Nine years of patch testing with isocyanates in a clinic of occupational dermatology.

BACKGROUND: Isocyanates are used as starting materials of polyurethane (PU) products. They are relatively important occupational skin sensitizers. OBJECTIVES: To analyse results of a large isocyanate patch test series of 19 isocyanate test substances and 4,4'-diaminodiphenylmethane (MDA), a marker of 4,4'-diphenylmethane diisocyanate (MDI) hypersensitivity. METHODS: Test files were screened for positive reactions in the isocyanate series. Patients with positive reactions were analysed for occupation, exposure and diagnosis. RESULTS: In 2010-2019, 53 patients had positive reactions in the series (16% of 338 patients tested). MDA, the well-established screening substance for MDI allergy, was positive in 30 patients, an in-house monomeric MDI test substance in 23 patients and 3 different polymeric MDI test substances in 19-21 patients. We diagnosed 16 cases of occupational allergic contact dermatitis (OACD) from MDI including 3 pipe reliners. Hexamethylene-1,6-diisocyanate (HDI) oligomers in paint hardeners caused 5 cases of OACD, more cases than 2,4-toluene diisocyanate (TDI; n = 3) and isophorone diisocyanate (IPDI; n = 1) put together. CONCLUSIONS: In contrast to previous studies, polymeric MDI test substances were not superior to a monomeric MDI. Pipe reliners may get sensitised not only by epoxy products and acrylates but also by MDI in hardeners of PU pipe coatings. HDI oligomers were the second most important causes of OACD after MDI.

Acrylates in artificial nails-Results of product analyses and glove penetration studies.

BACKGROUND: Artificial nail materials are mixtures that are prone to contain several sensitizing (meth)acrylates. It is not known whether the listing of (meth)acrylates is correct in these products' packages. Protective gloves suited for nail work are needed. OBJECTIVES: To analyse (meth)acrylates in gel nail and acrylic nail products chemically and to compare the results with the information in the product labels, and to study penetration of artificial nail materials through selected disposable gloves. METHODS: We analysed 31 gel nail products and 6 acrylic nail products for their (meth)acrylate content by gas chromatography-mass spectrometry (GC-MS). We tested the penetration of two nail products through three disposable gloves: nitrile rubber, neoprene rubber and polyvinyl chloride (PVC). RESULTS: Altogether 32/37 products contained (meth)acrylates. In all of them, there was discrepancy between the listed (meth)acrylates and those discovered in the analysis. The commonest (meth)acrylates were hydroxyethyl methacrylate (HEMA, 20/37 samples) and hydroxypropyl methacrylate (HPMA, 9/37 samples), but many of the product packages failed to declare them. Isobornyl acrylate (IBA) was discovered in nine gel nail products. The neoprene glove could withstand nail gel for 20 min and thin nitrile glove and PVC glove for 5 min. Acrylic nail liquid penetrated through disposable gloves quickly. CONCLUSIONS: Labelling of artificial nail products was notably incorrect on most products. Requirements for product labelling must be updated so that the risk of sensitization associated with artificial nail products is clearly indicated. Disposable gloves can probably be used short-term in gel nail work, whereas disposable gloves do not protect the user from acrylic nail liquids.

The additive value of patch testing non-commercial test substances and patients' own products in a clinic of occupational dermatology.

BACKGROUND: Commercial patch test substances do not cover all occupational contact allergens. Workplace materials and in-house test substances are tested to complement the investigation of occupational skin disease (OSD). OBJECTIVES: To quantify the additional value of testing workplace materials and non-commercial in-house test substances in the diagnosis of OSD. MATERIALS AND METHODS: Patients files of 544 patients patch tested at the Finnish Institute of Occupational Health in 2015-2019 were reviewed for occupation, diagnoses and patch test results. RESULTS: OSD was diagnosed in 353 (64.9%) of the patients. A total of 206 (37.9%) patients had occupational allergic contact dermatitis (OACD). In 19 (3.5%) patients, the only clues to the diagnoses of OACD were positive reactions to workplace materials, and in 20 (3.7%) patients, the diagnosis of OACD was based on commercially unavailable test substances. In 167 OACD cases diagnosed by commercial test substances, additional causes were found in 17 by testing patients' own and non-commercial test substances. In 43 (7.9%) cases, positive reactions to workplace materials reinforced diagnoses based on commercial test substances. The overall additive value of testing own products was 16.7% (91 cases). CONCLUSION: We would have missed 39 (18.9%) of our 206 OACD cases if we had solely used commercial test substances.

Characterization of patients with occupational allergy to two new epoxy hardener compounds.

BACKGROUND: The practical importance of two recently described epoxy hardener allergens-1,3-benzenedimethanamine, N-(2-phenylethyl) derivatives (1,3-BDMA-D) and hydrogenated formaldehyde benzenamine polymer (FBAP)-as occupational allergens remains to be defined. OBJECTIVES: To describe patients diagnosed at the Finnish Institute of Occupational Health (FIOH) with positive reactions to 1,3-BDMA-D or FBAP. METHODS: We searched FIOH's patch-test files from January 2017 to December 2020 for patients examined due to suspected occupational contact allergy to epoxy compounds. We analyzed the patch-test results and sources of exposure to various epoxy hardeners and focused on occupations, symptoms, and the sources of exposure to 1,3-BDMA-D and FBAP. RESULTS: During the study period, 102 patients were examined at FIOH for suspected occupational contact allergy to epoxy compounds. Of these, 19 (19%) were diagnosed with contact allergy to 1,3-BDMA-D (n = 10) or FBAP (n = 12). The largest occupational group was sewage pipe reliners (n = 8). Seven different hardener products contained FBAP, whereas 1,3-BDMA-D was present in only one hardener used by spray painters. CONCLUSIONS: A substantial number of patients with suspected occupational epoxy resin system allergy tested positive to in-house test substances of 1,3-BDMA-D and/or FBAP.

Patterns of positive patch test reactions to formaldehyde and formaldehyde releasers at the Finnish Institute of Occupational Health from 2007 to 2020.

BACKGROUND: Formaldehyde is an important contact sensitizer. Formaldehyde releasing substances induce positive reactions in formaldehyde-allergic patients, but there are also reactions independent of formaldehyde allergy. In an earlier study, stronger formaldehyde reactions led to more positive reactions to quaternium-15. OBJECTIVES: To analyze patterns of positive patch test reactions to formaldehyde and different formaldehyde releasers. METHODS: Patch test files of 1497 patients investigated during the period November 2007-August 2020 were retrospectively reviewed for positive reactions to formaldehyde and its releasers. During the study period, almost all (≥99.3%) patients were tested with a formaldehyde dilution series and six formaldehyde releasers. RESULTS: Ninety-three patients tested positive to formaldehyde; 80% of these had positive reactions to at least one formaldehyde releaser, most often benzylhemiformal. There were only nine independent contact allergies to formaldehyde releasers. There were only two reactions to 2-bromo-2-nitropropane-1,3-diol and they occurred in formaldehyde-negative patients. In patients with extreme (+++) reactions to formaldehyde, concomitant positive reactions to any of the other 11 investigated formaldehyde releasers were more common than in patients with milder formaldehyde reactions. CONCLUSIONS: Strong formaldehyde reactions were associated with positive reactions to formaldehyde releasers.

Allergic contact dermatitis and other occupational skin diseases in health care workers in the Finnish Register of Occupational Diseases in 2005-2016.

BACKGROUND: Health care workers are an important risk group for occupational skin disease (OSD). AIMS: To study diagnoses and causes of OSDs in health care workers in the Finnish Register of Occupational Diseases (FROD) in 2005-2016. METHODS: We searched the FROD for dermatological cases (a) in health care-related occupations defined by ISCO-08 and (b) in the industrial branch of health care defined by European industry standard classification system (NACE rev. 2). RESULTS: Health care workers comprised 19% of all OSD cases in the FROD, and irritant contact dermatitis dominated the diagnoses. Nurses and assistant nurses were the largest occupational groups with incidence rates of 3.3 and 2.7/10 000 person years, respectively. Rubber chemicals were by far the most common causative agents of allergic contact dermatitis (ACD) followed by preservatives, the latter mainly comprising isothiazolinones and formaldehyde. Acrylates were important allergens in dental professions. Metals and coconut fatty acid derivatives were the next largest causative groups for ACD. Drugs caused only 1% of the ACD cases. CONCLUSIONS: Workers in different health care occupations do not have a uniform risk for OSD, but they share the risk for ACD due to rubber chemicals and various preservatives.

Ten years of contact allergy from acrylic compounds in an occupational dermatology clinic.

BACKGROUND: Contact allergy from acrylic compounds is a "hot topic". Knowledge on the exact chemical composition of acrylic products is superficial. AIMS: To retrospectively describe patients with allergic reactions to acrylic compounds. METHODS: We included patients who had been tested with acrylate patch test series and displayed allergic reactions to at least one acrylic compound. Chemical analyses were often performed when safety data sheets of implicated products failed to reveal acrylic compounds to which the patient tested positive. RESULTS: In 2010-2019 a total of 55 patients met the inclusion criteria. Eight cases of allergic contact dermatitis were due to anaerobic sealants, seven to dental products, three to windscreen glues, seven to eyelash glues and/or nail products in the beauty sector, three to UV-cured printing inks, two to paints/lacquers, and one to polyester resin system. The origin of these contact allergies was occupational with the exception of four beauty sector workers who had developed eyelid symptoms from eyelash extensions glued onto their own eyelashes. We invariably detected methacrylate monomers in 15 chemical analyses of 12 different anaerobic sealants. CONCLUSIONS: Safety data sheets of anaerobic sealants often lack warnings for skin sensitization, although these products regularly contain sensitizing methacrylates.

Hairdressers' occupational skin diseases in the Finnish Register of Occupational Diseases in a period of 14 years.

BACKGROUND: Hairdressers have a high risk of occupational contact dermatitis caused by exposure to wet work and allergens in hairdressing chemicals. OBJECTIVES: To examine the distribution of diagnoses of occupational skin diseases (OSDs) and their main causes in hairdressers based on a national register data on occupational diseases. METHODS: We retrieved cases of recognized OSDs in hairdressers from the Finnish Register of Occupational Diseases (FROD) in years 2005-2018. RESULTS: During the 14-year period, a total of 290 cases of recognized OSD in hairdressers were registered in the FROD. Allergic contact dermatitis (ACD) was diagnosed in 54%, irritant contact dermatitis in 44%, and contact urticaria (CU) in 5% of them. ACD was most commonly caused by hair dye products and their ingredients (N = 57), persulfates (N = 35), and preservatives (N = 35; mainly isothiazolinones). Acrylates emerged as hairdressers' occupational contact allergens (N = 8) probably due to introduction of structure nails into hair salons. Persulfates was the most common cause of CU. CONCLUSIONS: ACD was the most common OSD in hairdressers. Our analysis confirms that preservatives are important causes of ACD in hairdressers in addition to hair dye products and persulfates. Acrylates emerged as hairdressers' occupational contact allergens, but contact allergy to perming agents remained rare.

Machine-learning-driven biomarker discovery for the discrimination between allergic and irritant contact dermatitis.

Contact dermatitis tremendously impacts the quality of life of suffering patients. Currently, diagnostic regimes rely on allergy testing, exposure specification, and follow-up visits; however, distinguishing the clinical phenotype of irritant and allergic contact dermatitis remains challenging. Employing integrative transcriptomic analysis and machine-learning approaches, we aimed to decipher disease-related signature genes to find suitable sets of biomarkers. A total of 89 positive patch-test reaction biopsies against four contact allergens and two irritants were analyzed via microarray. Coexpression network analysis and Random Forest classification were used to discover potential biomarkers and selected biomarker models were validated in an independent patient group. Differential gene-expression analysis identified major gene-expression changes depending on the stimulus. Random Forest classification identified CD47, BATF, FASLG, RGS16, SYNPO, SELE, PTPN7, WARS, PRC1, EXO1, RRM2, PBK, RAD54L, KIFC1, SPC25, PKMYT, HISTH1A, TPX2, DLGAP5, TPX2, CH25H, and IL37 as potential biomarkers to distinguish allergic and irritant contact dermatitis in human skin. Validation experiments and prediction performances on external testing datasets demonstrated potential applicability of the identified biomarker models in the clinic. Capitalizing on this knowledge, novel diagnostic tools can be developed to guide clinical diagnosis of contact allergies.

Construction workers' skin disorders in the Finnish Register of Occupational Diseases 2005-2016.

BACKGROUND: Construction workers are a known risk group for occupational skin disease (OSD). OBJECTIVES: To study diagnoses and causes of OSD in construction workers in the Finnish Register of Occupational Diseases (FROD) 2005-2016. MATERIALS AND METHODS: We searched the FROD for dermatological cases in (a) construction-related occupations defined by the International Standard Classification of Occupations (ISCO-08) and (b) in the industrial branch of construction defined by the Statistical Classification of Economic Activities in the European Community (NACE Rev. 2). RESULTS: The two searches yielded the same number of cases, 329, although they were not identical subgroups. The number of allergic contact dermatitis (ACD) cases was 235 (71%) in construction-related occupations and 228 (69%) in the industrial branch of construction. In the latter analysis, synthetic resin systems caused 66% of ACD cases and 46% of all OSDs, epoxy compounds being the leading cause (122 cases; 54% of ACD cases; 37% of all OSDs). Metals were the second most common group of causes of ACD with 31 cases (chrome 22 cases; cobalt 8 cases). Isothiazolinones caused ACD in 21 cases, many of whom were painters. CONCLUSIONS: ACD dominated the OSDs of construction workers and epoxy products were by far the leading cause comprising 37% of all OSDs. Chrome and isothiazolinones were also prominent causes of ACD.

Contact urticaria and protein contact dermatitis in the Finnish Register of Occupational Diseases in a period of 12 years.

BACKGROUND: Although occupational contact urticaria (CU) and protein contact dermatitis (PCD) are considered frequent among workers with exposure to proteinaceous materials, data on occupations at risk and the main causes of these occupational skin diseases are relatively limited. OBJECTIVES: To report the causative agents and risk occupations for CU and PCD in the Finnish Register of Occupational Diseases (FROD). METHODS: We retrieved from the FROD all recognized cases of CU/PCD in the years 2005-2016. RESULTS: With 570 cases, CU and PCD constituted 11% of all recognized cases of occupational skin diseases in the study period. Occupations with the highest incidence of CU/PCD included bakers, chefs and cooks, farmers and farm workers, veterinarians, gardeners, and hairdressers. The most common causative agents were cow dander and flour and grain, followed by natural rubber latex (NRL) and other food. In food-related occupations, wheat and other flours were by far the most common cause of CU/PCD, with 76 cases, whereas fish and other animal-derived food caused 33 and other plant-derived food caused 23 cases. CONCLUSIONS: Apart from the Finnish peculiarity of cow dander allergy, a striking finding was a large share of CU/PCD caused by flours in food handlers as compared to other food.

12-year data on skin diseases in the Finnish Register of Occupational Diseases II: Risk occupations with special reference to allergic contact dermatitis.

BACKGROUND: Detailed epidemiological studies on occupational skin diseases (OSDs) are scarce. OBJECTIVES: To analyze risk occupations for OSDs in the Finnish Register of Occupational Diseases (FROD). METHODS: We retrieved numbers of OSD cases (excluding skin infections) for different occupations from the FROD in 2005-2016. In the FROD, Finnish ISCO-08-based classification of occupations was used since 2011, and the preceding ISCO-88-based version until 2010. We combined cases from the earlier and the later period using conversion tables provided by Statistics Finland. We included occupations with at least five cases and analyzed them in detail. We calculated incidence rates for OSDs and separately for allergic contact dermatitis (ACD) in different risk occupations using national labor force statistics. We also studied causes of ACD in these occupations. RESULTS: Risk occupations with the largest number of OSD cases included farmers, hairdressers, assistant nurses, cooks, cleaners, machinists, and nurses. Occupations with the highest incidences of OSDs comprised spray painters (23.8/10 000 person years), bakers (20.4), and dental technicians (19.0). Epoxy compounds and acrylates were prominent causes of ACD in occupations with the highest incidences of ACD. CONCLUSIONS: Uniform use of International Standard Classification of Occupations (ISCO) would facilitate comparisons of OSD figures in different countries.

12-year data on dermatologic cases in the Finnish Register of Occupational Diseases I: Distribution of different diagnoses and main causes of allergic contact dermatitis.

BACKGROUND: Skin diseases are among the most common occupational diseases, but detailed analyses on their epidemiology, diagnoses, and causes are relatively scarce. OBJECTIVES: To analyze data on skin disease in the Finnish Register of Occupational Diseases (FROD) for (1) different diagnoses and (2) main causes of allergic contact dermatitis (ACD). METHODS: We retrieved data on recognized cases with occupational skin disease (OSD) in the FROD from a 12-year-period 2005-2016 and used national official labor force data of the year 2012. RESULTS: We analyzed a total of 5265 cases, of which 42% had irritant contact dermatitis (ICD), 35% ACD, 11% contact urticaria/protein contact dermatitis (CU/PCD), and 9% skin infections. The incidence rate of OSD in the total labor force was 18.8 cases/100 000 person years. Skin infections concerned mainly scabies in health care personnel. Twenty-nine per cent of the ACD cases were caused by plastics/resins-related allergens, mainly epoxy chemicals. Other important causes for ACD were rubber, preservatives, metals, acrylates, and hairdressing chemicals. Cases of occupational ACD due to isothiazolinones reached a peak in 2014. CONCLUSION: Our analysis confirms that epoxy products are gaining importance as causes of OSD and the isothiazolinone contact allergy epidemic has started to wane.

A survey of members of the European Surveillance System on Contact Allergy and the EU project "StanDerm" to identify allergens tested in cosmetic series across Europe.

BACKGROUND: There is currently no agreed cosmetic series for use across Europe. OBJECTIVES: To establish allergens currently tested in local and national cosmetic series. METHOD: Members of the European Surveillance System on Contact Allergy and the European Cooperation in Science and Technology project TD1206 ("StanDerm") were surveyed to establish their current practice. RESULTS: A wide range of allergens was tested but there was significant variation between centres on the allergens considered to be important in screening for allergy to cosmetics. The number of allergens tested in addition to the baseline series varied between 2 and 50. CONCLUSIONS: There is a need for further investigation to establish the frequency and relevance of reactions to cosmetic allergens to enable an agreed evidence-based cosmetic series to be produced. Criteria for inclusion need to be established.

Allergic reactions to lower concentrations of nickel sulfate and formaldehyde often appear later than reactions to higher concentrations.

BACKGROUND: A late-appearing patch test reaction may be a sign of active sensitization or represent a delayed elicitation reaction. OBJECTIVES: To retrospectively study the effect of concentration on the time course of allergic reactions to routine concentration dilution series of formaldehyde and nickel sulfate. METHODS: We tested concentration dilution series of 2%, 1%, 0.32% and 0.1% formaldehyde and 5%, 1.6%, 0.5% and 0.16% nickel sulfate, respectively. The last readings were performed on day 4 to day 6. We included patients with allergic reactions to either of the two lowest concentrations in each dilution series and whose tests had been read three times. RESULTS: Forty-two nickel-allergic and 23 formaldehyde-allergic patients fulfilled the inclusion criteria. In 26 (62%) of the nickel-sensitive patients, reactions to lower concentrations appeared later than reactions to the highest concentration. Of the formaldehyde-sensitive patients, 17 (74%) developed one or two allergic reactions to lower concentrations later than reactions to the highest concentration, and one (4%) patient developed allergic reactions to lower concentrations sooner than a reaction to the highest concentration. The remaining patients showed all allergic reactions at the same reading. CONCLUSIONS: In these selected, relatively strongly sensitized patients, allergic reactions to lower concentrations quite regularly appeared later than reactions to higher concentrations.

Occupational allergic contact dermatitis caused by colophonium.

BACKGROUND: Colophonium is a common contact allergen that is present not only in household products but also in occupational settings. OBJECTIVES: To describe the sources of occupational exposure to colophonium and the occupations at risk of colophonium allergy. METHODS: We reviewed patch test files from the years 2002 to 2017 at the Finnish Institute of Occupational Health for patients with allergic reactions to colophonium and abietic acid. We analysed the patch test, occupation and exposure data of 39 patients diagnosed with occupational allergic contact dermatitis (OACD) caused by colophonium. RESULTS: Of the patients examined for suspected occupational dermatitis, 4.6% (n = 118) reacted positively to colophonium. The majority of the OACD patients worked in the wood industry, as machinists, or were involved in soldering or agriculture. The most common occupational sources of exposure were coniferous wood and wood-derived materials, followed by glues, metalworking fluids, and soldering materials. Colophonium is not always mentioned in safety data sheets (SDSs), and the sources of colophonium exposure are often materials for which there are no SDSs. CONCLUSION: OACD caused by colophonium is quite common and occurs in a variety of occupations. SDSs provide poor information for exposure assessment. Patch testing with the patient's own materials was often useful in establishing the diagnosis.

Skin exposure to epoxy chemicals in construction coating, assessed by observation, interviews, and measurements.

BACKGROUND: Epoxy resin systems (ERSs) are among the leading causes of occupational allergic contact dermatitis. OBJECTIVES: To identify riskful exposures and sources of skin exposure, and to quantify skin exposure to diglycidyl ether of bisphenol A (DGEBA) epoxy monomer, in construction coating work. METHODS: Skin exposure to epoxy chemicals was studied in 5 coating companies through (a) interviews and visual observation, (b) quantifying DGEBA on 12 workers' skin by tape-stripping, (c) measuring DGEBA on 23 surfaces by wipe-sampling, and (d) quantifying DGEBA in new sewage pipe. Acetone extracts of the tapes, wipes and sawdust from a newly hardened sewage pipe were analysed by gas chromatography/mass spectrometry. RESULTS: Identified riskful exposures were, for example, mixing ERSs, handling coating pots, and working above shoulder level. Epoxy stains on, for example, tools, equipment and clothing were seen in all workplaces. Protective gloves were of varying quality, and were not always suitable for chemicals. The amount of DGEBA on the workers' skin varied considerably. All screened tool handles were contaminated. Two-day-old epoxy sewage pipe contained 3.2% DGEBA. CONCLUSIONS: Construction coating entails skin contact with ERSs directly and via contaminated surfaces, personal protective equipment, and recently hardened epoxy materials. Observation is a useful method for assessing skin exposure in coating work.