2-Cyanoethyl dimethyldithiocarbamate, a new contact allergen found in accelerator-free nitrile gloves.

BACKGROUND: Allergic contact dermatitis (ACD) from rubber glove usage is usually caused by rubber additives such as the accelerators. However, in analyses of the suspected gloves, ordinary rubber allergens are not always found. Accelerator-free rubber gloves are available, but some patients with accelerator allergy do not tolerate them and might also be patch test positive to them. OBJECTIVES: To identify and chemically characterize a new allergen, 2-cyanoethyl dimethyldithiocarbamate (CEDMC), in rubber gloves. We describe two patient cases: patient 1 that led us to the identification of CEDMC and patient 2 with occupational ACD caused by CEDMC. METHODS: The patients were examined with patch testing including baseline and rubber series, and their own rubber gloves. High-performance liquid chromatography (HPLC) was used for chemical analysis of rubber gloves. The allergen was synthesized and identified by nuclear magnetic resonance, mass spectrometry and infrared spectrometry, and tested on patient 2. RESULTS: CEDMC was identified by HPLC in a nitrile glove associated with hand eczema in patient 1. Patient 2 whose nitrile gloves contained CEDMC was patch test positive to CEDMC. CONCLUSIONS: CEDMC is a new contact allergen in nitrile gloves and probably forms during vulcanization from residual monomer acrylonitrile and rubber additives.

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.

Occupational contact allergy: The European perspective-Analysis of patch test data from ESSCA between 2011 and 2020.

BACKGROUND: Occupational skin diseases have led the occupational disease statistics in Europe for many years. Especially occupational allergic contact dermatitis is associated with a poor prognosis and low healing rates leading to an enormous burden for the affected individual and for society. OBJECTIVES: To present the sensitization frequencies to the most relevant allergens of the European baseline series in patients with occupational contact dermatitis (OCD) and to compare sensitization profiles of different occupations. METHODS: The data of 16 022 patients considered having OCD after patch testing within the European Surveillance System on Contact Allergies (ESSCA) network between January 2011 and December 2020 were evaluated. Patients (n = 46 652) in whom an occupational causation was refuted served as comparison group. RESULTS: The highest percentages of OCD were found among patients working in agriculture, fishery and related workers, metal industry, chemical industry, followed by building and construction industry, health care, food and service industry. Sensitizations to rubber chemicals (thiurams, carbamates, benzothiazoles) and epoxy resins were associated with at least a doubled risk of OCD. After a decline from 2014 onwards, the risks to acquire an occupation-related sensitization to methyl(chloro)isothiazolinone (MCI/MI) and especially to methylisothiazolinone (MI) seem to increase again. Sensitization rates to formaldehyde were stable, and to methyldibromo glutaronitrile (MDBGN) slightly decreasing over time. CONCLUSIONS: Among allergens in the European Baseline Series, occupational relevance is most frequently attributed to rubber accelerators, epoxy resins and preservatives.

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.

Patch test results with the European baseline series, 2019/20-Joint European results of the ESSCA and the EBS working groups of the ESCD, and the GEIDAC.

BACKGROUND: Continual analyses of patch test results with the European baseline series (EBS) serve both contact allergy surveillance and auditing the value of included allergens. OBJECTIVES: To present results of current EBS patch testing, obtained in 53 departments in 13 European countries during 2019 and 2020. METHODS: Anonymised or pseudonymised individual data and partly aggregated data on demographic/clinical characteristics and patch test rest results with the EBS were prospectively collected and centrally pooled and analysed. RESULTS: In 2019 and 2020, 22 581 patients were patch tested with the EBS. Sensitization to nickel remained most common (19.8 [19.2-20.4]% positivity [95% confidence interval]). Fragrance mix I and Myroxylon pereirae yielded very similar results with 6.80 (6.43-7.19)% and 6.62 (6.25-7.00)% positivity, respectively. Formaldehyde at 2% aq. yielded almost one percentage point more positive reactions than 1% concentration (2.49 [2.16-2.85]% vs. 1.59 [1.33-1.88]); methylchloroisothiazolinone/methylisothiazolinone (MCI/MI) and MI alone up to around 5% positives. Among the new additions, propolis was most commonly positive (3.48 [3.16-3.82]%), followed by 2-hydroxyethyl methacrylate (2.32 [2.0-2.68]%). CONCLUSION: Ongoing surveillance on the prevalence of contact sensitization contributes to an up-to-date baseline series containing the most frequent and/or relevant contact sensitizers for routine patch testing in Europe.

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.

European patch test results with audit allergens as candidates for inclusion in the European Baseline Series, 2019/20: Joint results of the ESSCAA and the EBSB working groups of the ESCD, and the GEIDACC.

BACKGROUND: In 2019, a number of allergens (haptens), henceforth, "the audit allergens," were considered as potential additions to the European Baseline Series (EBS), namely, sodium metabisulfite, 2-bromo-2-nitropropane-1,3-diol, diazolidinyl urea, imidazolidinyl urea, Compositae mix II (2.5% or 5% pet), linalool hydroperoxides (lin-OOH), limonene hydroperoxides (lim-OOH), benzisothiazolinone (BIT), octylisothiazolinone (OIT), decyl glucoside, and lauryl glucoside; Evernia furfuracea (tree moss), was additionally tested by some departments as well. OBJECTIVES: To collect further data on patch test reactivity and clinical relevance of the audit allergens in consecutive patients across Europe. METHODS: Patch test data covering the audit allergens in 2019 and 2020 were collected by those departments of the European Surveillance System on Contact Allergies testing these, as well as further collaborators from the EBS working group of the European Society of Contact Dermatitis (ESCD), and the Spanish Grupo Español de Investigación en Dermatitis de Contacto y Alergia Cutánea. As patch test outcome, reactions between day (D) 3 and D5 were considered. RESULTS: Altogether n = 12 403 patients were tested with any of the audit allergen. Positive reactions were most common to lin-OOH 1% pet. (8.74% [95%CI: 8.14-9.37%]), followed by lin-OOH 0.5% pet., and lim-OOH 0.3% pet (5.41% [95% CI: 4.95-5.89%]). Beyond these terpene hydroperoxides, BIT 0.1% pet. was the second most common allergen with 4.72% (95% CI: 4.2-5.28%), followed by sodium metabisulfite 1% pet. (3.75% [95%CI: 3.32-4.23%]) and Compositae mix 5% pet. (2.31% [95% CI: 1.84-2.87%]). For some allergens, clinical relevance was frequently difficult to ascertain. CONCLUSIONS: Despite many positive patch test reactions, it remains controversial whether lin- and lim-OOH should be tested routinely, while at least the two preservatives BIT and sodium metabisulfite appear suitable. The present results are a basis for further discussion and ultimately decision on their implementation into routine testing among the ESCD members.

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.

European Surveillance System on Contact Allergies (ESSCA): Characteristics of patients patch tested and diagnosed with irritant contact dermatitis.

BACKGROUND: Irritant contact dermatitis (ICD) is caused by the acute locally toxic effect of a strong irritant, or the cumulative exposure to various weaker physical and/or chemical irritants. OBJECTIVES: To describe the characteristics of patients with ICD in the population patch tested in the European Surveillance System on Contact Allergies (ESSCA; www.essca-dc.org) database. METHODS: Data collected by the ESSCA in consecutively patch-tested patients from January 2009 to December 2018 were analyzed. RESULTS: Of the 68 072 patients, 8702 were diagnosed with ICD (without concomitant allergic contact dermatitis [ACD]). Hand and face were the most reported anatomical sites, and 45.7% of the ICD was occupational ICD (OICD). The highest proportions of OICD were found in metal turners, bakers, pastry cooks, and confectionery makers. Among patients diagnosed with ICD, 45% were found sensitized with no relevance for the current disease. CONCLUSIONS: The hands were mainly involved in OICD also in the subgroup of patients with contact dermatitis, in whom relevant contact sensitization had been ruled out, emphasizing the need for limiting irritant exposures. However, in difficult-to-treat contact dermatitis, unrecognized contact allergy, or unrecognized clinical relevance of identified allergies owing to incomplete or wrong product ingredient information must always be considered.

Formaldehyde 2% is not a useful means of detecting allergy to formaldehyde releasers- results of the ESSCA network, 2015-2018.

BACKGROUND: Studies suggest that patch testing with formaldehyde releasers (FRs) gives significant additional information to formaldehyde 1% aq. and should be considered for addition to the European baseline series (EBS). It is not known if this is also true for formaldehyde 2% aq. OBJECTIVES: To determine the frequency of sensitization to formaldehyde 2% aq. and co-reactivity with FRs. To establish whether there is justification for including FRs in the EBS. MATERIALS AND METHODS: A 4-year, multi-center retrospective analysis of patients with positive patch test reactions to formaldehyde 2% aq. and five FRs. RESULTS: A maximum of 15 067 patients were tested to formaldehyde 2% aq. and at least one FR. The percentage of isolated reactions to FR, without co-reactivity to, formaldehyde 2% aq. for each FR were: 46.8% for quarternium-15 1% pet.; 67.4% imidazolidinyl urea 2% pet.; 64% diazolidinyl urea 2% pet.; 83.3% 1,3-dimethylol-5, 5-dimethyl hydantoin (DMDM) hydantoin 2% pet. and 96.3% 2-bromo-2-nitropropane-1,3-diol 0.5% pet. This demonstrates that co-reactivity varies between FRs and formaldehyde, from being virtually non-existent in 2-bromo-2-nitropropane-1,3-diol 0.5% pet. (Cohen's kappa: 0, 95% confidence interval [CI] -0.02 to 0.02)], to only weak concordance for quaternium-15 [Cohen's kappa: 0.22, 95%CI 0.16 to 0.28)], where Cohen's kappa value of 1 would indicate full concordance. CONCLUSIONS: Formaldehyde 2% aq. is an inadequate screen for contact allergy to the formaldehyde releasers, which should be considered for inclusion in any series dependant on the frequency of reactions to and relevance of each individual allergen.

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.

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.

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.

Occupational buckwheat allergy as a cause of allergic rhinitis, asthma, contact urticaria and anaphylaxis-An emerging problem in food-handling occupations?

Buckwheat is a known, though uncommon, allergen in occupational settings. It has recently gained popularity as healthy food and as an ingredient in gluten-free diets. We describe a series of six patient cases with occupational immediate allergy to buckwheat. Three cooks, two bakers, and a worker in a grocery store were occupationally exposed to buckwheat flour and developed immediate allergy to buckwheat, which was confirmed by skin prick testing and measurement of specific immunoglobulin E antibodies. Four of the patients were diagnosed with occupational asthma, four with occupational rhinitis, and two with occupational contact urticaria caused by buckwheat. Three of the six patients suffered anaphylaxis as consequence of their occupational buckwheat allergy after ingestion of food that contained buckwheat. The high rate of life-threatening reactions, together with a short exposure time to buckwheat before sensitization occurred in these cases, highlights the importance of a detailed occupational history and a high index of suspicion for occupational food allergens.

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.