Subclinical immune responses to nickel in sensitized individuals-a dose-response study.

BACKGROUND: Nickel is the leading cause of contact allergy in Europe, with 14.5% of the adult population being sensitized. Despite regulations limiting nickel release from consumer items, the incidence and prevalence of nickel allergy remain high. OBJECTIVE: To investigate the clinical and subclinical immune response to low-dose nickel exposure on nickel pre-exposed skin to assess the adequacy of current regulatory limits. METHOD: Nickel-allergic and healthy controls were patch tested with nickel twice with a 3-4 weeks interval. The first exposure used the diagnostic concentration of 2000 µg/cm2 nickel sulphate, and the same skin areas were then re-exposed to 0.2, 0.5, 12.8 and 370 µg/cm2 nickel sulphate. After 48 h, the patch reactions were examined for clinical signs of eczema, and skin biopsies were collected. The transcriptomic immune profile was analysed with Nanostring nCounter and quantitative polymerase chain reaction. RESULTS: Two nickel-allergic participants (15%) had clinical reactions to the regulatory limiting doses for nickel (0.2/0.5 µg/cm2) following re-exposure. There was immune activation in all skin areas following re-exposure to nickel, predominantly mediated by up-regulation of cytokines and chemokines. In all nickel re-exposed skin areas, 81 genes were up-regulated independent from the clinical response. In skin areas exposed to 0.2 µg/cm2, 101 immune-related genes were differentially expressed, even when no clinical response was observed. Healthy controls showed up-regulation of three genes in response to nickel re-exposures without any clinical reactions. CONCLUSION: Immune activation can be induced in skin with local memory to nickel upon challenge with nickel doses within the regulatory limits. Our findings suggest that the regulatory limits in the European nickel regulation may not provide sufficient protection for consumers against low-dose exposures.

Regulation of immune response genes in the skin of allergic and clinically tolerant individuals exposed to p-phenylenediamine.

BACKGROUND: p-Phenylenediamine (PPD) is a potent contact allergen found in many hair colour products. However, not all individuals develop allergic contact dermatitis (ACD) although they are regularly exposed to PPD. It is unclear whether these asymptomatic individuals are true non-responders to PPD or whether they mount a response to PPD without showing any symptoms. METHODS: Skin biopsies were collected from 11 asymptomatic hairdressers regularly exposed to PPD and from 10 individuals with known ACD on day 4 after patch testing with 1% PPD in petrolatum and petrolatum exclusively as control. RNA sequencing and confocal microscopy were performed. RESULTS: T cell activation, inflammation and apoptosis pathways were up-regulated by PPD in both asymptomatic and allergic individuals. Compared to asymptomatic individuals with a negative patch test, individuals with a strong reaction to PPD strongly up-regulated both pro- and anti-inflammatory cytokines genes. Interestingly, PPD treatment induced significant up-regulation of several genes for chemokines, classical type 2 dendritic cell markers and regulatory T cell markers in both asymptomatic and allergic individuals. In addition, apoptosis signalling pathway was activated in both non-responders and allergic individuals. CONCLUSION: This study demonstrates that there are no true non-responders to PPD but that the immune response elicited by PPD differs between individuals and can lead to either tolerance, subclinical inflammation or allergy.

Impact of atopic dermatitis on occupational contact dermatitis among young people: A retrospective cohort study.

BACKGROUND: Occupational contact dermatitis (OCD) is a common occupational disease. Atopic dermatitis (AD) is a known risk factor for OCD. OBJECTIVES: To determine the prevalence of previously diagnosed AD among young workers with recognized OCD and assess its impact on OCD prognosis. METHODS: A retrospective cohort study. A questionnaire was sent to 6251 workers with recognized OCD who were under 35 years at notification (response rate: 47%). Of the respondents, 2392 answered a question about previous doctor-diagnosed AD and were included in the study. Eczema severity, occupational consequences and quality of life were examined using statistical analyses comparing workers with and without previously diagnosed AD. RESULTS: The prevalence of previously diagnosed AD was 41.8% (95% CI: 39.8-43.8). Women had a higher AD prevalence, and workers with AD reported OCD at a younger age. Workers with AD reported more frequent and severe eczema symptoms and had a higher risk of OCD negatively affecting job and occupation choices. Health-related quality of life was more adversely affected in workers with AD. CONCLUSIONS: AD significantly impacts severity and has long-term consequences for young people with OCD. Targeted prevention strategies need to be developed.

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.

Assessing the efficacy of a German-inspired intervention on occupational contact dermatitis in Denmark: A randomised controlled trial with 3-month follow-up.

BACKGROUND: Occupational contact dermatitis (OCD) is a prevalent, often chronic disease that poses a risk for job loss and decreased quality of life. In Germany, a multi-step prevention programme emphasising early detection and highly specialised multidisciplinary treatment has been implemented with great success. OBJECTIVES: To examine the effectiveness of a Danish-adapted version of the German prevention effort on OCD severity, quality of life and occupational consequences at 3-month follow-up. METHODS: Randomised, controlled trial. Participants were recruited after the first referral from General Practitioner to Dermatologist with suspected OCD. The intervention group (IG) received a Danish-adapted, multidisciplinary intervention, while the control group (CG) navigated the Danish healthcare system without interference from the study. OCD severity, occupational consequences and quality of life were assessed at 3-month follow-up using self-reported questionnaires. RESULTS: A statistically significant decrease in the severity of eczema was found at 3-month follow-up in the IG compared to the CG. The IG were statistically significantly more likely to have seen a dermatologist at 3-month follow-up. Higher treatment level in the IG was indicated by the results but was not statistically significant. No significant difference was found in quality of life or occupational consequences. CONCLUSIONS: These initial findings suggest that early and specialised treatment of OCD improves OCD prognosis.

Diagnostics and Prevention of Occupational Allergy in Hairdressers.

PURPOSE OF REVIEW: This study aims to provide an overview on current knowledge on occupational allergic diseases in hairdressers and up-to-date perspectives of prevention. RECENT FINDINGS: Hand eczema (dermatitis) is common in hairdressers, often caused by contact allergy to one or multiple small molecules (haptens) used, e.g., for dyeing, bleaching, and waving/relaxing or by ancillary substances such as preservatives. Hairdressers, compared to other patch-tested patients, have an up to fivefold increased risk to be found sensitized, e.g., against p-phenylenediamine, ammonium persulfate, and glyceryl thioglycolate. Some of these small molecules may induce respiratory sensitization causing allergic rhinitis and/or asthma, notably persulfate salts. Occupational hazards in hairdressing are well described. This knowledge needs to be put into use for risk reduction, mainly by substitution of allergenic ingredients by less allergenic ones, education, and use of ventilation and suitable single-use gloves.

Circulating biomarkers are associated with disease severity of chronic hand eczema and atopic dermatitis.

BACKGROUND: Although chronic hand eczema (CHE) is a highly prevalent and disabling skin disease, it is currently unknown if CHE is associated with systemic inflammation. OBJECTIVES: To characterize the plasma inflammatory signature of CHE. METHODS: Using Proximity Extension Assay technology, we assessed 266 inflammatory and cardiovascular disease risk proteins in the plasma of 40 healthy controls, 57 patients with atopic dermatitis (AD) with active lesions, 11 with CHE and a history of AD (CHEPREVIOUS_AD), and 40 with CHE and no history of AD (CHENO_AD). Filaggrin gene mutation status was also assessed. Protein expression was compared between groups and according to disease severity. Correlation analyses for biomarkers, and clinical- and self-reported variables, were performed. RESULTS: Very severe CHENO_AD was associated with systemic inflammation when compared with controls. Levels of T helper (Th)2- and Th1-, general inflammation and eosinophil activation markers increased with severity of CHENO_AD, primarily being significantly increased in very severe disease. Significant, positive correlations were found between markers from these pathways and severity of CHENO_AD. Moderate-to-severe but not mild AD displayed systemic inflammation. The Th2 markers C-C motif chemokine (CCL)17 and CCL13 (also known as monocyte chemotactic protein 4) were the top differentially expressed proteins in both very severe CHENO_AD and moderate-to-severe AD, showing a higher fold change and significance in AD. CCL17 and CCL13 levels further correlated positively with disease severity in both CHENO_AD and AD. CONCLUSIONS: Systemic Th2-driven inflammation is shared between very severe CHE with no history of AD, and moderate-to-severe AD, suggesting that Th2 cell targeting could be effective in several CHE subtypes.

Genotoxicity of oxidative hair dye precursors: A systematic review.

This systematic review, conducted according to the PRISMA guidelines, focuses on genotoxicity of oxidative hair dye precursors. The search for original papers published from 2000 to 2021 was performed in Medline, Web of Science, Cochrane registry, Scientific Committee on Consumer Safety of the European Commission and German MAK Commission opinions. Nine publications on genotoxicity of p-phenylenediamine (PPD) and toluene-2,5-diamine (p-toluylenediamine; PTD) were included, reporting results of 17 assays covering main genotoxicity endpoints. PPD and PTD were positive in bacterial mutation in vitro assay, and PPD tested positive also for somatic cell mutations in the Rodent Pig-a assay in vivo. Clastogenicity of PPD and PTD was revealed by in vitro chromosomal aberration assay. The alkaline comet assay in vitro showed DNA damage after PPD exposure, which was not confirmed in vivo, where PTD exhibited positive results. PPD induced micronucleus formation in vitro, and increased micronucleus frequencies in mice erythrocytes following high dose oral exposure in vivo. Based on the results of a limited number of data from the classical genotoxicity assay battery, this systematic review indicates genotoxic potential of hair dye precursors PPD and PTD, which may present an important health concern for consumers and in particular for professional hairdressers.

The Proteome of Hand Eczema Assessed by Tape Stripping.

Hand eczema (HE) is a prevalent skin disease. However, the classification of HE into different subtypes remains challenging. A limited number of previous studies have employed invasive biopsy-based strategies; yet, studies of the HE proteome using noninvasive tape-stripping methodology have not been reported. In this study, we wanted to assess whether global proteomic analysis of skin tape strip samples can be used for subclassification of patients with HE. Tape strips were collected from patients with HE and healthy skin. Liquid chromatography-mass spectrometry proteomics was performed, and the global protein expression was analyzed. We identified 2,919 proteins in stratum corneum-derived skin cells from tape strip samples. Compared with healthy skin, the lesional samples from patients with HE exhibited increased expression of immune-related markers and a decreased expression of structural barrier proteins. The difference between HE subtypes was restricted to the lesional skin areas and included an increased expression of skin barrier-related proteins independently of the concurrent AD. In conclusion, we found that the noninvasive tape strip method used in combination with liquid chromatography-mass spectrometry proteomics can be used for analysis of skin protein expression in patients with HE. Thus, the method shows potential for assessing the proteomic differences between subtypes of HE and biomarker discovery.

The European baseline series and recommended additions: 2023.

The European baseline series was last updated in 2019. This article discusses the reasoning behind a further iteration of the series for 2023.

Aetiology of occupational hand eczema in hairdressers: Tackling the complexity of exposure combinations to identify patterns associated with increased risk of hand eczema.

INTRODUCTION: Hairdressers are exposed to wet work and manifold allergens at work, rendering exposure complex and the aetiology of occupational hand eczema (OHE) often multifactorial in this occupational group. OBJECTIVES: To identify exposure patterns associated with increased risk of hand eczema in hairdressers. METHODS: All hairdressers graduating from 2004 to 2007 and 2015 to 2018 received a questionnaire in 2009 and 2020, respectively. Current exposures (with or without regular glove use) and OHE were self-reported, and their association examined. Patterns of exposure were identified by latent class analysis (LCA). RESULTS: A total response of 39.9% (668/1675) was obtained. Six exposure profiles (#1-6) were identified by LCA across 11 tasks performed with or without gloves as well as deep conditioning, that is, 23 task items. Compared to profile #1 with the lowest OHE risk (reference) an increased risk of current OHE were seen in profile #4 [adjusted odds ratio [aOR] 6.5, 95% confidence interval [CI] 1.5-44.8 and #6 (aOR 39.4, 95%CI 6.1-362.8)] in logistic regression analysis. Profile #1 and #6 had performed the same tasks, but in profile #6 regular glove use was performed in 9.1% (1/ 11) of tasks compared to 72.7% (8/11) of tasks in profile #1 (p = 0.002). CONCLUSION: Although occupational exposures in hairdressing are complex, meaningful patterns associated with a wide range of OHE risk can be identified by LCA. The increase of OHE risk seems predominantly to be due to poor compliance with protective gloves. LCA could be applied to further fields of complex (skin) exposures.

Systematic review on skin adverse effects of important hazardous hair cosmetic ingredients with a focus on hairdressers.

BACKGROUND: The burden of occupational hand eczema in hairdressers is high, and (partly strong) allergens abound in the hair cosmetic products they use. OBJECTIVES: To systematically review published evidence concerning contact allergy to an indicative list of active ingredients of hair cosmetics, namely, p-phenylenediamine (PPD), toluene-2,5-diamine (PTD), persulfates, mostly ammonium persulfate (APS), glyceryl thioglycolate (GMTG), and ammonium thioglycolate (ATG), concerning the prevalence of sensitization, particularly in terms of a comparison (relative risk; RR) between hairdressers and non-hairdressers. METHODS: Following a PROSPERO-registered and published protocol, eligible literature published from 2000 to February 2021 was identified, yielding 322 publications, and extracted in standardized publication record forms, also considering risk of bias. RESULTS: Based on 141 publications, the contact allergy prevalence to PPD was 4.3% (95% CI: 3.8-4.9%) in consecutively patch tested patients. Other ingredients were mostly tested in an aimed fashion, yielding variable, and partly high contact allergy prevalences. Where possible, the RR was calculated, yielding an average increased sensitization risk in hairdressers of between 5.4 (PPD) and 3.4 (ATG). Additional evidence related to immediate-type hypersensitivity, experimental results, exposures, and information from case reports was qualitatively synthesized. CONCLUSIONS: An excess risk of contact allergy is clearly evident from the pooled published evidence from the last 20 years. This should prompt an improvement in working conditions and product safety.

Contact allergy to metals in metalworkers: A systematic review and meta-analysis.

Occupational hand eczema is frequent in metalworkers. The contribution of metal allergies is poorly elucidated even though such exposures are common at the workplace. To estimate the prevalence of metal allergy to cobalt (Co), chromium (Cr) and nickel (Ni) in metalworkers and compare these to estimates from the European Surveillance System on Contact Allergies (ESSCA). Two authors independently searched PubMed for studies reporting on the prevalence of metal allergy in metalworkers. Proportion meta-analyses were performed to calculate the pooled proportions of metal allergy in metalworkers. In total, 29 studies (22 from Europe) were included yielding 5691 subjects for quantitative analysis. The pooled proportion (95% confidence interval) of Co, Cr and Ni in European metalworkers with dermatitis referred to patch test clinics was 8.2% (5.3%-11.7%), 8.0% (5.1%-11.4%), and 11.0% (7.3%-15.4%), respectively. The corresponding estimates for unselected metalworkers from workplace studies were 4.9% (2.4%-8.1%), 5.2% (1.0%-12.6%), and 7.6% (3.8%-12.6%), respectively. In comparison, the prevalence of metal allergy in 13 382 consecutive European males with dermatitis was 3.9% (3.6%-4.2%), 4.4% (4.1%-4.8%) and 6.7% (6.3%-7.0%) for Co, Cr and Ni, respectively. Data on sex, age, body piercings and atopic dermatitis in metalworkers with metal allergy was mostly lacking. Metal allergy to all three metals was significantly more common in European metalworkers with dermatitis attending patch test clinics as compared to ESSCA data, indicating a relationship to occupational exposures, however, confounders could not be accounted for.

Artificial Nails and Long-lasting Nail Polish in Danish Hairdressers: Self-use, Occupational Exposure and Related Eczema.

Artificial nail modelling systems (ANMS), encompassing artificial nails and long-lasting nail polish, are sources of acrylate exposure in beauticians and users of ANMS. Hairdressers' exposure to ANMS from self-use and occupational exposure is currently unknown. In 2020 a questionnaire was sent to all hairdressers graduating during 2008 to 2018 in Denmark (n = 4,830). Self-use of ANMS was reported by 87.6% of respondents (1,251/1,428), and application of ANMS to others was reported by 22.1% (316/1,428). Of these, application to others was performed in a salon by 37.1% (109/294), privately by 51.0% (150/294) and in both settings by 11.9% (35/294). Compliance with glove use was seen in 23.0% (67/291) among those applying ANMS to others. Among hairdressers exposed to ANMS, 4.3% (52/1,218) reported ANMS-related hand eczema. Being a trained beautician (adjusted odds ratio 3.26, 95% confidence interval 1.06-9.99) and having had a positive patch-test to acrylates (adjusted odds ratio 7.70, 95% confidence interval 1.44-41.13) were associated with ANMS-related hand dermatitis. In conclusion, hairdressers have a high prevalence of exposure to ANMS and ANMS-related hand dermatitis. Compliance with glove use when applying ANMS to others is poor. Patch-testing with acrylates is valuable in the diagnostic work-up of hand eczema in hairdressers.

Association of hairdressing with cancer and reproductive diseases: A systematic review.

OBJECTIVES: To review recent epidemiological studies investigating carcinogenic or reprotoxic effects among hairdressers who seem to be at greater risk for systemic adverse effects of chemicals released from hair care products than consumers. METHODS: A systematic review according to the PRISMA-P guidelines was performed and included studies published from 2000 to August 2021, in which cancer or adverse reproductive effects were diagnosed in 1995 and onward. Data were synthetized qualitatively due to the small number of studies, heterogeneity of study designs, outcomes, and methods. RESULTS: Four studies investigating cancer frequencies and six studies investigating effects on reproduction among hairdressers were identified. All were of good quality and with low risk of bias. Only one of the four studies found an increased risk of cancer reporting nine times higher odds for bladder cancer in hairdressers than the population-based controls. Three other studies investigating bladder and lung cancer, and non-Hodgins lymphoma did not find an increased risk in hairdressers. Regarding reprotoxic effects, numerous outcomes were investigated including menstrual disorders, congenital malformations, fetal loss, small-for-gestational age newborns, preterm delivery, and infertility. Increased risk was found for ventricular septal defect in newborns of fathers working as hairdressers. Furthermore, several indices of poor neonatal or maternal health were significantly associated with mothers working as hairdresser. CONCLUSIONS: Despite the scarce evidence that hairdressers are at increased risk of carcinogenic or reprotoxic effects related to their trade, such health risks cannot be ruled out. Therefore, preventive efforts to diminish occupational exposures to hairdressing chemicals should be targeted.

A nationwide skin protection program introduced in hairdressing vocational schools was followed by a decreased risk of occupational hand eczema.

BACKGROUND: Compliance with glove use and safe work practices are important factors in primary prevention of occupational hand eczema (OHE) in hairdressers. OBJECTIVE: To assess the risk OHE and compliance with skin protective measures in hairdressers trained before and after implementation of a nationwide skin protection program in Danish hairdressing vocational schools in 2011. METHODS: A repeated cross-sectional study was performed. A questionnaire was sent in 2009 and 2020. The Danish Labour Market Supplementary Pension Scheme provided information on yearly payments from the hairdressing profession. RESULTS: A response rate of 66.6% (305/460) was obtained in the 2009 survey and of 29.9% (363/1215) in the 2020 survey. The career time prevalence of OHE decreased from 42.8% to 29.0% (adjusted odds ratio 0.55 95% confidence interval [CI] 0.40-0.77) and the incidence rate of OHE decreased from 57.5 (95%CI 48.4-68.4) to 42.0 (95%CI 34.6-50.9) per 1000 person years (incidence rate ratio 0.73 [95%CI 0.56-0.95] between the two surveys). A statistically significant (P < .05) increase in glove use when doing wet-work and when handling hair dyes, permanent wave solutions and bleaching products was observed in the 2020 compared to the 2009 survey. CONCLUSION: Our data suggest that skin protection training during apprenticeship reduces the risk of OHE in hairdressers. The lack of primary prevention of OHE in hairdressing vocational schools may be a missed opportunity in the prevention of the disease.

Occupational Exposure of Hairdressers to Airborne Hazardous Chemicals: A Scoping Review.

INTRODUCTION: Exposure to hazardous chemicals released during hairdressing activities from hair care products puts hairdressers at risk of adverse health effects. Safety assessments of hair products are mainly focused on consumers, but exposure for professional hairdressers might be substantially higher. OBJECTIVE: To identify and assess available research data on inhalation exposures of professional hairdressers. METHODS: A systematic search of studies between 1 January 2000 and 30 April 2021 was performed in Medline, Embase, Web of Science and in Cochrane registry, toxicological dossiers of the Scientific Committee on Consumer Safety (SCCS) of the European Commission as well as the German MAK Commission. Studies reporting quantitative data on airborne concentrations of chemicals in the hairdresser's workplace were considered. The outcome was an airborne concentration of chemicals in the working environment, which was compared, when possible, with current occupational exposure limits (OEL) or guidance levels. RESULTS: In total, 23 studies performed in 14 countries were included. The average number of hairdressing salons per study was 22 (range 1-62). Chemicals most frequently measured were formaldehyde (n = 8), ammonia (n = 5), total volatile organic compounds (TVOC) (n = 5), and toluene (n = 4). More than fifty other chemicals were measured in one to three studies, including various aromatic and aliphatic organic solvents, hydrogen peroxide, persulfate, and particulate matter. Most studies reported environmental air concentrations, while personal exposure was measured only in seven studies. The measured air concentrations of formaldehyde, ammonia, and TVOC exceeded OEL or guidance values in some studies. There was large variability in measuring conditions and reported air concentrations differed strongly within and between studies. CONCLUSION: Hairdressers are exposed to a wide spectrum of hazardous chemicals, often simultaneously. Airborne concentrations of pollutants depend on salon characteristics such as ventilation and the number of customers but also on used products that are often country- or client-specific. For exposure to formaldehyde, ammonia, and TVOC exceeding OELs or guidance values for indoor air was observed. Therefore, occupational exposure should be taken into account by safety regulations for hair care products.