Contact allergy to rubber accelerators in consecutively patch tested Danish eczema patients: A retrospective observational study from 1990 to 2019.

BACKGROUND: Rubber accelerators are used in the production of rubber gloves and may cause contact allergy. OBJECTIVES: To estimate long-term trend and prevalence of contact allergy to rubber accelerators for a 30-year period in Denmark, high-risk occupations, and exposures. METHODS: Data from all patients with contact dermatitis consecutively patch tested at the department of Skin and Allergy Gentofte hospital with the rubber accelerators from the European baseline series (EBS) from 1990 to 2019, were analysed. Further, patients under suspicion of rubber accelerator contact allergy were additionally patch-tested with rubber accelerators from the specialised rubber series from 2005 to 2019 and these were additional extracted. RESULTS: The overall prevalence of contact allergy to one or more of the rubber accelerators from the EBS series was 2.7% with a significant decline in the first 12-years, followed by a stable frequency in the past 18-years. Associations with occupational contact dermatitis, hand dermatitis, and leg/foot dermatitis were found. Wet-work occupations were most often affected and gloves the most frequent exposure. CONCLUSIONS: Contact allergy to one or more of the rubber accelerators from the EBS is frequent and has been unchanged for several decades, which calls for prevention.

Isothiazolinones are still widely used in paints purchased in five European countries: a follow-up study.

BACKGROUND: An increasing incidence of contact allergy to methylisothiazolinone (MI) has been seen, caused, in particular, by cosmetic products and paints. A study from 2015 showed that 93.0% of paints bought in five European countries contained MI. New regulations have been discussed for paints in the EU, which may have influenced this market. OBJECTIVES: To re-evaluate the use and concentrations of MI and four other isothiazolinones in water-based wall paints. METHODS: Water-based white wall paints (n = 60) were purchased in retail stores in five European countries: Denmark, France, Germany, Sweden, and the United Kingdom. The paints were analysed for isothiazolione content by the use of high-performance liquid chromatography coupled to ultraviolet detection, and the results were confirmed with high-performance liquid chromatography-tandem mass spectrometry. RESULTS: MI was identified in 55 (91.7%) of the paints, with concentrations ranging from 1.1 to 142.7 ppm. The other isothiazolinones were identified in 20.0% [methylchloroisothiazolinone (MCI)] to 88.3% [benzisothiazolinone (BIT)] of the paints. BIT concentrations varied significantly between countries, whereas MI and MCI concentrations did not. There were no statistically significant differences in MI, MCI and BIT concentrations between the current study and the 2015 study. CONCLUSIONS: MI and other isothiazolinones are widely used in paints available in Europe. Their use does not seem to be decreasing.

The epidemic of methylisothiazolinone: a European prospective study.

BACKGROUND: The use of methylisothiazolinone (MI) in cosmetic products has caused an unprecedented epidemic of MI contact allergy. Current data concerning exposures at a European level are required. OBJECTIVES: To describe demographics and MI exposures for European patients with MI contact allergy. METHODS: Eleven European dermatology departments from eight European countries prospectively collected data between 1 May and 31 October 2015 among consecutive patients who had positive patch test reactions to MI (2000 ppm aq.). RESULTS: A total of 6.0% (205/3434; range 2.6-13.0%) of patients had positive patch test reactions to MI. Dermatitis most frequently affected the hands (43.4%), face (32.7%), arms (14.6%), and eyelids (11.7%); 12.7% had widespread dermatitis. For 72.7% (149/205), MI contact allergy was currently relevant mainly because of exposure to cosmetic products (83.2%; 124/149). Of these 124 patients, 19.5% were exposed to leave-on and rinse-off cosmetic products, 24.8% only to leave-on cosmetic products and 38.9% only to rinse-off cosmetic products containing MI or methylchloroisothiazolinone/MI. The majority of these (79%) noted onset of their dermatitis between 2013 and 2015. Fifteen patients (7.3%) had previously experienced allergic reactions when they were in newly painted rooms. CONCLUSION: Clinically relevant MI contact allergy remains prevalent across European countries, mainly because of exposure to rinse-off and leave-on cosmetic products.

Contact Allergy in Danish Healthcare Workers: A Retrospective Matched Case-control Study.

Contact dermatitis in healthcare workers is a world wide problem. We conducted a retrospective observational study of the patch-test results of 1402 healthcare workers and 1402 matched controls with contact dermatitis who were treated at 3 hospitals departments in Denmark between 2007 and 2014. The primary objective was to determine whether healthcare work was associated with contact allergy to thiuram mix. Unadjusted univariate analyses revealed that healthcare work was significantly associated with occupational contact dermatitis and hand dermatitis. Contact allergy to thiuram mix was more common in healthcare workers was significantly associated with having occupational contact dermatitis, hand dermatitis and older age. In conclusion, we report here a potential problem of contact allergy to thiurams in healthcare workers with contact dermatitis. Legislative authorities may in the future focus on the use of rubber accelerators in, for example, protective gloves, which are widely used by healthcare professionals.

Failures in risk assessment and risk management for cosmetic preservatives in Europe and the impact on public health.

BACKGROUND: In view of the current and unprecedented increase in contact allergy to methylisothiazolinone (MI), we characterized and evaluated two recent epidemics of contact allergy to preservatives used in cosmetic products to address failures in risk assessment and risk management. OBJECTIVE: To evaluate temporal trends of preservative contact allergy. METHODS: The study population included consecutive patch tested eczema patients seen at a university hospital between 1985 and 2013. A total of 23 138 patients were investigated for a contact allergy. RESULTS: The overall prevalence of contact allergy to at least one preservative increased significantly over the study period, from 6.7% in 1985 to 11.8% in 2013 (p < 0.001). Importantly, the preservatives methyldibromo glutaronitrile and MI rapidly resulted in high sensitization prevalence rates, which reached epidemic proportions. Although the proportion of patients with current clinical disease attributable to methyldibromo glutaronitrile contact allergy decreased significantly following the ban on its use in cosmetic products (p < 0.001), the sudden and high proportion of current sensitization to MI requires immediate attention (p < 0.001). CONCLUSIONS: The introduction of new preservatives in Europe with inadequate pre-market risk assessment has rapidly increased the overall burden of cutaneous disease caused by preservatives. We suggest that the cosmetic industry has a responsibility to react faster and replace troublesome preservatives when a preservative contact allergy epidemic is recognized, but the European Commission has the ultimate responsibility for failures in risk management after new, major sensitizing preservatives are introduced onto the market.

Methylisothiazolinone and benzisothiazolinone are widely used in paint: a multicentre study of paints from five European countries.

BACKGROUND: In view of the current epidemic of contact allergy to methylisothiazolinone (MI), it is important to clarify the extent of use of MI and related isothiazolinones in paints currently available for the consumer and worker in Europe. OBJECTIVES: To elucidate the use and concentrations of MI, methylchloroisothiazolinone (MCI) and benzisothiazolinone (BIT) in paints on the European retail market. METHODS: Wall paints (n = 71) were randomly purchased in retail outlets in five European countries. The paints were quantitatively analysed for their contents of MI, MCI and BIT by high-performance liquid chromatography coupled to tandem mass spectrometry. RESULTS: MI was found in 93.0% (n = 66) of the paints, with concentrations ranging from 0.7 to 180.9 ppm, MCI in 23.9% (n = 17), ranging from 0.26 to 11.4 ppm, and BIT in 95.8% (n = 68), ranging from 0.1 to 462.5 ppm. High concentrations of MI were found in paints from all five countries. Paints purchased in Denmark and Sweden contained especially high concentrations of BIT. CONCLUSION: The use of MI across European countries is extensive. In view of the ongoing epidemic of MI contact allergy, an evaluation of the safety of MI in paints is needed.

The combined diagnosis of allergic and irritant contact dermatitis in a retrospective cohort of 1000 consecutive patients with occupational contact dermatitis.

BACKGROUND: The diagnosis of combined allergic and irritant contact dermatitis is an accepted subdiagnosis for hand dermatitis, and it is often considered in a patient with contact dermatitis, a positive and relevant patch test result, and wet work exposure. We therefore hypothesize that it is arbitrary for wet work exposure to be taken into consideration in a patient with newly diagnosed relevant contact allergy. Furthermore, an overestimation of the diagnosis will probably occur if the criteria for wet work exposure are applied correctly, as many occupations have an element of wet work. OBJECTIVES: To find the statistically expected number of combined allergic and irritant contact dermatitis cases in 1000 patients, and to evaluate the diagnostic criteria for the diagnosis. METHODS: One thousand consecutive patients with occupational contact dermatitis from a hospital unit in Denmark were assessed. RESULTS: The expected number of cases with the diagnosis of combined allergic and irritant contact dermatitis was 0.33%, as compared with the observed number of 6.4%. Females occupied in wet occupations were often diagnosed with combined allergic and irritant contact dermatitis (p < 0.005). CONCLUSION: The diagnosis of combined allergic and irritant contact dermatitis should be used critically to avoid misclassification, and possible criteria for the diagnosis are proposed.

Occupations at risk of developing contact allergy to isothiazolinones in Danish contact dermatitis patients: results from a Danish multicentre study (2009-2012).

BACKGROUND: In recent years, the prevalence of contact allergy to isothiazolinones has reached epidemic levels. Few studies have presented data on occupations at risk of developing contact allergy to isothiazolinones. OBJECTIVES: To present demographics and examine risk factors for sensitization to methylisothiazolinone (MI), methylchloroisothiazolinone (MCI) in combination with MI and benzisothiazolinone (BIT) in Danish dermatitis patients. MATERIALS AND METHODS: A retrospective epidemiological analysis of data from three Danish hospitals departments was conducted. All patients consecutively patch tested with MI, MCI/MI and BIT between 2009 and 2013 were included. RESULTS: MI contact allergy showed a significantly increased trend in prevalence from 1.8% in 2009 to 4.2% in 2012 (p < 0.001). Females with facial dermatitis mainly drove the increase in 2012. Adjusted logistic regression analysis showed that MI sensitization was significantly associated with occupational exposures, hand and facial dermatitis, age > 40 years, and the occupational groups of tile setters/terrazzo workers, machine operators, and painters. MCI/MI contact allergy was significantly associated with the following high-risk occupations: painting, welding (blacksmiths), machine operating, and cosmetology. The occupational group of painting was frequent in the group of patients with BIT contact allergy. CONCLUSION: Several high-risk occupations for sensitization to isothiazolinones exist. Regulation on the allowed concentration of isothiazolinones, and especially MI, in both consumer products and industrial products is needed.

Occupational irritant contact dermatitis diagnosed by analysis of contact irritants and allergens in the work environment.

BACKGROUND: Irritant contact dermatitis (ICD) is a common diagnosis in patients with occupational contact dermatitis (OCD). Studies are lacking on the usefulness of material safety data sheets (MSDSs) in making the diagnosis of ICD. OBJECTIVE: To characterize irritant exposures leading to the diagnosis of occupational ICD (OICD), and to evaluate the occurrence of concomitant exposures to contact allergens. METHODS: We included 316 patients with suspected occupational hand dermatitis, referred to the Department of Dermato-Allergology, Copenhagen University Hospital Gentofte, Denmark during January 2010-August 2011, in a programme consisting of a clinical examination, exposure assessment, and extensive patch/prick testing. RESULTS: OCD was diagnosed in 228 patients. Of these patients, 118 were diagnosed with OICD. The main irritant exposures identified were wet work (n = 64), gloves (n = 45), mechanical traumas (n = 19), and oils (n = 15). Exposure to specific irritant chemicals was found in 9 patients, and was identified from MSDSs/ingredients labelling in 8 of these patients. Review of MSDSs and ingredients labelling showed that 41 patients were exposed to 41 moderate to potent contact allergens, and 18 patients were exposed to 25 weak workplace contact allergens. CONCLUSION: In the present study, the systematic exposure assessment did not reveal any new irritants. MSDSs have a limited role in the investigation of ICD.

Occupational contact dermatitis in blue-collar workers: results from a multicentre study from the Danish Contact Dermatitis Group (2003-2012).

BACKGROUND: Blue-collar workers have a high risk of occupational contact dermatitis, but epidemiological studies are scarce. OBJECTIVES: To investigate allergic contact dermatitis in blue-collar workers with dermatitis registered by the Danish Contact Dermatitis Group. METHODS: A retrospective analysis of patch test data from 1471 blue-collar workers and 1471 matched controls tested between 2003 and 2012 was performed. A logistic regression was used to test for associations. RESULTS: The blue-collar workers often had occupational hand dermatitis (p < 0.001). Atopic dermatitis was less commonly observed among blue-collar workers (19.6%) than among controls (23.9%) (p = 0.005). Allergens with a statistically significant association with the occupational group of blue-collar workers were epoxy resins, methyldibromo glutaronitrile, 2-bromo-2-nitro-1,3-propanediol, potassium dichromate, and methylchloroisothiazolinone (MCI)/methylisothiazolinone (MI). The following occupations were additionally identified as risk factors for contact sensitization to MCI/MI and MI, epoxy resins, and potassium dichromate, respectively: painting, construction work, and tile setting/terrazzo work. CONCLUSION: Contact allergy is a major problem among blue-collar workers. The data indicate a healthy worker effect among blue-collar workers diagnosed with dermatitis, as blue-collar workers were diagnosed significantly less often with atopic dermatitis than were controls.

Occupational contact dermatitis in hairdressers: an analysis of patch test data from the Danish contact dermatitis group, 2002-2011.

BACKGROUND: Occupational contact dermatitis among hairdressers is frequent, owing to daily exposure to irritants and allergens. OBJECTIVES: To identify sensitization to the most common allergens associated with the occupation of hairdressing. METHODS: Patch test results of 399 hairdressers and 1995 matched controls with contact dermatitis, registered by the Danish Contact Dermatitis Group between January 2002 and December 2011, were analysed. All patients were patch tested with the European baseline series, and hairdressers were additionally tested with the hairdressing series. RESULTS: Occupational contact dermatitis (p < 0.001) and hand eczema (p < 0.001) were observed significantly more often among hairdressers than among controls. Atopic dermatitis was less commonly observed among hairdressers (21.3%) than among controls (29.4%) (p < 0.01). Allergens from the European baseline series with a statistically significant association with the occupation of hairdressing were p-phenylenediamine, thiuram mix, and benzocaine. Frequent sensitizers from the hairdressing series were ammonium persulfate, toluene-2,5-diamine, 3-aminophenol, and 4-aminophenol. Cysteamine hydrochloride and chloroacetamide emerged as new sensitizers. CONCLUSIONS: These results indicate a healthy worker effect among hairdressers diagnosed with eczema. Ammonium persulfate and p-phenylenediamine remain frequent sensitizers in hairdressers with contact dermatitis. Cysteamine hydrochloride and chloroacetamide should be included in future surveillance studies.

Recent trends in epidemiology, sensitization and legal requirements of selected relevant contact allergens.

Numerous studies have focused on emerging allergens causing contact allergy and allergic contact dermatitis in eczema populations and the general population, whereas only a few European multicenter studies systematically manage to detect prevalence rates of various contact allergies over time in eczema populations. Contact allergy is a life-time condition, which may lead to allergic contact dermatitis in individuals who do not manage to avoid exposure to the ascertained allergen in question. It is therefore of utmost importance that clinicians and dermatologists have sufficient knowledge on common allergens causing contact allergies in the general and working population. This review aimed to highlight the newest knowledge of frequent allergens of clinical importance. Literature was sought from the Pubmed™ database, Google™ scholar and textbooks. On the basis of the literature within the last 5 years, a comprehensive review of methylisothiazolinone, chromium, cobalt, rubber accelerators and fragrance ingredients were conducted. Of each allergen we discuss in detail the temporal trend of prevalence, source of exposure, clinical manifestation of allergic contact dermatitis and legislative measurements on how to regulate the exposure.