.19; 95% CI 1.10-4.33), and in bartenders (OR 2.10; 95% CI 1.03-4.26). CONCLUSIONS: Some occupational groups are more likely to develop nickel, cobalt and chromium cosensitization.

Incidence of COVID-19 infection in hospital workers from March 1, 2020 to May 31, 2021 routinely tested, before and after vaccination with BNT162B2.

To evaluate the incidence of COVID-19 infection in health care workers from the start of the COVID-19 pandemic in NE Italy, vaccination with BNT162b2. This was a retrospective cohort study. Healthcare workers were routinely tested for SARS-CoV-2 infection using real-time polymerase chain reaction tests in nasopharyngeal swabs. Logistic regression was used to calculate the incidence rate ratios (IRRs) of the factors associated with COVID-19. A total of 4251 workers were followed up, and the prevalence of COVID-19 was 13.6%. In March 2021 the incidence of infection was 4.88 and 103.55 cases for 100,000 person-days in vaccinated and non-vaccinated workers, respectively, with an adjusted IRRs of 0.05 (95% CI 0.02-0.08). Our study evaluated the monthly incidence in health care workers in Trieste hospitals before and after vaccination, finding an estimated vaccine effectiveness of 95% in health care workers routinely tested.

Patch Test Positivity to Palladium: A 5-Year Retrospective Study in Triveneto Region, Italy.

BACKGROUND: The use of palladium (Pd) is increasing in metal objects after the banning of nickel in items in prolonged contact with the skin. The properties of Pd make this metal useful in various industrial fields. OBJECTIVE: The aim of the study was to evaluate the prevalence of Pd sensitization in patients who underwent patch tests for suspected allergic contact dermatitis in the Triveneto region from 2013 to 2018. METHODS: A total of 4816 patients with symptoms and/or signs of suspected contact allergic dermatitis were patch tested. Individual characteristics were assessed using a standardized questionnaire. RESULTS: The overall prevalence of Pd sensitization was 7.6% and 10.8% using PdCl2 1% or 2% petrolatum, respectively, with a higher prevalence in women (odds ratio, 2.6; 95% confidence interval, 1.9-3.7) and in 26- to 55-year-old patients. Monosensitization occurred in 1%-1.5% of the patients tested. Health care workers and technicians were more sensitized to Pd than clerks, but the data did not reach statistical significance. CONCLUSIONS: Palladium sensitization was high, but it was mainly associated with nickel sensitization. A possible occupational role was found for workers with potential contact with Pd-containing objects, but more data are needed to reach statistical significance.

COVID-19 susceptibility and vaccination coverage for measles, rubella and mumps in students and healthcare workers in Trieste hospitals (NE Italy).

BACKGROUND: Measles, mumps, and rubella (MMR) vaccines have been suggested as preventive measures to protect subjects from the worst sequelae of COVID-19 infection because neutralizing antibodies can cross-react with other viruses. AIM: To verify COVID-19 infection in MMR vaccinated and non-vaccinated healthcare workers and medical students in Trieste Hospitals. RESULTS: Nurse aids resulted in significantly more infections than structured physicians (OR 1.80; 95% CI 1.14-2.80) while students resulted in less infections (OR, 0.66; 95% CI 0.43-1.01). The presence of an MMR vaccination was inversely associated with COVID-19 (OR, 0.77; 95% CI 0.61-0.96) but only in univariate analysis. In the multivariable logistic regression analysis, MMR vaccination lost statistical significance (OR, 0.86; 95%CI 0.62-1.20).On 13 HCWs hospitalized for COVID-19, 11 resulted not vaccinated for MMR. DISCUSSION: Our study found a mild, non-significant reduction in SARS-CoV-2 infections in workers vaccinated with MMR.

Occupational Asthma: The Knowledge Needs for a Better Management.

The management of occupational asthma (OA) may be influenced by several factors and removal from exposure is the main tertiary prevention approach, but it is not always feasible without personal and socioeconomic consequences. Reducing the delay between the onset of suggestive symptoms of OA and the diagnosis of OA is associated with a better prognosis. Workers' education to increase awareness to trigger agents and a medical surveillance program directed especially at at-risk workers could be helpful in reducing this latency time. An early identification of workers who develop rhinitis and conjunctivitis which often precede the onset of asthma symptoms could be important for an early identification of OA. This is particularly important for cases of asthma caused by high-molecular-weight sensitizers and in the early years of employment. The availability of financial support and compensation measures for workers with OA may influence the latency time before diagnosis and, consequently, may influence the OA outcomes. In conclusion, there is a need for high-quality cohort studies that will increase knowledge about risk factor that may influence the timing of diagnosis of OA. This knowledge will be useful for implementation of future surveillance and screening programs in workplaces.

SARS-CoV-2 Breakthrough Infections: Incidence and Risk Factors in a Large European Multicentric Cohort of Health Workers.

BACKGROUND: The research aimed to investigate the incidence of SARS-CoV-2 breakthrough infections and their determinants in a large European cohort of more than 60,000 health workers. METHODS: A multicentric retrospective cohort study, involving 12 European centers, was carried out within the ORCHESTRA project, collecting data up to 18 November 2021 on fully vaccinated health workers. The cumulative incidence of SARS-CoV-2 breakthrough infections was investigated with its association with occupational and social-demographic characteristics (age, sex, job title, previous SARS-CoV-2 infection, antibody titer levels, and time from the vaccination course completion). RESULTS: Among 64,172 health workers from 12 European health centers, 797 breakthrough infections were observed (cumulative incidence of 1.2%). The primary analysis using individual data on 8 out of 12 centers showed that age and previous infection significantly modified breakthrough infection rates. In the meta-analysis of aggregated data from all centers, previous SARS-CoV-2 infection and the standardized antibody titer were inversely related to the risk of breakthrough infection (p = 0.008 and p = 0.007, respectively). CONCLUSION: The inverse correlation of antibody titer with the risk of breakthrough infection supports the evidence that vaccination plays a primary role in infection prevention, especially in health workers. Cellular immunity, previous clinical conditions, and vaccination timing should be further investigated.

Gene expression changes in peripheral blood mononuclear cells in occupational exposure to nickel.

Allergic contact dermatitis is preceded by a clinically silent phase of sensitisation. In this study, we investigated whether the expression levels of six genes were related to nickel exposure and/or nickel sensitisation, and whether they could predict allergic manifestations to nickel. 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, including healthy controls (n=51), nickel-exposed workers (n=23) and patients allergic to nickel (n=36). Our findings show 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. Changes in ETS2 and CASP8 expression are likely to be related to nickel exposure rather than to allergy.

Skin decontamination procedures against potential hazards substances exposure.

Decontamination of unprotected skin areas is crucial to prevent excessive penetration of chemical contaminants after criminal or accidental release. A review of literature studies was performed to identify the available decontamination methods adopted to treat skin contamination after chemical, radiological and metal exposures. In this bibliographic review, an overview of the old and recent works on decontamination procedures followed in case of potential hazards substances contaminations with a comparison between these systems are provided. Almost all data from our 95 selected studies conducted in vitro and in vivo revealed that a rapid skin decontamination process is the most efficient way to reduce the risk of intoxication. The commonly-used or recommended conventional procedures are simple rinsing with water only or soapy water. However, this approach has some limitations because an easy removal by flushing may not be sufficient to decontaminate all chemical deposited on the skin, and skin absorption can be enhanced by the wash-in effect. Other liquid solutions or systems as adsorbent powders, mobilizing agents, chelation therapy are also applied as decontaminants, but till nowadays does not exist a decontamination method which can be adopted in all situations. Therefore, there is an urgent need to develop more efficient and successful decontaminating formulations.

Nickel, cobalt and chromate sensitization and occupation.

BACKGROUND: Exposure to nickel, cobalt and chromate are important causes of occupational contact dermatitis. OBJECTIVES: To estimate the prevalence of nickel, cobalt and chromate allergy in a population of consecutive patients and to investigate the possible association with individual and occupational risk factors. PATIENTS/METHODS: A total of 14 464 patients (67.6% women and 32.4% men) with suspected allergic dermatitis underwent patch tests. The associations between patch test results and occupations were studied by multivariate logistic regression analysis. RESULTS: About 24.6% of the patients reacted positively to nickel sulphate, 10.2% to cobalt chloride and 8.7% to potassium dichromate. Nickel sensitization was higher in women aged 26-35 years in comparison with the youngest group (15-25 years) and the older group (> 45 years). In women, the prevalence of positive reactions to nickel 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). CONCLUSIONS: Our study showed interesting associations between some occupations and nickel, chromate and cobalt allergy.